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%/s² (IQR 1.0-1.6%/s²), elevated PT median Min2 5.2%/s² (3.6-5.7%/s²), elevated aPTT median Max2 (clot deceleration) 1.3%/s² (IQR 0.8-1.4%/s²) elevated PT median Max2 3.8%/s² (IQR 2.6-4.2%/s²), 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.

Keywords: Coronavirus; Hypercoagulability; Sepsis; Thrombophilia; Thrombosis.

Fig. 1

a Hypercoagulable aPTT Clot Waveform tracing and parameters of a 35-year-old male with severe COVID-19 infection complicated by acute right ischaemic limb secondary to extensive thromboembolic disease in the abdominal aorta, right external iliac and right popliteal arteries. *Patient’s clot waveform tracing in black, healthy controls in multicolour (for reference). Patient’s haemostatic and clot waveform parameters: PT 14.2 s (11.7–14.0 s), aPTT 38.7 s (27.0–37.0 s), fibrinogen 5.0 g/L (1.8–4.5 g/L), D-Dimer 2.26 μg/ml (<0.50 μg/ml), Platelets 337 × 10⁹/L (150–360 x10⁹/L). Factor II 122% (70–120%), Factor VIII 196% (60–150%), Factor × 106% (70–120%), vWF 200% (56–160%), anti-thrombin III 74% (80–130%), Protein C 61% (70–150%), Protein S 79% (55–130%). Absent lupus anticoagulant and antiphospholipid antibodies. CWA: Min1 9.715%/s (2.86–6.78%/s), Min2 1.493%/s² (0.46–1.10%/s²), Max2 1.243%/s² (0.37–0.93%/s²), Delta change 81.2% (25.21–63.09%). b aPTT Clot Waveform tracing of a 40-year-old male on mechanical ventilation for severe COVID-19 pneumonia, Day 18 of illness (Day 2 ECMO), with probable pulmonary intravascular coagulopathy with concurrent bacterial pneumonia and sepsis induced coagulopathy, not initiated on anticoagulation yet. Clots were seen in the ECMO oxygenator as well as the dialysis circuit. *Patient’s clot waveform tracing in black, healthy controls in multicolour (for reference). Patient’s haemostatic and clot waveform parameters. PT 18.2 s (11.7–14.0 s), aPTT 53.2 s (27.0–37.0 s), fibrinogen 3.8 g/L (1.8–4.5 g/L), D-Dimer >20 μg /ml (<0.5 μg /ml), Platelets 115 × 10⁹/L (150–360 × 10⁹). Factor II 46% (70–120%), Factor V 68% (70–120%), Factor VIII 196% (60–150%), Factor IX 115% (60–150%) Factor × 68% (70–120%), vWF 387% (56–160%), anti-thrombin III 54% (80–130%), Protein C 28% (70–130%), Protein S 19% (55–130%). Lupus anticoagulant moderately present and anti cardiolipin IgG < 20 (0–20 GPL units), anti cardiolipin IgM 23 (0–20 MPL units), anti B2 glycoprotein-1 < 2 RU/ml (0–20 RU/ml). CWA: Min1 4.123%/s (2.86–6.78%/s), Min2 0.457%/s² (0.46–1.10%/s²), Max2 0.351%/s² (0.37–0.93), Delta change 68.2% (25.21–63.09%). c aPTT Clot Waveform tracing of a 73-year-old male on Day 13 of illness with severe COVID-19 pneumonia with probable pulmonary intravascular coagulopathy and concurrent sepsis induced coagulopathy from stenotrophomonas maltophilia bacteraemia and ventilator associated pneumonia. *Patient’s clot waveform tracing in black, healthy controls in multicolour (for reference). Patient’s haemostatic and clot waveform parameters. PT 15.3 s (11.7–14.0 s), aPTT 41.3 s (27.0–37.0 s), fibrinogen 4.0 g/L (1.8–4.5 g/L), D-Dimer >20 μg/ml (<0.5 μg/ml), Platelets 120 × 10⁹/L. Factor II 56% (70–120%), Factor V 93% (70–120%), Factor VIII 195% (60–150%), Factor IX 105% (60–150%), Factor × 68% (70–120%), Factor XI 47% (60–150%), vWF 200% (56–160%), anti-thrombin III 74% (80–130%), Protein C 61% (70–150%), Protein S 79% (55–130%). Lupus anticoagulant and antiphospholipid antibodies absent. CWA: Min1 5.005%/s (2.86–6.78%/s), Min2 0.641%/s² (0.46–1.10%/s²), Max2 0.512%/s² (0.37–0.93%/s²), Delta change 63.6% (25.21–63.09%)