Patients with Congenital Bleeding Disorders Appear to be Less Severely Affected by SARS-CoV-2: Is Inherited Hypocoagulability Overcoming Acquired Hypercoagulability of Coronavirus Disease 2019 (COVID-19)?

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is the gravest current challenge worldwide, with approximately 5 million infected patients, more than 300,000 deaths, and an overall mortality rate of approximately 7% at the time of writing.[1] Although the underlying disease, coronavirus disease 2019 (COVID-19), is the major medical challenge for the general population, it is more threatening for patients with underlying risk factors such as diabetes, cardiovascular disorders, hypertension, obesity, cancer, and chronic renal and hepatic failures.[2] Coagulopathy is a major pathophysiological characteristic of COVID-19, and the virus can affect all patients including those with congenital bleeding disorders (CBDs). However, due to a paucity of data, it is not clear whether these patients are more or less prone to the severe form of the disease. In this context, we report our observations of COVID-19 patients with CBDs. For this purpose, we collected laboratory and clinical data of patients with identified CBDs receiving a diagnosis of COVID-19 with reverse transcriptase–polymerase chain reaction (RT-PCR) and/or a computed tomography (CT) scan. The latter is now an accepted surrogate marker of COVID-19, in particular ground-glass opacities, when aligned to other clinical features of COVID-19,[3] [4] considering also the potential for false-negative RT-PCR. Clinical presentations and laboratory phenotypes for our patient cohort were collected through patient interviews and medical files. Nine patients could be identified, who were noted to be suffering from hemophilia A (HA) (n = 5 [∼55.5%]), von Willebrand disease (VWD) (n = 2 [22.2%]), hemophilia B (HB) (n = 1 [11.1%]), and factor XIII (FXIII) deficiency (n = 1 [11.1%]). All but one of these patients (n = 8 [∼89%]) were male, with a mean age of 48.2 years (range: 26–59 years), and most were symptomatic with COVID-19 at the time of SARS-CoV-2 infection (n = 7 [∼78%]). Of interest, two were asymptomatic for COVID-19: one was a hospital employee identified to have SARS-CoV-2 following routine employee screening and another was randomly referred to undergo testing. Among the nine patients, two (∼22%) experienced bleeding and one (∼11%) experienced thrombosis. Both patients with bleeding events had contributing risk factors: one with lymphoma and another with factor VIII inhibitor. Thrombosis was observed in a young patient with type 1 VWD, the only hospitalized patient, who was treated in the intensive care unit for 2 days. It is worth noting that this was the patient who was RT-PCR-negative for SARS-CoV-2 and was hence hospitalized based on CT findings and clinical presentation. Although molecular studies failed to confirm an active infection by SARS-CoV-2 at admission, we believe this may have been a false-negative finding, and further repeat testing was not performed. D-dimer was only available for two patients, with these yielding normal results, and prothrombin time (PT) also was normal in all cases with available data (n = 4). Platelet count was also available in four cases; only one of these experienced mild thrombocytopenia ([Table 1]).