A mild deficiency of ADAMTS13 is associated with severity in COVID-19: comparison of the coagulation profile in critically and noncritically ill patients

Abstract

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.

Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis

“…The final full-text review included 163 reports, from which 123 studies did not meet the inclusion criteria and were excluded. A total of 40 studies comprising of 3764 patients met the including criteria and were included in this systematic review and meta-analysis [24] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] , [77] , [78] , [79] , [80] , [81] , [82] , [83] , [84] , [85] , [86] , [87] . Fig.…”

“…The exact dynamic changes of VWF multimeric pattern after COVID-19 still need further study. The majority of studies reported normal or mildly to moderately decreased ADAMTS13:Ac levels [51] , [62] , [70] , [72] , [80] , [87] , and a strongly elevated VWF:Ag/ADAMTS13:Ac ratio in patients with COVID-19 when compared to healthy controls, especially in those with worse illness or in non-survivors [55] , [70] , [80] . We confirmed that lower levels of ADAMTS13:Ac and higher VWF:Ag/ADAMTS13:Ac ratio and VWF:Rco were related to poor clinical outcomes.…”

High levels of von Willebrand factor with reduced specific activities in hospitalized patients with or without COVID-19

“…1) which is consistent with findings reported by other authors. [ 14 – 17 ] Of interest, these patients had reduced VWF activity-to-antigen ratio. There are limited studies regarding activity-to-antigen ratios, two of the four which reported significant differences (Table 1 ).…”

Mikroangiopathien in der Schwangerschaft

“…In 1–3/10.000 Schwangerschaften findet sich eine Immunthrombozytopenie (ITP) mit Thrombozytenzahlen < 50.000/μl [ 12 ]. Die ca.…”

“…So kann neben der typischen Thrombose eine COVID-19-Mikroangiopathie (TMA) auftreten. Die Krankheitsbilder ähneln den vorbeschriebenen Erkrankungen einer TTP oder auch eines HUS [ 12 ].…”