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Introduction: Coagulation activation on medical devices remains a significant problem as it can lead to dramatic thromboembolic complications. Understanding its poorly described mechanisms and finding optimal pharmacological prevention means is crucial to improve patient safety., Methods: We developed an in vitro model to study thrombin generation (TG) initiated by the contact of plasma with the surface of catheters. Interventional cardiology catheters were cut into segments and inserted in the bottom of multi-well plates; TG was then measured with the calibrated automated thrombogram (CAT). Model performance (analytical, intra- and inter-individual variability) was investigated and compared with activation of thrombin generation by tissue factor (TF) or contact pathway activator (ellagic acid), in the presence (PRP) and absence (PPP) of platelets. Model response to unfractionated heparin (UFH) was also assessed., Results: TG was greater when measured in presence of catheter segments, compared to conditions without activators. The analytical variability of the model was good (CV ≤ 5 %), both with PPP and PRP. Intra-individual variability was between 15 and 30 % with PPP and between 10 and 15 % with PRP. Inter-individual variability was between 15 and 30 % with both kinds of plasma samples. The analytical performance of the catheter-initiated TG model was equivalent to that observed when TG was initiated with TF or ellagic acid. Catheter-initiated TG was measurable until 0.1 IU/mL UFH with PPP and until 1.0 IU/mL UFH with PRP, highlighting the crucial requirement of platelets., Conclusion: Our model is suitable for studying TG initiated with catheters. Inhibition of TG by UFH is overestimated in the absence of platelets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael hardy reports financial support was provided by Fund for Scientific Research. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of interest MH, BR, OX, SL, TL: none. JD is the CEO and founder of QUALIblood s.a., a contract research organization manufacturing the DP-Filter, is a coinventor of the DP-Filter (patent application number: PCT/ET2019/052903) and reports personal fees from Daiichi-Sankyo, Mithra Pharmaceuticals, Diagnostica Stago, Roche and Roche Diagnostics, outside the submitted work. FM reports institutional fees from Stago, Werfen, Nodia, Roche Sysmex and Bayer. He also reports speaker fees from Boehringer-Ingelheim, Bayer Healthcare, Bristol-Myers Squibb-Pfizer, Diagnostica Stago, Sysmex and Aspen, all outside the submitted work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Since the risk factors for heparin resistance (HR) before cardiopulmonary bypass (CPB) have not been fully clarified, this study investigated the contributing factors for HR after the initial unfractionated heparin (UFH) dose of 500 IU/kg. We retrospectively analyzed the data of 371 patients who underwent CPB surgery, with the initial UFH dose of 500 IU/kg, between May 2017 and December 2021. We defined HR as the failure to achieve activated clotting time (ACT) of > 480 s after the initial UFH dose of 500 IU/kg. HR was observed in 36 patients (9.7%) (HR group), while HR was not observed in 335 patients (control group). The HR group included significantly more patients with preoperative use of UFH, with significantly higher white blood cell counts, fibrinogen, fibrinogen degradation products, D-dimer, and C-reactive protein, and lower hemoglobin and albumin. The multivariable logistic regression analysis identified albumin (OR: 3.09, 95% CI 1.3504-7.0845, p = 0.0075) and fibrinogen (OR: 0.99, 95% CI 0.9869-0.9963, p = 0.0003) as independent predictors for HR. Using the Youden index, the cutoffs of albumin and fibrinogen were calculated as 3.8 g/dL and 303 mg/dL, respectively. The receiver operating characteristic curves showed the predictive performance of albumin (area under the curve (AUC): 0.78, sensitivity: 65%, specificity: 81%) and fibrinogen (AUC: 0.77, sensitivity: 56%, specificity: 88%). The incidence of HR after the initial UFH dose of 500 IU/kg was 9.7%. The preoperative albumin < 3.8 g/dL and fibrinogen > 303 mg/dL were independent predictors for HR., Competing Interests: Declarations. Conflict of interest: The authors have no conflicts of interest to disclose., (© 2024. The Japanese Society for Artificial Organs.)

Background: Finding the balance between the reduction in ischemic events and bleeding complications is crucial for the success of percutaneous coronary intervention (PCI). The activated clotting time (ACT) is used routinely worldwide to monitor and titrate anticoagulation therapy with unfractionated heparin (UFH) during the procedure., Objectives: We aimed to test the accuracy of ACT measurements from the guiding catheter compared to the arterial access sheath., Methods: Patients undergoing PCI with UFH therapy were prospectively enrolled. Blood samples were drawn from the coronary guide catheter and the arterial access sheath. ACT values were determined in the same ACT machine, and potential interactions with clinical variables were analyzed., Results: The study included 331 patients with post PCI ACT measurements. The mean ACT value of the catheter samples was statistically higher than the arterial access sample [294 ± 77 s Vs. 250 ± 60 s, p < 0.001]. The mean difference between the guiding catheter and the arterial line sheath samples was 43 ± 27 s (P < 0.001). We found that in 101/331 [30 %] patients the ACT from the guiding catheter was above 250 s, while from the access sheath it was below 250 s. Notably, in 40/331 [12 %] the ACT from the guiding catheter was above 200 s, while from the access sheath it was below 200 s., Conclusions: Large proportion of patient may be considered to have therapeutic ACT if measured from guide catheter during PCI, while the corresponding ACT from arterial sheath is subtherapeutic. This difference may have clinical and safety significance., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. There are no conflicts of interest by the authors., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Unfractionated heparin (UFH) is commonly used as an anticoagulant in sepsis treatment and has recently been found to have non-anticoagulant effects, but underlying mechanisms remain unclear. This retrospective clinical data showed that UFH has significant protective effects in sepsis compared to low-molecular-weight heparin and enoxaparin, indicating potential benefits of its non-anticoagulant properties. Recombinant protein chip screening, surface plasmon resonance, and molecular docking data demonstrated that UFH specifically bound to the cytoplasmic Drp1 protein through its zone 2 non-anticoagulant segment. In-vitro experiments verified that UFH's specific binding to Drp1 suppressed Drp1 translocation to mitochondria following "sepsis" challenge, thereby improving mitochondrial morphology, function and metabolism in vascular endothelial cells. Consequently, UHF comprehensively protected mitochondrial quality, thus reducing vascular leakage and improving prognosis in a sepsis rat model. These findings highlight the potential of UFH as a sepsis treatment strategy targeting non-anticoagulation mechanism., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Anti-β2-glycoprotein I (β2GPI)/human leukocyte antigen (HLA)-DR antibodies may be a risk factor for recurrent pregnancy loss (RPL). The therapeutic modality for women with RPL and anti-β2GPI/HLA-DR antibody positivity has not been evaluated. This prospective, multicenter, observational study aimed to assess whether low-dose aspirin (LDA) and/or heparin therapies improve pregnancy outcomes in women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies., Methods: Between August 2019 and December 2021, 462 women with RPL underwent anti-β2GPI/HLA-DR antibody measurements and risk assessments for RPL. Each attending physician decided the treatment modality for women with RPL who tested positive for anti-β2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-β2GPI/HLA-DR antibody positivity were included in the analysis and were divided into two groups regarding whether they were treated with LDA and/or unfractionated heparin (UFH) (LDA/UFH group, n = 39) or with neither of them (non-LDA/non-UFH group, n = 8). The rates of live birth and pregnancy complications (i.e., preeclampsia and preterm delivery before 34 gestational weeks due to placental insufficiency) were compared between the two groups., Results: The live birth rate in the LDA/UFH group was higher than that in the non-LDA/non-UFH group (87.2% vs 50.0%, p = 0.03). The pregnancy complication rate in the LDA/UFH group was significantly lower than that in the non-LDA/non-UFH group (5.9% vs 50.0%, p = 0.048). Among 21 women who tested positive for anti-β2GPI/HLA-DR antibodies and had no other risk factors for RPL, the live birth rate in the LDA/UFH group (n = 14) was much higher than that in the non-LDA/non-UFH group (n = 7) (92.9% vs 42.9%, p = 0.03)., Discussion: This study, for the first time, demonstrated that LDA and/or UFH therapies are effective in improving pregnancy outcomes in women with RPL and aβ2GPI/HLA-DR antibody positivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tanimura, Saito, Tsuda, Ono, Deguchi, Nagamatsu, Fujii, Nakatsuka, Kobashi, Arase and Yamada.)

Purpose: Anticoagulation therapy aims to improve the outcome of critically ill patients with severe COVID-19-associated pneumonia. Activated partial thromboplastin time (aPTT) is commonly used to maintain the target therapeutic range of continuous infusion of unfractionated heparin (UFH). The UFH infusion efficacy can be evaluated by determining the time in therapeutic range (TTR) using a modified Rosendaal method. The present study's primary aim was to evaluate TTR based on the aPTT in critically ill patients with severe forms of COVID-19 pneumonia and its influence on survival. The secondary aim was to evaluate the time spent above (TATR) and below the therapeutic range (TBTR)., Patients and Methods: We performed a retrospective analysis of critically ill patients with COVID-19-associated pneumonia. All patients received a continuous infusion of UFH from the 2nd to 8th day since admission to the ICU. TTR, TATR, and TBTR were calculated using the modified Rosendaal method, and survival days were analyzed by regression (censored after 60 days)., Results: Of 103 patients, the median TTR was 49% (IQR 38-63%), TATR 11% (IQR 5-20%), and TBTR 33% (IQR 22-51%). The regression analysis indicated a positive impact of higher TTR and TATR on the number of survival days [β=0.598 (p=0.0367) and β=1.032 (p=0.0208), respectively] and a negative impact of higher TBTR [β=-0.681 (p=0.0033)] on the number of survival days., Conclusion: Higher TTR and TATR were associated with better survival of critically ill patients with a severe course of COVID-19-associated pneumonia. Higher TBTR was associated with worse survival in these patients., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Romanová et al.)

