Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study

Abstract

Severe COVID-19 patients demonstrate hypercoagulability, necessitating thromboprophylaxis. However, less is known about the haemostatic profile in mild COVID-19 patients. We performed an age and gender-matched prospective study of 10 severe and 10 mild COVID-19 patients. Comprehensive coagulation profiling together with Thromboelastography and Clot Waveform Analysis were performed. FBC, PT, APTT, D-dimer, fibrinogen and CWA were repeated every 3 days for both groups and repeat TEG was performed for severe patients up till 15 days. On recruitment, severe patients had markers reflecting hypercoagulability including raised median D-dimer 1.0 μg/mL (IQR 0.6, 1.4) ( p = 0.0004), fibrinogen 5.6 g/L (IQR 4.9, 6.6) ( p = 0.002), Factor VIII 206% (IQR 171, 203) and vWF levels 265.5% (IQR 206, 321). Mild patients had normal values of PT, aPTT, fibrinogen and D-dimer, and slightly elevated median Factor VIII and von Willebrand factor (vWF) levels. Repeated 3-day assessments for both groups showed declining trends in D-dimer and Fibrinogen. CWA of severe COVID-19 group demonstrated hypercoagulability with an elevated median values of aPTT delta change 78.8% (IQR 69.8, 85.2) ( p = 0.001), aPTT clot velocity (min1) 7.8%/s (IQR 6.7, 8.3) ( p = 0.001), PT delta change 22.4% (IQR 19.4, 29.5) (p = 0.004), PT min1 7.1%/s (IQR 6.3, 9.0) ( p = 0.02), PT clot acceleration (min 2) 3.6%/s 2 (IQR 3.2, 4.5) ( p = 0.02) and PT clot deceleration (max2) 2.9%/s 2 (IQR 2.5, 3.5) ( p = 0.02). TEG of severe patients reflected hypercoagulability with significant increases in the median values of CFF MA 34.6 mm (IQR 27.4,38.6) ( p = 0.003), CRT Angle 78.9° (IQR 78.3, 80.0) ( p = 0.0006), CRT A10 67.6 mm (IQR 65.8, 69.6) ( p = 0.007) and CFF A10 32.0 mm (IQR 26.8, 34.0) ( p = 0.003). Mild COVID-19 patients had absent hypercoagulability in both CWA and TEG. 2 severe patients developed thromboembolic events while none occurred in the mild COVID-19 group. Mild COVID-19 patients show absent parameters of hypercoagulability in global haemostatic tests while those with severe COVID-19 demonstrated parameters associated with hypercoagulability on the global haemostatic tests together with raised D-Dimer, fibrinogen, Factor VIII and vWF levels. Supplementary Information The online version contains supplementary material available at 10.1007/s11239-021-02575-4.

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.…”

Dysregulation of Protein S in COVID-19

“…White et al [ 63 ] also looked at free PS antigen and compared it between 34 noncritical and 75 critical COVID-19 patients and observed similar extent of reduction (mean 52.1 vs 54.5 IU/dL; reference range 65–135). Fan et al [ 64 ] also looked at PS activity between 10 mild and 10 severe patients and found mild reduction, but no difference between mild and severe patients (median 74% vs 71%; reference range 55–130%).…”

“…The majority of studies that have reported PS deficiency in COVID-19 patients have either reported free PS or PS activity, a clot time-based measurement of the APC cofactor activity of free PS [ 49 , 50 , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] ]. It is possible for total PS antigen to remain normal but free PS, and PS anticoagulant activity, to decrease.…”

Global haemostatic tests demonstrate the absence of parameters of hypercoagulability in non-hypoxic mild COVID-19 patients: a prospective matched study—Reply to comment from Muzaffar et al.

“…We thank Muzaffar et al [ 1 ] for providing feedback on our study [ 2 ]. The aim of our study was to evaluate the haemostatic profile of mildly ill and severely ill COVID-19 patients.…”