DISCUSSION

To our best knowledge, this is the first case report describing a patient with severe hemophilia A and NSTEMI who needs a combined procedure of CABG and closure of an underlying giant coronary aneurysm. Severe hemophilia A is defined when factor VIII level < 1%. This case also highlights the occurrence of NSTEMI as a consequence of underlying CAA and its management challenge during the open-heart surgery. CAA is defined as artery dilation more than 1.5 times the diameter of normal adjacent segments or the diameter of the largest coronary artery.¹ Giant coronary aneurysm refers to an aneurysm with a diameter > 20 mm.¹ CAA is typically diagnosed incidentally during coronary angiography.² CAA is associated with thrombus formation due to abnormal laminar flow, as well as abnormal platelet and endothelial-derived pathophysiologic factors within the CAA. Once formed, mural thrombus may potentiate the deposition of additional thrombus within aneurysmal segments.²

Besides the underlying CAA and hypercholesterolemia as risk factors of thrombosis in this case, we also looked at the possibility of a treatment-related event. Acute coronary events have been found to be associated with hemophilia treatment. Studies have discovered that replacement of deficient factors especially in large amounts of concentrates to achieve high levels as those required for major surgery (level of 80-100%) have the highest thrombotic risk.³ There were reports of thrombotic cases occurring during or shortly after supernormal factor concentrates infusion.⁴ However, there is no report of similar thrombosis events associated with the usual prophylactic dose of factor infusions.

Cardiac surgery is associated with significant coagulation abnormalities leading to an increased intra- and post-operative bleeding risk, secondary to heparinization, surgical trauma, extracorporeal circulation, hypothermia, and increased fibrinolysis.⁵ Hence cardiac surgery on hemophilia patients poses an extreme hemostatic challenge. Unfortunately, there is lack of guidelines available on how best to strategize the treatment plan. Moreover, a standardized hemostatic treatment protocol will seem to be an unlikely solution, based on the small number of hemophilia patients needing cardiac surgery, and the difference in disease severity.

P Lin et al ⁶ did a retrospective analysis of published literatures on perioperative management of hemophilia A patients undergoing cardiac surgery. Analysis of fifty articles showed that among 72 patients, 25 (35%) were severe hemophilia A. Factor VIII concentrates were given to ensure normalization of perioperative coagulation function. Although an eventful clinical outcome was achieved in the majority of cases, 20% of patients developed complications with different severities. The analysis concluded that a thorough factor replacement with careful monitoring of factor levels is the key to an optimal outcome.

In another retrospective survey done on 10 patients with hemophilia by Shalabi A et al,⁷ the authors suggested factor level to be maintained above 80% at the end of surgery until 48-hour post-operatively. Thereafter, factor level to be maintained above 50%. All their patients received antifibrinolytics intraoperatively, but not postoperatively except in cases of bleeding despite optimal factor replacement. During the immediate post-operative period, the authors preferred to use continuous infusion of factor VIII than bolus factor replacement, as it reduced total factor use, improved safety with stable factor VIII activity, and guarded against a lack of deep troughs below the hemostatic range.

Current literature is sparse regarding the use of long-term antithrombotic or anti-platelet treatment in hemophilia patients after cardiac surgery. However, several case studies reported safe anti-thrombotic and anti-platelet treatment in hemophilia patients, on the condition that there is adequate replacement therapy.⁸ Low-dose aspirin is generally well tolerated in hemophilia patients and can be used as prophylaxis for life.

The management strategies of CAA include medical therapy, surgery and percutaneous coronary intervention (PCI). To date, there is no consensus on the optimal treatment of CAA because the natural history and long-term outcomes of CAA remain unclear. Previous studies have reported good short- and long-term outcomes for CABG performed in patients with CAA.^{9, 10} In a study by Khubber S et al ¹¹ that looked into outcomes of CAA following medical, PCI and surgery found that CABG was associated with a lower rate of major cardiovascular and cerebrovascular events over a period of 10 years, compared to medical management, but no significant difference was noted between PCI and CABG. A CABG was performed on this case as he also presented with significant coronary arteries occlusion, in which the management was aimed towards both revascularization and repair of CAA.