Background: This retrospective observational study aimed to examine whether clinical inflammatory parameters were associated with the requirement dosage of unfractionated heparin (UFH) to maintain the range of ACT in veno-arterial extracorporeal membrane oxygenation (V-A ECMO) during lung transplantation surgery., Methods: Among all patients who underwent lung transplantation using V-A ECMO from January 2021 to May 2022, 27 patients were included. These patients were divided into two groups based on whether the infusion rate of UFH was increased from the initial infusion rate (7-8 units/kg/h) (increased group, n = 10) or the infusion rate was maintained or decreased (non-increased group, n = 17). The infusion rate was adjusted with an activated clotting time (ACT) target of 160-200 s., Results: At 1-2 h after starting ECMO, ACT was significantly lower (179.0 (166.5-188.5) versus 224.0 (193.0-242.0) sec, p = 0.006) and white blood cell (WBC) counts were higher in the increased group (12.6 ± 3.3 versus 9.5 ± 4.0 × 10 3 /μL, p = 0.046). The UFH infusion rates were higher in the increased group during the surgery. The cutoff value of WBC count at 1-2 h after starting ECMO for discriminating the need for increasing the UFH dosage was determined as 10.2 × 10 3 /μL (sensitivity 90.0%, specificity 58.8%, area under the curve 0.712) and discrimination of this cut-off value was confirmed as statistically significant (p = 0.018)., Conclusion: These data suggested that WBC count was associated with the requirement of an increase in the UFH infusion rate of V-A ECMO during lung transplantation surgery. Further evaluation is necessary to clarify the role of WBC count in determining the optimal UFH dosage., (© The Author(s), published by EDP Sciences, 2024.)

Background: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years., Methods: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here., Results: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups., Conclusions: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT02311231., Competing Interests: Declaration of competing interest Elmir Omerovic reports grants from Astra Zeneca, personal fees from Astra Zeneca, MSD, Bayer, Janssen outside the submitted work. Stefan James reports grants from Astra Zeneca, grants from The Medicines Company, grants from Swedish Heart and Lung Foundation, and grants from Swedish Research Council during the conduct of the study; personal fees from Bayer and grants from Jansen outside the submitted work. Truls Råmunddal reports personal fees from Boston Scientific and personal fees from Abbot outside the submitted work. Ole Fröbert reports personal fees from GE Medical and from Astra Zeneca outside the submitted work. Pontus Lindroos reports personal fees from Astra Zeneca outside the submitted work. Anders Ulvenstam reports personal fees from Boston Scientific outside the submitted work. Matthias Götberg reports grants and personal fees from Volcano Corporation, personal fees from Boston Scientific, and personal fees from Medtronic Corporation outside the submitted work. Oskar Angerås Dr. reports personal fees from Astra Zeneca outside the submitted work. Olie Östlund reports grants from AstraZeneca, grants from The Medicines Company. Cleas Held reports grants and personal fees from AstraZeneca, grants from GlaxoSmithKline, grants from BristolMyers Squibb, and grants from Merck outside the submitted work. Sasha Koul reports personal fees from Pfizer, personal fees from BMS, and personal fees from Astra Zeneca outside the submitted work. David Erlinge reports personal fees from Astrazeneca and The Medicines Company outside the submitted work. All others co-authors have nothing to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The current guidelines for acute coronary syndrome (ACS) discourage the use of anticoagulation after percutaneous coronary intervention (PCI) without specific indications, although the recommendation is not well supported by evidence. In this post hoc analysis of the ShorT and OPtimal Duration of Dual AntiPlatelet Therapy-3 (STOPDAPT-3) trial, 30-day outcomes were compared between the 2 groups with and without post-PCI heparin administration among patients with ACS who did not receive mechanical support devices. The co-primary end points were the bleeding end point, defined as the Bleeding Academic Research Consortium type 3 or 5 bleeding, and the cardiovascular end point, defined as a composite of cardiovascular death, myocardial infarction, definite stent thrombosis, or ischemic stroke. Among 4,088 patients with ACS, 2,339 patients (57.2%) received post-PCI heparin. The proportion of patients receiving post-PCI heparin was higher among those with ST-elevation myocardial infarction compared with others (72.3% and 38.8%, p <0.001), and among patients with intraprocedural adverse angiographic findings compared with those without (67.6% and 47.5%, p <0.001). Post-PCI heparin compared with no post-PCI heparin was associated with a significantly increased risk of the bleeding end point (4.75% and 2.52%, adjusted hazard ratio 1.69, 95% confidence interval 1.15 to 2.46, p = 0.007) and a numerically increased risk of the cardiovascular end point (3.16% and 1.72%, adjusted hazard ratio 1.56, 95% confidence interval 0.98 to 2.46, p = 0.06). Higher hourly dose or total doses of heparin were also associated with higher incidence of both bleeding and cardiovascular events within 30 days. In conclusion, post-PCI anticoagulation with unfractionated heparin was frequently implemented in patients with ACS. Post-PCI heparin use was associated with harm in terms of increased bleeding without the benefit of reducing cardiovascular events. Trial identifier: STOPDAPT-3 ClinicalTrials.gov number, NCT04609111., Competing Interests: Declaration of competing interest Dr. Watanabe reports lecturer's fees from Abbott Medical Japan during the conduct of the study and from Daiichi Sankyo, Pfizer, Amgen, and Astellas outside the submitted work. Dr. Natsuaki reports honoraria from Abbott Medical Japan, Daiichi Sankyo, Medtronic, Terumo, Japan Lifeline, Asahi Intecc, Bristol-Myers Squibb, Otsuka, Amgen, Sanofi, Takeda, and Bayer. Dr. Morimoto reports lecturer's fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Japan Lifeline, Pfizer (New York, New York, United States), Tsumura, and UCB; manuscript fee from Pfizer; and advisory board membership for GlaxoSmithKline, Novartis, and Teijin. Dr. Obayashi reports lecturer's fee from Abbott Medical Japan. Dr. Suwa reports personal fees from Abbott Medical Japan and Daiichi Sankyo outside the submitted work. Dr. Ogita reports personal fees from Daiichi Sankyo, Abbott Medical Japan, and Japan Lifeline outside the submitted work. Dr. Suzuki reports grants from Abbott Medical Japan during the conduct of the study. Dr. Morishima reports honoraria from Abbott Medical Japan and Daiichi Sankyo. Dr. Kimura reports grants from Abbott Medical Japan and Boston Scientific and being an advisory board member for Abbott Medical Japan and Terumo Japan. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Heparin resistance (HR) is observed before cardiopulmonary bypass (CPB), despite with normal antithrombin III (AT-III) levels. The relationships between preoperative AT-III activity and activated clotting time (ACT) after the first heparin dose should be clarified. We retrospectively analyzed the data of 818 patients who underwent CPB surgery, with the initial heparin of 300, 400, and 500 IU/kg, between 2017 and 2021. We defined HR as the failure to achieve ACT after the initial heparin dose (Post ACT) of > 480 s.There were no significant correlations between the AT-III activity and Post ACT in all patients, including 143 patients with AT-III activity < 80% and 675 patients with AT-III activity of ≥ 80%. Also, there were no significant correlations between the AT-III activity and Post ACT in 74 patients who received heparin of 300 IU/kg, in 186 patients with 400 IU/kg, and in 339 patients with 500 IU/kg. After identifying smoking, HR, activated partial thromboplastin time, fibrinogen degradation products (FDP), and ACT as influencing factors, multiple comparisons using the Steel-Dwass test showed significant difference in FDP and HR among the patients who received heparin of 300 IU/kg, 400 IU/kg, and 500 IU/kg. There is no association between preoperative AT-III activity and ACT after the first heparin administration for CPB, even in different dose of heparin. Rather, the higher the initial UFH dose is, the higher ACT may be, regardless of the AT-III activity., (© 2024. The Japanese Society for Artificial Organs.)

Aim: Several studies have shown the efficacy and safety of low-molecular-weight heparin use in coronavirus disease 2019 (COVID-19), but that of unfractionated heparin (UFH) has not been investigated. We investigated the prevalence of bleeding complications during UFH administration, its impact on mortality, and the risk factors of bleeding outcomes associated with UFH., Methods: This retrospective cohort study was conducted at a single-center tertiary care hospital, including hospitalized patients with COVID-19. The primary outcomes were measured as the prevalence of bleeding complications during hospitalization, and the secondary outcomes were thromboembolic events and 60-day mortality rates. Logistic regression analysis and propensity score matching were used to assess risk factors for bleeding complications and their impact on mortality., Results: Among 1035 included patients, 516 patients were treated with UFH. Twelve (2.3%) patients in the UFH group experienced major bleeding. The prevalence of major bleeding in patients treated with therapeutic-dose UFH was 9.2%. Logistic regression analysis showed that age ≥ 60 years (adjusted odds ratio [aOR], 3.89; 95% confidence interval [CI], 1.01-15.0; P＜.05) and COVID-19 severity (aOR, 35.9; 95% CI, 4.57-282; P＜.05) were associated with major bleeding complications. After propensity score matching, 11 major and 11 non-major bleeding cases (including minor bleeding) were matched. The 60-day cumulative mortality rate between the two groups did not differ significantly (P=.13, log-rank test)., Conclusions: The incidence of major bleeding in COVID-19 patients using therapeutic-dose UFH was relatively high. Critical COVID-19 and older age were risk factors for bleeding complications.

