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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. [ABSTRACT FROM AUTHOR]

Unfractionated heparin (UFH) was uncovered in 1916, has been used as an anticoagulant since 1935, and has been listed in the World Health Organization's Model List of Essential Medicines. Despite the availability of many other anticoagulants, the use of heparin (either low molecular weight heparin [LMWH] or UFH) is still substantial. Heparin has pleotropic effects including anticoagulant and several nonanticoagulant properties such as antiproliferative, anti-inflammatory activity, and anticomplement effects. Although UFH has been widely replaced by LMWH, UFH is still the preferred anticoagulant of choice for patients undergoing cardiopulmonary bypass surgery, extracorporeal membrane oxygenation, and patients with high-risk mechanical cardiac valves requiring temporary bridging with a parenteral anticoagulant. UFH is a highly negatively charged molecule and binds many positively charged molecules, hence has unpredictable pharmacokinetics, and variable anticoagulant effect on an individual patient basis. Therefore, anticoagulant effects of UFH may not be proportional to the dose of UFH given to any individual patient. In this review, we discuss the anticoagulant and nonanticoagulant activities of UFH, differences between UFH and LMWH, when to use UFH, different methods of monitoring the anticoagulant effects of UFH (including activated partial thromboplastin time, heparin anti-Xa activity level, and activated clotting time), while discussing pros and cons related to each method and comparison of clinical outcomes in patients treated with UFH monitored with different methods based on available evidence. [ABSTRACT FROM AUTHOR]

Introduction: Anti-b2-glycoprotein I (b2GPI)/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-b2GPI/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 antib2GPI/HLA-DR antibodies. Methods: Between August 2019 and December 2021, 462 women with RPL underwent anti-b2GPI/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-b2GPI/HLA-DR antibodies, and their pregnancy outcomes were followed up until December 2023. Finally, 47 pregnancies in 47 women with RPL and anti-b2GPI/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-b2GPI/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 ab2GPI/HLA-DR antibody positivity. [ABSTRACT FROM AUTHOR]

Continuous renal replacement therapy (CRRT) in children is quite challenging to manage because of their increased propensity for circuit clotting. The anticoagulant strategies are paramount in reducing the downtime in pediatric CRRT. The most commonly used anticoagulants in pediatrics are unfractionated heparin and citrate anticoagulation. The other less explored options include regional heparin protamine anticoagulation, prostacyclin, low-molecular-weight heparin, and thrombin antagonists. The choice of anticoagulant primarily depends on the patient’s condition, availability and cost of the anticoagulant, potential side effects, and the local expertise for troubleshooting. This article aims to bring about the merits and demerits of the different anticoagulants available for CRRT and the available evidence for the use of each of these anticoagulants.

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 × 103/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 × 103/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.

Tereza Romanová,1,2 Filip Burša,1,2 Peter Sklienka,1,2 Ji&rcaron;í Sagan,3 Michelle Va&ncaron;ková,1 Denis Buršík,1,2 Markéta Bílená,1,2 Martin Pulcer,4 Michal Burda,5 Jan Máca1,2,6 1Department of Anesthesiology and Intensive Care Medicine, University Hospital, Ostrava, Czech Republic; 2Department of Intensive Medicine, Emergency Medicine and Forensic Studies, Faculty of Medicine, University of Ostrava, Ostrava, Czech Republic; 3Department of Infectious Diseases, University Hospital Ostrava, Ostrava, Czech Republic; 4Institute of Laboratory Medicine, University Hospital Ostrava, Ostrava, Czech Republic; 5Institute for Research and Applications of Fuzzy Modeling, CE IT4Innovations, University of Ostrava, Ostrava, Czech Republic; 6Institute of Physiology and Pathophysiology, Faculty of Medicine, University of Ostrava, Ostrava, Czech RepublicCorrespondence: Jan Máca, Department of Anesthesiology and Intensive Care Medicine, University Hospital Ostrava, 17. listopadu 1790/5, Ostrava, 708 52, Czech Republic, Tel +420597371111, Email jan.maca@fno.czPurpose: 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.Keywords: unfractionated heparin, COVID-19, pneumonia, critical care

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. 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. 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. 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. • A large-scale trial involving 6006 MI patients compared the outcomes of bivalirudin and heparin. • Two-year outcomes show no significant difference in MI patients treated with bivalirudin vs. heparin. • Consistent results were observed in both STEMI and NSTEMI patient groups. • Long-term follow-up confirmed similar safety and efficacy profiles for both drugs. [ABSTRACT FROM AUTHOR]

