Search

Acquired haemophilia A (AHA) is an uncommon but severe acquired bleeding disorder caused by the development of antibodies against clotting factor VIII, impairing secondary haemostasis. It is more common in older individuals and characteristically presents with spontaneous soft tissue bleeding that can rapidly become life-threatening. Definitive treatment requires immunosuppression to eradicate anti-FVIII antibodies, while providing haemostatic support to manage bleeding. Transfusions of fresh frozen plasma or cryoprecipitate, typically used to treat severe bleeding, are ineffective in patients with AHA. Instead, highly specialised clotting factor concentrates are required. While the appearance and extent of the soft tissue bleeding and the markedly prolonged activated partial thromboplastin time are characteristic, lack of familiarity with this disease process can lead to significant treatment delays. We report the clinical course and management of a 65-year-old woman who presented with severe anaemia of unclear aetiology with unrecognised soft tissue bleeding who was subsequently diagnosed with AHA.

Purpose – determine the characteristics of changes of procoagulant, anticoagulant and fibrinolytic links of the hemostatic system in patients with hypertension in combination with coronary heart disease. Materials and methods. 127 people were examined - 14 healthy (control), 61 patients with stage II hypertension with concomitant coronary heart disease (group 2), 52 hypertensive patients with stage III with concomitant coronary heart disease (group 3). There were evaluated indicators of hemostasis system: thrombin time, activated partial thromboplastin time, prothrombin index, soluble fibrin monomer complex, fibrinogen, protein C, antithrombin III of, and the time of XII-dependent fibrinolysis. Results. Patients on both study groups SFMC content significantly higher than the control group. SFMC content in patients with stage II hypertension with concomitant coronary heart disease exceed normative value of 3 times, and in the group of hypertensive patients with stage III with with concomitant coronary heart disease of 3.65 times. The content of fibrinogen in the third group of patients exceeded the indicators of the control group by 27.6%, the difference was significant (p

Background and Aims Standard coagulation tests such as prothrombin time, activated partial thromboplastin time, and international normalized ratio are determined by liver-synthesized coagulation factors. Despite an increased international normalized ratio, patients with cirrhosis are in a “rebalanced” state of hemostasis as the concomitant effect of reduced protein C, protein S, and thrombomodulin is not evaluated in standard coagulation tests. The cell-based model of hemostasis indicates additional mechanisms such as systemic inflammation, sepsis, and organ failures tip the delicate coagulation balance to an anticoagulant type in acute-on-chronic liver failure. In acute liver failure, thrombin generation and platelet function remain intact despite a marked prolongation in prothrombin time. We aimed to explain the principles, application, and utility of viscoelastic tests such as thromboelastography, rotational thromboelastometry, and Sonoclot. Methods We reviewed the available literature from MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trial with the search terms 'coagulation', 'cirrhosis', 'acute-on-chronic liver failure', 'thromboelastography', 'thromboelastometry' and 'sonoclot' for cross sectional studies, cohort studies and randomized trials Results The point-of-care viscoelastic tests provide actionable targets for correcting the coagulation defect in a patient with bleeding and provide evidence-based algorithms for use in liver disease. A limitation of these tests is the inability to assess vessel injury and endothelial elements. Conclusion Global coagulation tests provide a comprehensive estimate of coagulation in vitro; however, their use has only been validated in the setting of liver transplantation. Newer guidelines for hemostatic resuscitation are now accepting these POC tests, but additional data are required to validate their use as standard of care.

Objectives : The COVID-19 pandemic has been associated with cases of refractory acute respiratory distress syndrome (ARDS) sometimes requiring support with extracorporeal membrane oxygenation (ECMO). Bivalirudin can be used for anticoagulation in patients on ECMO support, but its efficacy and safety in patients with COVID-19 is unknown. We set out to compare the pharmacologic characteristics and dosing requirements of bivalirudin in patients requiring ECMO support for ARDS due to COVID-19 versus ARDS from other etiologies. Design and Setting : This retrospective case control study was performed at Indiana University Health Methodist Hospital in Indianapolis, IN. Participants : Patients were included if they were on veno-venous (VV) ECMO support between June 2019 and June 2020 and divided into two groups: ARDS secondary to COVID-19 and those with ARDS from another etiology (Non-COVID). Interventions : Patient demographics such as age, sex, weight, chronic comorbid conditions, baseline antiplatelet and anticoagulant use, antiplatelet use during ECMO, and need for renal replacement therapy were collected and compared between groups. Time to activated partial thromboplastin time (aPTT) goal, percentage of time at aPTT goal, bivalirudin rates, total bivalirudin requirements, total duration on bivalirudin, total duration on ECMO, mortality, and complications associated with ECMO were collected and compared between groups. Measurements and Main Results : A total of forty-two patients met inclusion criteria (n = 19 COVID-19, n = 23 Non-COVID). However, percentage of aPTTs at goal were maintained more consistently in patients with COVID-19 versus non-COVID (86% vs. 74%: p < 0.01). Higher median (IQR) daily rates (3.1 mCg/kg/min (2.3-5.2) vs. 2.4 mCg/kg/min (1.7-3.3): p = 0.05) and higher median (IQR) maximum rates of bivalirudin (5 mCg/kg/min (3.7-7.5) vs. 3.8 mCg/kg/min (2.5-5): p = 0.03) were required in the COVID-19 group versus the non-COVID group. Time to goal aPTT was similar between groups. There was no difference in complications associated with anticoagulation as demonstrated by similar rates of bleeding and thrombosis between both groups. Conclusions : Patients on ECMO with ARDS from COVID-19 require more bivalirudin overall and higher rates of bivalirudin to maintain goal aPTTs compared to patients without COVID-19. However, COVID-19 patients more consistently maintain goal aPTT. Future randomized trials are needed to support efficacy and safety of bivalirudin for anticoagulation of COVID-19 patients on ECMO.

Background Cancer-associated venous thromboembolism (VTE) is a distinct pathological entity with much higher incidence and unique risk factors compared to general VTE. A previous study reported that cancer associated-VTE incidence in Taiwan is much lower than that reported for western countries and also lower than our anecdotal observations. To address this issue further, we initiated an investigation locally using a more detailed approach than used previously with comprehensive review of medical records to gain new insight into the incidence and risk factors for cancer-associated VTE. Methods Medical records of all adult patients with lung, pancreatic and gastric cancers, and lymphoma diagnosed from January 2011 to December 2013 in National Taiwan University Hospital indexed through the local cancer registry database were reviewed. VTE patients were identified through diagnosis coding and comprehensive medical chart review. Results Among 5620 consecutive lung, gastric and pancreatic cancer, and lymphoma patients, VTE was diagnosed in 246 (4.4%). Overall VTE incidence was 36.3 per 1000 patient-year. Multivariate analysis showed that not only high but also low body mass index (BMI) was associated with VTE risk with different cutoff levels by gender. Mildly to moderately anemic patients were at higher risk of VTE. Activated partial thromboplastin time (aPTT) had proportionally and reversely correlation to VTE risk. Conclusion We reported higher incidence of cancer associated VTE in Taiwan. Low BMI and short aPTT were found to be related to higher VTE risk that was not reported before.

Pulmonary endarterectomy (PEA) is the main treatment for chronic thromboembolic pulmonary hypertension (CTEPH). Postoperative unfractionated heparin dosing can be monitored by activated partial thromboplastin time (APTT) or by anti-factor Xa activity (anti-Xa). In pseudo heparin resistance, APTT response to heparin is blunted due to elevated Factor VIII (FVIII) which can underestimate anticoagulation. We examined possible pseudo heparin resistance after PEA and assessed the impact of FVIII. APTT response to heparin before and after operation was determined in 13 PEA patients anticoagulated with unfractionated heparin. APTT and anti-Xa concordance was analyzed from paired postoperative samples, and antithrombin, fibrinogen and FVIII levels were measured. Single-cell RNA sequencing was used to characterize FVIII gene expression in PEA specimens of 5 patients. APTT response to heparin was blunted after PEA. APTT and anti-Xa were discordant in 36% of postoperative samples and most common discordant patterns were subtherapeutic APTT with therapeutic (16%) or supratherapeutic (11%) anti-Xa. Overall, APTT underestimated anticoagulation relative to anti-Xa in one-third of the samples. FVIII levels were elevated before surgery, increased substantially 1 and 3 days (median 4.32 IU/mL) after PEA, and were higher in discordant than concordant samples. Single-cell RNA sequencing showed FVIII gene expression in PEA specimen endothelial cells. Pseudo heparin resistance is common after PEA likely due to highly elevated postoperative FVIII levels indicating that anti-Xa reflects postoperative heparinization better than APTT in these patients. FVIII production by the pulmonary artery endothelium may participate in local prothrombotic processes important for CTEPH pathogenesis.

Background: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49–75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging. Methods: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model. Results: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00–56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels. Conclusions: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities.