Background: Pregnant patients with preterm prelabor rupture of membranes (PPROM) may experience prolonged hospitalization, which is an indication for pharmacologic venous thromboembolism (VTE) prophylaxis according to certain international guidelines. The proportion of patients who deliver unexpectedly and within a period during which pharmacologic prophylaxis would be expected to impact coagulation is unknown., Objective: To estimate the proportion of patients with PPROM who would deliver within 12 hours of typical dosing of pharmacologic VTE prophylaxis if administered routinely for antepartum admissions >72 hours., Study Design: This is a retrospective cohort study from a database including patients admitted for expectant management of PPROM January 2011 to September 2020. The outcome of the study was the proportion of patients who remained undelivered 72 hours after admission and experienced an unplanned delivery potentially within 12 hours of enoxaparin administration. We evaluated patients undelivered after 72 hours due to international recommendations to initiate VTE prophylaxis in hospitalized patients after 72 hours. Unplanned delivery was defined as onset of spontaneous labor or other indication for immediate delivery. Timing of delivery was analyzed based on usual timing of enoxaparin administration daily at approximately 8 am and the recommendation to withhold regional anesthesia until 12 hours after a prophylactic dose., Results: 1381 deliveries were identified as PPROM out of the 49,322 deliveries in our database. 139 cases were included after the following exclusions: delivery >35 weeks (N=641), rupture of membranes >34 weeks (N=145), delivery <72 hours after admission (N=409), insufficient data (N=35), and duplicates (N=12). Sixty of the 139 (43%) had an unplanned delivery, while 33 of these (24% of total) occurred within 12 hours of enoxaparin administration., Conclusion: A quarter of patients admitted for PPROM had an unplanned delivery within 12 hours of typical enoxaparin dosing. This cohort may experience harm (ineligibility for regional anesthesia, risks of general anesthesia, increased risk of bleeding) if given routine pharmacologic VTE prophylaxis. Risk/benefit considerations should be discussed with patients in considering pharmacologic versus mechanical prophylaxis during prolonged hospitalization for PPROM., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Subcutaneous injection of unfractionated heparin (UH) or low molecular weight heparin (LMWH) is frequently utilized for venous thromboembolism chemoprophylaxis. We previously discovered that nurses believe patients experience more pain with UH compared to the LMWH enoxaparin; however, no published studies that are appropriately powered exist comparing pain associated with subcutaneous chemoprophylaxis. Our objective was to assess if differences exist in pain associated with subcutaneous administration of UH and enoxaparin. We conducted an observational study of patients who underwent major abdominal surgery between 11/2017-4/2019. All patients received one of three prophylactic regimens: (1) UH only, (2) Initial dose of UH followed by enoxaparin, or (3) enoxaparin only. Of the 74 patients observed, 40 patients received UH followed by enoxaparin, 17 received UH only, and 17 received enoxaparin only. There was a significant difference in patients' mean perceived pain between subcutaneous UH and enoxaparin injections (mean post-injection pain after UH 3.3 vs. enoxaparin 1.5; p  < 0.001). There was no significant difference in perceived pain for patients who received consecutive UH or enoxaparin injections. Differences in pain associated with different chemoprophylaxis agents may be an unrecognized driver of patient refusals of VTE chemoprophylaxis and may lead to worse VTE outcomes., Competing Interests: None., (© 2024 The Authors. Published by Elsevier Inc.)

Background: Prosthetic valve thrombosis (PVT) is a severe and life-threatening complication. Surgery and thrombolytic therapy (TT) carry a high risk, and in several circumstances, optimal anticoagulation with unfractionated heparin (UFH) infusion may be an alternative treatment. This study aimed to assess the results of UFH in patients diagnosed with both obstructive and non-obstructive PVT., Methods: This observational retrospective study enrolled patients who had contraindications for TT and surgery underwent UFH therapy., Results: A total of 136 patients were enrolled [male: 55 (40.4%), mean age: 50.3 ± 14.6 years] in the study. In the successful group, 66 patients (48,5%) showed >75% regression in the thrombus burden without facing death or major non-fatal complications.In the unsuccessful group, 56 had less than a 50% reduction in thrombus load and 14 (10.3%) suffered major complications. The presence of obstruction (27.1% vs. 12.1%; p = 0.028), thrombus area 1.1 cm 2 vs. 0.8 cm 2 ; p = 0.005] and the duration of UFH treatment (15.1 vs. 11.8 (days); p = 0.005) were significantly higher in the unsuccessful UFH group.In multivariate regression analyses the presence of obstruction (RR: 3.088, p = 0.020), increased thrombus area (RR: 2.400; p = 0.015), and increased duration of UFH therapy (RR: 1.073 95%, p = 0.012) were identified as independent predictive parameters for a failed UFH therapy., Conclusions: This study suggests that UFH therapy may be considered a relatively beneficial treatment strategy for some patients with PVT. The most significant factors affecting success are the obstructive nature and area of the thrombus., Competing Interests: Declaration of competing interest All of the authors have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial anticoagulation that allows for therapeutic adjustment or manipulation is important. The preferred choice of anticoagulation management includes direct oral anticoagulants. Vitamin K antagonists and low-molecular-weight heparin are preferred in special populations or selected patients such as breastfeeding mothers, those with end-stage renal disease, or obese patients, among others. This article reviews the primary and longer-term considerations for anticoagulation management in patients with PE and highlights special patient populations and risk factor considerations., Competing Interests: The author has no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Use of unfractionated heparin (UFH) during the peripartum period is considered to be a higher risk of critical obstetric bleeding compared to low-molecular-weight heparin (LMWH). However, the evidence for the safety of using LMWH during the peripartum period is currently lacking., Methods: This study retrospectively investigated a nationwide medical database to clarify the safety of using LMWH during childbirth. The Japanese Nationwide Diagnosis Procedure Combination database was retrospectively reviewed, and data from women with childbirth between 2018 and 2022 were collected., Results: Among the overall 354,299 women with childbirth, 3,099 were with obstetric disseminated intravascular coagulation (DIC), 484 were with critical obstetric bleeding requiring massive red blood cell (RBC) transfusion ≥4,000 cc, and 38 were with maternal death. Among the overall women, each of the anticoagulants other than LMWH was associated with critical obstetrical bleeding with an adjusted odds ratio (aOR) greater than 1.0, while LMWH was not associated with critical obstetrical bleeding (aOR, 0.54 (95% confidence interval, 0.11-2.71)). This finding did not change in subgroup analyses among those with Cesarean section. Furthermore, UFH was associated with critical bleeding among the 3,099 women with obstetrical DIC (aOR, 3.91 (2.83-5.46)), while LMWH was not (aOR, 0.26 (0.03-1.37))., Conclusion: The use of UFH was significantly associated with an increased critical obstetric hemorrhage requiring massive RBC transfusion or total hysterectomy. Meanwhile, the use of LMWH was not associated with increased critical obstetric bleeding. LMWH would be safer than UFH to be used for women during childbirth., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Akaishi et al.)

Objective: To compare bleeding and thromboembolic events in low body weight patients receiving reduced-dose venous thromboembolism (VTE) prophylaxis versus standard-dose VTE prophylaxis., Design: Multicenter, retrospective, cohort study., Setting: Five Ascension Health Hospitals., Patients: Adult, critically ill, low body weight (≤50 kg) patients who received either reduced-dose VTE prophylaxis (n = 140) or standard-dose VTE prophylaxis (n = 279) for at least 48 h., Intervention: Reduced-dose prophylaxis (enoxaparin 30 mg daily or heparin 5000 units every 12 h subcutaneously) or standard-dose prophylaxis (enoxaparin 40 mg daily, enoxaparin 30 mg every 12 h, or heparin 5000 units every 8 h subcutaneously)., Measurements and Main Results: A total of 419 patients were included with a mean weight of 45.1 ± 4.2 kg in the standard-dose group and 44.0 ± 5.1 kg in the reduced-dose prophylaxis group ( P  = .02). The primary endpoint, composite bleeding, was significantly lower in patients receiving reduced-dose prophylaxis (5% vs 12.5%, P  = .02). After adjusting for confounding factors, results remained consistent demonstrating reduced composite bleeding with reduced-dose prophylaxis (odds ratio: 0.36, 95% confidence interval: 0.14-0.96). Major bleeding events occurred in 3.6% of reduced-dose patients compared with 8.6% in standard-dose patients ( P  = .056). Clinically relevant nonmajor bleeding (5.4% vs 2.9%, P  = .24) and VTE (2.2% vs 0%, P  = .08) events were similar between groups., Conclusions: A reduced-dose VTE prophylaxis strategy in low body weight, critically ill patients was associated with a lower risk of composite bleeding and similar rate of thromboembolism., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Treating deep vein thrombosis (DVT) using a once-daily dose of enoxaparin offers greater convenience and the possibility of home-based care for certain patients, as opposed to a continuous infusion of unfractionated heparin (UFH). The study aimed to determine the most cost-effective thromboprophylaxis between low-molecular-weight heparin (LMWH) and UFH for hospitalized patients., Materials and Methods: After obtaining clearance from the institutional ethical committee, the study was conducted in the Department of General Surgery, Sri Devaraj Urs Medical College, over a period of six months. Informed consent was obtained from all 46 patients included in this study. The participants were divided into two groups: group A received LMWH and group B received UFH., Results: The mean age in group A was 59.8 + 10.6 years and in group B was 54.9 + 12.3 years. There was no significant difference in the girth of the lower limb between the groups during the follow-up period (p > 0.05). In group A, there was a highly significant reduction in lower limb girth from day one to day five (p < 0.0001), day five to day 10 (p < 0.0001), and day one to day 10 (p < 0.0001). In group B, there was no significant reduction from day one to day five (p = 0.06), but there was a significant reduction from day five to day 10 (p = 0.001) and day one to day 10 (p = 0.001)., Conclusion: Treatment with LMWH as an anticoagulant significantly reduced the lower extremity girth and thrombus thickness in cases of DVT when compared to UFH., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ullalkar et al.)

