Written by: David Clark, PhD, chair of the Coalition for Hemophilia B

NOTE: This article will appear in Factor Nine Newsletter Spring 2020. It is not intended as medical advice. Readers should seek the advice of their own physician. Because information regarding COVID-19 (novel coronavirus) is ever changing, readers are also asked to check for frequent updates.

A 35-year-old man in Wuhan, China, who has severe hemophilia A experienced aching pain in his limbs. Thinking he might be having a bleed, he took his usual 400 IU dose of factor VIII, but the pain continued. The next day, he felt fatigue, chills, a low-grade fever; he was vomiting and lost his appetite. For two days he treated himself with oral antibiotics and traditional Chinese medicine. When the fever did not stop, he went to the emergency department, where he was diagnosed with COVID-19. He had no other underlying disease except hemophilia A, with his left knee as a target joint.

At this writing, there is only published report of a hemophilia patient with COVID-19.

Since there was no room in the hospital, he was treated with intravenous immunoglobulin and sent home to self-quarantine. He was also treated with oseltamivir (an antiviral), cefdinir (an antibiotic), and Lianhua Qingwen (traditional Chinese medicine). On the third day of treatment (7 days after his first symptoms), his appetite suddenly improved and the muscle (limb) pain, vomiting, and chills went away. Two days later, his fever ceased, but he still had a dry cough, difficulty breathing, and chest pain. It took two more weeks for those symptoms to end. In all, it took from January 19, when his limb pain began, until March 10, when he was declared asymptomatic. He had no unusual bleeding events during that time. Unfortunately, because of the isolation measures in Wuhan, they lost track of him and thus have no further follow-up to report.[1]

This is the first and, so far, only published report we have of a hemophilia patient with COVID-19. In spite of the patient’s underlying hemophilia, the doctors report that his clinical course was typical for COVID patients. Another article from a group of physicians and specialists treating hemophilia patients in Belgium states: “There is no reason to suspect that the clinical presentation of COVID-19, its severity and complications, are influenced by haemophilia.”[2] They go on to present practical, commonsense advice for management of COVID-19 in patients with hemophilia. They recommend that you inform your Hemophilia Treatment Center (HTC) or hematologist of any suspicion or confirmed diagnosis of COVID-19 and involve your doctors in any care decisions.

They also recommend that you practice social distancing as appropriate and possible for your situation. You should continue your regular factor infusions and not delay treating bleeds. You should make sure you have an adequate supply of factor at home in case of shortages or difficulty receiving shipments. You should also maintain physical activities to avoid joint deterioration and prevent muscle loss. If you need to seek care, it is important to make physicians and nurses aware of your hemophilia and treatment regimen. Also, inform them if you are, or have recently been, involved in any clinical studies. Some medications may interfere with diagnostic tests, especially clotting assays. Your factor product could also interfere with anticoagulants administered to prevent thrombosis (unwanted internal clotting).

We have been learning that in addition to respiratory issues, another significant symptom of COVID-19 is thrombosis. At this point, we are not sure of the cause and whether hemophilia would give you any protection from it. The excess clotting could be caused by other pathways that don’t depend on factors VIII or IX. As a compromise between the risks of bleeding and thrombosis, the authors of the Belgium report recommend that hospitalized hemophilia patients’ factor levels be kept at 50–100% for factor VIII (hemophilia A) and 30–60% for factor IX, preferably by continuous infusion with short-acting factor concentrates. Extended half-life (EHL) factor concentrates may be used, but patients’ levels should be monitored to determine the appropriate dosing interval. Patients on ventilators should also be monitored for von Willebrand factor (vWF) levels since ventilators can cause a depletion of vWF.

COVID-19 will also have effects on other aspects of living with hemophilia. Elective surgeries and clinical studies have all been delayed. Some researchers have shifted their focus from hemophilia to COVID-19 for the time being.

Patients should also be monitored for inhibitor development. The stress of COVID-19 symptoms and treatments, as well as the accompanying inflammation, can spark development of inhibitors, even in patients without hemophilia.[3] It can also cause previously eliminated inhibitors to be reactivated. One patient in Italy, who did not previously have hemophilia but developed acquired hemophilia A after COVID-19 infection, was treated successfully with activated factor VII. Again, a careful balance needs to be maintained between bleeding and clotting.

COVID-19 will also have effects on other aspects of living with hemophilia. Elective surgeries and clinical studies have all been delayed. Some researchers have shifted their focus from hemophilia to COVID-19 for the time being. Meetings and educational programs have been delayed or canceled. It also appears that much of the community could end up in difficult financial situations.

I’ll end with a quote from an editorial from the World Federation of Hemophilia (WFH): “Our bleeding disorders global community has experienced more than one crisis. This one is as different as it is unexpected. Together we can all face it and learn the necessary lessons from it.”[4]

REFERENCES: All the references used for this article are free online.

1. D. Cui et al., “Clinical Findings in a Patient with Haemophilia A Affected by COVID-19,” Haemophilia. DOI: 10.1111/hae.14000.

2. C. Hermans et al., “In-Hospital Management of Persons with Haemophilia and COVID-19: Practical Guidance.” Haemophilia. DOI: 10.1111/hae.14045.

3. M. Franchini et al., “The First Case of Acquired Hemophilia Associated with SARS-CoV-2 Infection.” American Journal of Hematology. DOI: 10.1002/ajh.25865.

4. C. Hermans et al., “The COVID-19 Pandemic: New Global Challenges for the Haemophilia Community.” Haemophilia. DOI: 10.1111/hae.14001.