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Long-term anticoagulation is used worldwide to prevent or treat thrombotic events. Anticoagulant therapy using vitamin K antagonists (VKAs) is well established; however, anticoagulants carry an increased risk of potentially life-threatening bleeding. In cases of bleeding or need for surgery, patients require careful management, balancing the need for rapid anticoagulant reversal with risk of thromboembolic events. Prothrombin complex concentrates (PCCs) replenish clotting factors and reverse VKA-associated coagulopathy. Two forms of PCC, 3-factor (3F-PCC) and 4-factor (4F-PCC), are available. Using PRISMA methodology, we systematically reviewed whether 4F-PCC is superior to 3F-PCC for the reversal of VKA-associated coagulopathy. Of the 392 articles identified, 48 full texts were reviewed, with 11 articles identified using criteria based on the PICOS format. Data were captured from 1,155 patients: 3F-PCC, n = 651; 4F-PCC, n = 504. ROBINS-I was used to assess bias. Nine studies showed international normalized ratio (INR) normalization to a predefined goal, ranging from ≤1.5 to ≤1.3, following PCC treatment. Meta-analysis of the data showed that 4F-PCC was favorable compared with 3F-PCC overall (odds ratio [OR]: 3.50; 95% confidence interval [CI]: 1.88–6.52, p

The role of extracorporeal membrane oxygenation (ECMO) in the management of critically ill COVID-19patients remains unclear. Our study aims to analyze the outcomes and risk factors from patients treated with ECMO. Methods: This retrospective, single-center study includes seventeen COVID-19 patients treated with ECMO. Univariate andmultivariate parametric survival regression identified predictors of survival. Result: Nine patients (53%) were successfully weaned from ECMO and discharged. The incidence of in-hospital mortalitywas 47%. In a univariate analysis, only four out of 83 pre-ECMO variables were significantly different;IL-6, PCT, and NT-proBNP were significantly higher in non-survivors compared with survivors. The Respiratory Extracorporeal MembraneOxygenation Survival Prediction (RESP) score was significantly lower in survivors. After a multivariate parametric survivalregression, IL-6, NT-proBNP and RESP scores remained significant independent predictors, with hazard ratios (HR) of 1.069[95% CI: 0.986-1.160], p = 0.016 1.001 [95% CI: 1.000-1.001], p = 0.012;and 0.843 [95% CI: 0.564-1.260], p = 0.040,respectively. A prediction model consisting of IL-6, NT-proBNP, and RESP score showed an area under the curve (AUC) of0.87, with a sensitivity of 87.5% and specificity of 77.8%, compared with an AUC of 0.79 for the RESP score alone. Conclusion: The present study suggests that ECMO is a potentially lifesaving treatment for select critically ill COVID-19patients. Considering IL-6 and NT-per-BNP, in addition to the RESP score, may enhance outcome predictions.

Background Factor X (FX) deficiency (FXD) is an extremely rare autosomal recessive hereditary hematologic disorder, affecting approximately one in 1,000,000 of the general population. Case report This case report describes an infant with hereditary severe FXD who presented with a spontaneous, life-threatening intracranial hemorrhage and was treated with the first licensed plasma-derived FX (pdFX) concentrate. On admission, laboratory assays showed severe coagulopathy of unknown cause; the patient was empirically treated using a multimodal hemostatic approach with prothrombin complex concentrate, fresh-frozen plasma, and tranexamic acid. Subsequent single-factor coagulation and genetic analyses confirmed the hereditary FXD diagnosis, and the therapeutic regimen was changed to a targeted regimen of 250 IU pdFX daily. Based on careful monitoring of the coagulation profile, pdFX administration frequency was increased to twice daily, followed by a reduction to once every 18 hours. The patient was discharged after 7 weeks of hospitalization in good clinical condition and now receives prophylactic pdFX three times weekly.

Orale Antikoagulanzien sind fur die Schlaganfallpravention bei Vorhofflimmern sowie die Therapie und Prophylaxe venoser Thromboembolien unverzichtbar. In den letzten Jahren ist mit den nicht Vitamin-K-abhangigen oralen Antikoagulanzien (NOAKs) eine Wirkstoffgruppe in den Vordergrund geruckt, die hinsichtlich ihrer Wirksamkeit und Sicherheit gegenuber den klassischen Antikoagulanzien, wie Vitamin-K-Antagonisten, relevante Vorteile bietet. Blutungskomplikationen gehoren jedoch nach wie vor zu den moglichen Nebenwirkungen. Mit der Entwicklung NOAK-spezifischer Antidote wird nun ein weiterer Fortschritt in der Sicherheit der antithrombotischen Therapie erzielt: Mit Idarucizumab ist bereits ein spezifisch und rasch wirksames Antidot gegen den direkten Thrombininhibitor Dabigatran auf dem Markt verfugbar. Zur Wirkungsaufhebung der Faktor-Xa-Inhibitoren ist Andexanet alfa in Phase III der klinischen Entwicklung.

SummaryAlthough prothrombin complex concentrate (PCC) is increasingly used for the treatment of trauma-induced coagulopathy, few studies have investigated the impact and safety of PCC for this indication. The present study was performed to assess PCC for treatment of coagulopathy after blunt liver injury under severe hypothermia. Coagulopathy in 14 anaesthetised pigs was induced by haemodilution. Subsequently, standardised blunt liver injury was induced under severe hypothermia (32.8–33.2°C). Animals were randomised to receive either PCC (35 IU kg-1) or saline (control). Coagulation was assessed over the following 2 hours by thromboelastometry and thrombin generation. Internal organs were examined to determine presence of emboli. The administration of PCC showed a significant reduction in blood loss (p=0.002 vs. controls) and a significant increase in the rate of survival (p=0.022 vs. controls). Plasma thrombin generation in the PCC group increased considerably above baseline levels, with significant increases in peak thrombin levels and endogenous thrombin potential versus controls throughout the follow-up period. In addition, PT decreased significantly in the PCC group versus the control group. However, only slight improvements in thromboelastometry variables were observed. Histology showed an equal degree of liver injury in both groups, and no thromboembolism. In severely hypothermic pigs, the application of PCC corrected trauma-induced coagulopathy and reduced blood loss. Thus, the infusion of PCC might be a reasonable approach to reduce the need for blood cell transfusion in trauma. Furthermore, the impact and safety of PCC application can be monitored through thrombin generation and thromboelastometry under hypothermia.Note: This study was performed at the RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany.