From Crystal Wilson: Hello George, I am writing to ask if you could help me to understand how, on rare occasions, patients suffering from bleeding disorders such as von Willebrand disease or hemophilia have suffered from hypercoagulable episodes such as pulmonary emboli or deep vein thrombosis. Thanks.
Hello, Crystal, I sent your question to several colleagues for advice. I received this comprehensive message from Bob Gosselin on 8-5-21: Hey CW + GF, looking at
US/FDA approved [as opposed to EMA approved which may be different] drug prescribing information, the newer factor VIII replacement products Advate, Adynovate, Eloctate, Esperoct, Jivi, Novoeight or porcine factor VIII (Obizur) do not indicate thrombotic risk, whereas the factor IX products Alprolix, Idelvion, Rebinyn and the VWF
treatment Humate-P all suggest thrombotic risk after administration. Afstyla factor VIII clinical trials excluded patients with recent history of thrombosis, but indicated catheter thrombosis may occur. Refacto had a thrombosed catheter adverse event listed, whereas in the UK
prescribing information they indicate thrombophlebitis being a rare event. Fibrinogen [Fibryga, RiaSTAP] and factor XIII replacement Tretten also suggest thrombotic risk, whereas the factor X replacement Coagadex does not. All of the activated prothrombin complex concentrates such as FEIBA
or unactivated PCCs such as Kcentra or Profilnine suggest thrombotic risk. The bypassing agent, HemLibra has black box warning about thrombosis.
I am not sure whether any gene Rx patients have developed any thrombosis to date considering some have gain-in-function characteristics.
Drug prescribing information gets updated if there are changes to dosing, indications, or adverse events, so case reports may be observational and cause-effect conclusions seem premature unless they are known adverse events, but theoretically it would seem plausible. If the hemophilia patients are the older variety and have secondary liver disease due to earlier treatments, the liver disease can be associated with thrombotic risk due to hemostatic imbalance. BG.
Also, on 8-4-21 my colleague Dan Kaczor provided two references:
Girolami A, Scandellari R, Zanon E, Sartori R, Girolami B. Non-catheter associated venous thrombosis in hemophilia A and B. A critical review of all reported cases.
J Thromb Thrombolysis 2006; 21: 279–84.
Crystal, come back to this entry from time to time as we gather additional information, and meanwhile thank you for your thought-provoking question.