Haemophilia A is an X-linked recessive genetic disorder due to a defective or deficient factor VIIIc protein, resulting in a tendency to bleed. It affects approximately 1/10 000 males. Continuous infusions of factor VIIIc concentrate have been used during surgical procedures in such patients [1,2]. However, the proposed infusion rates may not be adequate during open-heart surgery involving cardiopulmonary bypass (CPB) and associated haemodilution. We report our experience in a patient with haemophilia A, who underwent triple coronary artery bypass and mitral valve replacement.
This 53-yr-old male (body weight 80 kg) had a history of haemophilia A, and arterial hypertension, and stable angina pectoris. No incidence of significant bleeding was reported. His preoperative medications included bisoprolol and nitrates; aspirin was stopped 10 days before surgery. A coronary angiogram demonstrated two-vessel disease with occlusion of the right coronary artery (RCx) and a triple stenosis of left anterior descending coronary artery. Echocardiography revealed conserved left ventricular function and grade III mitral regurgitation. Relevant preoperative laboratory data were as follows (with reference values):
• haematocrit: 43% (40-54%)
• platelet count: 143 × 109 L−1 (150-400 × 109 L−1)
• prothrombin time: 76% (70-100%)
• activated partial thromboplastin time: 49 s (28-42 s)
• bleeding time: 4.5 min (<4 min)
• factor VIIIc: 10% of normal
• factor VIIIvW: 116% of normal
• factor IX: 134% of normal.
Two hours prior to surgery, a bolus of 50 IU kg−1 of factor VIIIc solvent/detergent (Central Fractioning Department, Belgian Red Cross) was slowly injected, thus obtaining a factor VIIIc concentration of 129% of normal (Fig. 1). This was followed by a continuous infusion of 3 IU kg−1 h−1. Tranexamic acid 1 g was given before incision. Heparin 300 IU kg−1 before CPB resulted in an activated clotting time >999 s (ACT II, Medtronic Hemotec Inc., Englewood, CO, USA). The bypass system was primed with Hartman's solution to obtain a haematocrit of 22%. Triple bypass was performed with the left internal mammary artery sequentially to the left anterior descending artery and the first diagonal, and the gastroepiploic artery to the right posterior descending artery. The mitral valve was replaced with a Carbomedics mechanical prosthesis. Mild hypothermia to 31.4°C was achieved during valve replacement. Total bypass time was 175 min. Heparin was reversed with 380 mg of protamine, which gave a protamine/heparin ratio of 1.52. The post-protamine activated clotting time was 190 s.
Factor VIIIc values were difficult to obtain when the patient was heparinized. Despite the continuous infusion, the factor VIIIc level gradually fell to 28% after protamine (Fig. 1). A second bolus of 33 IU kg−1 of factor VIIIc was administered, as well as four units of fresh frozen plasma to control severe bleeding before would closure (prothrombin time 27%). Intraoperatively, 916 mL of blood from a cell-saver device and four units of packed red blood cells were transfused to maintain the haematocrit greater than 20%. At the end of the procedure the platelet count was 65 × 109 L−1 and the haematocrit was 19%. Therefore, six units of pooled platelets and two units of packed red cells were given on arrival in the intensive care unit (ICU) where the patient remained stable. Catheters and chest drains (total drainage volume 1590 mL) were removed during continued factor VIIIc infusion. The patient was transferred to the ward on the 2nd postoperative day. The course was uneventful and the infusion of factor VIIIc was stopped on day 3. The patient was discharged on the 9th post-operative day with a residual factor VIIIc level of 27%. Coumarin therapy was instituted to prevent mitral valve clotting. At 6 weeks follow-up the patient was doing well and had no bleeding complications.
Only a few cases of complex cardiac surgery procedures in patients with haemophilia A have been reported in the literature. In most of them bolus injections of factor VIIIc were given. However, MacKinlay and colleagues reported the use of continuous infusions of factor VIIIc in three cases . Although the biological half-life of factor VIIIc is about 8-12 h, a continuous infusion compensates for factor VIIIc consumption and optimizes safety .
Other therapeutic options include tranexamic acid, desmopressin and aprotinin, alone or in combinations. Desmopressin administration in haemophilia A patients undergoing coronary artery bypass grafting (CABG) is controversial as it seems to increase the von Willebrand factor but not factor VIIIc . Tranexamic acid has been used in haemophilia patients and was administered to reduce intra- and postoperative bleeding.
It has been reported that a factor VIIIc bolus of 50 IU kg−1 usually achieves a blood level of 100%. We combined this standard bolus with a continuous infusion at 3 IU kg−1 h−1 aiming at a factor VIIIc level above 50% during surgery and for the first 4 postoperative days . This proved not to be sufficient and a second bolus of 33 IU kg−1 was needed at the end of bypass. This can be explained by haemodilution during bypass and possible consumptive coagulopathy. Moreover, cell-saver blood has a very low concentration of coagulation factors ; we have previously found a concentration of 3% of factor VIIIc in blood reinfused after cell-saver processing in a non-haemophilic patient.
In conclusion, complex heart surgery is feasible in patients with haemophilia A. A bolus dose of 50 IU kg−1 of factor VIIIc, followed by a continuous infusion of 3 IU kg−1 h−1 was not sufficient during CPB combined with a cell-saver device. A second, half-dose bolus compensated for the defect and stopped the bleeding. Continuous infusions can be stopped after chest drain removal. More experience is needed in order to standardize factor VIIIc infusion protocols during complex cardiac surgery in haemophilic patients.
D. De Bels
E. Van der Vorst
Department of Anaesthesiology; Clinique Générale St Jean; Brussels, Belgium
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