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COVID-19 associated coagulopathy in critically ill patients: A hypercoagulable state demonstrated by parameters of
Bingwen Eugene Fan1,2,3,4, Jensen Ng5,6,7, Stephrene Seok Wei Chan8,9,6,7
1Department of Haematology, Tan Tock Seng Hospital, Singapore, Singapore. Bingwen_Eugene_Fan@ttsh.com.sg.
Insights
Severe COVID-19 patients exhibit hypercoagulability, indicated by abnormal clot waveform analysis and elevated markers like Factor VIII and D-dimer. These findings confirm a pro-thrombotic state in critical SARS-CoV-2 infection.
Area of Science:
- Hematology
- Infectious Diseases
- Critical Care Medicine
Background:
- COVID-19 patients face high risks of venous, arterial, and microvascular thrombosis.
- Severe SARS-CoV-2 infection can trigger an excessive immuno-thrombogenic response.
- Critically ill patients may present with overlapping syndromes of coagulopathy, consumptive coagulopathy, and microangiopathy.
Purpose of the Study:
- To investigate the hemostatic parameters and clot waveform analysis (CWA) in mechanically ventilated or high-flow oxygen COVID-19 patients.
- To identify laboratory markers associated with hypercoagulability in severe COVID-19.
- To assess the prevalence of antiphospholipid antibodies in this patient cohort.
Main Methods:
- Blood samples were collected from 12 Intensive Care Unit (ICU) patients with severe COVID-19.
- Laboratory tests included parameters of hemostasis, clot waveform analysis (CWA), and antiphospholipid antibodies.
- Analysis focused on specific CWA parameters (velocity, acceleration, deceleration, Delta change) for activated partial thromboplastin time (aPTT) and prothrombin time (PT).
Main Results:
- Elevated CWA parameters indicated increased clot velocity, acceleration, deceleration, and formation.
- Significantly raised median levels of Factor VIII (262.5%), fibrinogen (7.5 g/L), von Willebrand factor antigen (320%), and D-dimer (1.7 μg/dL) were observed.
- A lupus anticoagulant was detected in 50% of the patients, alongside other coagulopathy markers.
Conclusions:
- Severe SARS-CoV-2 infection is strongly associated with a hypercoagulable state.
- Abnormalities in hemostasis and CWA support the diagnosis of COVID-19-associated coagulopathy.
- Findings highlight the pro-thrombotic nature of severe COVID-19, necessitating further investigation into management strategies.
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.
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