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 x 103/lL, 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 x 103/lL (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. [ABSTRACT FROM AUTHOR]

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. We aimed to test the accuracy of ACT measurements from the guiding catheter compared to the arterial access sheath. 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. 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. 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. [ABSTRACT FROM AUTHOR]

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

Anticoagulant and antiplatelet therapies are used to prevent life-threatening complications associated with thrombosis. While there are numerous clinical guidelines for antithrombotic medications, there is an incomplete understanding of whether these interventions yield similar effects in preclinical models, potentially impacting their predictive value for translational studies on the development of medical devices, therapies, and surgical techniques. Due to their close physiologic similarities to humans, we employed nonhuman primates (NHPs) using a reverse translational approach to analyze the response to clinical regimens of unfractionated heparin, low-molecular-weight heparin (LMWH) and aspirin to assess concordance with typical human responses and evaluate the predictive validity of this model. We evaluate activated clotting time (ACT) in nine rhesus and six cynomolgus macaques following the intraoperative administration of intravenous unfractionated heparin (100–300 U/kg) reflecting the clinical dose range. We observed a significant dose-dependent effect of heparin on ACT (low-dose average = 114.1 s; high-dose average = 148.3 s; p = 0.0011). LMWH and aspirin, common clinical antithrombotic prophylactics, were evaluated in three rhesus macaques. NHPs achieved therapeutic Anti-Xa levels (mean = 0.64 U/mL) and ARU (mean = 459) via VerifyNow, adhering to clinical guidance using 1.0 mg/kg enoxaparin and 81 mg aspirin. Clinical dosing strategies for unfractionated heparin, LMWH, and aspirin were safe and effective in NHPs, with no development of thrombosis or bleeding complications intraoperatively, postoperatively, or for prophylaxis. Our findings suggest that coagulation studies, performed as an integrative part of studies on biologics, bioengineered devices, or transplantation in NHPs, can be extrapolated to the clinical situation with high predictive validity.

BackgroundObesity 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.ObjectiveThis study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH).MethodsA 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 E66.0x, 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).ResultsAmong 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

