Global haemostatic tests demonstrate the absence of hypercoagulability in non-supplemental oxygen dependent COVID-19 patients

ABSTRACT

Background: Critically-ill COVID-19 patients demonstrate a hypercoagulable state, hence necessitating thromboprophylaxis. However, in non-critically ill COVID-19 patients, the haemostatic profile is unknown. Aims: A prospective, observational study was performed to evaluate coagulation parameters, and thrombotic outcomes in critically and non-critically ill COVID-19 patients. Methods: Informed consent was obtained from 10 critically ill (oxygen dependent, PaO2/FiO2 ratio<300) PCR positive COVID-19 patients matched for age and gender with 10 non-critically ill patients (nonoxygen dependent). On recruitment, laboratory (FBC/LDH/CRP/ procalcitonin) and coagulation tests (PT/APTT/D-Dimer/Fibrinogen/ TCT/Factors II,V,VII,VIII,IX,X,XI/vWF/anti-thrombinIII/ProteinC/ ProteinS/antiphospholipid antibodies), Thromboelastography(TEG), Clot Waveform Analysis(CWA) were performed, with repeat TEG/ CWA every 3 days, till 21 days of admission or discharge. This study was DSRB approved and supported by an NHG-NCID grant. Results: The median age was 60 years(49.5, 64.5) with 16 males and 4 females. Median Padua score of critically ill patients was 5 with PaO2/FiO2 ratio 194.5 (174, 241). Hypercoagulability was present in critically ill patients with elevated median levels of Fibrinogen 5.6 g/L(4.9, 6.6), D-dimer 1.0 μg/ml(0.6, 1.4), Factor VIII 206%(171, 230), von Willebrand Factor 265%(206, 321) as compared with lower levels in non-critically ill patients. Hypercoagulability was shown in TEG with increased CRT Angle 78.9°(78.3, 80.0), CFF MA 34.6 mm(27.4, 38.6) and CFF A10 30.9 s (25.5, 34.0);and CWA had increased clot velocity, aPTT Min1 7.7%/s(6.4, 8.3). CK K, CK Angle, CK MA, CRT MA were higher in critically ill patients (Table 1). In noncritically ill patients, D-dimer levels were normal, 0.3 μg/mL(0.3, 0.4) while Factor VIII levels of 176%(157, 192) and vWF levels of 225%(158, 237) were mildly elevated, with TEG and CWA demonstrating no hypercoagulability. 2 critically-ill patients developed thromboembolism(stroke, DVT) while no non-critically ill patients (not on thromboprophylaxis) had thrombosis. Conclusions: Critically ill COVID-19 patients demonstrate a hypercoagulable state with raised fibrinogen and Factor VIII levels correlating with raised CK, CRT, CFF maximal amplitude and increased CWA clot velocity(min1), while non-critical patients showed an absence of hypercoagulability in global tests of haemostasis.