Background This study evaluated E-selectin inhibition with GMI-1271 (Uproleselan [GMI]) alone and in combination with the standard of care low-molecular-weight heparin (LMWH) to improve vein recanalization, decrease vein wall inflammation and protect against adverse bleeding in a primate model. We sought to examine this novel treatment of venous thrombosis. Methods Using a well-documented primate animal model, iliac vein thrombosis was induced by balloon occlusion of the iliac vein for 6 hours. Starting on day 2 after thrombosis, animals began treatment in two phases. In phase one, nontreated controls received no treatment (n = 5) vs animals treated with the E-selectin inhibitor GMI, 25 mg/kg, subcutaneous (SC), once daily (n = 4) for 21 days (previously published data). In phase two, animals were treated with GMI plus a combination of LMWH 1.5 mg/kg or 40 mg (GMI + LMWHc) SC once daily (n = 8) for 19 days; and animals treated with LMWH 1.5 mg/kg or 40 mg (LMWHc) SC once daily (n = 6) for 19 days. Animals were evaluated by magnetic resonance venography for vein recanalization and inflammation by gadolinium extravasation, duplex ultrasound, coagulation tests (thromboelastography, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen) and complete blood count at baseline, days 2, 7, 14, and 21 at euthanasia. Statistical analysis included using unpaired t test with Welch's correction for direct comparisons and one-way analysis of variance for comparison between the groups. Results Percent vein recanalization by magnetic resonance venography was highest in the GMI alone group followed by GMI + LMWHc, both significantly different from control. On ultrasound examination, animals treated with GMI alone had no decrease in open vein lumen by day 21, whereas decreases were observed in groups GMI + LMWHc (–26%), LMWHc (–27%), and controls (–80%). Vein wall inflammation decreased significantly in all treated groups. Intimal fibrosis and intimal thickness was best preserved in the GMI alone group. An analysis of total vein wall collagen revealed a trend in all treatment groups of decreasing vein wall collagen. No clinically significant bleeding events were noted in any group. The LMWH groups trended to have prolonged coagulation test values, whereas E-selectin inhibition with GMI did not cause clinically significant changes in coagulation measures. Conclusions Treatment with E-selectin inhibition results in improved vein recanalization, a decrease in vein wall inflammation and vein wall intimal thickness and fibrosis, with no changes in markers of coagulation. E-selectin inhibition with GMI alone is superior to E-selectin inhibition combined with LMWH, LMWH alone, and no treatment in this deep vein thrombosis model of iliac vein thrombosis.

Apixaban is used to treat venous thromboembolism (VTE) at 10 mg twice daily (BID) for 7 days, followed by 5 mg BID without dose adjustment, and non-valvular atrial fibrillation (NVAF) at 5 mg BID or 2.5 mg BID with dose adjustment criteria (DAC) including age, body weight, and renal function. The anti-factor Xa activity (AXA), prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients with VTE receiving 10 mg BID of apixaban remains unclear. Twenty-six patients (70.8±15.4 years, 10 males) with VTE receiving 10 mg BID of apixaban were enrolled. The patients were divided into two groups based on whether they met the DAC of NVAF: DAC group (n=8) and non-DAC group (n=18). Trough and peak AXA values, PT, and APTT were measured at 10 mg BID dosage and then at 5 mg BID dosage. Coagulation markers in recipients of 10 mg BID therapy were significantly higher than those of 5 mg BID recipients. A significant and strong positive correlation was observed between AXA and PT at trough and peak times. The AXA values and PT in the DAC group were significantly higher than those in the non-DAC group. No significant inter-group differences were seen in APTT. This study provides the first report of AXA distribution in VTE patients receiving 10 mg BID of apixaban. Our findings indicate that coagulation markers may differ in patients with VTE-prescribed higher doses of apixaban and a DAC may be warranted in such patients.

Purpose The study objective was to explore whether prophylaxis with vitamin K1 improves abnormal coagulation function–associated cefoperazone-sulbactam in patients treated in the long term with low-dose aspirin. Methods This retrospective, observational study assessed patients treated with long-term low-dose aspirin in a naval military hospital in China from 2004 to 2018, including all patients treated concurrently with cefoperazone-sulbactam with or without vitamin K1. Differences in the coagulation index were analyzed statistically before and after receipt of cefoperazone-sulbactam. Findings The cohort included 227 patients. After cefoperazone-sulbactam treatment, the mean (SD) prothrombin time (PT) was 14.07 (3.07) seconds, activated partial thromboplastin time (aPTT) was 35.15 (4.78) seconds, and international normalized ratio (INR) was 1.49 (0.49) in the cefoperazone-sulbactam group, which was significantly higher than the PT of 11.55 (1.29), aPTT of 31.37 (2.20), and INR of 1.12 (0.35) before cefoperazone-sulbactam treatment. No significant difference was in the cefoperazone-sulbactam plus vitamin K1 group. In addition, no significant difference was found in the thrombin time or fibrinogen level between before and after cefoperazone-sulbactam treatment in both groups. The mean (SD) platelet counts of the 2 groups were 197.34 (71.82) × 109/L and 187.75 (72.66) × 1 09/L after cefoperazone-sulbactam treatment, respectively, which was significantly lower than 231.77 (77.05) × 109/L and 232.08 (84.48) × 109/L before cefoperazone-sulbactam treatment. There were greater proportions of coagulation disorders (prolongation of PT, aPTT, INR, and bleeding) after cefoperazone-sulbactam treatment in the cefoperazone-sulbactam group compared with that in the cefoperazone-sulbactam plus vitamin K1 group. Implications Results indicate that, after adding cefoperazone-sulbactam to the regimens of patients receiving long-term low-dose aspirin, therapy contributed to remarkable increase in abnormal coagulation function and coagulation disorders. Prophylaxis with vitamin K1 decreased the risk of these abnormalities in blood coagulation parameters associated with cefoperazone-sulbactam in patients taking long-term aspirin.

Introduction Continuous intravenous unfractionated heparin (UFH) is a mainstay of therapeutic anticoagulation in the acute setting. The two most common laboratory tests for monitoring UFH are the activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) heparin assay. We reviewed the available evidence to evaluate if the choice of monitoring test for UFH therapy is associated with a difference in the clinical outcomes of bleeding, thrombosis, or mortality. Materials and methods MEDLINE, Cochrane database, and conference abstracts from the Society of Critical Care Medicine, the American Society of Hematology, and the American College of Clinical Pharmacy were searched for all studies comparing aPTT and anti-Xa monitoring for therapeutic UFH that evaluated outcomes for bleeding, thrombotic events, or mortality. Risk of bias was assessed with the Cochrane Risk of Bias Tool and Newcastle Ottawa Scale. Pooled relative risk ratios were calculated using an inverse variance-weighted random-effects model. Results Ten studies (n = 6677) were included for analysis. The use of anti-Xa compared to aPTT was not associated with an increased risk of bleeding (RR 1.03; 95% CI 0.8–1.22 I2 = 4%) or an increased risk of thrombotic events (RR 0.99; 95% CI 0.76–1.30, I2 = 3%). There was no difference in mortality within individual studies but the data were not suitable for pooled analysis. Conclusions Pooled data comparing aPTT vs. anti-Xa for monitoring therapeutic UFH did not suggest differences in the outcomes of bleeding or thrombosis.

A 55-year-old male presented to our emergency department with haematuria and abdominal pain. Investigations including a computed tomography (CT) scan revealed an intraluminal filling defect within the left collecting system, consistent in appearance with blood clot. With an initial working diagnosis of upper tract urothelial cell carcinoma, he was discharged with plans for an urgent cystoscopy and ureteroscopy. He subsequently represented with ongoing frank haematuria, anasarca, dropping haemoglobin and new right collecting system blood clot. Subsequent investigations showed that the patient had acquired haemophilia A resulting in the episodes of haematuria, highlighted after an elevated activated partial thromboplastic time prompted a thrombophilia screen. The patient was subsequently treated with factor eight inhibitor bypass activity, corticosteroids and cyclophosphamide.

To evaluate the hypothesis that patients with a history of intravenous drug misuse (IVDM) initiated on weight-based heparin infusions require higher than expected infusion rates to achieve therapeutic activated partial thromboplastin time (aPTT). This study is a multicenter, retrospective chart review of patients with a history of IVDM who were admitted to an acute care site between 10/1/2015 and 9/30/2020 and treated with continuous heparin infusions. Patients were identified using ICD9 and ICD10 codes and included if they had a documented history of IVDM within the past six months. Variables of particular interest included: median heparin infusion rates to maintain therapeutic aPTT, average time to reach therapeutic aPTT, and International Society of Thrombosis and Haemostasis Criteria for moderate to severe bleeding. Of the 41 patients who met the inclusion and exclusion criteria, 39 achieved therapeutic aPTT while on a weight-based heparin infusion. All heparin infusions were initiated at a rate of 18 units/kg/hr then titrated per institutional heparin infusion protocols. The mean time to therapeutic aPTT was 38.48 h ± 26.4 h with a mean infusion rate of 27.64 ± 7.14 units/kg/hr. To maintain therapeutic anticoagulation, infusion rates 150% higher than the initial rate were required. Of the 39 patients who achieved therapeutic aPTT, 85% (33) met criteria for heparin resistance, defined as greater than 35,000 units of heparin daily. No statistical significance could be derived from this retrospective chart review as therapeutic heparin rates were evaluated in comparison to initial infusion rate, rather than a control group. The findings in this study demonstrate a possible clinical association of the reduced antithrombin activity previously described in opiate misusers. To efficiently achieve therapeutic anticoagulation, it may be appropriate to consider use of heparin antiXa monitoring in place of aPTT or utilization of increased initial heparin infusion rates. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02615-z.

