Current Overview on Hypercoagulability in COVID-19

Namrata Singhania; Saurabh Bansal; Divya P. Nimmatoori; Abutaleb A. Ejaz; Peter A. McCullough; Girish Singhania


Am J Cardiovasc Drugs. 2020;20(5):393-403. 

In This Article

Clinical Evaluation

All patients admitted to the hospital with COVID-19 should get a complete blood count (CBC), and PT, aPTT, fibrinogen, and D-dimer levels should be checked. D-dimer levels have shown to be directly proportional to the severity of the disease. High D-dimer and fibrinogen levels, normal or mildly prolonged PT and aPTT, mild thrombocytopenia or thrombocytosis, or normal platelet count are typically seen. The values of these typical tests were also found to correlate with 28-day mortality based on multivariate analysis of 447 patients in a retrospective study.[9] PT (OR 1.107, 95% CI 1.008–1.215) and D-dimer (OR 1.058, 95% CI 1.028–1.090) levels correlated positively, while platelet count (OR 0.996, 95% CI 0.993–0.998) correlated negatively, with 28-day mortality.[9] Few studies have evaluated D-dimer levels at various cut-off values to predict VTE in patients with COVID-19.[27] Cui et al. showed that if a cut-off value of 1.5 μg/mL was used to predict VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value was 94.7%.[27] According to ASH, a normal D-dimer may be enough to rule out PE in most stable COVID-19 patients with low to moderate pretest probability, as calculated using the Wells score.[3]

Although Yao et al. did not specifically study the correlation between various D-dimer levels and VTE, they showed that D-dimer at a cut-off value of 0.5 μg/mL was present in more than 70% of patients with COVID-19, and an increase in D-dimer levels correlated significantly with disease severity.[28] As many COVID-19 patients may present with high levels of D-dimer due to inflammation, it is difficult to rule out VTE based on D-dimer alone in patients with high pretest probability.[29] Additional testing, including ultrasonography of the extremities and computed tomography angiography (CTA) of the chest are recommended and should be used readily depending on clinical presentation, due to the high risk of VTE associated with this disease. A ventilation-perfusion (VQ) scan is recommended in patients with contraindications to CTA, such as those with poor renal function. An echocardiogram may be considered in some patients, especially those in whom CTA cannot be performed and in whom a VQ scan has limited value due bilateral infiltrates. An echocardiogram may show right heart strain and a dilated/hypokinetic right ventricle. Additional work-up is recommended in those patients with unexplained hypotension, tachycardia, worsening respiratory status, or other risk factors for thrombosis. Patients with atypical findings such as severe thrombocytopenia and/or markedly prolonged PT/aPTT require further investigation. If thrombotic microangiopathy is suspected, serum lactate dehydrogenase, haptoglobin, ADAMTS13 activity, and peripheral blood smear are recommended. Antiphospholipid antibody testing is not routinely recommended as it can be transiently present in viral infections.