Background: Unfractionated heparin (UFH) is a high-risk medication that can cause bleeding and/or thrombotic complications if not managed appropriately. Between January and July 2019, our institution experienced a high number of patient safety events related to UFH infusion for the treatment of venous thromboembolism (VTE). Purpose: The aim of this quality improvement (QI) initiative was to prevent these safety events by improving compliance with our institution's nurse-driven VTE UFH infusion protocol. Methods: Baseline data for patients on the VTE UFH protocol were collected to identify improvement opportunities. Compliance with eight standards of care related to the VTE UFH infusion protocol was measured. Time to first therapeutic activated partial thromboplastin time (aPTT) was recorded to assess the benefit of improved compliance. Interventions: Institutional policy updates were made to clarify the management of UFH infusions and documentation in the electronic health record. A multidisciplinary workgroup implemented order set changes, nursing communication orders, UFH infusion reports, and a nursing education module to promote compliance with the protocol. Results: The overall rate of compliance with the VTE UFH infusion protocol increased from 79.4% at baseline to 85.2% following implementation of the QI initiative, and the median time to first therapeutic aPTT decreased from 831.5 minutes to 808 minutes over the same period. Conclusions: A multidisciplinary initiative to address improvement opportunities in a nurse-driven UFH protocol for VTE treatment increased compliance with the protocol and decreased the time to first therapeutic aPTT. The authors describe a quality improvement initiative to reduce patient safety events related to unfractionated heparin (UFH) infusions by increasing compliance with their institution's venous thromboembolism UFH protocol. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Anticoagulant and antiplatelet therapies are used to prevent life-threatening complications associated with thrombosis. While there are numerous clinical guidelines for antithrombotic medications, there is an incomplete understanding of whether these interventions yield similar effects in preclinical models, potentially impacting their predictive value for translational studies on the development of medical devices, therapies, and surgical techniques. Due to their close physiologic similarities to humans, we employed nonhuman primates (NHPs) using a reverse translational approach to analyze the response to clinical regimens of unfractionated heparin, low-molecular-weight heparin (LMWH) and aspirin to assess concordance with typical human responses and evaluate the predictive validity of this model. We evaluate activated clotting time (ACT) in nine rhesus and six cynomolgus macaques following the intraoperative administration of intravenous unfractionated heparin (100–300 U/kg) reflecting the clinical dose range. We observed a significant dose-dependent effect of heparin on ACT (low-dose average = 114.1 s; high-dose average = 148.3 s; p = 0.0011). LMWH and aspirin, common clinical antithrombotic prophylactics, were evaluated in three rhesus macaques. NHPs achieved therapeutic Anti-Xa levels (mean = 0.64 U/mL) and ARU (mean = 459) via VerifyNow, adhering to clinical guidance using 1.0 mg/kg enoxaparin and 81 mg aspirin. Clinical dosing strategies for unfractionated heparin, LMWH, and aspirin were safe and effective in NHPs, with no development of thrombosis or bleeding complications intraoperatively, postoperatively, or for prophylaxis. Our findings suggest that coagulation studies, performed as an integrative part of studies on biologics, bioengineered devices, or transplantation in NHPs, can be extrapolated to the clinical situation with high predictive validity. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Nonbacterial thrombotic endocarditis (NBTE) presents nonbacterial vegetation on cardiac valves. NBTE requires appropriate anticoagulant therapy to prevent recurrence after surgery. However, there has not yet been established evidence for anticoagulant therapy in NBTE, and low molecular weight heparin is not approved in Japan. We present a case of NBTE that was successfully managed with anticoagulant therapy using subcutaneous unfractionated heparin. A 59-year-old woman was diagnosed with NBTE on the mitral and tricuspid valve associated with breast cancer, underwent valve replacement. Warfarin and continuous intravenous unfractionated heparin were started. However, disseminated intravascular coagulation occurred after heparin was discontinued. Continuous intravenous unfractionated heparin injection was resumed immediately, and subcutaneous unfractionated heparin was administered before discharge. Postoperative echocardiography revealed no vegetation on the prosthetic valves thereafter. Subcutaneous unfractionated heparin therapy is useful to prevent the recurrence of NBTE as the anticoagulation in outpatients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Highlights: Acute cerebral venous thrombosis (CVT) management involves treatment with parenteral anticoagulation prior to transitioning to an oral anticoagulant. Although a recent randomized control trial has utilized a minimum of 5 days, there remains a lack of guidance surrounding the optimal treatment duration of parenteral anticoagulation prior to transitioning to oral therapy. Patients with CVT may attain stability within fewer than 5 days of treatment. This often prompts clinicians to reconsider the necessity of prolonged parenteral anticoagulation. In this retrospective, observational cohort study, CVT patients treated with < 5 days of parenteral anticoagulation achieved a favorable functional outcome at discharge. Further research is needed to establish a causal relationship between functional outcomes and the duration of parenteral anticoagulation. [ABSTRACT FROM AUTHOR]

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.

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). 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 m2. 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. 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). 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. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Portuguese estimates point out that nearly 20% of aortic aneurysms are treated in a ruptured setting, with in-hospital mortality reaching up to 50%. Although unfractionated heparin (UFH) is routine during elective surgery, this technical point is debatable when treating ruptured aneurysms. The authors aimed to review the literature on the topic of intraoperative heparinization with UFH within the intraoperative period of ruptured aortic aneurysms. METHODS: A MEDLINE and Scopus database search using the terms “unfractionated heparin," “aortic aneurysm," and “ruptured aortic aneurysm” was performed. No time or language limitations were imposed. The last search was run in July 2023. Manuscripts were considered irrespective of study design. Additional articles of scientific interest for the purpose of this non-systematic review were included by cross-referencing. RESULTS: In the rupture setting, UFH usage rates have widely varied throughout time and geographical sites, and they are reported to be as low as 16%. Overall, the evidence of UFH in clinical practice in this scenario is limited. Notwithstanding, there is some evidence from observational studies of an increased pro-coagulant activity in this clinical scenario, favoring a theoretical physiologic benefit. A prospective, non-randomized study of 131 OSR patients found that patients treated with UFH had improved 30-day survival (84% vs 67%, P=0.001). Non-significant differences in blood product usage were noted. Therefore, societal guideline recommendations about intraoperative UFH in ruptured aortic aneurysms are often missing. CONCLUSION: UFH may potentially reduce death after open repair of rAAA. These findings should be carefully interpreted, as the evidence is scarce and heterogeneous and only portrays open repair.

