Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19

Since December 2019,a novel type of coronavirus disease(COVID-19)in Wuhan led to an outbreak throughout China and the rest of the world.To date,there have been more than 1,260,000 COVID-19 patients,with a mortality rate of approximately 5.44%.Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19.Therefore,the People’s Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection.This consensus includes an overview of COVID-19-related coagulation dysfunction,tests for coagulation,anticoagulation therapy,replacement therapy,supportive therapy and prevention.The consensus produced 18 recommendations which are being used to guide clinical work.

Acquired coagulation dysfunction resulting from vitamin Kdependent coagulation factor deficiency associated with rheumatoid arthritis: A case report

BACKGROUND Rheumatoid arthritis(RA)is a common chronic inflammatory autoimmune disease with the main clinical feature of progressive joint synovial inflammation,which can lead to joint deformities as well as disability.RA often causes damage to multiple organs and systems within the body,including the blood hemostasis system.Few reports have focused on acquired coagulation dysfunction resulting from vitamin K-dependent coagulation factor deficiency associated with RA.CASE SUMMARY A 64-year-old woman with a history of RA presented to our hospital,complaining of painless gross hematuria for 2 wk.Blood coagulation function tests showed increased prothrombin time,international normalized ratio,and activated partial thromboplastin time.Abnormal blood coagulation factor(F)activity was detected(FII,7.0%;FV,122.0%;and FX,6.0%),indicating vitamin K-dependent coagulation factor deficiency.Thromboelastography and an activated partial thromboplastin time mixed correction experiment also suggested decreased coagulation factor activity.Clinically,the patient was initially diagnosed with hematuria,RA,and vitamin K-dependent coagulation factor deficiency.The patient received daily intravenous administration of vitamin K120 mg,etamsylate 3 g,and vitamin C 3000 mg for 10 d.Concurrently,oral leflunomide tablets and prednisone were administered for treatment of RA.After the treatment,the patient's symptoms improved markedly and she was discharged on day 12.There were no hemorrhagic events during 18 mo of follow-up.CONCLUSION RA can result in vitamin K-dependent coagulation factor deficiency,which leads to acquired coagulation dysfunction.Vitamin K1 supplementation has an obvious effect on coagulation dysfunction under these circumstances.

Chinese expert consensus on diagnosis and treatment of trauma-induced hypercoagulopathy

Trauma-induced coagulopathy(TIC)is caused by post-traumatic tissue injury and manifests as hypercoagulability that leads to thromboembolism or hypocoagulability that leads to uncontrollable massive hemorrhage.Previous studies on TIC have mainly focused on hemorrhagic coagulopathy caused by the hypocoagulable phenotype of TIC,while recent studies have found that trauma-induced hypercoagulopathy can occur in as many as 22.2%–85.1%of trauma patients,in whom it can increase the risk of thrombotic events and mortality by 2-to 4-fold.Therefore,the Chinese People’s Liberation Army Professional Committee of Critical Care Medicine and the Chinese Society of Thrombosis,Hemostasis and Critical Care,Chinese Medicine Education Association jointly formulated this Chinese Expert Consensus comprising 15 recommendations for the definition,pathophysiological mechanism,assessment,prevention,and treatment of trauma-induced hypercoagulopathy.

Clinical characteristics and risk factors of COVID-19 patients with chronic hepatitis B:a multi-center retrospective cohort study

The coronavirus disease 2019(COVID-19)has spread globally.Although mixed liver impairment has been reported in COVID-19 patients,the association of liver injury caused by specific subtype especially chronic hepatitis B(CHB)with COVID-19 has not been elucidated.In this multi-center,retrospective,and observational cohort study,109 CHB and 327 non-CHB patients with COVID-19 were propensity score matched at an approximate ratio of 3:1 on the basis of age,sex,and comorbidities.Demographic characteristics,laboratory examinations,disease severity,and clinical outcomes were compared.Furthermore,univariable and multivariable logistic and Cox regression models were used to explore the risk factors for disease severity and mortality,respectively.A higher proportion of CHB patients(30 of 109(27.52%))developed into severe status than non-CHB patients(17 of 327(5.20%)).In addition to previously reported liver impairment markers,such as alanine aminotransferase,aspartate aminotransferase,alkaline phosphatase,and total bilirubin,we identified several novel risk factors including elevated lactate dehydrogenase(≥245 U/L,hazard ratio(HR)=8.639,95%confidence interval(CI)=2.528–29.523;P<0.001)and coagulation-related biomarker D-dimer(≥0.5μg/mL,HR=4.321,95%CI=1.443–12.939;P=0.009)and decreased albumin(<35 g/L,HR=0.131,95%CI=0.048–0.361;P<0.001)and albumin/globulin ratio(<1.5,HR=0.123,95%CI=0.017–0.918;P=0.041).In conclusion,COVID-19 patients with CHB were more likely to develop into severe illness and die.The risk factors that we identified may be helpful for early clinical surveillance of critical progression.

Thrombosis after SARS-CoV2 infection or COVID-19 vaccination:will a nonpathologic anti-PF4 antibody be a solution?—A narrative review

The coronavirus disease 2019(COVID-19)pandemic was triggered by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a previously unknown strain of coronavirus.To fully understand the consequences and complications of SARS-CoV-2 infections,we have reviewed current literature on coagulation dysfunctions that are related to the disease and vaccination.While COVID-19 is more commonly considered as a respiratory illness,studies indicate that,in addition to respiratory illness,a coagulation dysfunction may develop in individuals after the initial infection,placing them at the risk of developing thrombotic events.Patients who died of COVID-19 had higher levels of D-dimer,a biomarker for blood clot formation and breakdown.Effective treatments for coagulation dysfunctions are critically needed to improve patient survival.On the other hand,antibodies against platelet factor 4(PF4)/heparin may be found in patients with rare instances of vaccine-induced immunological thrombotic thrombocytopenia(VITT)following vaccination with adenovirus-based vaccines.VITT is characterized by atypical thrombosis and thrombocytopenia,similar to immune-mediated heparin-induced thrombocytopenia(HIT),but with no need for heparin to trigger the immune response.Although both adenovirus-based and mRNA-based vaccines express the Spike protein of SARS-CoV-2,VITT is exclusively related to adenovirus-based vaccines.Due to the resemblance with HIT,the use of heparin is highly discouraged against treating patients with thrombotic thrombocytopenia after SARS-CoV-2 infection or with VITT after vaccination.Intravenous immunoglobulin therapy coupled with anticoagulation is recommended instead.The well-studied anti-PF4 monoclonal antibody RTO,which does not induce pathologic immune complexes in the presence of heparin and has been humanized for a potential treatment modality for HIT,may provide a nonanticoagulant HIT-specific solution to the problem of increased blood coagulation after SARS-CoV-2 infection or the VITT after immunization.