Cardiovascular Interventions in Patients with Hemophilia and Severe Von Willebrand Disease.

The management of cardiovascular interventions in patients with hemophilia and severe von Willebrand disease (VWD) is challenging. The procedure itself as well as the use of anti-platelet drugs and anticoagulants implies a risk of bleeding. On the other hand, factor replacement therapy as well as withdrawal of anti-platelet drugs or anticoagulants may increase the risk of cardiovascular events and thrombosis. Information on the management of such interventions is limited to very few case reports. Here, we report a retrospective analysis of 28 patients with hemophilia A (n=16), hemophilia B (n=4) or VWD (n=8, all with VWF:RCo <30 IU/dl), who underwent a total of 39 cardiovascular interventions including coronary angiography (CA, n=11), percutaneous coronary interventions (PCI, n=18), or cardiac surgery (CS, n=10) including coronary artery bypass grafting (CABG) and heart valve surgery with the use of cardiopulmonary bypass (CPB). Patients had a median age of 66 years (range 47–85) and had a median factor activity of 3 IU/dl (range <1–35). Six patients were on regular prophylaxis prior to the intervention. Patients undergoing CA received replacement therapy for a median of 2 days (range 1–15) with a median starting dose of 36 IU/kg (range 24–67). Minor bleeding at the site of puncture occurred in 5 of 11 patients. Major bleeding or bleeding requiring transfusion did not occur. Patients undergoing PCI received replacement therapy for a median of 4 days (range 1–41) with a starting dose of 40 IU/kg (range 12–63) given before or during the intervention. 12 of 14 patients receiving bare metal stents were on aspirin and clopidogrel for 4 to 6 weeks; 7 of these including all patients with severe hemophilia received prophylactic replacement therapy for the time of dual anti-platelet therapy. Two patients received shorter courses of single anti-platelet agents due to bleeding. Three patients receiving drug-eluting stents were on aspirin and clopidogrel for 8 to 12 weeks; 2 of these also received prophylactic replacement therapy, whereas one patient with mild hemophilia did not. Minor bleeding at the site of puncture occurred in 15 of 18 patients undergoing PCI; major bleeding at the site of puncture occurred in 1 patient and required transfusion. Major bleeding at distant sites occurred in 3 patients with 1 patient requiring transfusion. Two of these three patients received anti-platelet therapy without prophylactic factor replacement. No patient experienced stent thrombosis or other thromboembolic complications. Patients undergoing cardiac surgery received replacement therapy for a median of 23 days (range 11–46) with a median starting dose of 57 IU/kg (range 23–107). Unfractionated heparin was used for anticoagulation during CPB. Minor wound bleeding occurred in 8 of 10 patients. Four patients received transfusions of 2 to 5 units of packed red blood cells. Five of seven patients undergoing CABG received aspirin. One patient with VWD undergoing CABG and biological aortic valve replacement received oral anticoagulation and experienced gross hematuria; he was switched to aspirin after 6 weeks. A patient with mild hemophilia on long-term oral anticoagulation because of atrial fibrillation remained on oral anticoagulants without signs of bleeding. In summary, this is the largest cohort of patients with hemophilia and severe VWD undergoing cardiovascular interventions. Combining replacement therapy with anti-platelet agents or anticoagulants appears to be a safe strategy, despite of frequent minor bleeding. Major bleeding mainly occurred in patients on anti-platelet agents without concomitant prophylactic replacement therapy.