Characteristics of coagulation/fibrinolysis abnormalities in severe novel coronavirus disease 2019 (COVID-19) patients —Case series—

Abstract

未満に低下したのは 1 例のみであった．prothrombin time-international normalized ratio(PT-INR)は経過を通じて概ね正常で，activated partial thromboplastin time(APTT)は経過中 5 例で正常上限を上回ったが，1 例を除き大きく延長する事は無かった．一方，FDP と D-dimer は経 過中，正常上限を超えて推移し，2 例は第 7 病日以降に著明な再上昇を来した．以上より，重症 COVID-19 患者は感染症にも関わらず，凝固線溶異常は「線溶抑制型」でなく，あたかも「線溶亢 進型」の様相を呈していた．6 例中 4 例が Japanese Association for Acute Medicine criteria(JAAM) disseminated intravascular coagulation(DIC)診断基準で DIC と診断され，遺伝子組換え型ヒト可溶性 トロンモジュリン(rhsTM)が投与され，3 例が投与終了時点で DIC から離脱した．

Therapeutic Strategies for Disseminated Intravascular Coagulation Associated with Aortic Aneurysm

“…The first of the three types is "enhanced-fibrinolytic-type DIC", as represented by the DIC associated with aortic aneurysms. Underlying diseases causing enhanced-fibrinolytictype DIC include hemangiomas and vascular malformations (e.g., Kasabach-Merritt syndrome [27,28], Klippel-Trenaunay-Weber syndrome [29], blue rubber bleb nevus syndrome [30][31][32]), acute promyelocytic leukemia [13,[33][34][35], prostate cancer [36,37], and severe coronavirus disease 2019 (COVID-19) (Table 2) [38][39][40][41][42][43][44]. In enhanced-fibrinolytic-type DIC, multiple fibrin clots produced by marked coagulation activation dissolve one after another due to the marked activation of fibrinolysis.…”

“…Since some patients with severe COVID-19 present with enhanced-fibrinolytic-type DIC [38][39][40][41][42][43][44] and nafamostat also has anti-coronaviral effects [44,[79][80][81], combination therapy with heparin and nafamostat appears to offer a promising strategy for the treatment of enhanced-fibrinolytic-type DIC with severe COVID-19. It is also a promising strategy for treatment.…”

Coagulopathy and Fibrinolytic Pathophysiology in COVID-19 and SARS-CoV-2 Vaccination

“…Important detailed and longitudinal follow-up reports of changes to coagulation/fibrinolysis markers in COVID-19 have been published in China [ 45 ] and Japan [ 94 ].…”

“…A report by Ishikura et al from Japan [ 94 ] described the detailed clinical course, PT, APTT, fibrinogen, FDP, D-dimer, and AT, along with TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) in six patients (four survivors, two non-survivors) admitted to the ICU. In addition to PT, APTT, fibrinogen, FDP, D-dimer, and AT, the coagulation activation marker TAT, the fibrinolytic activation marker PIC, and the fibrinolytic inhibition marker PAI-1 were tracked daily.…”

“…Such a large increase in PIC is rarely seen in patients other than those with COVID-19 [ 100 ]. In addition, Ishikura et al [ 94 ] reported cerebral hemorrhage in patients with markedly increased PIC, suggesting that fibrinolytic activation in COVID-19 is associated with hemorrhage.…”