In managing cerebral venous sinus thrombosis (CVT), the standard approach has been administering parenteral anticoagulation for at least five days, despite limited supporting evidence. This study aimed to determine the optimal duration of parenteral anticoagulation for CVT patients and its potential impact on their functional outcomes upon discharge. This retrospective observational cohort study was conducted across multiple healthcare centers and included adult CVT patients who received varying durations of parenteral anticoagulation: less than 5 days (n = 25) or 5 days or more (n = 16). The primary focus was on the duration of acute anticoagulation treatment, with secondary endpoints including hospital stay length and functional outcomes. The study found that a shorter duration of anticoagulation treatment (< 5 days) was linked to more favorable outcomes, as measured by the modified Rankin Scale (mRS) (68% vs. 25%, RR = 0.37, CI 0.15-0.90, p = 0.007). However, regression analysis showed non statistically significant associations for all variables except gender. Female patients were significantly more likely to receive a shorter duration of anticoagulation (Odds Ratio: 2.6, 95% CI: 2.2-3.1, P-Value: <0.001). These findings suggest a potential connection between shorter anticoagulation duration (< 5 days) and improved CVT patient outcomes, as indicated by their mRS scores at discharge. The observed relationship between female gender and shorter anticoagulation duration warrants further exploration. Nevertheless, caution is necessary when interpreting these findings due to the small sample size and specific patient characteristics. Further research in a larger and more diverse cohort is essential to validate these results and understand their implications fully., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Venous thromboembolism (VTE) is a common complication in critically ill patients, including severe burn cases. Burn patients respond differently to medications due to pharmacokinetic changes. This study aims to assess the feasibility and safety of different VTE pharmaco-prophylaxis in patients admitted to the ICU with severe burns., Methods: A pilot, open-label randomized controlled trial was conducted on ICU patients with severe burns (BSA ≥ 20%). By using block randomization, patients were allocated to receive high-dose enoxaparin 30 mg q12hours (E30q12), standard-dose enoxaparin 40 mg q24hours (E40q24), or unfractionated heparin (UFH) 5000 Units q8hours. In this study, the primary outcomes assessed were the recruitment and consent rates, as well as bleeding or hematoma at both the donor and graft site. Additionally, secondary measures were evaluated to provide further insights., Results: Twenty adult patients out of 114 screened were enrolled and received E30q12 (40%), E40q24 (30%), and UFH (30%). The recruitment rate was one patient per month with a 100% consent rate. Donor site bleeding occurred in one patient (16.7%) in the UFH group. On the other hand, graft site bleeding was only reported in one patient (12.5%) who received E30q12. Major bleeding happened in two patients, one in E30q12 and one in the UFH group. Five patients (25.0%) had minor bleeding; two patients (25.0%) received E30q12, two patients E40q24, and one patient UFH. RBC transfusion was needed in four patients, two on E30q12 and two on UFH. Only one patient had VTE, while four patients died in the hospital., Conclusion: The study observed a low recruitment rate but a high consent rate. Furthermore, there were no major safety concerns identified with any of the three pharmacologic prophylaxis regimens that were evaluated., Trial Registration Number: NCT05237726., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background:  The conventional method of heparin and protamine management during cardiopulmonary bypass (CPB) is based on total body weight which fails to account for the heterogeneous response to heparin in each patient. On the other hand, the literature is inconclusive on whether individualized anticoagulation management based on real-time blood heparin concentration improves post-CBP outcomes., Methods:  We searched databases of Medline, Excerpta Medica dataBASE (EMBASE), PubMed, Cumulative Index to Nursing and Allied Health Literature (CINHL), and Google Scholar, recruiting randomized controlled trials (RCTs) and prospective studies comparing the outcomes of dosing heparin and/or protamine based on measured heparin concentration versus patient's total body weight for CPB. Random effects meta-analyses and meta-regression were conducted to compare the outcome profiles. Primary endpoints include postoperative blood loss and the correlation with heparin and protamine doses, the reversal protamine and loading heparin dose ratio; secondary endpoints included postoperative platelet counts, antithrombin III, fibrinogen levels, activated prothrombin time (aPTT), incidences of heparin rebound, and re-exploration of chest wound for bleeding., Results:  Twenty-six studies, including 22 RCTs and four prospective cohort studies involving 3,810 patients, were included. Compared to body weight-based dosing, patients of individualized, heparin concentration-based group had significantly lower postoperative blood loss (mean difference (MD)=49.51 mL, 95% confidence interval (CI): 5.33-93.71), lower protamine-to-heparin dosing ratio (MD=-0.20, 95% CI: -0.32 ~ -0.12), and higher early postoperative platelet counts (MD=8.83, 95% CI: 2.07-15.59). The total heparin doses and protamine reversal were identified as predictors of postoperative blood loss by meta-regression., Conclusions:  There was a significant correlation between the doses of heparin and protamine with postoperative blood loss; therefore, précised dosing of both could be critical for reducing bleeding and transfusion requirements. Data from the enrolled studies indicated that compared to conventional weight-based dosing, individualized, blood concentration-based heparin and protamine dosing may have outcome benefits reducing postoperative blood loss. The dosing calculation of heparin based on the assumption of a one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model and linear relationship between the calculated dose and blood heparin concentration may be inaccurate. With the recent advancement of the technologies of machine learning, individualized, precision management of anticoagulation for CPB may be possible in the near future., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Raner et al.)

Introduction: This study aimed to determine the impact of augmented renal clearance (ARC) on anticoagulation therapy in critically ill patients with coronavirus disease 2019 (COVID-19)., Methods: This retrospective cohort study included adult patients with severe COVID-19 with ARC who had been treated at our hospital between 2020 and 2021. We measured the estimated glomerular filtration rate calculated by the Chronic Kidney Disease Epidemiology Collaboration formula (eGFR CKD-EPI ) every morning, and ARC condition was defined as eGFR CKD-EPI ≥ 130 mL/min/1.73 m 2 . Multivariate regression analysis with Huber-White sandwich estimator was performed to examine the association of unfractionated heparin (UH) dosage between blood test timings with activated partial thromboplastin time (APTT) compared with and without ARC., Results: We identified 38 enrolled patients: seven and 31 in the ARC and non-ARC groups, respectively. In the ARC coexisting condition, a higher dose of UH, which corresponded to the total dose in 24 h from the previous day, was required to achieve the same APTT prolongation, with a significant difference (p < 0.001)., Conclusions: Our study suggests that careful monitoring and consideration of higher UH doses in critically ill patients with COVID-19 is necessary because anticoagulation failure can occur during ARC., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Objective: There are no studies to date that examine the association between anti-factor-Xa (AFXa)-based heparin monitoring and clinical outcomes in the setting of cerebral venous thrombosis (CVT)., Methods: This pilot study included adults aged ≥18 admitted with CVT between 1 January 2018 and 1 January 2021, who were treated with unfractionated heparin (UFH) and were monitored via AFXa-based nomogram within 24 h of arrival. Comparisons were made between patients with AFXa levels within the target therapeutic range (0.25-0.5 IU/mL) and patients whose levels were not within the therapeutic range within 24 h of arrival; the time (hours) from arrival to reach the therapeutic range was also examined. Outcomes were length of stay (LOS) in the hospital, major (actionable) bleeding events, and discharge home (vs. higher acuity location). Continuous data are reported in the form of the median (interquartile range)., Results: Among 45 patients, treatment with UFH was initiated 2 (1-11) h after arrival, and the majority (84%) of UFH infusions did not need dose adjustment. AFXa assays were conducted every 6 (5.5-7) h. Thirty patients (67%) fell within the therapeutic range. Outcomes were similar for patients with levels within the therapeutic range vs. not: major bleeding events, 10% vs. 0% ( p  = 0.54); discharge home, 77% vs. 80% ( p  = 1.0); LOS, 5 days in each group ( p  = 0.95). There was also no association between outcomes and time to reach the therapeutic range., Conclusion: Our findings demonstrate the practicability of monitoring UFH based on AFXa values in this population of patients with CVT, but reaching target AFXa levels within 24 h of arrival may not necessarily be prognostic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Pirahanchi, Salottolo, Burrell, Tang, Bar-Or and Bartt.)