Purpose: This study investigated whether an activated clotting time (ACT) between 200 and 300 sec could be achieved with a100 IU/kg unfractionated heparin (UHF) loading dose in patients with congenital heart disease (CHD) during pediatric cardiac catheterization. Materials and Methods: We included 264 patients aged 0-18 years with CHD undergoing cardiac catheterization between January 2022-March 2023. Data on patient characteristics, UHF doses, and ACT values were retrospectively obtained. The patients were intravenously administered 100 IU/kg UFH after sheath placement. We aimed to obtain a value between 200 and 300 sec according to the ACT measured at the 5th minute. If the measured ACT value at the 5th min was < 200 sec, additional heparin doses between 20 and 50 IU/kg were administered such that the total heparin loading dose did not exceed 150 IU/kg. Patients were divided into two groups based on whether the ACT value was below or above 200 sec. Results: Median age, weight, and ACT value at procedure were 6.41(IQR:2.01–32.21) months, 6.13(IQR:3.79-11.9) kg, and 212(IQR:190-240) sec, respectively. The ACT value of 170(64.4%) of the 264 patients was between 200-300 sec, which was considered the target value. The ACT value of 86(32.6%) of the 264 patients was below the target value and that of eight (3%) patients was above the target value. Hematoma occurred at the access site in four patients (1.5%). We did not detect retroperitoneal hematoma, other bleedings at location, or thromboembolism in any of the patients. No significant differences were observed in comparisons between age subgroups and ACT distribution, or between age subgroups and ACT subgroups (p>0.05) Conclusion: This study revealed that a 100 IU/kg UFH loading dose produced the target ACT value in 64.4% of the patients and that the UFH loading dose should be individualized according to the ACT value in the remaining patients.

ObjectiveThere 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).MethodsThis 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).ResultsAmong 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.ConclusionOur 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.

Background: The present meta-analysis aims to investigate the effectiveness of heparin administration in suppressing physiological myocardial 18F-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 (I2 = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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). [ABSTRACT FROM AUTHOR]

Purpose: This study investigated whether an activated clotting time (ACT) between 200 and 300 sec could be achieved with a100 IU/kg unfractionated heparin (UHF) loading dose in patients with congenital heart disease (CHD) during pediatric cardiac catheterization. Materials and Methods: We included 264 patients aged 0-18 years with CHD undergoing cardiac catheterization between January 2022-March 2023. Data on patient characteristics, UHF doses, and ACT values were retrospectively obtained. The patients were intravenously administered 100 IU/kg UFH after sheath placement. We aimed to obtain a value between 200 and 300 sec according to the ACT measured at the 5th minute. If the measured ACT value at the 5th min was < 200 sec, additional heparin doses between 20 and 50 IU/kg were administered such that the total heparin loading dose did not exceed 150 IU/kg. Patients were divided into two groups based on whether the ACT value was below or above 200 sec. Results: Median age, weight, and ACT value at procedure were 6.41(IQR:2.01–32.21) months, 6.13(IQR:3.79-11.9) kg, and 212(IQR:190-240) sec, respectively. The ACT value of 170(64.4%) of the 264 patients was between 200-300 sec, which was considered the target value. The ACT value of 86(32.6%) of the 264 patients was below the target value and that of eight (3%) patients was above the target value. Hematoma occurred at the access site in four patients (1.5%). We did not detect retroperitoneal hematoma, other bleedings at location, or thromboembolism in any of the patients. No significant differences were observed in comparisons between age subgroups and ACT distribution, or between age subgroups and ACT subgroups (p>0.05) Conclusion: This study revealed that a 100 IU/kg UFH loading dose produced the target ACT value in 64.4% of the patients and that the UFH loading dose should be individualized according to the ACT value in the remaining patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background. Currently, there is no internationally approved protocol for anticoagulant therapy (ACT) in patients with COVID-19 that describes the different types of ACT programs depending on the severity of COVID-19. The objective: to determine optimal ACT programs. Materials and methods. A retrospective ana­lysis of ACT programs was conducted in 268 patients with extremely severe COVID-19 who were treated in the intensive care units. Results. The article presents the results of retrospective analysis of ACT programs in 268 patients with a very severe course of COVID-19 treated in the general intensive care unit in 2021. ACT programs in 162 patients who died because of COVID-19 and in 106 survived patients were studied separately. The total duration of hospital stay was from 9 to 55 days. ACT programs were mostly in line with Euro­pean guidelines/instructions. ACT included a stepwise combination of unfractionated heparin, low-molecular-weight heparins, and oral anticoagulants depending on the clinical course, concomitant pathology, and laboratory parameters. The systemic inflammatory response was characterized by the concentration of C-reactive protein in the blood plasma within the range of 54.7–331.4 mg/l (on average 95.4 ± 73.4 mg/ml), ferritin of 208–2094 μg/l (on average 947.16 ± 872.00 μg/l), interleukin-6 of 33.9–507.4 pg/ml (on average 152.60 ± 201.15 pg/ml). The level of D-dimer in blood plasma ranged from 3.74 to 82.0 μg/ml (on average 8.200 ± 3.525 μg/ml). Platelet content in peripheral blood ranged from 372 × 109/l to 72 × 109/l. Conclusions. The optimal ACT program in patients with severe and extremely severe COVID-19 is a program of sequential change of anticoagulant drugs to enhance their anticoagulant effect, which can be controlled by laboratory tests.

