Board Review

A 45-year-old woman is evaluated before surgery; she is scheduled to undergo elective hysterectomy for fibroid tumors. Her medical history is significant for type 1 von Willebrand disease (vWD), long-standing iron deficiency anemia, and heavy menstrual bleeding. Family history is notable for vWD in the patient's father, sister, and two sons. Her only medication is iron sulfate.

On physical examination, vital signs are normal. The patient has palpable lower abdominal masses along the midline consistent with fibroids.

Which of the following is the most appropriate perioperative treatment?

A) Cryoprecipitate

B) Fresh frozen plasma

C) Recombinant factor VIII

D) Tranexamic acid

E) von Willebrand factor–containing factor VIII concentrates

Answer: E - von Willebrand factor–containing factor VIII concentrates

Objective: Manage von Willebrand disease perioperatively.

Key Point

Patients with von Willebrand disease scheduled to undergo major surgery should be treated with factor VIII concentrates containing von Willebrand factor.

The most appropriate perioperative treatment for this patient is von Willebrand factor (vWF)–containing factor VIII concentrates. She has type 1 von Willebrand disease (vWD) and is scheduled for abdominal surgery. The best products to give are the vWF-containing factor VIII concentrates. These so-called “intermediate purity,” plasma-derived products have undergone viral inactivation (of viruses such as HIV and hepatitis B and C), and their use has not led to transmission of any serious illness. Desmopressin, which leads to release of vWF and factor VIII from endothelial cells and thus provides hemostasis, can be used for less invasive procedures. However, unless a trial of desmopressin shows a robust, sustained response, it should not be used for a major surgery.

Cryoprecipitate contains a concentrated source of factor VIII, vWF, factor XIII, fibronectin, and fibrinogen and is the treatment of choice in bleeding patients with hypofibrinogenemia from liver disease, thrombolytic therapy, or disseminated intravascular coagulation (DIC). Cryoprecipitate is not virally inactivated and is therefore not a first-line agent for this patient with vWD.

Fresh frozen plasma (FFP) contains all the blood clotting factors and is indicated for warfarin reversal in actively bleeding patients (alone or concomitantly with a 3-factor prothrombin complex concentrate), treatment of thrombotic thrombocytopenic purpura, dilutional coagulopathy during massive transfusion, and in bleeding patients with several factor deficiencies such as in DIC or liver disease. However, the concentration of vWF in FFP is too low to correct the patient's vWF levels without producing volume overload. Other risks include viral transmission, transfusion-related acute lung injury, and febrile, allergic, and anaphylactic reactions.

Recombinant factor VIII is used to treat patients with hemophilia A. Recombinant factor VIII is devoid of any vWF and would not improve hemostasis in this patient with vWD.

Antifibrinolytic agents such as ε-aminocaproic acid and tranexamic acid can be used in patients with mild vWD to prevent dissolution of the hemostatic plug, particularly those associated with mucocutaneous bleeding. Prolonged use of these agents is associated with the potential for thrombosis, especially in patients with an underlying thrombophilia. Used as a single agent, tranexamic acid is unlikely to provide sufficient hemostasis for a patient undergoing abdominal surgery.

Lillicrap D. von Willebrand disease: advances in pathogenetic understanding, diagnosis, and therapy. Hematology Am Soc Hematol Educ Program. 2013;2013:254-60. Link Out