Background: The present meta-analysis aims to investigate the effectiveness of heparin administration in suppressing physiological myocardial 18 F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT), as its role in this regard has not been well investigated., Methods: PRISMA guidelines were used to interrogate the PubMed, Embase, Cochrane library, Web of Knowledge, and www.clinicaltrail.gov databases from the earliest records to March 2023. The final analysis included five randomized controlled trials (RCTs). Meta-analysis was conducted to compare the effectiveness of unfractionated heparin (UFH) administration versus non-UFH administration, and subgroup analysis based on fixed and variable fasting durations was conducted. Effect sizes were pooled using a random-effects model, and the pooled odds ratios (ORs) were calculated., Results: Five eligible RCTs with a total of 910 patients (550 with heparin, 360 without heparin) were included. The forest plot analysis initially indicated no significant difference in the suppression of myocardial FDG uptake between the UFH and non-UFH groups (OR 2.279, 95% CI 0.593 to  8.755, p = 0.23), with a high degree of statistical heterogeneity (I 2  = 91.16%). Further subgroup analysis showed that the fixed fasting duration group with UFH administration had statistically significant suppression of myocardial FDG uptake (OR 4.452, 95% CI 1.221 to 16.233, p = 0.024), while the varying fasting duration group did not show a significant effect., Conclusions: According to the findings of our meta-analysis, we suggest that intravenous administration of UFH can be considered as a supplementary approach to suppress myocardial FDG uptake., (© 2023. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Objective: Portuguese nationwide estimates indicate that 20% of abdominal aortic aneurysms (AAAs) are treated when ruptured. In these cases, intra-operative unfractionated heparin (UFH) usage rates vary widely. Evidence on this topic is scarce and focused on patients treated by open repair (OSR). The aim was to determine the influence of UFH on peri-operative thromboembolic events (TEs) and death in a cohort of ruptured AAA (rAAA)., Methods: Retrospective, single-centre, comparative study. From 2011 to April 2023, all consecutive rAAAs (endovascular repair [EVAR] and OSR) were considered. Primary outcomes were 30-day TE free survival and TE rates. The secondary outcome was 30-day death. Safety endpoints were procedural blood loss, blood product requirements, and secondary interventions due to haemorrhage. Using propensity score matching (PSM) each UFH patient was matched with one no UFH patient in a 1:1 ratio., Results: The study included 250 patients. After PSM, 190 patients were analysed (EVAR: 60.0% no-UFH vs. 64.4% UFH). TE free survival estimates favoured the UFH group (67.3% vs. 47.2%, p = .009; UFH adjusted odds ratio [aOR] 2.01, 95% confidence interval [CI] 1.04-4.17). TEs were more frequent in the no UFH group (20.0% vs. 44.2% patients, p < .001; UFH aOR 0.31, 95% CI 0.15-0.65 for any TE), driven by an increase in bowel ischaemia (17.9% no UFH vs. 3.2% UFH, p = .001). Most events occurred in the first 72 hours. EVAR was associated with reduced TE and improved TE free survival (aOR 0.20, 95% CI 0.09-0.45 and aOR 5.54, 95% CI 2.34-13.08, respectively). No significant differences in 30-day survival were noted (75% no-UFH vs. 83% UFH, p = .26; aOR 1.08, 95% CI 0.48-2.43) nor in blood loss, peri-operative red blood cell and fresh frozen plasma requirements, or secondary interventions due to haemorrhage ( p = .10; p = .11; p = .13 and p = .18 respectively)., Conclusion: In this cohort, intra-operative UFH was safe and associated with improved TE free survival, driven by a reduction in bowel ischaemia. Conversely, mortality remained unaffected. Randomised controlled trials are required to confirm these findings., Competing Interests: Frederico Bastos Gonçalves has received speaker and proctoring fees from W.L. Gore, Medtronic, and Cook Medical., (© 2023 The Author(s).)

Background: Anti-Xa assays are used for unfractionated heparin (UFH) monitoring. Dextran sulfate (DS) is used in some assays to overcome the artifactual preanalytical release of platelet factor 4. However, the practical implications of this test modification have not been studied extensively., Objectives: To investigate the impact of the presence of DS in the anti-Xa assay for UFH laboratory monitoring., Methods: We studied factor Xa inhibition, using an assay without DS (Stago Liquid Anti-Xa), in normal pool plasma spiked with various concentrations of UFH (up to 1 IU/mL) in the presence of increasing concentrations of DS (up to 2560 μg/mL). We also investigated the effect of DS on FXa inhibition measured after the addition of UFH and heparin antagonists (protamine and Polybrene; Sigma Aldrich). Eventually, we compared the anti-Xa levels measured using the assay without DS to those measured with an assay containing DS (BIOPHEN Heparin LRT, Hyphen BioMed)., Results: DS per se had a detectable anti-Xa effect. FXa inhibition in UFH-spiked plasma linearly increased with increasing concentrations of added DS, with a plateau at approximately 160 μg/mL DS, at which the apparent anti-Xa level had almost doubled. In the presence of heparin antagonists, the addition of DS increased anti-Xa levels, corresponding to the dissociation of the UFH-antagonists complexes in vitro . With the anti-Xa assay containing DS, UFH inhibition was not detected., Conclusion: In the presence of high concentrations of DS, FXa inhibition was much higher than that predicted from added UFH amounts, presumably related to the greater availability of UFH for interaction with antithrombin. While the relevance of measuring this "masked" heparin has not been demonstrated, the presence of DS renders the result inaccurate in the presence of protamine or Polybrene., (© 2023 The Author(s).)

Aim: Comparative analysis of the results of open thrombectomy and conservative therapy in patients with acute thrombosis of the lower limb arteries against the background of the XBB.1.5 ("Kraken") subvariant of Omicron Severe acute respiratory syndrome-related coronavirus-2 (Sars-cov-2)., Material and Methods: The present prospective, open, multicenter comparative study for the period 04/01/2022 to 12/01/2023 included 167 patients with acute thrombosis of the lower limb arteries against the background of the XBB.1.5 ("Kraken") subvariant of the XBB.1.5 ("Kraken") subvariant of Omicron Sars-cov-2.Depending on the treatment strategy, two groups were formed: group 1 - open thrombectomy ( n  = 136) and drug treatment with an anticoagulant (unfractionated heparin in a therapeutic dosage) and an antiplatelet (acetylsalicylic acid 125 mg once a day); group 2 - only drug therapy ( n  = 31). This group consisted of patients who refused surgical revascularization and were on a prophylactic dose of unfractionated heparin (5000 U 3 times a day subcutaneously). On the development of acute arterial thrombosis, 80 U/kg (maximum 5000 U) of unfractionated heparin was injected intravenously in a bolus, followed by transfer to intravenous infusion using an infusion pump with an initial rate of 18 U/kg per hour under control of activated partial thromboplastin time. Analgesic and antiplatelet therapy was also prescribed (acetylsalicylic acid 125 mg once a day)., Results: No significant intergroup differences either in mortality rates (group 1: n  = 58, 38.2%; group 2: n  = 7, 22.6%; p  = 0.09) or limb amputation (group 1: n  = 63, 46.3%; group 2: n  = 9, 29.0%; p  = 0.07) were found. However, there was a trend towards a decrease in the incidence of these events in the drug treatment group. After open thrombectomy, rethrombosis developed in 50.7% ( n  = 69) cases; and thrombosis after rethrombectomy followed by amputation in 46.3% ( n  = 63). There were no hemorrhagic complications in both groups. Myocardial infarction and ischemic strokes were not recorded., Conclusion: Anticoagulant therapy demonstrates several advantages over aggressive surgical management. However, probably due to the small size of the studied sample, significant differences were not obtained. Further study of this issue is required with the identification of the optimal reperfusion method in this complex cohort of patients., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© Indian Association of Cardiovascular-Thoracic Surgeons 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: The use of extracorporeal membrane oxygenation (ECMO) in the postoperative cardiac critical care setting is evolving. Anticoagulation monitoring is among the most challenging aspects of pediatrics. However, there is no consensus on the optimal dosing and monitoring of unfractionated heparin in this setting. To address this, we developed an anti-Xa assay-based protocol derived from the best available clinical and anecdotal evidence of ECMO use and assessed its effectiveness in achieving the anti-Xa assay therapeutic target., Methods: This prospective single-arm study was conducted in the pediatric carcardiac-surgery intensive care unit of a large tertiary hospital. We used two different anti-Xa assay intensity levels based on the patients' bleeding status., Results: The median patient age was 7 (interquartile range [IQR]: 5-11.25) months, and the median weight was 5.7 (IQR: 3.8-13.82) kg. The median ECMO duration was 6 (IQR: 4.5-7.5) days. The bleeding protocol was used for most patients. Seventy percent achieved the anti-Xa assay therapeutic target during the study period (median: 75.5 h, IQR: 60.5-117.5 h). Hemorrhagic complications were reported in 40% of the patients, and thrombotic complications were reported in 25%. The median length of stay was 37 (IQR: 22-43) days, with a survival-to-discharge rate of 75%., Conclusions: Despite a failure to achieve the anti-Xa assay target within the first ECMO days, most patients achieved the target by the median ECMO duration. Moreover, using two different anti-Xa assay levels reduced thrombotic complications., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