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.

Simple Summary: People with cancer are at an increased risk of developing blood clots. Both cancer and anti-cancer treatment are responsible for this risk. In some types of cancer, such risk is higher than in others. There are different types of blood thinners also known as anticoagulants. Blood thinners prevent the recurrence of deep venous thrombosis (a blood clot in the limbs) or pulmonary embolism (a blood clot in the lungs) in people with cancer. In some clinical situations and, specifically, in patients with active cancer, injectable blood thinners are safer than tablets to be taken orally and work just as well. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract Background Thrombotic events are common in critically ill patients with COVID-19 and have been linked with COVID-19- induced hyperinflammatory state. In addition to anticoagulant effects, heparin and its derivatives have various anti-inflammatory and immunomodulatory properties that may affect patient outcomes. This study compared the effectiveness and safety of prophylactic standard-doses of enoxaparin and unfractionated heparin (UFH) in critically ill patients with COVID-19. Methods A multicenter, retrospective cohort study included critically ill adult patients with COVID-19 admitted to the ICU between March 2020 and July 2021. Patients were categorized into two groups based on the type of pharmacological VTE thromboprophylaxis given in fixed doses (Enoxaparin 40 mg SQ every 24 hours versus UFH 5000 Units SQ every 8 hours) throughout their ICU stay. The primary endpoint was all cases of thrombosis. Other endpoints were considered secondary. Propensity score (PS) matching was used to match patients (1:1 ratio) between the two groups based on the predefined criteria. Multivariable logistic, Cox proportional hazards, and negative binomial regression analysis were used as appropriate. Results A total of 306 patients were eligible based on the eligibility criteria; 130 patients were included after PS matching (1:1 ratio). Patients who received UFH compared to enoxaparin had higher all thrombosis events at crude analysis (18.3% vs. 4.6%; p-value = 0.02 as well in logistic regression analysis (OR: 4.10 (1.05, 15.93); p-value = 0.04). Although there were no significant differences in all bleeding cases and major bleeding between the two groups (OR: 0.40 (0.07, 2.29); p-value = 0.31 and OR: 1.10 (0.14, 8.56); p-value = 0.93, respectively); however, blood transfusion requirement was higher in the UFH group but did not reach statistical significance (OR: 2.98 (0.85, 10.39); p-value = 0.09). The 30-day and in-hospital mortality were similar between the two groups at Cox hazards regression analysis. In contrast, hospital LOS was longer in the UFH group; however, it did not reach the statistically significant difference (beta coefficient: 0.22; 95% CI: -0.03, 0.48; p-value = 0.09). Conclusion Prophylactic enoxaparin use in critically ill patients with COVID-19 may significantly reduce all thrombosis cases with similar bleeding risk compared to UFH.

Venous thromboembolic (VTE) prophylaxis in acute traumatic brain injury (TBI) is a controversial topic with wide practice variations. This study examined the association of VTE chemoprophylaxis with inpatient mortality and VTE events among isolated TBI patients. This was a retrospective cohort study of 87 trauma centers within a large hospital system in the United States analyzing 23,548 patients with isolated TBI, 7977 of whom had moderate-to-severe TBI. Primary outcomes were inpatient mortality and VTE events. The control group received no chemoprophylaxis. Other groups received low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), and combined LMWH and UFH chemoprophylaxis. Multi-variable regression accounted for confounders. Outcomes were stratified by timing of administration, body mass index (BMI), and TBI type. Patients without VTE prophylaxis had the least VTE events. LMWH had the lowest mortality for both all-isolated and moderate-to-severe isolated TBI populations at adjusted odds ratio (aOR) 0.24 (95% confidence interval [CI], 0.14?0.43) and aOR 0.25 (95% CI, 0.14?0.44), respectively. Clinically significant progression of TBI was lowest among the LMWH group (0.1%; p value, 0.001). After stratifying by timing of VTE chemoprophylaxis, only patients with subdural hematoma and LMWH between 6 and 24?h (N?=?62), as well as patients with ?35 BMI and LMWH between 6 and 24?h (N?=?65) or >24?48?h (N?=?54), had no VTE events. VTE chemoprophylaxis timing may have prevented VTE in certain subgroups of isolated TBI patients. Though VTE chemoprophylaxis did not prevent VTE for most TBI patients, LMWH VTE chemoprophylaxis was associated with reduced mortality.

