Hemophilia doesn’t protect against severe COVID-19 outcomes: Study

Bleeding history, older age ID'd as risk factors for patients

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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People with hemophilia showed no heightened protection against COVID-19 severity or mortality, a large retrospective U.S. outcomes study found.

“Having hemophilia was not a risk factor for death,” the researchers wrote, noting, however, that hemophilia patients “were more likely to have moderate COVID-19 severity and to be hospitalized.”

Older age, other medical conditions, and a bleeding history were identified as risk factors that negatively influenced patients’ outcomes.

“Future studies are needed to better understand how to best use hemophilia therapeutics and anticoagulation therapy for optimal management of [patients with hemophilia] with COVID-19,” the team wrote.

The study, “COVID-19 outcomes in persons with hemophilia: results from a US-based national COVID-19 surveillance registry,” was published in the Journal of Thrombosis and Haemostasis.

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Investigating if lack of blood clotting factors could offer protection to patients

People with inherited or acquired hypercoagulable states have a higher tendency for making blood clots — essentially the opposite of hemophilia — which increases their risk of venous thromboembolism (VTE), or blood flow obstruction in a vein.

When infected with SARS-CoV-2, the virus that causes COVID-19, patients with hypercoagulable states are more likely to develop severe disease. That, in turn, raises the question of whether hemophilia, a genetic blood disorder characterized by the lack of certain clotting factors — proteins that promote blood clotting — may be protected against severe COVID-19.

To answer this, a team led by researchers at the University of Iowa conducted a study in which they compared the outcomes of hemophilia patients with COVID-19 with those of people without hemophilia, but also infected with SARS-CoV-2. The researchers focused particularly on VTE and bleeding risks.

Their analysis used retrospective data collected through January 2022 from the National COVID Cohort Collaborative (N3C), a U.S. national surveillance system established to follow trends and outcomes of COVID-19.

From the more than 4 million male patients who were part of the dataset, 300 men with hemophilia and diagnosed with COVID-19 were selected to be included in the study. Their outcomes were compared with those of 900 patients without hemophilia who also contracted COVID-19, who served as controls.

Close to three-quarter of the participants (70%) were overweight or obese, and high blood pressure was detected in 40% of the cases.

Additional disorders, or comorbidities, were seen more frequently in hemophilia patients than controls, with the exception of kidney disease.

Compared with controls, more hemophilia patients reported a clinical history of VTE (4% vs. 6.9%), but fewer reported being on anticoagulation therapy before being diagnosed with COVID-19 (8.3% vs, 5.7%).

The clinical outcomes following COVID-19 were similar in both groups, although hemophilia patients were significantly more likely to develop moderate to severe COVID-19 than controls.

While hospitalization rates were significantly higher in hemophilia patients (40% vs. 30%), intensive care unit admission rates were similar in both groups, at around 3%.

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No real differences seen in blood flood obstructions in brain

Also, no significant differences were seen between controls and hemophilia patients regarding the rates of VTE (2.9% vs. 3.8%). However, bleeds occurring outside the brain and spinal cord were significantly more frequent in hemophilia patients than in controls (19% vs. 5.9%).

Researchers then conducted a series of statistical analyses to identify risk factors of adverse outcomes following SARS-CoV-2 infection in hemophilia patients.

Older age, heart failure, advanced liver disease, dementia, high blood pressure, malignancy, and kidney disease all were identified as significant risk factors for adverse outcomes in hemophilia patients. A clinical history of VTE, use of anticoagulation therapy, and pre-existing pulmonary disease were all linked to a significantly higher risk of VTE in this group.

Hemophilia is not protective against COVID-19 adverse outcomes and VTE [blood flow obstruction in a vein].

The risk of bleeds during COVID-19 was higher in hemophilia patients who were tobacco smokers and among those with moderate liver disease, hepatitis C, and joint bleeds. Hemophilia patients who had experienced bleeds outside the brain and spinal cord before contracting COVID-19 also were found to have a greater risk of bleeds.

The majority of previously identified factors — older age, cardiovascular disease, liver disease, pulmonary disease, bleeding, smoking, VTE, anticoagulation therapy — also significantly increased the risk of adverse outcomes in controls, the data showed.

In statistical analyses taking multiple factors into account, both older age and past use of anticoagulation therapy were significantly linked to a higher risk of VTE. Hemophilia did not reduce adverse outcomes, nor VTE, but increased the risk of bleeds, along with liver disease.

Overall, these findings suggest that “hemophilia is not protective against COVID-19 adverse outcomes and VTE,” the researchers wrote.

“The management of COVID-19 in [patients with hemophilia] needs careful assessments of bleeding and thrombotic risk and an ongoing investigation as the pandemic is transitioning towards an endemic state,” they wrote.