COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of haemostasis and clot waveform analysis

Abstract

Patients with COVID-19 are known to be at risk of developing both venous, arterial and microvascular thrombosis, due to an excessive immuno-thrombogenic response to the SARS-CoV-2 infection. Overlapping syndromes of COVID-19 associated coagulopathy with consumptive coagulopathy and microangiopathy can be seen in critically ill patients as well. Blood was collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19 who were on either mechanical ventilation or on high flow oxygen with a PaO2/FiO2 ratio of <300 mmHg. Laboratory tests were performed for parameters of haemostasis, clot waveform analysis and anti-phospholipid antibodies. CWA parameters were raised with elevated aPTT median Min1 (clot velocity) 9.3%/s (IQR 7.1–9.9%/s), elevated PT median Min1 10.3%/s (IQR 7.1–11.1%/s), elevated aPTT median Min2 (clot acceleration) 1.5%/s 2 (IQR 1.0–1.6%/s 2 ), elevated PT median Min2 5.2%/s 2 (3.6–5.7%/s 2 ), elevated aPTT median Max2 (clot deceleration) 1.3%/s 2 (IQR 0.8–1.4%/s 2 ) elevated PT median Max2 3.8%/s 2 (IQR 2.6–4.2%/s 2 ), increased aPTT median Delta change (decreased light transmission due to increased clot formation) 87.8% (IQR 70.2–91.8%) and PT median Delta change 33.0%. This together with raised median Factor VIII levels of 262.5%, hyperfibrinogenemia (median fibrinogen levels 7.5 g/L), increased median von Willebrand factor antigen levels 320% and elevated median D-dimer levels 1.7 μg/dl support the diagnosis of COVID-19 associated coagulopathy. A lupus anticoagulant was present in 50% of patients. Our laboratory findings further support the view that severe SARS-CoV-2 infection is associated with a state of hypercoagulability.

Emergency Department Management of Severe Hypoxemic Respiratory Failure in Adults With COVID-19

“…The pathophysiology of all ARDS includes microthrombi and macrothrombi formation in the pulmonary vasculature ( 34 ). Similarly, COVID-19 critical illness is associated with a hypercoagulable state and clinical and histopathologic data have confirmed microthromboembolic disease and associated decreases in pulmonary perfusion in patients with COVID-19 ( 23 , 25 , 26 , 35 , 36 ). The degree of microthrombi in COVID-19 specimens is greater than patients with ARDS from other etiologies, but the clinical implications are unclear ( 25 , 26 ).…”

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

“…As a result, 17 studies [10–26] with a total of 1187 patients were subjected to qualitative analysis and meta-analysis (Figure 1 and Table 1). Quality assessment with NOS showed that 13 studies [10,13– 19,21–24,26] 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).…”

Clot waveform of APTT has abnormal patterns in subjects with COVID-19

“…4 ) and that fibrinogen theoretically enhances the speed and acceleration of clot formation, high fibrinogen levels could explain these modulations in COVID-19 subjects. Fan, B.E.,et al demonstrated that Factor VIII levels and VWF levels increased together with the raised APTT clot waveform parameters and fibrinogen 27 . As shown in Supplementary Figure S1 , we observed the existence of abnormal clot waveform in the subjects with hemophilia, suggesting the possible involvement of Factor IX as well as Factor VIII in the abnormal clot waveform.…”

“…Actually, HCoV-229E, another type of coronavirus, reportedly disturbs phospholipid homeostasis in infected cells 32 . Regarding the clot waveform analyses and COVID-19, recent reports have demonstrated that the first-derivative and second-derivative peak levels were higher, and the minimum second-derivative peak level were lower or tended to be lower in critically ill COVID-19 subjects 27 , 33 , 34 . Although in the present study, we observed no difference in the APTT clot waveform parameters among mild, moderate, and severe COVID-19 subjects (Supplemental Figure S5 ), the modulation of these parameters in the COVID-19 subjects would be concordant with the previous studies, considering the time course of these parameters (Fig.…”