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. [ABSTRACT FROM AUTHOR]

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 (R2 = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We report a case of retroperitoneal hematoma during prophylactic heparin therapy for coronavirus disease 2019 (COVID-19). A 79-year-old man was diagnosed with COVID-19 pneumonia with possible exacerbation of fibrotic hypersensitivity pneumonia. He received a prophylactic dose of subcutaneous heparin therapy, methylprednisolone pulse therapy and Intravenous remdesivir but developed a spontaneous iliopsoas muscle hematoma, and transcatheter arterial embolization was performed. Even with a prophylactic dose of subcutaneous heparin therapy, the course should be carefully monitored, especially in patients with preexisting risk factors for hemorrhagic complications. Once retroperitoneal hematoma develops, aggressive procedures, such as transcatheter arterial embolization, should be considered to avoid fatal outcomes. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) is a method that makes it possible to compensate for critical changes caused by acute respiratory failure, with the ineffectiveness of treatment with rigid modes of artificial lung ventilation (ventilator) in patients with acute respiratory distress syndrome in intensive care units. The search for the optimal state of the hemostasis system is one of the main tasks in the treatment of critical patients in ECMO conditions.The objective: to study changes in hemostatic parameters in patients with COVID-19 undergoing ECMO and determine the need for their correction.Subjects and Methods. According to the inclusion and exclusion criteria, 100 patients were included in the study: 72 men and 28 women aged 26 to 75 years old, the median age made 55 years [47; 60]. VV-ECMO was performed in all observations. In 100% of cases, the cause of respiratory failure which required VV-ECMO was COVID-19-associated pneumonia.Results. 49 episodes of hemorrhagic complications and 76 episodes of thrombotic complications were recorded from the 1st to the 7th day from the moment of ECMO initiation. We found that the chance of developing thrombosis decreased by an average of 0.3% with an increase in the activity of antithrombin-3 by 1%. A statistically significant association of thrombosis risk was also found for prothrombin and prothrombin time.Conclusion. During the first 7 days of ECMO, patients with COVID-19 demonstrate the increase in APTT, prothrombin time and a decrease in the number of platelets, prothrombin activity, and fibrinogen concentration. The risk of thrombosis in this group of patients significantly decreases with the increasing activity of antithrombin-3 and prothrombin and increases with rising need of the higher dose of unfractionated heparin. The tactics of restrictive anticoagulant therapy when using unfractionated heparin can be taken into account as a way to reduce the risk of thrombosis and requires further research.

BackgroundObesity 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.ObjectiveThis study aims to compare clinical and economic outcomes among adult medical inpatients with obesity who received thromboprophylaxis with enoxaparin or unfractionated heparin (UFH).MethodsA 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 E66.0x, 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).ResultsAmong 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

Background: Evidence supporting the effectiveness of therapeutic protocols for nonassociative immune‐mediated hemolytic anemia (na‐IMHA) is weak. Hypothesis/Objectives: Investigate the efficacy of various drugs in na‐IMHA. Animals: Two hundred forty‐two dogs. Methods: Multi‐institutional retrospective study (2015‐2020). Immunosuppressive effectiveness was determined by time to packed cell volume (PCV) stabilization and duration of hospitalization through analysis by mixed model linear regression. Occurrence of disease relapse, death, and antithrombotic effectiveness, were analyzed using mixed model logistic regression. Results: Use of corticosteroids vs a multi‐agent protocol had no effect on time to PCV stabilization (P =.55), duration of hospitalization (P =.13), or case fatality (P =.06). A higher rate of relapse (P =.04; odds ratio: 3.97; 95% confidence interval [CI]: 1.06‐14.8) was detected in dogs receiving corticosteroids (11.3%) during follow‐up (median: 28.5 days, range: 0‐1631 days) compared to multiple agents (3.1%) during follow up (median: 47.0 days, range: 0‐1992 days). When comparing drug protocols, there was no effect on time to PCV stabilization (P =.31), relapse (P =.44), or case fatality (P =.08). Duration of hospitalization was longer, by 1.8 days (95% CI: 0.39‐3.28 days), for the corticosteroid with mycophenolate mofetil group (P =.01) compared to corticosteroids alone. Use of clopidogrel vs multiple agents had no effect on development of thromboses (P ≥.36). Conclusions and Clinical Importance: Addition of a second immunosuppressive agent did not alter immediate outcome measures but might be associated with a reduction in relapse. Use of multiple antithrombotic agents did not reduce incidence of thrombosis. [ABSTRACT FROM AUTHOR]