Purpose: The study examined the use of factor XIII and fibrin degradation products in diagnosing early cases of NEC and neonatal sepsis. Methods: Sixty neonates were divided into two groups. 30 preterm neonates suspected with early NEC Diagnosis of NEC was confirmed by modified Bell’s score and 30 preterm neonates with symptoms of neonatal sepsis; where sepsis was confirmed by blood culture and CRP. Laboratory evaluation of FDPs and plasma factor XIII was done for all the patients. The study was carried out in a tertiary NICU of the pediatric department, Ain Shams University Hospital. All enrolled neonates had a matched mean birth weight and gestational age. They were either moderate preterms >32 weeks, but 34 weeks, but

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered to have multiple roles in the development of atherosclerosis, which is recently reported to participate in the thrombotic process. We aimed to examine the relationship between PCSK9 concentration, coagulation indexes and cardiovascular events. Methods A total of 2293 consecutive patients with angina-like chest pain and without lipid-lowering drugs treatment were enrolled and followed up for major adverse cardiovascular events (MACEs). Circulating PCSK9 concentration was determined by ELISA. The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time were performed. The associations between PCSK9 concentration, routine coagulation indicators and MACEs were analyzed. Results Patients with high PCSK9 levels had lower PT and APTT levels (all p p Conclusions Our study firstly suggested that PCSK9 concentration was negatively correlated with plasma levels of PT. Furthermore, high PCSK9 and low PT were associated with MACEs and the combination of PCSK9 with PT had an addictive effect on predicting cardiovascular outcomes in patients with chest pain, which was useful for further subdivision of cardiovascular risks.

OBJECTIVE Coagulopathy is a well-recognized risk factor for poor outcomes in patients with traumatic brain injury (TBI). Differences in the time courses of coagulation and fibrinolytic parameters between pediatric and adult patients with TBI have not been defined. METHODS Patients with TBI and an Abbreviated Injury Scale of the head score ≥ 3, in whom the prothrombin time (PT)–international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen concentration, and plasma D-dimer levels were measured on arrival and at 3, 6, and 12 hours after injury, were retrospectively analyzed. Propensity score–matched analyses were performed to adjust baseline characteristics between pediatric patients (aged < 16 years) and adult patients (aged ≥ 16 years). RESULTS A total of 468 patients (46 children and 422 adults) were included. Propensity score matching resulted in a matched cohort of 46 pairs. Higher PT-INR and APTT values at 1 to 12 hours after injury and lower fibrinogen concentrations at 1 to 6 hours after injury were observed in the pediatric group compared with the adult group. Plasma levels of D-dimer were elevated in both groups at 1 to 12 hours after injury, but no significant differences were seen between the groups. Multivariate logistic regression analysis of the initial coagulation and fibrinolytic parameters in the pediatric group revealed no prognostic significance of the coagulation parameter values, but elevation of the fibrinolytic parameter D-dimer was an independent negative prognostic factor. CONCLUSIONS In the acute phase of TBI, pediatric patients were characterized by prolongation of PT-INR and APTT and lower fibrinogen concentrations compared with adult patients, but these did not correlate with outcome. D-dimer was an independent prognostic outcome factor in terms of the Glasgow Outcome Scale in pediatric patients with TBI.

Acquired hemophilia A, caused by autoantibodies that bind to and neutralize the activity of coagulation factor VIII (FVIII), almost universally presents as a severe bleeding diathesis. Lupus anticoagulants (LAs), autoantibodies directed against phospholipids or protein-phospholipid complexes, manifest clinically with an increased risk of thrombosis. While these autoantibodies are uncommon, the distinctive clinical presentation in conjunction with the typical laboratory findings often enable straightforward identification of the underlying autoantibody. However, the presence of a concomitant acquired FVIII inhibitor and LA is exceedingly rare with fewer than 20 documented cases. All prior patients presented with life-threatening hemorrhage, thrombosis, or both, prompting comprehensive hematologic evaluation and subsequent identification of the pathologic antibodies. We describe a novel case of a patient with no signs of hemorrhage or thrombosis who was incidentally found to have both a FVIII inhibitor and LA during evaluation of a prolonged partial thromboplastin time (PTT). This finding resulted in FVIII inhibitor-directed management, including immunosuppressive therapy. The unique presentation of an incidental FVIII inhibitor and LA in an asymptomatic patient without thrombotic or bleeding complications highlights the potential challenge in elucidating the etiology of a prolonged PTT, as LAs and FVIII inhibitors both prolong the PTT, and each entity can interfere with assays designed to detect the presence of the other autoantibody. This case underscores the importance of recognizing that patients with major underlying disturbances in their hematologic physiology, but in whom clinical symptoms have yet to manifest, may potentially be overlooked until such symptoms are evident.

Background: Anticoagulation-free continuous renal replacement therapy (CRRT) was recommended by the current clinical guideline for patients with increased bleeding risk and contraindications of citrate. Nevertheless, anticoagulation-free CRRT yielded heterogeneous filter lifespan. Furthermore, the specific cutoff values for traditional coagulation parameters to predict sufficient filter lifespan of anticoagulation-free CRRT have not yet been determined. The purpose of our present study was to develop and validate a model for predicting sufficient filter lifespan in anticoagulation-free CRRT patients. Methods: Patients who underwent anticoagulation-free CRRT in our center between June 2013 and June 2019 were retrospectively included. The primary outcome was sufficient filter lifespan (≥24 h). Thirty-seven predictors were included for modeling based on their clinical significance and previous reports. The final model was developed by using multivariable logistic regression analysis and was validated in a separate external cohort. Results: The development cohort included 170 patients. Sufficient filter lifespan was observed in 80 patients. Thirteen variables were independent predictors for sufficient filter lifespan by logistic regression: body temperature, mean arterial pressure, activated partial thromboplastin time, direct bilirubin, alkaline phosphatase, blood urea nitrogen, vasopressor use, body mass index, white blood cell, platelet count, D-dimer, uric acid, and pH. The area under the curve (AUC) of the stepwise model and internal validation model was 0.82 (95% confidence interval [CI] [0.76–0.88]) and 0.8 (95% CI [0.74–0.87]), respectively. The positive predictive value and the negative predictive value of the stepwise model were 0.77 and 0.79, respectively. The validation cohort included 44 eligible patients and the AUC of the external validation model was 0.82 (95% CI [0.69–0.96]). Conclusions: The use of a prediction model instead of an assessment based only on coagulation parameters could facilitate the identification of the patients with filter lifespan of ≥24 h when they accepted anticoagulation-free CRRT.

BACKGROUND To assess patients with indirect carotid-cavernous fistulas (CCF) for evidence of hypercoagulable state (HS) by combination of comprehensive medical questionnaire and laboratory testing. METHODS Patients with confirmed diagnosis of CCF treated between 2003 and 2019 were included and administered a questionnaire screening for HS risk factors and undergone laboratory investigations which included complete blood count (CBC), prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, antiphospholipid antibodies (lupus anticoagulant and anticardiolipin antibody titres), Factor V Leiden, prothrombin, protein C, protein S, antithrombin III, homocysteine, prothrombin G20210, CALR and JAK2 mutation screening. Participants with abnormal laboratory testing and/or past history of ischemic stroke, atrial fibrillation, cancer or hypercoagulability-associated hereditary disorders were deemed to have HS. RESULTS Twenty-two patients were enrolled. Seventeen were women and the mean age at diagnosis was 60. Fourteen (64%) had evidence of HS: six on medical history, three with laboratory evidence and five with both. Eight (36%) had current abnormal hypercoagulability markers. One had a diagnosis of Klippel-Trenaunay Syndrome, but no others had evidence of hereditary thrombophilia. Nine were on anti-coagulation initiated after diagnosis of stroke or atrial fibrillation discovered on average 5.5 years after the diagnosis of CCF. CONCLUSION A total of 64% percent of patients with previous indirect CCF had evidence of underlying HS indicating that hypercoagulability might play a role in the pathogenesis of CCF. The results support need for comprehensive testing for underlying HS in patients with indirect CCFs to better identify, manage, and prevent further thromboembolic events.

