Evidence for secondary thrombotic microangiopathy in COVID-19

Abstract

The causes of coagulopathy associated with COVID-19 disease are poorly understood. We aimed to investigate the relationship between markers of endothelial activation, intravascular hemolysis, coagulation, and organ damage in COVID-19 patients and study their association with disease severity and mortality. We conducted a retrospective study of 181 hospitalized COVID-19 patients randomly selected with equal distribution of survivors and non-survivors. Patients who died had significantly lower ADAMTS13 activity, significantly higher LDH, schistocytes and von Willebrand Factor levels compared to patients discharged alive. Only 30% of patients with an initial ADAMTS13 activity <43% survived vs. 60% with ADAMTS13 >43% who survived. In conclusion, COVID-19 may manifest as a TMA-like illness in a subset of hospitalized patients. Presence of schistocytes on admission may warrant a work-up for TMA. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of TMA treatments in COVID-19.

No Evidence for Classic Thrombotic Microangiopathy in COVID-19

“…Some authors reported that severe COVID-19 may cause thrombotic microangiopathy (TMA) [ 20 , 29 , 30 , 31 ]. Therefore, we examined patients for microangiopathic haemolytic anaemia (MAHA) and consumptive thrombocytopenia as hallmarks of classic TMA [ 21 ].…”

“…Other investigators have labelled the coagulopathy in COVID-19 as thrombotic microangiopathy (TMA) [ 30 , 31 , 45 , 46 , 47 , 48 ]. Nevertheless, the hallmarks of classic TMA, consumptive thrombocytopenia and microangiopathic haemolysis with erythrocyte fragmentation resulting in schistocytes in the peripheral blood smear [ 21 ], have neither been found in any of our 22 patients subjected to detailed investigation for TMA ( Table 4 ) nor in most studies from other investigators [ 49 , 50 ].…”

Correlation of Coagulation Parameters With Clinical Outcomes During the Coronavirus-19 Surge in New York: Observational Cohort

“…This difference is likely a reflection of the higher hemodialysis needs in non-survivors compared to survivors (90% vs. 48%). Nonetheless, the observation of ex vivo clots in hemodialysis lines despite anticoagulation suggests that this disease may present with more of a thrombotic microangiopathy (TMA) picture and may be more amenable to TMA therapeutics ( Henry et al, 2020 ; Sweeney et al, 2020 ; Wang et al, 2020 ; Cugno et al, 2021 ). Studies are ongoing looking at therapies with anticoagulation, anti-complement, fibrinolysis ( Bikdeli et al, 2020 ; Laurence et al, 2020 ).…”

Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis

“…Screening on titles and abstracts excluded 465 articles, and the remaining 27 full-text articles were assessed according to eligibility criteria. As a result, 17 studies [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] with a total of 1187 patients were subjected to qualitative analysis and metaanalysis (Figure 1 and Table 1). Quality assessment with NOS showed that 13 studies [10,[13][14][15][16][17][18][19][21][22][23][24]26] were of good quality with ≥ 7 NOS score and four studies [11,12,20,25] were considered as moderate quality with six NOS score (Supplementary Table S2).…”