Study Objective: To compare bleeding and thromboembolic events in patients receiving therapeutic doses of apixaban or rivaroxaban versus unfractionated heparin (UFH) in patients with acute kidney injury (AKI). Design: Single‐center, retrospective, observational study. Setting: Ascension St. John Hospital in Detroit, Michigan. Patients Hospitalized adult patients who received therapeutic doses of factor Xa inhibitors (n = 250) or UFH (n = 250) for at least 24 h in the setting of AKI. Measurements and Main Results: After adjusting for confounding factors, patients who received a factor Xa inhibitor experienced a lower risk of composite major and clinically relevant nonmajor bleeding (CRNMB) events compared with UFH (OR: 0.57, 95% CI: 0.34–0.94; p = 0.03). There was a significantly decreased risk of CRNMB events in the factor Xa inhibitor group (OR: 0.55, 95% CI: 0.33–0.91, p = 0.02); however, no significant differences in major bleeding or venous thromboembolism (VTE) were noted. Conclusions: Our results suggest that it may be preferable to continue patients in AKI on factor Xa inhibitors versus transitioning to UFH due to the lower risk of bleeding events. [ABSTRACT FROM AUTHOR]

Levels of extracellular histones are highly increased in sepsis and may facilitate microcirculatory dysfunction. Unfractionated heparin (UFH) binds histones and neutralizes their cytotoxicity. We investigated the effect of UFH on microcirculatory dysfunction by interacting with extracellular histones in endotoxemic rats. Twenty-four Wistar rats were randomly divided into three groups: control, lipopolysaccharide (LPS) group, and LPS + UFH group. In the LPS and LPS + UFH groups, 10 mg/kg LPS was injected to induce endotoxemia, and 100 IU/kg/h UFH was administered intravenously in the LPS + UFH group. The rats underwent midline laparotomy, and then intestinal microcirculation was evaluated using an incident dark field microscope. Circulating histones and microstructures of the rat intestinal microvascular endothelium were also detected. Additionally, the antagonistic effect of UFH on histone-induced cytotoxicity was investigated in human intestinal microvascular endothelial cells. UFH protected the microcirculation of the intestinal serosa and mucosa in endotoxemic rats, as evidenced by increased total vessel density, perfused vessel density, and proportion of perfused vessels of both the serosa and mucosa, and increased microcirculatory flow index of the mucosa in the LPS + UFH group. UFH treatment decreased the levels of circulating histones and alleviated intestinal microvascular endothelial injuries in endotoxemic rats. Furthermore, UFH inhibited histone cytotoxicity in vitro. UFH attenuated microcirculatory dysfunction in endotoxemic rats by antagonizing extracellular histones, thereby providing a potential therapeutic strategy for sepsis. [ABSTRACT FROM AUTHOR]

Background: When undergoing tonsillectomy, patients at high risk of thrombosis who require chronic anticoagulation therapy pose a special challenge as bleeding may occur up to 2 weeks after surgery. Because of a lack of evidence‐based data, there is no consensus on the best management for such patients. The objective of our study was to review perioperative anticoagulation bridging strategies in children undergoing tonsillectomy. Methods: The study group were a retrospective series of patients on chronic anticoagulation therapy at high risk of a thromboembolic event, who underwent tonsillectomy from 2010 to 2021. Patients whose anticoagulation treatment was discontinued because of a low risk of thromboembolic events were excluded. Results: Four patients met the inclusion criteria (age range, 1.5–16.1 years). All patients were admitted prior to surgery for bridging therapy with intravenous unfractionated heparin (UFH), drip‐titrated to a therapeutic dose until 4–6 h prior to surgery. The estimated blood loss during surgery was minimal in all surgeries. Unfractionated heparin was readministered according to the hospital protocol on the night of surgery and titrated to a therapeutic dose. Warfarin was restarted within 2 days postsurgery for all patients. High‐risk patients were kept in hospital until postoperative day 6–8 because of concern for delayed bleeding. One patient was noticed to have blood‐tinged sputum requiring no intervention; none of the patients developed early or delayed hematemesis. Conclusions: Our data show that bridging therapy with UFH has been successful in chronically anticoagulated patients undergoing tonsillectomy. These patients require multidisciplinary care for the management of their pre‐ and postoperative course. [ABSTRACT FROM AUTHOR]

