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A 29-year-old female (G1P1) is readmitted two weeks post–vaginal delivery due to increased vaginal bleeding. She reports that the bleeding began on the tenth day after delivery and has increased in severity each subsequent day. The delivery was uncomplicated with minimal blood loss and the patient did not receive any epidural anesthesia. She has taken 200 mg of ibuprofen daily since delivery. The patient reports a medical history of iron deficient anemia due to menorrhagia. She is adopted and does not know her family history.

Since admission, the patient has received three units of blood. The obstetrics team has ruled out retained placental tissue and uterine atony as the cause of bleeding. Her laboratory values are as follows:

What hematologic disease is most likely contributing to her bleeding?

1. NSAID-induced platelet dysfunction
2. Acquired factor VIII inhibitor
3. von Willebrand disease
4. Disseminated intravascular coagulation
5. Microangiopathy hemolytic anemia

Answer

3. von Willebrand disease

Explanation

This patient is presenting with secondary postpartum hemorrhage with a clinical and laboratory history suggestive of von Willebrand disease (vWD). Overall, there is a 20 percent risk of peripartum bleeding with vWD, and 75 percent of women with moderate to severe vWD can experience severe bleeding. Bleeding can be seen from any type of vWD. For women with mild forms of vWD, the peripartum period can be the first manifestation of the disease.¹ Furthermore, since peripartum bleeding unrelated to a bleeding disorder is common, the diagnosis of an underlying bleeding diathesis may not be considered.

During pregnancy both factor VIII and von Willebrand factor (vWF) levels increase, with peaks at 29 to 32 weeks gestation and at 35 weeks gestation, respectively.² Following delivery, vWF levels may fall precipitously within the first few weeks resulting in delayed uterine bleeding.³ Management of women with known vWD includes monitoring vWF levels during pregnancy and for three to four weeks post-partum to ensure return to baseline. Prophylaxis and treatment of vWD during pregnancy is based upon the severity of disease and specific type of vWD.

Acquired factor VIII inhibitors are a rare but serious cause of secondary postpartum hemorrhage.⁴ The activated partial thromboplastin time (aPTT) is typically significantly prolonged if there is a factor VIII inhibitor. Disseminated intravascular coagulation is an important cause of post-partum hemorrhage. Significant prolongations of the aPTT and PT as well as low fibrinogen levels are necessary to make the diagnosis. Microangiopathic hemolytic anemia may occur in the peripartum period and is associated with low hemoglobin and platelets. However, this diagnosis results in manifestations of microvascular thrombosis rather than hemorrhage.

Case study submitted by James N. Cooper, MD, of the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.

1. Ragni MV, Bontemp FA, Hassett AC. . Haemophilia. 1999; 5:313-317
2. Sié P, Caron C, Azam J, et el. . Br J Haematol. 2003; 121:897-903.
3. Kujovich JL. . J Thromb Haemost. 2005; 3:246-253.
4. Paidas MJ, Hossain N. . Am J Perinatol. 2014 31:645-654