Use of Recombinant Factor VIIa (rVIIa) for Treatment of Bleeding in Type II B Von Willebrand Disease: A Case Report

Background: Von Willebrand disease (vWD) is an inherited bleeding disorder caused by a deficiency or dysfunction of von Willebrand’s factor (VWF). Type 2 vWD is a qualitative deficiency of VWF with the IIB variant being caused by a “gain of function” mutation that results in increased affinity of the vWF for platelet GPIb. Treatment of choice for bleeding episodes is factor VIII-VWF concentrate or DDAVP in selected cases. We are reporting a case of type IIB vWD where rVIIa was used successfully for hemostasis.

Case report: A 28 year old white female with type IIB vWD had being doing well with Humate-P® which she used most frequently for menorrhagia. She had also been treated successfully with Humate-P® for peri-operative hemostasis during back surgery but approximately 3 years after this developed anaphylactic reaction while getting humate-P for an episode of severe menorrhagia. A test dose of a different lot of Humate-P® in the hospital also resulted in a severe reaction. Administration of Koâte®-DVI and Alphanate® was subsequently attempted but caused similar anaphylactic reactions after the first few doses. She had normal IgA levels. Amicar and hormonal therapy was used to control the menorrhagia to where she was able to maintain a relatively stable Hgb level and not require frequent PRBC transfusion. Unfortunately, a few months later the patient developed GI bleeding from what was initially an occult source and ended up needing upwards of 40 units of PRBC transfusion over a period of two months. She was offered options of trying cryoprecipitate as well as DDAVP but refused after weighing the risks and benefits. At this time, rVIIa was given and the bleeding appeared to slow down resulting in lesser frequency of transfusion but it did not entirely stop. After several unsuccessful attempts to locate the source, a tagged RBC study finally found the bleed originating near the cecal area which eventually turned out to be a malignant ileocecal carcinoid that had been missed on initial colonoscopy as well as on capsule camera endoscopy. There was no clincally overt carcinoid syndrome. Patient underwent a right hemicolectomy and received rVIIa perioperatively according to the protocol approved for patients with hemophilia with factor inhibitor. She received NovoSeven® 90 mcg/kg before the surgery and then q2h for the first 24 hours. She had rVIIa q3h on post-op day one. The dose frequency was dropped to q4h on day 2 followed by q6h on post-op days 3 to 7. This provided excellent perioperative hemostasis. She has done well with no further GI bleed or recurrence of the tumor after more than a year and her menorrhagia is fairly well controlled with hormonal therapy and amicar.

Discussion: Factor VII, a vitamin K-dependent glycoprotein, promotes hemostasis by activating the extrinsic pathway of the coagulation cascade. Although it does not affect the vWF level it probably bypasses the deficiency via thrombin generation on platelet surface. In literature search we found two case reports regarding utilizing rFVII in vWD, both with uncontrolled bleeding despite adequate factor replacement. First case with acquired vWD and GI bleed and the second case was inherited vWD with GI angiodysplasia. The precise mechanism of action in this setting however is not fully understood.

Conclusion: To our knowledge this is the first report of utilizing rVIIa in a patient intolerant to vWF without inhibitors to vWF. rVIIa should be considered a viable option for hemostasis in patients unable to tolerate vWF due to severe allergy.