Introduction: Cerebral venous thrombosis (CVT) is a life-threatening neurological condition. There is limited evidence for the use of direct oral anticoagulants (DOAC) for long-term anticoagulation in this patient population. We report a case series of patients treated with apixaban and their clinical course. Methods: This was a retrospective cohort study. Patients diagnosed with CVT in a defined time period at our institution were screened for long-term anticoagulation and patients who were treated with apixaban were included in this study. Results: A total of nine patients were included in this study. The mean age was 36 years and 56% of the patients included were women. All received initial anticoagulation with unfractionated heparin (UFH) infusion for at least twenty-four hours, except for one patient who had anti-thrombin III deficiency and was treated with argatroban infusion. For long-term anticoagulation, 56% of patients received apixaban 10 mg twice daily for the first five to seven days followed by 5 mg twice daily, while the remaining 44% were transitioned from IV anticoagulation to apixaban 5 mg twice daily. There were no adverse events reported, except for one patient who developed anemia after 7 months of treatment and required a blood transfusion. Complete recanalization was achieved in 78% while 22% had partial recanalization. Follow-up time ranged from six to twenty-three months. Conclusion: The use of apixaban for long-term anticoagulation in CVT resulted in recanalization in all of the patients in this case series without any major side effects. This case series adds to the emerging studies demonstrating the utility of apixaban for CVT. [ABSTRACT FROM AUTHOR]

Parenteral administration of high (therapeutic) doses of anticoagulants is a mandatory component of the initial treatment of acute coronary syndrome (ACS) unless contraindicated. In ACS, intravenous administration of unfractionated heparin, the use of low molecular weight heparin enoxaparin, selective antagonist of activated X clotting factor fondaparinux sodium and direct thrombin antagonist bivalirudin are possible. The review presents current approaches to the choice of drugs and the specifics of parenteral anticoagulant use depending on ACS variant (with or without persistent ST-segment elevations on ECG), approaches to myocardial revascularization, previous use of oral anticoagulants, renal function, risk of major bleeding, presented in current versions of European Society of Cardiology and Russian Society of Cardiology guidelines, approved by the Russian Ministry of Health. It is shown that, according to the results of randomized controlled trials and expert opinion, for most ACS treatment scenarios (streptokinase thrombolytic therapy or no reperfusion therapy in ACS with persistent ST elevation on ECG, ACS without persistent ST elevation) the optimal approach is parenteral administration of sodium fondaparinux. Exceptions include primary percutaneous coronary intervention and very early invasive treatment of ACS without persistent ST-segment elevation, but initial treatment with sodium fondaparinux does not prevent these approaches. Additional advantages of sodium fondaparinux are the absence of the need to monitor the coagulation system, a fixed dose, as well as the possibility of use in patients with significant thrombocytopenia. If short-term use of parenteral anticoagulant is expected (in early invasive treatment of ACS), there are contraindications or limitations to the use of sodium fondaparinux and sodium enoxaparin, the means of choice for most cases is intravenous administration of unfractionated heparin.

BACKGROUND. The world currently has a huge clinical experience in the treatment of SARS-CoV-2 infection. However, emerging scientific data opens up new information on the manifestations of coronavirus disease (COVID-19) and its consequences, which can affect both the changes of its clinical picture and the quality of patients’ life. OBJECTIVE. To summarize the results of literature search and own experience of intensive care of endothelial dysfunction in COVID-19. MATERIALS AND METHODS. The work is based on the results of an internet search with a help of Google and PubMed using the following key words: “intensive care of SARS-CoV-2”, “pathophysiological changes in coronavirus infection”, and “endothelial dysfunction”. RESULTS. This review describes the links of COVID-19 pathogenesis, mechanisms of viral endothelial damage and hypercoagulopathy, and the main directions of prevention and treatment of endothelial dysfunction. CONCLUSIONS. SARS-CoV-2 infection promotes endotheliitis in various organs as a result of viral infection. The presence of COVID-19-induced endotheliitis can explain the systemic microcirculation disorders in various vascular beds and their clinical consequences.