Somebody’s organ dysfunctions are associated with the cardiopulmonary bypass in open-heart surgery such as liver dysfunction. This study aimed at the impact of the N-acetyl cysteine for improvement of liver function subsequently on-pump coronary artery bypass graft. Following a clinical trial design, 60 candidates of on-pump CABG, age 30 to 70 years, normal liver function, and normal renal function were selected. The candidates were randomly divided into intervention: IV100 mg/kg N-acetyl cysteine in three doses (2 intraoperative and 1 postoperative) over 24 h, and control groups (normal saline as placebo) (n = 30 in each group). The main outcomes were serum alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, bilirubin, partial thromboplastin time, and the international normalized ratio at first and second postoperative day after surgery. Secondary outcomes were the hemodynamic variables and blood product transfusion. There were significant differences in ALP (P

Background We aim to determine the clinical utility of reflex coagulation investigations (RCI) for prolonged lupus insensitive activated partial thromboplastin time (aPTT) at our institution. Methods We retrospectively reviewed all potential RCI (lupus insensitive aPTT of ≥32s) from April 2014 to June 2019. Our diagnostic algorithm requires completion of RCI only if samples had no interfering medications to explain a prolonged aPTT and were either from a preoperative sample or from a patient presenting with unexplained bleeding. Appropriate RCI samples undergo further investigations with one-stage factor activity testing for factors 8(FVIII), 9(FIX), and 11(FXI) reflexively. Data were obtained through electronic medical records to capture clinical characteristics, laboratory findings, prophylactic hemostatic replacement, and bleeding outcomes. Results Three thousand and three hundreds seventeen samples from 2940 distinct patients were considered as potential RCI during the study period. 263/3317 (8%) samples had RCI completed. Of those, 55/263 (21%) had abnormal factor testing, with the majority from preoperative setting (43/55; 78%). 5/43 (12%) patients were referred to hematology for preoperative evaluation. 5/43 patients received preoperative hemostatic support. A total of 5 patients (5/43) developed postop bleeding. Six patients (6/55) had RCI for unexplained bleeding, and five patients (83%) had a newly identified clinically significant bleeding disorder. Conclusion Reflex coagulation investigations benefited patients presenting with unexplained bleeding as this expedited the diagnosis and management of clinically significant bleeding disorders. RCI for preoperative evaluation infrequently led to additional hemostatic support/referral to hematology. The lack of additional workup for an abnormal factor activity level suggests laboratory alert fatigue as a potential contributory factor.

Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.

OBJECTIVE Although various guidelines have been established for the management of antithrombotic therapy during surgical treatments, surgical tracheostomy (ST) under continued antithrombotic therapy (CAT) remains challenging. Here, we investigated the risk factors for complications after ST by focusing on the application of CAT during ST. DESIGN A retrospective cohort study with medical records from 2009 to 2020. SETTING A single-center study. PARTICIPANTS This study included patients who had undergone ST at the Department of Otolaryngology of our hospital MAIN OUTCOME MEASURES: The primary outcomes were the incidence of complications and blood test results. Secondary outcomes were risk factors for postoperative complications. RESULTS We identified 288 patients (median age: 64 years; 184 men [64%]), among whom 40 (median age: 67 years; 29 men [73%]) underwent CAT. Although the patients undergoing CAT had significantly longer activated partial thromboplastin time (p=0.002) and a higher prothrombin time-international normalized ratio (p=0.006) compared to antithrombotic naive patients, no statistically significant intergroup differences were observed for the risk of bleeding, infection, or subcutaneous emphysema. Instead, ST under local anesthesia (p=0.01) and ST for airway emergency (p=0.02) significantly increased the risk of early postoperative complications. CONCLUSION These results suggest that ST under CAT can be safely performed without any increased risk of postoperative complications. Nevertheless, surgeons should be extra cautious about early complications after ST under local anesthesia without intubation or ST for airway emergencies.

Background: Hemophilia is an X-linked heritable coagulopathy with an overall prevalence of approximately 1 in 10,000 individuals. Hemophilias are rare X linked hereditary bleeding disorders. Platelets may be among the determinants of variability in bleeding phenotype. Objective: To evaluate the platelet function tests in patients with hemophilia, and to explore the influence of platelet dysfunction on hemophilia bleeding score. Patients and Methods: The study was conducted on 40 hemophilic patients and 20 normal persons as a control in outpatient clinics at Kafr El-Sheikh Governorate Hospitals and Al-Azhar University Hospitals (Al-Hussein and Sayed Galal) to evaluate the platelet function tests in patients with hemophilia, and to explore the influence of platelet dysfunction on hemophilia bleeding score. Results: The majority of cases (35 patients 87.5%) were type A and (5 patients 12.5%) were type B. As regard to hemophilia scoring system (HSS), 3 patients (7.5%) were type 1, 19 patients (47.5%) were type 2 and 18 patients (45%) were type 3. Bleeding from the knee occurred in the majority of patients (77.5%), from the elbow occurred in 32.5%, from the ankle occurred in 5%, from the vagina occurred in 15% and from the nose and the gum occurred in 7.5%. Platelets and maual platelet count showed insignificant difference between both groups. Platelets aggregation tests (ADP) test, collagen and restocetin agonists test) were significantly lower in cases group than control group. Prothrombin time (PT), international normalized ratio (INR), bleeding time (BT) showed insignificant differences between both group. On the other hands, activated partial thromboplastin time (APTT) significantly prolonged cases group than control group. No hemophilia C cases were detected in our study. Conclusion: There was a statistical significant relationship between bleeding phenotype in hemophilia B and platelet function. Diagnosis of hemophilia was confirmed by factor VIII assay for hemophilia A and factor IX assay for hemophilia B.

BACKGROUND Liver cirrhosis is associated with immune deficiency, which causes these patients to be susceptible to various infections, including cryptococcus infection. Mortality in cirrhotic patients with cryptococcosis has increased. The present study was to explore the risk factors of mortality and the predictive ability of different prognostic models. METHODS Forty-seven cirrhotic patients with cryptococcosis at a tertiary care hospital were included in this retrospective study. Data on demographics, clinical parameters, laboratory exams, diagnostic methods, medication during hospitalization, severity scores and prognosis were collected and analyzed. Student's t test and Mann-Whitney test were used to compare characteristics of survivors and non-survivors at a 90-day follow-up and cerebrospinal fluid (CSF) manifestations of cryptococcal meningitis. Multivariate Cox regression analysis was used to identify the independent risk factors for mortality. Kaplan-Meier curves were used to analyze patient survival. Receiver operating characteristic (ROC) curves were used to evaluate the different prognostic factors. RESULTS The 30- and 90-day survival rates were 93.6% and 80.9%, respectively, in cirrhotic patients with cryptococcosis. Cryptogenic liver diseases [hazard ratio (HR) = 7.567, 95% confidence interval (CI): 1.616-35.428, P = 0.010], activated partial thromboplastin time (APTT) (HR = 1.117, 95% CI: 1.016-1.229, P = 0.022) and Child-Pugh score (HR = 2.146, 95% CI: 1.314-3.504, P = 0.002) were risk factors for 90-day mortality in cirrhotic patients with cryptococcosis. Platelet count (HR = 0.965, 95% CI: 0.940-0.991, P = 0.008) was a protective factor. APTT (HR = 1.120, 95% CI: 1.044-1.202, P = 0.002) and Child-Pugh score (HR = 1.637, 95% CI: 1.086-2.469, P = 0.019) were risk factors for 90-day mortality in cirrhotic patients with cryptococcal meningitis. There was significant difference in the percentage of lymphocytes in CSF between survivors and non-survivors [60.0 (35.0-75.0) vs. 95.0 (83.8-97.2), P < 0.001]. The model of end-stage liver disease-sodium (MELD-Na) score was more accurate for predicting 30-day mortality both in patients with cryptococcosis [area under curve (AUC): 0.826, 95% CI: 0.618-1.000] and those with cryptococcal meningitis (AUC: 0.742, 95% CI: 0.560-0.924); Child-Pugh score was more useful for predicting 90-day mortality in patients with cryptococcosis (AUC: 0.823, 95% CI: 0.646-1.000) and those with cryptococcal meningitis (AUC: 0.815, 95% CI: 0.670-0.960). CONCLUSIONS These results showed that cryptogenic liver diseases, APTT and Child-Pugh score were associated with mortality in cirrhotic patients with cryptococcosis and cryptococcal meningitis. MELD-Na score was important for predicting 30-day mortality, and Child-Pugh score was critical for predicting 90-day mortality.

