Surgeryand Invasive Procedure With Bypassing Agents In Hemophilic Patients With Inhibitors: A Single Center Experience

Inhibitory antibodies to factor VIII (FVIII) or factor IX (FIX) are one of the most important complications of managing patients with hemophilia A and B. For hemophiliacs with inhibitors, recent advances in the use of bypassing agents such as recombinant activated FVII (rFVIIa, NovoSeven^®) and Factor VIII Inhibitor Bypassing Activity (FEIBA^®) have enabled them to aggressively manage their diseases in emergency or elective surgery. This report shows an updated evaluation of the safety and effectiveness of bypassing agents in the treatment of peri-operative bleeding in this patient population.

We reviewed the cases of patients with hemophilia and inhibitors underwent surgery or other invasive procedures between May 2008 and July 2013 using bypassing agents or high dose FVIII concentrates at a single center. Thirty two procedures (23 orthopedic surgeries and 9 other surgeries and procedures) were conducted in 16 hemophilia patients with inhibitors. The median age of the patients was 30.5 years old (range, 7-52). Most patients (14/16, 87.5%) are hemophilia A and 2 patients (12.5%) were hemophilia B. The median titer of inhibitors at procedures was 15 BU (range, 0.7-1900). Patients with low responding inhibitors were 2 cases, and high dose factor VIII concentrates were used. Most patients had high responding inhibitors and one of two bypassing agents was used. Twenty one cases were covered using FEIBA^®, nine with rFVIIa initially. The median duration of hospitalization was 14 days (range, 1-58). In most cases, bleeding stopped or controlled well. But, in 5 cases, patients’ bleeding was controlled by sequential bypassing therapy. 4 cases were performed at emergency conditions, and those are segmental resection of small bowel, craniectomy with intracerebral hematoma removal, exploratory thoracotomy, and angiography with embolization. Efficacy of bypassing agents at various surgeries and procedures, based on final patient outcome, was 93.8% (30/32). Two deaths occurred at emergency condition as a result of hypovolemic shock secondary to intracranial hemorrhage or retroperitoneal bleeding.

Good control of hemostasis can be achieved with bypassing agents in hemophilia patients with inhibitors undergoing invasive procedures. If surgery or procedure would perform at emergency condition, more active and aggressive management should be needed. The use of bypassing agents in peri-operative period can allow invasive procedure and surgery to be safe and successful in hemophilic patients with inhibitors.