In vitro hypercoagulability and ongoing in vivo activation of coagulation and fibrinolysis in COVID-19 patients on anticoagulation

Background COVID-19 is associated with a substantial risk of venous thrombotic events, even in the presence of adequate thromboprophylactic therapy. Objectives We aimed to better characterize the hypercoagulable state of COVID-19 patients in patients receiving anticoagulant therapy. Methods We took plasma samples of 23 patients with COVID-19 who were on prophylactic or intensified anticoagulant therapy. Twenty healthy volunteers were included to establish reference ranges. Results COVID-19 patients had a mildly prolonged prothrombin time, high von Willebrand factor levels and low ADAMTS13 activity. Most rotational thromboelastometry parameters were normal, with a hypercoagulable maximum clot firmness in part of the patients. Despite detectable anti-activated factor X activity in the majority of patients, ex vivo thrombin generation was normal, and in vivo thrombin generation elevated as evidenced by elevated levels of thrombin-antithrombin complexes and D-dimers. Plasma levels of activated factor VII were lower in patients, and levels of the platelet activation marker soluble CD40 ligand were similar in patients and controls. Plasmin-antiplasmin complex levels were also increased in patients despite an in vitro hypofibrinolytic profile. Conclusions COVID-19 patients are characterized by normal in vitro thrombin generation and enhanced clot formation and decreased fibrinolytic potential despite the presence of heparin in the sample. Anticoagulated COVID-19 patients have persistent in vivo activation of coagulation and fibrinolysis, but no evidence of excessive platelet activation. Ongoing activation of coagulation despite normal to intensified anticoagulant therapy indicates studies on alternative antithrombotic strategies are urgently required

A multicenter analysis of the role of prophylactic transfusion of blood products in patients with cirrhosis and esophageal varices undergoing endoscopic band ligation

Cirrhosis; Endoscopic band ligation; Esophageal varices; Platelet transfusionCirrosis; Ligadura endoscópica con banda; Varices esofágicas; Transfusión de plaquetasCirrosi; Lligadura de banda endoscòpica; Varices esofàgiques; Transfusió de plaquetesBackground & aims: Prophylactic administration of platelets and fresh frozen plasma (FFP) has been recommended in patients with cirrhosis with low platelets and/or prolonged international normalized ratio (INR) without scientific evidence to support this practice. In this analysis, we evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation (EBL). Methods: This is a multicenter retrospective analysis of consecutive EBL procedures in patients with cirrhosis at 4 hospitals in Spain from 01/2010-01/2017. FFP and/or platelet transfusion were given at the discretion of the physician if INR was >1.5 and/or platelet count <50x109/L. Patient demographics, endoscopic findings, bleeding events after EBL, and the use of prophylactic FFP or platelets were recorded. Results: A total of 536 patients underwent 1,472 EBL procedures: 72% male; main etiology HCV and alcohol (72%); median MELD score 11; Child-Pugh A/B/C (59/33/8%). EBL procedures were performed for primary (51%) or secondary (49%) prophylaxis. A median of 2 procedures per patient were performed.1-4 FFP and/or platelets were administered in 41 patients (7.6%). The prophylactic transfusion protocol was followed in 16% and 28% of procedures with high INR and/or low platelets, respectively. Post-EBL bleeding occurred in 26 out of 536 patients (4.8%) and in 33 out of 1,472 procedures (2.2%). Bleeding was due to post-EBL ulcers in 21 patients and due to band dislodgment in 5. In 6 patients, bleeding occurred within 24 hours and in the remaining patients it occurred within 2 weeks after EBL. In those that bled, 7 met criteria for transfusion (2 for FFP and 5 for platelets), of whom only 1 received FFP and 4 received platelets; the remaining 19 patients did not meet criteria for transfusion. There was no association between INR or platelet count and bleeding events. Univariate and multivariate analysis revealed that Child-Pugh and MELD scores were risk factors for post-EBL bleeding. Conclusions: The incidence of post-EBL bleeding is low and is associated with advanced liver disease. Post-EBL bleeding was not related to baseline INR/platelet count and most outpatients with post-EBL bleeding did not meet criteria for prophylactic transfusion. Lay summary: Patients with chronic liver disease or cirrhosis and enlarged veins (varices) of the esophagus that can potentially bleed commonly need an endoscopy to treat these varices with elastic rubber bands (endoscopic band ligation). Some patients have low platelet counts or prolonged coagulation tests. This analysis of 4 centers evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation. The results showed that bleeding after band ligation is uncommon and that if bleeding occurs it does not seem to be related with coagulation tests or the administration of blood products to prevent bleeding after band ligation of esophageal varices