We investigated in vitro the management of intraprocedural anticoagulation in patients requiring immediate percutaneous coronary intervention (PCI) while using regular direct oral anticoagulants (DOACs). Twenty-five patients taking 20 mg of rivaroxaban once daily comprised the study group, while five healthy volunteers included the control group. In the study group, a beginning (24 h after the last rivaroxaban dose) examination was performed. Then, the effects of basal and four different anticoagulant doses (50 IU/kg unfractionated heparin (UFH), 100 IU/kg UFH, 0.5 mg/kg enoxaparin, and 1 mg/kg enoxaparin) on coagulation parameters were investigated at the 4th and 12th h following rivaroxaban intake. The effects of four different anticoagulant doses were evaluated in the control group. The anticoagulant activity was assessed mainly by anti-factor Xa (anti-Xa) levels. Beginning anti-Xa levels were significantly higher in the study group than in the control group (0.69 ± 0.77 IU/mL vs. 0.20 ± 0.14 IU/mL; p < 0.05). The study group's 4th and 12th-h anti-Xa levels were significantly higher than the beginning level (1.96 ± 1.35 IU/mL vs. 0.69 ± 0.77 IU/mL; p < 0.001 and 0.94 ± 1.21 IU/mL vs. 0.69 ± 0.77 IU/mL; p < 0.05, respectively). Anti-Xa levels increased significantly in the study group with the addition of UFH and enoxaparin doses at the 4th and 12th h than the beginning (p < 0.001 at all doses). The safest anti-Xa level (from 0.94 ± 1.21 to 2.00 ± 1.02 IU/mL) was achieved 12 h after rivaroxaban with 0.5 mg/kg enoxaparin. Anticoagulant activity was sufficient for urgent PCI at the 4th h after rivaroxaban treatment, and additional anticoagulant administration may not be required at this time. Twelve hours after taking rivaroxaban, administering 0.5 mg/kg of enoxaparin may provide adequate and safe anticoagulant activity for immediate PCI. This experimental study result should confirm with clinical trials (NCT05541757)., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Underweight patients may be at an increased risk of bleeding while receiving venous thromboembolism (VTE) prophylaxis. Additional evidence is needed to identify patient-specific factors associated with bleeding. The objective of the study was to describe the incidence and identify risk factors associated with bleeding in low-weight (⩽ 60 kg) adult patients receiving subcutaneous unfractionated heparin (SQH) for VTE prophylaxis., Methods: This was a single-center, retrospective, nested case-control study of low-weight patients receiving SQH for VTE prophylaxis for ⩾ 48 hours. Cases, patients with clinically relevant bleeding while receiving SQH, and controls, patients without a bleeding event, were matched in a 1:3 ratio for age, sex, primary service (surgical or medical), and time at risk of bleeding on SQH to determine factors associated with bleeding., Results: A total of 3761 patients met the inclusion criteria, of which 38 cases of clinically relevant bleeding were identified. The bleeding incidence was 1% at hospital day 6 and 2.8% at hospital day 14. Most patients in this study (69%) received SQH 5000 units three times daily. ICU admission at SQH start was associated with bleeding, OR 2.97 (95% CI 1.21-7.29)., Conclusion: Bleeding in low-weight patients on prophylactic SQH was uncommon. Patients admitted to the ICU at time of SQH start may be at a higher risk of bleeding. Further studies are needed to detect additional risk factors associated with bleeding and investigate the effects of reduced dosing in this population., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cancer-associated thrombosis (CAT) is a leading cause of death among patients with cancer. CAT can manifest itself as venous thromboembolism (VTE), in the form of deep vein thrombosis or pulmonary embolism, or arterial thromboembolism. The pathophysiology of CAT is complex and depends on cancer-, patient-, treatment- and biomarkers-related factors. Treatment of VTE in patients with cancer is complex and includes three major classes of anticoagulant agents: heparin and its derivatives, e.g., low molecular weight heparins, direct oral anticoagulants (DOACs), and vitamin K inhibitors. Given the tremendous heterogeneity of clinical situations in patients with cancer and the challenges of CAT, there is no single universal treatment option for patients suffering from or at risk of CAT. Initial studies suggested that patients seemed to prefer an anticoagulant that would not interfere with their cancer treatment, suggesting the primacy of cancer over VTE, and favoring efficacy and safety over convenience of route of administration. Recent studies show that when the efficacy and safety aspects are similar, patients prefer the oral route of administration. Despite this, injectables are a valid option for many patients with cancer.

Unfractionated heparin (UFH) is commonly used for several life-threatening conditions requiring anticoagulant therapy but failure to reach therapeutic levels in 24 h can be associated with adverse outcomes. Use of low molecular weight heparin (LMWH) may provide an alternative while providing superior outcomes as compared to UFH. We studied 100 patients who underwent UFH therapy for >24 h and found that theoretically 80 % were eligible for LMWH therapy. Only 29 % and 40 % of the total aPTT draws were in the therapeutic window within the first 24 h and at 25-48 h respectively. This study reports that a vast majority of patients remain outside of therapeutic aPTT within first 24-48 h when anticoagulated with UFH. With high eligibility for LMWH therapy, its substitution can potentially lead to better patient outcomes, higher levels of therapeutic efficacy, and decrease in hospital resources., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Unfractionated heparin (UH), a commonly used anticoagulant, can rarely cause skin necrosis following heparin-induced thrombocytopenia (HIT). A 38-year-old female, a case of chronic inflammatory demyelinating polyneuropathy (CIDP) admitted to the neurology ward, developed extensive skin necrosis following a change in UH dose at the exact site of UH injection. A sudden fall in the platelet count was observed within 48 h of increasing the UH dose. Necrosis of the outer layer of the skin along with clot formation and inflammation in the inner layers was detected after histopathological evaluation. UH was discontinued, and rivaroxaban was started for the patient as soon as the complication was detected. The patient was discharged in good condition after completing treatment for CIDP without any need for surgical removal of the necrotic tissue. Extensive skin necrosis, as a result of HIT, requires immediate discontinuation of UH and substitution of a nonheparin-based anticoagulation treatment., Competing Interests: None

Purpose: Anticoagulants often cause adverse drug events (ADEs), comprised of medication errors and adverse drug reactions, in patients. Our study objective was to determine the clinical characteristics, types, severity, cause, and outcomes of anticoagulation-associated ADEs from 2015-2020 (a contemporary period following implementation of an electronic health record, infusion device technology, and anticoagulant dosing nomograms) and to compare them with those of a historical period (2004-2009)., Methods: We reviewed all anticoagulant-associated ADEs reported as part of our hospital-wide safety system. Reviewers classified type, severity, root cause, and outcomes for each ADE according to standard definitions. Reviewers also assessed events for patient harm. Patients were followed up to 30 days after the event., Results: Despite implementation of enhanced patient safety technology and procedure, ADEs increased in the contemporary period. In the contemporary period, we found 925 patients who had 984 anticoagulation-associated ADEs, including 811 isolated medication errors (82.4%); 13 isolated adverse drug reactions (1.4%); and 160 combined medication errors, adverse drug reactions, or both (16.2%). Unfractionated heparin was the most frequent ADE-related anticoagulant (77.7%, contemporary period vs 58.3%, historical period). The most frequent anticoagulation-associated medication error in the contemporary period was wrong rate or frequency of administration (26.1%, n = 253), with the most frequent root cause being prescribing errors (21.3%, n = 207). The type, root cause, and harm from ADEs were similar between periods., Conclusions: We found that anticoagulation-associated ADEs occurred despite advances in patient safety technologies and practices. Events were common, suggesting marginal improvements in anticoagulant safety over time and ample opportunities for improvement., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: A 2019 study by Prucnal and colleagues found that the majority of patients treated with unfractionated heparin for pulmonary embolism did not maintain therapeutic activated partial thromboplastin time levels during the first 48 h of therapy. Objective: The purpose of this study was to evaluate the ability of an institution's unfractionated heparin dosing protocol to achieve and maintain therapeutic anti-Xa levels within the first 48 h of therapy in patients with venous thromboembolism. Methods : This retrospective study included 205 patients from May 2016 through September 2020. Patients were divided into two cohorts: bolus plus infusion ( N  = 89) and infusion only ( N  = 116). The primary objective was to determine the number of patients who achieved at least one therapeutic level. Results: Overall, 200 patients (97.6%) had at least one therapeutic level with no statistically significant difference between cohorts ( p  = 0.65). No more than 60% of patients achieved a therapeutic level at any of the 6-h intervals throughout the timeframe. The median time to the first therapeutic level in the overall group was 12.8 h with no statistically significant difference between the bolus plus infusion and infusion-only cohorts (13.3 h versus 12.7 h, respectively, p  = 0.48). Conclusions: Most patients were able to achieve at least one therapeutic level within the first 48 h, but fewer were able to maintain therapeutic levels. Further studies are warranted to determine whether alternative dosing strategies would yield consistent achievement of therapeutic levels and affect patient-oriented outcomes., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Heparin is a glycosaminoglycans (GAGs) member and well-known FDA-approved anticoagulant that has been widely used in the clinic for 100 years. It has also been evaluated in various fields for further clinical applications, such as in anti-cancer or anti-inflammatory therapy beyond its anticoagulant effect. Here, we sought to utilize heparin molecules as drug carriers by directly conjugating the anticancer drug doxorubicin to the carboxyl group of unfractionated heparin. Given the molecular action of doxorubicin in intercalating DNA, it is expected to be less effective when structurally combined with other molecules. However, by utilizing doxorubicin molecules to produce reactive oxygen species (ROS), we found that the heparin-doxorubicin conjugates have significant cytotoxic ability to kill CT26 tumor cells with low anticoagulant activity. Several doxorubicin molecules were bound to heparin to provide sufficient cytotoxic capability and self-assembly ability due to their amphiphilic properties. The self-assembled formation of these nanoparticles was demonstrated through DLS, SEM and TEM. The cytotoxic ROS-generating doxorubicin-conjugated heparins could inhibit tumor growth and metastasis in CT26-bearing Balb/c animal models. Our results demonstrate that this cytotoxic doxorubicin-based heparin conjugate can significantly inhibit tumor growth and metastasis, thus showing promise as a potential new anti-cancer therapeutic., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jooho Park reports financial support was provided by Research Foundation of Korea. Jooho Park reports a relationship with National Research Foundation of Korea that includes: funding grants., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Coronavirus disease-2019 (COVID-19) is an extremely contagious illness caused by the SARS-CoV-2 virus and has been declared a pandemic by the World Health Organization (WHO). There are currently no particular treatments, however, nebulized heparin has been offered as a viable therapy. The purpose of this systematic review is to assess the efficacy of nebulized heparin in COVID-19 patients with respiratory symptoms., Methods: Relevant studies were identified through a systematic search of the PubMed, Medline, Embase, Cochrane Library and Web of Science, and Scopus databases. The search terms included "nebulized heparin," "COVID-19," and "SARS-CoV-2." Studies that evaluated the use of nebulized heparin in COVID-19 patients with respiratory symptoms were included. The rest of the studies along with those that were not published in English were excluded. The systematic review was registered under PROSPERO-CRD42023413927., Observations: Five studies have been included in this systematic review. Case reports, case series, observational studies, and randomized controlled trial (RCT) comprised the studies. The patient sample sizes ranged from 2 to 98. The studies assessed the efficacy of nebulized heparin in COVID-19 patients with variable disease severity. The evaluated outcomes included mortality, hospital stay duration, oxygen requirements, and laboratory parameters., Conclusion: Based on the clinical studies included in this systematic review, nebulized heparin may be useful in the management of COVID-19. Oxygen saturation was greater, inflammatory indicators were lower, and hospital stays were shorter in these patients. However, the studies had limitations, including inconsistent sample sizes, varying dosages of nebulized heparin, and no control groups. Nebulized heparin in patients with COVID-19 needs to be studied further to determine its safety and effectiveness., How to Cite This Article: Gupta B, Ahluwalia P, Gupta N, Gupta A. Role of Nebulized Heparin in Clinical Outcome of COVID-19 Patients with Respiratory Symptoms: A Systematic Review. Indian J Crit Care Med 2023;27(8):572-579., Competing Interests: Source of support: Nil Conflict of interest: None, (Copyright © 2023; The Author(s).)

Background: Bivalirudin reduces ischemic and hemorrhagic events in patients undergoing primary percutaneous coronary intervention (PCI), but the safety and efficacy for such individuals are unclear. Our aim was to evaluate the long-term safety and efficacy of bivalirudin in patients undergoing elective PCI., Methods: We examined 957 patients with bivalirudin anticoagulation and 1713 patients with unfractionated heparin (UFH) anticoagulation with and without glycoprotein IIb/IIIa inhibitors (GPI). The primary endpoint was net adverse clinical events (NACE), a composite of death, myocardial infarction, revascularization, stent thrombosis, stroke, and bleeding. The secondary endpoints were bleeding and major adverse cardiovascular and cerebrovascular events (MACCE)., Results: In one year of follow-up, 307 (11.5%) NACEs, 72 (2.7%) bleedings, and 249 (9.3%) MACCEs occurred. Statistically, patients with bivalirudin anticoagulation had less NACE [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.58-0.96, p = 0.021] and bleeding (HR: 0.58, 95% CI: 0.34-0.99, p = 0.045) but not less MACCE, than did those with UFH anticoagulation. Furthermore, the risk of bleeding in the bivalirudin group was lower than in the UFH with GPI group ( p = 0.001) but not lower than in the group of UFH without GPI ( p = 0.197)., Conclusions: In patients who undergo elective PCI, the use of bivalirudin significantly decreased the risk of NACE and bleeding without increasing the risk of MACCE; the reduction of bleeding risk with bivalirudin was mainly attributed to the presence of GPIs in the UFH group., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Background: Laboratory monitoring is not recommended when subcutaneous unfractionated heparin (SQ-UFH) is administered at prophylactic doses. However, aPTT prolongation and associated hemorrhage has been reported in the neurocritically ill. At our institution, Neuroscience Intensive Care Unit (Neuro-ICU) patients with prolonged aPTT are further evaluated with a follow up aPTT and anti-factor Xa., Purpose: The purpose of this study was to describe concordance between aPTT and anti-factor Xa in neurocritically ill patients receiving prophylactic SQ-UFH with evidence of aPTT prolongation., Methods: A retrospective chart review of adult patients admitted to the Neuro-ICU from June 2017 to June 2019 was performed. Patients were included if they received SQ-UFH with aPTT levels and at least one anti-factor Xa level drawn within one hour of each other. Concordance between paired aPTT and anti-factor Xa was evaluated using Cohen's weighted kappa., Results: Forty two patients with 56 paired aPTT and anti-factor Xa levels were included. The most prescribed SQ-UFH regimen was 5000 units every 8 hours (60.7%) and anti-factor Xa levels were drawn a median (IQR) of 5.7 (3.1-10.7) hours after the SQ-UFH dose. Only 16 (28.6%) pairs were in concordance. The analysis showed a weighted kappa of .09; 95% CI [-.05 to .22] indicating poor agreement., Conclusions: In neurocritically ill patients receiving prophylactic SQ-UFH with aPTT prolongation, there was poor concordance between aPTT and anti-factor Xa. This suggests that aPTT prolongation may not be solely driven by heparin activity and further evaluation of mechanistic drivers for coagulopathy in this population is necessary., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: Obesity is a frequent and significant risk factor for venous thromboembolism (VTE) among hospitalized adults. Pharmacologic thromboprophylaxis can help prevent VTE, but real-world effectiveness, safety, and costs among inpatients with obesity are unknown., Objective: This study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH)., Methods: A retrospective cohort study was performed using the PINC AI™ Healthcare Database, which covers more than 850 hospitals in the United States. Patients included were ≥18 years old, had a primary or secondary discharge diagnosis of obesity [International Classification of Diseases (ICD)-9 diagnosis codes 278.01, 278.02, and 278.03; ICD-10 diagnosis codes E66.0 x , E66.1, E66.2, E66.8, and E66.9], received ≥1 thromboprophylactic dose of enoxaparin (≤40 mg/day) or UFH (≤15,000 IU/day) during the index hospitalization, stayed ≥6 days in the hospital, and were discharged between 01 January 2010, and 30 September 2016. We excluded surgical patients, patients with pre-existing VTE, and those who received higher (treatment-level) doses or multiple types of anticoagulants. Multivariable regression models were constructed to compare enoxaparin with UFH based on the incidence of VTE, pulmonary embolism (PE)---------related mortality, overall in-hospital mortality, major bleeding, treatment costs, and total hospitalization costs during the index hospitalization and the 90 days after index discharge (readmission period)., Results: Among 67,193 inpatients who met the selection criteria, 44,367 (66%) and 22,826 (34%) received enoxaparin and UFH, respectively, during their index hospitalization. Demographic, visit-related, clinical, and hospital characteristics differed significantly between groups. Enoxaparin during index hospitalization was associated with 29%, 73%, 30%, and 39% decreases in the adjusted odds of VTE, PE-related mortality, in-hospital mortality, and major bleeding, respectively, compared with UFH (all p  < 0.002). Compared with UFH, enoxaparin was associated with significantly lower total hospitalization costs during the index hospitalization and readmission periods., Conclusions: Among adult inpatients with obesity, primary thromboprophylaxis with enoxaparin compared with UFH was associated with significantly lower risks of in-hospital VTE, major bleeding, PE-related mortality, overall in-hospital mortality, and hospitalization costs., Competing Interests: AK and NR are employees and shareholders of Premier Inc. KS and WN are employees and shareholders of Sanofi. AA has been a principal investigator or co-investigator of clinical trials sponsored by NIH/NIAID, NeuroRx Pharma, Pulmotect, Blade Therapeutics, Novartis, Takeda, Humanigen, Eli Lilly, PTC Therapeutics, Octapharma, Fulcrum Therapeutics, Alexion and has been a speaker and/or consultant for BMS, Pfizer, BI, Portola, Sunovion, Mylan, Salix, Alexion, AstraZeneca, Novartis, Nabriva, Paratek, Bayer, Tetraphase, Achaogen, La Jolla, Ferring, Seres, Spero, Eli Lilly, Gilead, Millenium, HeartRite, Aseptiscope, and Sprightly; these relationships were unrelated to the current work., (© 2023 Amin, Kartashov, Ngai, Steele and Rosenthal.)

Background: Neonatal acute respiratory distress syndrome (ARDS) is a clinical disorder characterized by excessive acute inflammatory response in lung parenchyma and has high morbidity and mortality. However, the therapeutic treatments are still lacking. The aim of this study is to evaluate the role of unfractionated heparin in neonatal ARDS and explore the underlying mechanism of its effects., Methods: To conduct the ARDS model, the mouse pups were treated by intraperitoneal injection of lipopolysaccharide (LPS) (10 mg/kg). For unfractionated heparin intervention group, C57BL/6 mouse pups received a single subcutaneous injection of unfractionated heparin (400 IU/kg) 30 minutes prior to LPS. The survival rate was recorded for each group. Histological analysis was used to evaluate lung injury. MPO (myeloperoxidase) concentration level in lung tissues and extracellular histones in serum were detected by enzyme linked immunosorbent assay (ELISA). A commercially available kit was used to detect inflammatory cytokine levels in serum. Real time quantitative polymerase chain reaction (qPCR) and western blot were used to detect the mRNA and protein in the JAK2/STAT3 signaling pathway, respectively., Results: Intervention of unfractionated heparin significantly increased the survival rate of mouse pups with ARDS, restored lung architecture, inhibited neutrophil infiltration as evidenced by reduced MPO concentration, and attenuated the LPS-induced inflammatory responses, characterized by the down-regulation of proinflammatoy factors and up-regulation of anti-inflammatory factor when compared with the ARDS group. In addition, the concentration of extracellular histones, which have been proven to be mediated in the pathogenesis of ARDS, was diminished by unfractionated heparin. Moreover, the protein expressions of p-JAK2 (Y1007/1008) and p-STAT3 (Y705) in the ARDS group were remarkably up-regulated, which were reversed by unfractionated heparin., Conclusions: Unfractionated heparin protects LPS-induced ARDS via inhibiting JAK2/STAT3 pathway in neonatal mice, which might present a novel therapeutic target for ARDS of neonates., Competing Interests: The authors declare no conflict of interest. YS is serving as Guest Editor of this journal. We declare that YS had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to GP., (© 2023 The Author(s). Published by IMR Press.)