Background: The liver is the primary site of synthesis of nearly all coagulation factors, along with several proteins involved in fibrinolysis and anticoagulation, The acute and chronic inflammation in the liver is associated with a bleeding diathesis due to deficiency in the synthesis of coagulation factors as well as a pro-coagulant state due to the defects in the synthesis of anticoagulant factors by the liver. Objective: To assess the tissue factor in cirrhotic and hepatocellular carcinoma (HCC) patients and their coagulation profile. Patients and methods: This was a case control study carried on Al-Mahala General Hospital, and conducted on 80 subjects. They were categorized into in to main two groups: Group A (60 patients) and Group B (20 control persons) from March 2019 till September 2019. Results: There was a statistical significant difference between tissue factor expression and other laboratory parameters among the studied group. There was a significant positive correlation between tissue factor and alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, total bilirubin, α-fetoprotein (AFP), international normalized ratio (INR) and activated partial thromboplastin time (APTT). Also there was a significant negative correlation between tissue factor and hemoglobin, albumin and platelets. Conclusion: Tissue factor (TF) enhances the inflammatory process within the liver parenchyma as it induces release of pro-inflammatory cytokines. This raises the possibility of a potential role for anti-inflammatory substances as a potential therapeutic option that can ameliorate liver damage in those patients.

Objectives Monitoring is essential to safe anticoagulation prescribing and requires close collaboration among pathologists, clinicians, and pharmacists. Methods We describe our experience in the evolving strategy for laboratory testing of unfractionated heparin (UFH). Results An intrainstitutional investigation revealed significant discordance between activated partial thromboplastin time (aPTT) and antifactor Xa (anti-Xa) assays, prompting a transition from the former to the latter in 2013. With the increasing use of oral factor Xa inhibitors (eg, apixaban, rivaroxaban, edoxaban, betrixaban), which interfere with the anti-Xa assay, we adapted our protocol again to incorporate aPTT in patients admitted on oral Xa inhibitors who require transition to UFH. Conclusions Our experience demonstrates key challenges in anticoagulation and highlights the importance of clinical pathologists in helping health systems adapt to the changing anticoagulation landscape.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening clinical syndrome in children, and the knowledge of it is still limited. Two hundred twenty-seven children with HLH in our hospital were retrospectively analyzed from January 2001 to December 2018. The age of the patients on admission ranged from 1 day to 14 years old. The 3 most common clinical manifestations include fever (98.7%), hepatomegaly (95.6%), and splenomegaly (92.1%). The decrease of high-density lipoprotein cholesterol (99.1%) is very common in children with HLH. Albumin65 s, and lactose dehydrogenase >1000 U/L were independent risk factors for poor early prognosis in children with HLH, and their odds ratio values were 2.515, 3.094, and 2.378, respectively, while age >28 months was identified as a protective factor (odds ratio=0.295). Of the 227 children, 67 (29.52%) died within 30 days of onset. The mortality rate in 2013 to 2018 was significantly lower than that in 2001 to 2012 (16.35% vs. 40.65%, P=0.000). The shortening of the time from onset to admission and the reduction of time from admission to definite diagnosis could be some of the reasons for the decrease of HLH mortality in 2013 to 2018 (P

To investigate the correlation of platelet and coagulation function with blood stasis syndrome (BSS) in coronary heart disease (CHD). The protocol for this meta-analysis was registered on PROSPERO (CRD42019129452). PubMed, Excerpta Medica Database (Embase), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched from inception to 1st June, 2020. Trials were considered eligible if they enrolled BSS and non-BSS (NBSS) patients with CHD and provided information on platelet and coagulation function. The platelet function, coagulation function, and fibrinolytic activity were compared between the BSS and NBSS groups. Forest plots were generated to show the SMDs or ESs with corresponding 95% CIs for each study. Subgroup analysis and sensitivity analysis were performed to explore potential sources of heterogeneity. The systematic search identified 1,583 articles. Thirty trials involving 10,323 patients were included in the meta-analysis. The results showed that mean platelet volume, platelet distribution width, platelet aggregation rate, platelet P selectin, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), thromboxane B2 (TXB2), 6-keto-prostaglandin F1alpha (6-keto-PGF1 α), and TXB2/6-keto-PGF1 α were higher in the BSS group than in the NBSS group (P

To determine the value of coagulation indicators: D-dimer (DD), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), in predicting the severity and prognosis of COVID-19.Around 150 patients with confirmed COVID-19 disease, who were admitted at Rajarajeswari Medical College and Hospital, Bangalore between April 15 2021 and July 15, 2021, were included in the study. The changes of D-Dimer, PT, APTT were tested, and the correlation with, clinical classifications, demographics, CT imaging, vaccination status against COVID-19 and prognosis were observed.Coagulation disorder occurred at the early stage of COVID-19 infection, in a total of 150 patients observed, 109 (72.66%, St. deviation of 4.26) patients having DD increased at time of admission and 148 patients (98.66%) having increased coagulation profile. The levels of DD and coagulation profile were correlated with clinical classification and also the CT severity and vaccination status. Among 41(27.33%) patients who died, 31(20.66%) patients had DD increased at the first lab test, 40 (26.66%) patients had DD increased on the fifth day of lab tests. The results shows that D-dimer is raised in severe category of COVID-19 infection. Also the CT severity is high (severe, with CT score>15) 71(47.33%) patients with increased D-dimer on admission. It was observed that 41(27.33%) patients who were vaccinated had increased D-dimer 70(46.66%) compared to unvaccinated patients. In addition, with the progression of the disease, the change of CT imaging was closely related to the increase of the DD value (P Coagulation dysfunction is more likely to occur in severe and critically ill patients. DD and PT could be used as the significant indicators in predicting the mortality of COVID-19 and measuring the level of D-dimer and coagulation parameters from the early stage of the disease can also be useful in controlling and managing of COVID-19 disease, also vaccinated patients had better outcome among the unvaccinated patients.

In recent decades, numerous scientific works are devoted to the study of the clinical and prognostic significance of albuminuria, methods of its detection, as well as treatment measures aimed at controlling this pathological condition. The objective of this work was to determine the features of changes of plasma hemostasis in patients with essential hypertension (EH), depending on the presence of albuminuria. Materials and methods. We have exa-mined 113 people: 14 apparently healthy ones (group 1, controls), 41 patients with EH stage II with concomitant albuminuria (group 2), 58 patients with EH stage II without concomitant albuminuria (group 3). We have conducted laboratory studies: measured activated partial thromboplastin time, prothrombin index, thrombin time, fibrinogen, soluble fibrin monomer complex (SFMC), time of XIIa-dependent fibrinolysis, antithrombin III, protein C. Results. There was found an increased content of SFMC, which in patients from group 3 was 135 % higher, and in patients of group 2 — 247 % higher than reference values. At that, in patients with albuminuria, this index was much higher even than in individuals with EH without albuminuria — exceeded by 48 %. Time of XIIa-dependent fibrinolysis in both group 2 and 3 was much longer than normal one. Expressed changes occurred in the system of natural anticoagulants, which were statistically significant in relation to the control group only in patients with albuminuria, and in the group of patients without albuminuria they were not significantly different from the control group. Conclusions. Patients with essential hypertension, regardless of the severity of albuminuria, showed a significant inhibition of fibrinolytic activity of the blood and activation of the last units of blood clotting — fibrin formation. Albuminuria was associated with a more significant activation of fibrin formation and was combined with inhibition of own anticoagulant activity of the blood, as evidenced by the decrease in the content of antithrombin III and protein C.

Yu Hong,1,2,&ast; Xian-Hui Wang,3,&ast; Yi-Tong Xiong,2 Jie Li,2 Chun-Feng Liu1 1Department of Neurology, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, 215004, People’s Republic of China; 2Department of Neurology, Affiliated Yixing People’s Hospital of Jiangsu University, Yixing, Jiangsu, 214200, People’s Republic of China; 3Department of Neurology, Taicang First People’s Hospital, Taicang, Jiangsu, 215400, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie LiDepartment of Neurology, Yixing People’s Hospital, No. 75 Tongzhenguan Road, Yicheng Street, Yixing, Jiangsu, 214200, People’s Republic of ChinaEmail jielee1983@163.comChun-Feng LiuDepartment of Neurology, The Second Affiliated Hospital of Soochow University, No. 1055 Sanxiang Road, Suzhou, Jiangsu, 215004, People’s Republic of ChinaEmail liuchunfeng@suda.edu.cnBackground: Hypophosphatemia was reported to frequently occur in patients with nontraumatic intracranial hemorrhage (ICH); however, the correlation between hypophosphatemia and outcomes of ICH remains unclear. This study aimed to examine the association between admission serum phosphate and all-cause mortality among patients with mild–moderate spontaneous ICH (sICH).Methods: A total of 851 patients with sICH were enrolled. Serum phosphate was acquired within 24 hours on admission, and participants were divided according to phosphate quartiles. The primary outcome was all-cause mortality within 90 days, and univariate and multivariate models were employed to estimate the mortality risk.Results: There were significant differences among sICH patients with different phosphate quartiles in terms of age, diastolic blood pressure (DBP), activated partial thromboplastin time (APTT), platelet count, and incidence of respiratory failure events on admission (P < 0.05). Log rank test showed a significant difference in the mortality risk among sICH patients with each phosphate quartile. Univariate Cox regression analysis revealed that age, smoking, DBP, APTT, NIH stroke scale (NIHSS) score, hematoma volume and serum phosphate might be associated with the 90-day all-cause mortality in patients with sICH (P < 0.05). Multivariable Cox regression analysis showed that the crude mortality was 4.3-fold greater in sICH patients with serum phosphate Q1 than those with Q4 (P < 0.001), and remained 3.18-fold higher after adjusting for age, smoking, DBP, APTT, NIHSS score, hematoma volume and early withdrawal of life-sustaining therapy (P = 0.011). Representative operating curve (ROC) analysis showed that admission serum phosphate was predictable for all-cause mortality within 90 days in patients with sICH (area under the ROC = 0.628, P < 0.001).Conclusion: Low admission serum phosphate is strongly associated with a high risk of mortality in patients with mild–moderate sICH, and hypophosphatemia may be a prognostic marker for all-cause mortality in patients with mild–moderate sICH.Keywords: spontaneous intracerebral hemorrhage, serum phosphate level, risk factor, all-cause mortality

