Managing gravidas with von Willebrand disease or factor XI deficiency

August 1, 2007

These patients have either a qualitative or quantitative deficiency of von Willebrand factor (VWF). Critical for primary hemostasis, VWF functions to bridge platelets to vascular subendothelium and to other platelets and to promote the formation of fibrin clots by serving as a carrier protein for factor VIII.

Von Willebrand disease (VWD)

These patients have either a qualitative or quantitative deficiency of von Willebrand factor (VWF). Critical for primary hemostasis, VWF functions to bridge platelets to vascular subendothelium and to other platelets and to promote the formation of fibrin clots by serving as a carrier protein for factor VIII.

Inherited VWD is classified into three types:

Although most patients with VWD lack symptoms, they may exhibit easy bruising and bleeding from the skin and mucosal surfaces. Women typically experience heavy menstrual bleeding and excessive postpartum bleeding. Surgical or dental procedures can bring on bleeding, as can drugs that inhibit platelet function, like aspirin or other nonsteroidal anti-inflammatory agents.

Most patients are type 1. Patients with type 1 VWD account for 70% to 80% of all von Willebrand patients. Their bleeding can be managed by administering desmopressin (DDAVP), an antidiuretic hormone analogue that rapidly increases plasma levels of VWF and factor VIII. (These levels increase within 30 to 60 minutes after IV administration and about 90 minutes after subcutaneous or intranasal administration of DDAVP.) The drug is often given prior to invasive procedures. Although for most patients, the effect of DDAVP on VWF and factor VIII levels allows dosing every 24 hours, some patients will require more frequent dosing.

Different approach for other types. Management of bleeding differs for patients with type 3 VWD and most patients with type 2. The usual approach for them is to give partially purified preparations of factor VIII that contains VWF. Humate P, for example, is a combined factor VIII and VWF concentrate that is treated to inactivate viruses. While fresh frozen plasma (FFP) can also be administered, this option is less practical, due to the large volumes required. Cryoprecipitate can also be used, although because it does not typically undergo viral inactivation, it's more likely to transmit viruses. Epsilon aminocaproic acid and platelets are sometimes given in addition to plasma concentrates and platelets.

Because VWF concentration roughly doubles during pregnancy, bleeding in pregnant patients with VWD is rare. However, hemorrhage can occur during delivery or postpartum. The incidence of primary and secondary postpartum hemorrhage in these patients is about 20%.1 Postpartum hemorrhage appears to be more frequent if factor VIII:c levels (factor VIII coagulant activity) are less than 40 IU/dL,2 so it's recommended that VWF and factor VIII levels be maintained at more than 50 IU/dL before delivery and for 3 to 5 days postpartum by administering either DDAVP or VWF concentrates.3 For cesarean, the factor VIII:c level should be maintained at more than 50 IU/dL.

Prenatal consult. Patients with VWD should consult with a hematologist prenatally to develop a management plan, considering that specialized laboratory tests are not typically available on a "stat" basis during labor. An anesthesiologist should also be consulted before labor begins to discuss options for regional analgesia and anesthesia. There are few data on the safety of regional analgesia and anesthesia in these patients. Epidural analgesia has been used in parturients with VWD,4,5 and regional anesthesia is not contraindicated if VWF and factor VIII levels are maintained at more than 50 IU/dL.3

Factor XI deficiency

An uncommon autosomal disorder, factor XI deficiency occurs chiefly in patients of Ashkenazi Jewish ancestry. Rarely, though, this coagulopathy can be acquired due to insufficient synthesis in patients with severe hepatic disease. The severity of bleeding in patients with factor XI deficiency varies with the type of insult. Echymoses and petechiae are uncommon. Laboratory studies reveal prolonged partial thromboplastin time (PTT) and normal prothrombin time (PT). A factor XI assay clinches the diagnosis.