Percutaneous Coronary Intervention in a Patient with Acute<br />
ST-Elevation Myocardial Infarction and Hemophilia A

Hemophilia A is an inherited X-linked recessive disorder of the intrinsic coagulation pathway which affects 1 in 10,000 males and is characterized by deficiency of factor VIII with resultant bleeding diathesis. Platelet function is normal. Clinical severity correlates with the assayed factor VIII activity with severe disease defined as factor VIII activity < 1% of normal, moderate as 1–5%, and mild as > 5% of normal.¹ Hemophilia A is reported to have a direct protective effect on the development of coronary artery disease (CAD).^2,3 Acute coronary syndromes are extremely unusual in hemophilia patients, possibly because of their short lifespan^4,5 or their inability to form thrombi in the arteries.^6,7 Infusions of human plasma-derived factor VIII, recombinant factor VIII concentrate, DDAVP and prothrombin complex have precipitated unstable angina^8–12 and have immediately preceded all of the 36 reported acute myocardial infarctions in hemophiliacs.^13–15 We report the first case of hemophilia A with an acute ST-elevation myocardial infarct (STEMI) not directly precipitated by clotting factor infusion and the second case successfully treated by primary coronary artery stenting.

Case Report

A 44-year-old male smoker with severe hemophilia A, treated with concentrated Factor VIII infusions only during bleeding episodes, presented to the emergency department with an acute inferior STEMI, no recent clotting factor infusions and a Factor VIII activity level of 1.7%. Urgent coronary angiography demonstrated a 75% stenosis of the proximal right coronary artery (RCA), a 99% stenosis at the mid vessel, and a radiolucent filling defect just distal to the 99% stenosis suggesting thrombus (Figure 1). After infusion of 2500 units of recombinant Factor VIII to achieve an activity level of 60–80% of normal, bare-metal stents were deployed in both the proximal and distal stenoses (Figure 2). Prior to stent deployment, the patient received 325 mg of aspirin, 600 mg of clopidogrel, and a single dose of bivalirudin (0.7 mg/Kg). Additional infusions of recombinant Factor VIII on days 2 and 3 maintained Factor VIII activity levels of 60–80% of normal. No bleeding complications occurred. He was discharged on aspirin 325 mg/day and clopidogrel 75 mg/day. At 4 months’ follow-up, clopidogrel was discontinued due to gingival bleeding and ecchymoses, while aspirin was continued. Two years after the event, the patient had not experienced further episodes of chest pain and a stress myocardial perfusion scan showed no evidence of ischemia.

Discussion
When available, percutaneous coronary intervention (PCI) is the treatment of choice for acute STEMI.¹⁶ However, patients with hemophilia that require invasive interventions pose a particular challenge because of high risk of periprocedural hemorrhage and subsequent bleeding side effects of antiplatelet therapy. Serious perioperative hemorrhage has occurred with coronary artery bypass surgery.¹⁷ To avoid bleeding, these patients should receive Factor VIII titrated to a Factor VIII activity level 80–100% of normal.¹⁸ There is no similar protocol for PCI in hemophilia patients. In the four previous reports in which PCI was performed in hemophilia patients, activity levels ranged from 70–200% of normal.¹⁹
Periprocedural anticoagulation is required during PCI, usually with heparin titrated to an optimal activated clotting time.¹¹ There are three reported cases of heparin use during stenting of patients with hemophilia and acute coronary syndrome.¹⁹ Importantly, the activated partial prothrombin time may be erroneous in hemophilia due to the dysfunctional intrinsic coagulation pathway. The activated clotting time is not affected. Bivalirudin offers the advantages of direct inhibition of circulating and clot-bound thrombin, no required monitoring and a low rate of bleeding complications. Patients treated with bivalirudin during coronary artery stenting for STEMI demonstrated acceptable coronary flow, even without the addition of glycoprotein IIb/IIIa inhibitors.²⁰ There have been two reports of bivalirudin use during coronary stenting in patients with severe hemophilia A.^21,22
Although hemophilia is not associated with abnormalities of platelet number or function, antiplatelet therapy can increase the hemorrhagic diathesis in these patients.^23–25 Current guidelines recommend double platelet inhibition using aspirin and clopidogrel for at least 1 month duration with bare-metal stents and at least 1 year for drug-eluting stents.²⁶ In our patient, we used bare-metal stents to allow the earliest withdrawal of antiplatelet therapy. In spite of disturbed coagulation, acute stent thrombosis has been reported in a hemophilia B patient not treated with aspirin or clopidogrel.²⁷ Thus, aggressive platelet inhibition seems to be required even in hemophilia patients.

Conclusion
Contrary to “conventional wisdom”, individuals with hemophilia A may experience acute myocardial infarction. This case demonstrates that primary stenting in acute STEMI can be safely performed using both anticoagulation and platelet inhibition in these challenging patients.

References

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