Vascular intervention-induced platelet and coagulation activation is often managed with a combination of antiplatelets and anticoagulants, with evident benefits, but with a risk of systemic bleeding. Antiplatelet and anticoagulant (APAC) is a dual antiplatelet and anticoagulant heparin bioconjugate, which targets vascular injury sites to act as a local antithrombotic. We assessed the nonclinical safety and exposure of intravenously infused APAC in rats and cynomolgus monkeys by using single-day and 14-day repeat dose toxicology and pharmacodynamic markers. Activated partial thromboplastin time (APTT) was used as a functional surrogate of anticoagulant exposure of APAC. Routine clinical in-life observations were followed by clinical pathology and necropsy. The no-observed-adverse-effect level (NOAEL) in rats for the single APAC dose was 20 mg/kg and for the repeated administration was 10 mg/kg/d. Monkeys tolerated a single APAC dose of 10 mg/kg, although the red blood cell count reduced 16%-19% correlating with tissue hemorrhage at vein puncture and affected muscle sites during handling of the animals. However, after 2-week recovery, all clinical signs were normal. The single dose NOAEL exceeded 3 mg/kg. The repeat administration of 3-6 mg/kg/d of APAC was tolerated, but some clinical signs were observed. The NOAEL for repeated dosing was 0.5 mg/kg/d. APAC prolonged APTT dose-dependently in both species, returning to baseline after 1.5 (

Tao Chang,1,&ast; Xigang Yan,2,&ast; Chao Zhao,3,&ast; Yufu Zhang,4 Bao Wang,4 Li Gao4 1Department of Emergency, The Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, Shaanxi Province, People’s Republic of China; 2Department of Anesthesiology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, Shaanxi Province, People’s Republic of China; 3Department of Neurology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, Shaanxi Province, People’s Republic of China; 4Department of Neurosurgery, The Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, Shaanxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li GaoDepartment of Neurosurgery, The Second Affiliated Hospital of Air Force Medical University, No. 1, Xinsi Road, Xi’an, 710038, Shaanxi Province, People’s Republic of ChinaTel +86 29-84777765Email gaoli553@163.comObjective: The purpose of this study was to explore the effect of coagulopathy in patients with traumatic brain injury (TBI) during the early postoperative period.Methods: The baseline characteristics, intraoperative management, and follow-up data of 462 patients with TBI between January 2015 and June 2019 were collected and retrospectively analyzed by multivariate logistic regression. Coagulopathy was defined as activated partial thromboplastin time > 40 s, international normalized ratio > 1.4, or platelet counts < 100× 109/L.Results: Multivariate logistic regression analysis revealed that the Glasgow Coma Scale (GCS) on admission, Injury Severity Score (ISS) on admission, pupil mydriasis, duration of surgery, intraoperative blood loss, and intraoperative crystalloid resuscitation were independent risk factors for patients who developed coagulopathy after surgery. There were statistical differences in mortality (p = 0.049), the Glasgow Outcome Scale-Extended (GCS-E; p = 0.024), and the modified Rankin Scale (p = 0.043) between the patients with and without coagulopathy 1 week after surgery. Coagulopathy within 72 h after surgery revealed the higher mortality at 1 week (66.7%), 3 months (71.4%), and 6 months (76.2%). Coagulopathy within 72 h after surgery in patients with a TBI predicted worse disease progression and unfavorable neurologic outcomes.Conclusion: Taking practical and reasonable measures to manage these risk factors may protect patients with TBI from postoperative coagulopathy.Keywords: traumatic brain injury, postoperative coagulopathy, surgery, risk factor, mortality

Background Hyperthyroid cats might have a predisposition to arterial thrombus formation. The mechanism for thrombogenesis currently is unknown but could be associated with systemic hypercoagulability as seen in hyperthyroid humans. Objective Our purpose was to evaluate markers of hemostasis in hyperthyroid cats compared to healthy cats, and in hyperthyroid cats before and after radioactive iodine treatment (RIT). Animals Twenty‐five cats with hyperthyroidism and 13 healthy euthyroid cats >8 years of age. Methods Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen concentration, antithrombin (AT), D‐dimers, thrombin‐antithrombin complexes (TAT), von Willebrand Factor antigen (vWF : Ag), and activity of factors VIII and IX were measured. An echocardiogram was performed in all cats. Hemostatic markers and echocardiogram were evaluated again 6 to 9 months after successful RIT in 7 cats. Results Hyperthyroid cats had higher fibrinogen concentration (P

Venous thromboembolism (VTE), in particular pulmonary embolism (PE), remains the leading cause of death among pregnant women. Low-molecular-weight heparin (LMWH), with preference for therapeutic doses given twice daily according to European guidelines, is the drug of choice for the treatment of VTE in pregnancy and the puerperium. The recommended therapeutic dose is calculated on early pregnancy body weight. Evidence to support anti-Xa monitoring in pregnancy is weak. Unfractionated heparin (UFH) with multiple activated partial thromboplastin time measurements is still used in the acute treatment of high-risk PE. American experts have suggested considering initial outpatient therapy over hospital admission also in pregnant women with low-risk acute VTE, but European experts suggest adopting such a strategy selectively, for example in isolated distal leg thrombosis. Scheduled delivery with prior discontinuation of anticoagulant therapy in pregnant women who received a therapeutic dose of LMWH is suggested with the restart of therapy 4–6 h after a vaginal birth and 6–12 h after a cesarean delivery. It is recommended that UFH, LMWH, warfarin, acenocoumarol, or fondaparinux, but not direct-acting oral anticoagulants, should be used in breastfeeding women. This review summarizes the key messages from current guidelines mainly based on low-quality evidence and expert consensus.

Covid-19 pandemic reveals that the virus causes Covid-19 associated coagulopathy and it is well known that thrombotic risk is associated with ethnicity. To describe the Covid-19 associated coagulopathy in Indian population and to correlate it with the disease severity and survivor status. A cross sectional descriptive study of 391 confirmed Covid-19 cases was carried out over a period of 1.5 months. Patients were categorised as mild to moderate, severe and very severe and also labelled as survivors and non survivors. Prothrombin time (PT), International normalised ratio (INR), activated partial thromboplastin time, D dimer, Fibrin degradation products (FDP), fibrinogen and thrombin time and platelet counts were investigated among the subgroups. Mean age was higher in patients with severe disease (57.62 ± 13.08) and among the non survivors (56.54 ± 12.78). Statistically significant differences in D dimer, FDP, PT, INR and age were seen among the 3 subgroups and survivors. Strong significant positive correlation was noted between D dimer and FDP (r = 0.838, p

Background Double-filtration plasmapheresis (DFPP), a selective therapeutic apheresis, can deplete pathogenic antibodies/substances, but also important coagulation factors. Aim To determine if the use of a separator filter with different characteristics (CascadefloEC-50 W) as compared to the reference filter (PlasmafloOP-08 W) is as efficient in terms of immunoglobulin loss, but can reduce coagulation factor losses and have similar tolerability. Patients/methods This is a single-center prospective study including 14 patients divided into two groups (7 each): that is, group1 = CascadefloEC-50 W and group2 = PlasmafloOP-08 W. We measured immunoglobulins, lipid profiles, blood-cell counts, hemostasis (prothrombin time, activated partial thromboplastin time), coagulation factors, and natural anticoagulants at before and after the first DFPP-session. Results In group 1, the loss of coagulation factors was significantly reduced as compared to group 2 for proteins with a molecular weight of >150 kDa: there was, respectively, an average decrease of 70% vs 31% for fibrinogen (P = 0.004), 66% vs 21% for factor V (P = 2.16e-07), 60% vs 32% for factor XI (P = 6.96e-06), 75% vs 17% for XIII-antigen (P = 0.0002), and 47% vs 0% for VWF-antigen(P = 0.02). The decrease in post-session IgG was, on average, 45% in group 1 and 50% in group 2 (P = 0.13). Those results remained significant even when adjusted to the treated-plasma volume and the pre-DFPP factor values. Conclusion DFPP, using a CascadefloEC-50W as a first-filter, reduces efficiently IgGs similarly to PlasmafloOP-08W but spares clotting factors.