There is a strong scientific rationale to use nebulised unfractionated heparin (UFH) in treating patients with COVID-19. This pilot study investigated whether nebulised UFH was safe and had any impact on mortality, length of hospitalisation and clinical progression, in the treatment of hospitalised patients with COVID-19. This parallel group, open label, randomised trial included adult patients with confirmed SARS-CoV-2 infection admitted to two hospitals in Brazil. One hundred patients were planned to be randomised to either "standard of care" (SOC) or SOC plus nebulized UFH. The trial was stopped after randomisation of 75 patients due to falling COVID-19 hospitalisation rates. Significance tests were 1-sided test (10% significance level). The key analysis populations were intention to treat (ITT) and modified ITT (mITT) which excluded (from both arms) subjects admitted to ITU or who died within 24 h of randomisation. In the ITT population (n = 75), mortality was numerically lower for nebulised UFH (6 out of 38 patients; 15.8%) versus SOC (10 out of 37 patients; 27.0%), but not statistically significant; odds ratio (OR) 0.51, p = 0.24. However, in the mITT population, nebulised UFH reduced mortality (OR 0.2, p = 0.035). Length of hospital stay was similar between groups, but at day 29, there was a greater improvement in ordinal score following treatment with UFH in the ITT and mITT populations (p = 0.076 and p = 0.012 respectively), while mechanical ventilation rates were lower with UFH in the mITT population (OR 0.31; p = 0.08). Nebulised UFH did not cause any significant adverse events. In conclusion, nebulised UFH added to SOC in hospitalised patients with COVID-19 was well tolerated and showed clinical benefit, particularly in patients who received at least 6 doses of heparin. This trial was funded by The J.R. Moulton Charity Trust and registered under REBEC RBR-8r9hy8f (UTN code: U1111-1263-3136)., Competing Interests: Declaration of competing interest TW reports receiving fees and grant support from Synairgen, Bergenbio, AstraZeneca, Janssen, UCB and Valneva in the area of the submitted work, and from GSK, Boehringer-Ingelheim, AZ, and Roche outside the area of the submitted work. CP reports receiving personal fees and grant support from EpiEndo, Eurodrug, Recipharm and Glycosynnovation, and has equity in Verona Pharma, outside of the submitted work. AW reports receiving fees from Theravance in the area of work, and personal fees from Boehringer-Ingelheim, GSK and Novartis outside the submitted work. JS has equity in Ockham Biotech Ltd. who are developing inhaled heparin for the treatment of respiratory diseases. DS has received personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona., (Copyright © 2023. Published by Elsevier Ltd.)

Background: To develop evidence-based clinical practice guidelines on venous thromboembolism (VTE) prevention in adults with trauma in inpatient settings., Methods: The Saudi Critical Care Society (SCCS) sponsored guidelines development and included 22 multidisciplinary panel members who completed conflict-of-interest forms. The panel developed and answered structured guidelines questions. For each question, the literature was searched for relevant studies. To summarize treatment effects, meta-analyses were conducted or updated. Quality of evidence was assessed using the Grading Recommendations, Assessment, Development, and Evaluation (GRADE) approach, then the evidence-to-decision (EtD) framework was used to generate recommendations. Recommendations covered the following prioritized domains: timing of pharmacologic VTE prophylaxis initiation in non-operative blunt solid organ injuries; isolated blunt traumatic brain injury (TBI); isolated blunt spine trauma or fracture and/or spinal cord injury (SCI); type and dose of pharmacologic VTE prophylaxis; mechanical VTE prophylaxis; routine duplex ultrasonography (US) surveillance; and inferior vena cava filters (IVCFs)., Results: The panel issued 12 clinical practice recommendations-one, a strong recommendation, 10 weak, and one with no recommendation due to insufficient evidence. The panel suggests starting early pharmacologic VTE prophylaxis for non-operative blunt solid organ injuries, isolated blunt TBIs, and SCIs. The panel suggests using low molecular weight heparin (LMWH) over unfractionated heparin (UFH) and suggests either intermediate-high dose LMWH or conventional dosing LMWH. For adults with trauma who are not pharmacologic candidates, the panel strongly recommends using mechanical VTE prophylaxis with intermittent pneumatic compression (IPC). The panel suggests using either combined VTE prophylaxis with mechanical and pharmacologic methods or pharmacologic VTE prophylaxis alone. Additionally, the panel suggests routine bilateral lower extremity US in adults with trauma with elevated risk of VTE who are ineligible for pharmacologic VTE prophylaxis and suggests against the routine placement of prophylactic IVCFs. Because of insufficient evidence, the panel did not issue any recommendation on the use of early pharmacologic VTE prophylaxis in adults with isolated blunt TBI requiring neurosurgical intervention., Conclusion: The SCCS guidelines for VTE prevention in adults with trauma were based on the best available evidence and identified areas for further research. The framework may facilitate adaptation of recommendations by national/international guideline policymakers., (© 2023. The Author(s).)

Activated clotting time (ACT) is used in cardiac surgery for monitoring unfractionated heparin (UFH). In endovascular radiology, ACT use is less established. We aimed to test the validity of ACT in UFH monitoring in endovascular radiology. We recruited 15 patients undergoing endovascular radiologic procedure. ACT was measured with ICT Hemochron ® device as point-of-care (1) before standard UFH bolus, (2) immediately after the bolus, and in some cases (3) 1 h into the procedure or a combination thereof (altogether 32 measurements). A total of two different cuvettes, ACT-LR and ACT+ were tested. A reference method of chromogenic anti-Xa was used. Blood count, APTT, thrombin time and antithrombin activity were also measured. UFH levels (anti-Xa) varied between 0.3-2.1 IU/mL (median 0.8) and correlated with ACT-LR moderately (R 2 = 0.73). The corresponding ACT-LR values were 146-337 s (median 214). ACT-LR and ACT+ measurements correlated only modestly with one another at this lower UFH level, with ACT-LR being more sensitive. Thrombin time and APTT were unmeasurably high after the UFH dose, rendering them of limited use in this indication. We adopted an ACT target of >200-250 s in endovascular radiology based on this study. While ACT correlation with anti-Xa is suboptimal, the readily available point-of-care nature increases its suitability.

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are often administered to prevent venous thromboembolism (VTE) in critically ill patients. However, the preferred prophylactic agent (UFH or LMWH) is not known. We compared the all-cause mortality rate in patients receiving UFH to LMWH for VTE prophylaxis. We conducted a retrospective propensity score adjusted analysis of patients admitted to neuro-critical, surgical, or medical intensive care units. Patients were included if they were screened with venous duplex ultrasonography or computed tomography angiography for detection of VTE. The primary outcome was all-cause mortality. Secondary outcomes included the prevalence of VTE, deep vein thrombosis (DVT), pulmonary embolism (PE), and hospital length of stay (LOS). Initially 2228 patients in the cohort were included for analysis, 1836 (82%) patients received UFH, and 392 (18%) patients received enoxaparin. After propensity score matching, a well-balanced cohort of 618 patients remained in the study (309 patients receiving UFH; 309 patients receiving enoxaparin). The use of UFH for VTE prophylaxis in ICU patients was associated with similar rates of all-cause mortality compared with enoxaparin [RR 0.73; 95% CI 0.43-1.24, p = 0.310]. There were no differences in the prevalence of DVT, prevalence of PE or hospital LOS between the two groups, DVT [RR 0.93; 95% CI 0.56-1.53, p = 0.889], PE [RR 1.50; 95% CI 0.78-2.90, p = 0.296] and LOS [9 ± 9 days vs 9 ± 8; p = 0.857]. A trend toward mortality benefit was observed in NICU [RR 0.37; 95% CI 0.13-1.07, p = 0.062] and surgical patients [RR 0.43; 95% CI 0.17-1.02, p = 0.075] favoring the enoxaparin group. The use of UFH for VTE prophylaxis in ICU patients was associated with similar rates of VTE, all-cause mortality and LOS compared to enoxaparin. In subgroup analysis, neuro-critical and surgical patients who received UFH had a higher rate of mortality than those who received enoxaparin., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Serum alanine aminotransferase (ALT), which is an indicator of liver dysfunction, may increase during treatment in patients in the acute phase of stroke. However, the cause of the ALT elevation is unclear, as multiple medications are often being used. We investigated the relationship between medications used in acute ischemic stroke, including cerebral infarction and transient ischemic attack, and ALT elevation., Methods: The subjects were 230 patients who had been diagnosed with cerebral infarction or TIA and treated at the Stroke Care Unit of Fukuoka University Hospital. We investigated ALT abnormalities that occurred from the start of the treatment over the subsequent 14 days. We also followed patients for an additional seven days to confirm the peak ALT levels. A binomial logistic regression analysis was performed to evaluate the association between medications used during the period and ALT elevation., Results: The incidence of ALT abnormality was 23.9% (55/230). ALT elevation was mostly mild and peaked within 21 days of treatment initiation in 93.2% of the patients, excluding indeterminate patients. A binary logistic regression analysis showed that unfractionated heparin (odds ratio [OR] 2.759, 95% confidence interval [CI] 1.328-5.729, p = 0.007) was extracted as a cause of ALT elevation. In a receiver operating characteristic (ROC) analysis for the administration period of unfractionated heparin, the cut-off value (area under the ROC curve) for ALT elevation was 6 days (0.575). Significant factors contributing to ALT elevation caused by unfractionated heparin included an unfractionated heparin administration period of ≥ 6 days (OR 2.951, 95% CI 1.244-7.000, p = 0.014) and edaravone combination (OR 2.594, 95% CI 1.159-5.808, p = 0.021)., Conclusion: In the acute phase of stroke, we believe that unfractionated heparin discontinuation is not necessary when hepatotoxicity of unfractionated heparin is suspected. However, physicians should be aware of the risk of liver toxicity when unfractionated heparin is administered for more than six days or when edaravone is used in combination., Competing Interests: Conflict of interest The authors declare no conflicts of interest in association with the present study., (Copyright © 2023 Elsevier B.V. All rights reserved.)