The approach for cardiovascular disease (CVD) was based on expert opinion, personal experience, and adaptation of evidence from people who did not have hemophilia.
With a lack of clinical trial data on the management of people with hemophilia (PWH) who also have cardiovascular disease (CVD), researchers have outlined their approach to managing these patients.
Throughout their paper, published in Haematologica, the researchers emphasized the importance of close collaboration between hematologists and other specialists, including cardiologists, in managing these patients to ensure optimization of treatment and mitigation of bleeding. Their approach was based on expert opinion, personal experience, and the adaption of evidence from people without hemophilia.
“Evidence-based recommendations on how to handle CVD in PWH are lacking due to the absence of clinical trials. Thus, the few available guidelines are mostly based on those originally prepared for persons without hemophilia,” wrote the researchers. “There is general consensus that PWH must be managed like their age-related peers, provided replacement therapy is adapted to the degree of plasma factor deficiency and the added risk of bleeding carried by invasive cardiac procedures and use of antithrombotic drugs. The balance between bleeding and thrombosis is indeed particularly delicate in PWH, thereby representing a major challenge when these patients develop CVD.”
The researchers outlined considerations for nonvalvular atrial fibrillation and coronary artery disease (CAD), the latter including stable angina and acute coronary syndrome (ACS). The researchers noted that both nonvalvular atrial fibrillation and CAD require the same management as people without hemophilia, although careful consideration is needed with the standard treatments.
For patients with stable angina, the researchers recommend long-term use of aspirin at a low dose of 100 mg/day or less, although for patients with severe hemophilia, they recommend clotting factor prophylaxis to mitigate worsening of bleeding.
Drawing on guidelines for managing ACS and personal experience, the researchers recommend quick use of percutaneous coronary intervention (PCI) because of its lower risk of bleeding complications, with use of thrombolysis considered only when PCI is not accessible. For patients undergoing PCI, the group prefers second-generation drug-eluting stents, which show superiority over other options, and a month of dual antiplatelet treatment.
“The unstable balance between coagulation and anticoagulation in PWH with ACS deserves special attention,” noted the researchers, who recommend a single intravenous bolus of unfractioned heparin (UFH) prior to PCI, a preferable choice due to it easily being measured through a simple point-of-care test, having a shorter half-life, and the availability of protamine sulfate as an antidote.
Based on guideline recommendations, dual antiplatelet treatment with aspirin and clopidogrel are used alongside UFH at loading doses of 325 and 600 mg, respectively. During PCI, recombinant activated factor VII is recommended every 3 to 4 hours for 24 hours at a dose of 90 to 100 mcg/kg on the day of the procedure and for the 4 weeks following.
The researchers flagged the particular challenges with managing patients with acute coronary syndrome who have alloantibodies that inactivate the coagulant activity of infused coagulation factors, present in approximately 1 in 3 patients with severe hemophilia. The group noted that for these patients, plasma-derived or recombinant products with activated coagulation factors able to bypass the inhibitor defect are required.
The group also provided their recommendations for nonvalvular atrial fibrillation, including consideration of oral anticoagulation for patients with hemophilia and atrial fibrillation and a CHA2DS2-VASc score of 2 or higher. Due to their reduced risk of cerebral hemorrhage, direct oral anticoagulants (DOACs) are recommended instead of vitamin K antagonists, although the researchers noted there are a lack of data on the safety and efficacy, as well as optimized dose, for DOACs. Oral anticoagulation is not recommended for patients with severe hemophilia; instead nonanticoagulants, such as cardioversion and catheter ablation, are recommended.
To reduce the risk of bleeding, the group recommends continuous prophylactic use of factor concentrate in patients with factor VIII/IX levels lower than 20% and advise against the use of antiplatelet drugs as they are no longer recommended to reduce the risk of stroke due to their aqssociation with a significant increased risk of bleeding.
Franchini M, Focosi D, Mannuccio P. How we manage cardiovascular disease in patients with hemophilia. Haematologica. Published online January 26, 2023. doi:10.3324/haematol.2022.282407