Introduction Combining an antiplatelet drug, clopidogrel, with the direct oral Factor Xa inhibitor, apixaban, could provide an effective antithrombotic strategy in dogs. Thus, a limited 3 + 3 phase I dose-escalation clinical trial in healthy dogs was conducted to evaluate bleeding (primary end-point) and pharmacodynamic (PD)/pharmacokinetic (PK) parameters (secondary end-point). Animals Eleven beagle dogs, median body weight 10.2 kg (9.7–10.9 kg), were enrolled. Methods Four doses of apixaban (three dogs/dose) administered for eight days. Clopidogrel dose was fixed at 18.75 mg per os (PO) q 24 h with escalation of apixaban dose at 5 mg PO q 12 h, 5 mg PO q 8 h, 10 mg PO q 12 h, and 10 mg PO q 8 h. Laboratory testing included fecal occult blood, coagulation parameters, Factor X activity, apixaban concentration, platelet aggregometry, and thromboelastography on days 1, 3, and 8. Results Evidence of bleeding was not observed at any dosage. Dose-dependent changes in PD/PK parameters between baseline and 3 h post-medication were observed including a prolongation of prothrombin time, a prolongation of activated partial thromboplastin time, a decrease of Factor X activity level, and increased apixaban concentration. Conclusions The combination of apixaban at a dosage range of approximately 0.5 mg/kg PO q 12 h to 1 mg/kg PO q 8 h and clopidogrel at approximately 1.8 mg/kg PO q 24 h did not cause bleeding over a one-week period in healthy dogs. Clinically relevant changes in PD/PK data occur at all dosage levels. This study provides a starting point for longer-term clinical trials to determine safety and efficacy.

Introduction Bed bugs are hematophagous insects that can be problematic in some urban emergency departments. The objective was to determine if red blood cell (RBC) and coagulation indices of bed bug–infested emergency department (ED) patients differed from those of noninfested control patients. Methods A chart review from a single health system was performed for ED patients between February 1, 2011, and February 1, 2017. Bed bug–infested patients were matched to noninfested control patients on the basis of age, sex, and the presenting ED. Variables were analyzed with the t-test and Pearson χ2 test and were modeled with multivariable logistic regression. Results The study had 332 bed bug–infested patients and 4952 controls. Infested patients had lower hemoglobin (11.7 g/dL vs 12.8 g/dL), hematocrit (35.0% vs 37.9%), RBC counts (4.1 × 109/L vs 4.4 × 109/L), mean corpuscular volume (86.0 vs 87.5 fL/cell), and mean corpuscular hemoglobin concentrations (33.2 vs 33.7 g/dL) and higher RBC distribution width-coefficient of variation (RDW-CV) (15.2% vs 14.2%) than noninfested patients (all P ≤ .003). Infested patients were more likely to be anemic (59.5% vs 36.9%) and to have severe anemia (4.4% vs 0.7%) (P Conclusion Bed bug infestated patients in the ED are associated with anemia.

The OBJECTIVE was to study the features of changes in the blood coagulation system that contribute to the development of postoperative complications in patients depending on the stage of non-tumor mechanical jaundice at admission.METHODS AND MATERIALS. A total of 537 patients with mechanical jaundice were examined and changes in the blood coagulation system were analyzed. Vascular-platelet hemostasis was characterized by the following tests: capillary resistance, the number of desquamated endothelial cells, the number of blood platelets. Plasma hemostasis was analyzed using activated partial thromboplastin time, plasma soluble fibrin level, thrombin time, prothrombin ratio, prothrombin index, and fibrinogen blood level. Then, XIIa-dependent fibrinolysis in the blood and the level of the fibrin D-dimer in the blood plasma were determined.RESULTS. It was found that in the first stage of mechanical jaundice, with cholestasis, there were no changes in blood coagulation system that go beyond the normal limits. In the second stage, during cytolysis of hepatocytes, hyperbilirubinemia and hypertransaminasemia contribute to the activation of platelet first, and then plasma hemostasis. In the third stage (cholangitis), the death of endotheliocytes increases and there is a deficiency of blood coagulation factors due to their consumption and increased fibrinolysis.CONCLUSION. In the stage of cholestasis in patients with non-tumors mechanical jaundice, the parameters of the coagulation system remain within the reference values. In the stage of cytolysis, as endotheliotoxicosis increases, platelet and plasma hemostasis begins to activate, which can lead to thrombosis and thromboembolism in vital organs. In the stage of cholangitis, further activation of plasma hemostasis causes hemorrhagic syndrome. The occurrence of the described disorders in blood coagulation system with the progression of MJ dictates the need to monitor the changes in the blood coagulation system and their correction for the prevention of intra-and postoperative complications.

BACKGROUND A systematic review and meta-analysis were conducted to explore the clinical efficacy and coagulation function of regional citrate anticoagulation (RCA) in continuous renal replacement therapy (CRRT) in critically ill patients, to provide an effective treatment options for CRRT in severe patients. METHODS The English databases Embase, Medline, PubMed, Ovid, Springer, and Web of Science were searched to screen for randomized controlled trials (RCTs) on RCA in the CRRT treatment of critically ill patients published before June 1, 2020. Meta analysis using the RevMan5.3 provided by the Cochrane collaboration network. The search terms included "citrate anticoagulation", "patient in severe condition", "CRRT", "clinical effect", and "coagulation function". RESULTS ten articles meeting requirements were included, comprising 1,411 subjects. Meta-analysis results showed that after treatment, total calcium/ionized calcium (totCa/ionCa) [mean difference (MD) =0.05; 95% confidence interval (CI): (-0.02 to 0.12); Z=1.31; P=0.19], prothrombin time [MD =4.51; 95% CI: (2.77, 6.24); Z=5.10; P

Objectives: To determine the influence of prolonged exposure to radiation based on dosimeter readings on hematological parameters among radiologic technologists (RTs) in Saudi Arabia. Methods: The study was specifically conducted on selected RTs with experience of more than 10 years and the highest thermoluminescent dosimeter (TLD) readings among all RTs in the Radiological Department, Sabya General Hospital, Ministry of Health, Saudi Arabia from August to October 2020. The RTs group was compared with a control group of non-irradiated participants. Blood samples were collected for hematological and coagulation profile evaluation. Results: The acquired radiation dose analysis revealed that the average accumulated dose in 10 years is 7.6 mSv. The medians of prothrombin time (PT) and activated partial thromboplastin time (APTT) of the RTs group were significantly lower when compared to the control group. In addition, RTs group exhibited a significant reduction in neutrophil count and an elevation in lymphocyte count. Conclusion: Chronic exposure to radiation revealed a significant change in blood tests and may reflect an effect on RTs tissues, leading to serious health problems. However, further investigation in a large cohort to study the association between alteration in hematological parameters and chronic radiation exposure is required.

Early descriptions of COVID-19 associated coagulopathy identified it as a disseminated intravascular coagulation (DIC). However, recent studies have highlighted the potential role of endothelial cell injury in its pathogenesis, and other possible underlying mechanisms are being explored. This study aimed to analyse the coagulation parameters of critically and noncritically ill patients with COVID-19 bilateral pneumonia, determine if coagulation factors consumption occurs and explore other potential mechanisms of COVID-19 coagulopathy. Critically and noncritically ill patients with a diagnosis of COVID-19 bilateral pneumonia were recruited. For each patient, we performed basic coagulation tests, quantification of coagulation factors and physiological inhibitor proteins, an evaluation of the fibrinolytic system and determination of von Willebrand Factor (vWF) and ADAMTS13. Laboratory data were compared with clinical data and outcomes. The study involved 62 patients (31 ICU, 31 non-ICU). The coagulation parameters assessment demonstrated normal median prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) in our cohort and all coagulation factors were within normal range. PAI-1 median levels were elevated (median 52.6 ng/ml; IQR 37.2-85.7), as well as vWF activity (median 216%; IQR 196-439) and antigen (median 174%; IQR 153.5-174.1). A mild reduction of ADAMTS13 was observed in critically ill patients and nonsurvivors. We demonstrated an inverse correlation between ADAMTS13 levels and inflammatory markers, D-dimer and SOFA score in our cohort. Elevated vWF and PAI-1 levels, and a mild reduction of ADAMTS13 in the most severe patients, suggest that COVID-19 coagulopathy is an endotheliopathy that has shared features with thrombotic microangiopathy.

INTRODUCTION Sigma metric offers a quantitative framework for evaluating process performance in clinical laboratories. This study aimed to evaluate the analytical performance of automated analyzers in hematology unit of Alexandria Main University Hospital using the sigma metric approach. MATERIALS AND METHODS Quality control data were collected for 6 months, and sigma value was calculated from hematology analyzers SYSMEX (XN 1000, XT 1800i), ADVIA (2120i, 2120), and coagulation analyzers SYSMEX CA 1500 (3610, 6336). RESULTS For the normal control level, satisfactory mean sigma value ≥3 was observed for all of the studied parameters by all analyzers. For the high control level, red blood cell count by ADVIA 2120, and hematocrit by ADVIA (2120i and 2120) performed poorly with a mean sigma value

Bleeding is considered to be an indicator of poor prognosis in Crimean-Congo hemorrhagic fever (CCHF) disease. In the prehemorrhagic period, clinical signs are usually non-specific. The hemorrhagic period usually begins 3 to 5 days after the onset of the disease. The aim of this study was to build a risk score to predict bleeding status in CCHF patients with clinical and laboratory findings. This methodological study was carried out in one of the largest centers which is located in the east part of Turkey and CCHF-endemic region between April 2014-October 2019 with 450 CCHF patients' data. Risk score was created with univariate and multivariate logistic regression analyzes with the data of 80% of the patients, and the diagnostic power of the created score was determined by ROC analysis. The data of the remaining 20% were used as the verification data set and the created score was tested by ROC analysis. The patients had a mean age of 47.83 ± 17.46 years (median 48; min-max: 16-90 years) and 209 (59.7%) were male. Hemorrhage was detected in 93 patients (26.6%). Of the hemorrhagic patients, 83 (23.7%) had multiple hemorrhage sites. In univariate analyzes, time between the onset of symptom and admission to the hospital (≥4 days), aspartate aminotransferase (≥228 U/L), alanine aminotransferase (≥143.5 U/L), lactate dehydrogenase (≥641 U/L), creatine kinase (≥227 U/L), white blood cell count (≤1810 × 106/L), platelet count (≤38385 × 106/L), activated partial thromboplastin time (≥38.5 s) and fibrinogen value (≤227 mg/dl) were found to be an independent risk factor for bleeding. As a result of multivariate analysis, the time between the onset of symptoms and admission to the hospital, white blood cell count, platelet count, aspartate aminotransferase, creatine kinase and fibrinogen values were included in the risk scoring. The area under the curve of the generated score is 0.875; sensitivity was 80.6% and specificity was 80.5%. Platelet count responsible for hemostasis, affected in terms of number and function in CCHF disease, LDH, AST and aPTT values used as indicators of liver functions that are the target of the virus can be used with high diagnostic prediction for bleeding. However, the predictive power of the generated score on bleeding is higher than the effect of each variable alone. In addition, it can be easily calculated during patient follow-up and can guide the treatment process.

Background: Unfractionated heparin (UFH) infusions are commonly managed with nurse-driven nomograms titrated to activated partial thromboplastin time (aPTT). In some patients, anti-Xa values may be more appropriate measures of anticoagulation. At the present institution, an update to the nurse-driven aPTT nomogram requires pharmacist notification and clinical assessment for critically supratherapeutic aPTT results. Objective: The purpose of this study was to evaluate the efficacy and safety of the nomogram update. Methods: A single-center, retrospective, pre-post analysis was conducted in patients treated with UFH who experienced a critical aPTT during the 6 months preceding and following the nomogram update. Patients with erroneous critical aPTT results were excluded. The primary endpoint was the time in therapeutic range (Rosendaal method) from the first critical aPTT until UFH discontinuation. Secondary endpoints included the proportion of patients transitioned to anti-Xa monitoring and the incidence of Bleeding Academic Research Consortium (BARC) 2, 3, 5 bleeding. Data were analyzed by the χ2 test. The study was institutional review board approved. Results: Of 277 UFH infusions, 142 belonged to the pre-implementation group and 135 to the post-implementation group. Baseline aPTTs were similar between the 2 groups. Time in therapeutic range was 58.1% versus 62.4% of between groups ( P = .467). UFH was transitioned to pharmacist-driven anti-Xa monitoring in 16.2% versus 40.3% of patients ( P < .001). BARC 2, 3, 5 bleeding occurred in 23.2% versus 13.4% of patients ( P < .001). Conclusions: Application of these data suggest improved safety and efficacy outcomes with directed pharmacist management of UFH in patients with critically elevated aPTTs.

An estimated 50,000 Nigerian women die each year from complications of pregnancy and childbirth, accounting for 10% of global estimates of pregnancy maternal death with about 2% resulting from drug induction. This cross-sectional study sets out to evaluate the Prothrombin time test (PT), activated partial thromboplastin time test (aPTT) Erythrocyte sedimentation rate (ESR), and Platelet count (PC) of pregnant women attending antenatal clinics at Oredo Health Centre in Benin City, Edo State. A total number of 130 subjects comprising 100 pregnant women and 30 non-pregnant women were recruited for the study. Prothrombin time (PT), Activated Partial Thromboplastin Time (APTT), Platelet count and Erythrocyte Sedimentation Rate (ESR) were studied using standard manual methods. The prothrombin time (sec) of the pregnant women 1st trimester (19.12±0.77b), 2nd trimester (19.90±1.02 b) and 3rd trimester (19.66±0.56 b), activated partial thromboplastin time (sec) 1st trimester (44.02±1.17 b), 2nd trimester (47.72±1.47 b) and 3rd trimester (45.88±1.10b), Erythrocyte sedimentation rate (mm/hr) 1st trimester (24.37±3.04 a), 2nd trimester (37.83±4.53 a) and 3rd trimester (43.25±5.24 a) and platelet count (X109/L) 1st trimester (248.29±23.18a), 2nd trimester (236.33±13.84 b) and 3rd trimester (239.10±16.07 a) were significantly higher than the prothrombin time (sec) 16.48±0.81 a, activated partial thromboplastin time (sec) 36.53±1.42 a, ESR (mm/hr) 29.83±4.14 a and platelet count (X109/L) 201±9.54 an of the non-pregnant women (p

La hemofilia A es una enfermedad hereditaria ligada al cromosoma X, causada por mutaciones en el gen F8 del factor VIII de la coagulación. Se considera una enfermedad huérfana, ya que su prevalencia es baja, de 26,6 por cada 100.000 nacidos vivos de sexo masculino. Los pacientes con hemofilia A tienen fases de inicio y amplificación de la coagulación relativamente normales y son capaces de formar el tapón plaquetario inicial en el lugar de la hemorragia, pero debido a la deficiencia del factor VIII, son incapaces de generar una cantidad de trombina en la superficie de las plaquetas, que sea suficiente para estabilizar el coágulo de fibrina. En un paciente masculino con hemorragias inusuales debe descartarse un trastorno de coagulación tipo hemofilia A, y se debe solicitar un recuento de plaquetas y un tiempo de protrombina (TP), los cuales usualmente son normales, y un tiempo de tromboplastina parcial activado (TPT) que se presenta prolongado. Para el diagnóstico diferencial con otras coagulopatías se realiza la medición de factores de coagulación, y pruebas de corrección cuando existe la sospecha de un inhibidor o de una hemofilia adquirida. Los pacientes afectados pueden presentar formas leves, moderadas o severas de la enfermedad, según el nivel plasmático del factor. En Colombia y en el mundo, la hemofilia fue reconocida como una enfermedad huérfana que representa un problema de salud pública, debido a su proceso de atención altamente especializado, que incrementa los costos asociados con la asistencia sanitaria, y afecta la calidad de vida de los pacientes y de aquellos que los rodean, además de que representa un reto diagnóstico que requiere constante actualización, para que pueda ser tratada de manera efectiva.

Supplemental digital content is available in the text., BACKGROUND Trauma patients have high concentrations of circulating extracellular vesicles (EVs) following injury, but the functional role of EVs in this setting is only partly deciphered. We aimed to describe in detail EV-associated procoagulant activity in individual trauma patients during the first 12 hours after injury to explore their putative function and relate findings to relevant trauma characteristics and outcome. METHODS In a prospective observational study of 33 convenience recruited trauma patients, citrated plasma samples were obtained at trauma center admission and 2, 4, 6, and 8 hours thereafter. We measured thrombin generation from isolated EVs and the procoagulant activity of phosphatidylserine (PS)-exposing EVs. Correlation and multivariable linear regression analyses were used to explore associations between EV-associated procoagulant activity and trauma characteristics as well as outcome measures. RESULTS EV–associated procoagulant activity was highest in the first 3 hours after injury. EV–associated thrombin generation normalized within 7 to 12 hours of injury, whereas the procoagulant activity of PS-exposing EVs declined to a level right above that of healthy volunteers. Increased EV-associated procoagulant activity at admission was associated with higher New Injury Severity Score, lower admission base excess, higher admission international normalized ratio, prolonged admission activated partial thromboplastin time, higher Sequential Organ Failure Assessment score at day 0, and fewer ventilator-free days. CONCLUSION Our data suggest that EVs have a transient hypercoagulable function and may play a role in the early phase of hemostasis after injury. The role of EVs in trauma-induced coagulopathy and posttraumatic thrombosis should be studied bearing in mind this novel temporal pattern. LEVEL OF EVIDENCE Prognostic/epidemiologic, level V.