Review Question - QID 103353

A patient presenting with menorrhagia with a family history of such and labs significant for prolonged PTT with normal PT is likely suffering from von Willebrand's disease.

Von Willebrand's disease (vWD) is the most common inherited bleeding disorder and is inherited in an autosomal dominant fashion. This coagulopathic disease results from a quantitative or qualitative defect in von Willebrand's factor (vWF), which is required for platelet aggregation. Factor VIII is also released with vWF and therefore a defect in vWF typically results in a normal PT and INR with a prolonged PTT. It is most commonly treated with desmopressin (which stimulates secretion of vWF from the endothelial cells). In urgent or refractory situations, it can also be treated with cryoprecipitate administration.

Ballas et al. discuss the diagnosis of bleeding disorders. For vWD, they state that the PTT is not always prolonged and at times, may be normal. For this reason, they first recommend a mixing study to determine whether the PTT prolongation corrects. If this is negative or if the PTT is normal, they recommend first testing levels of vWF and Factor VIII. Lastly, if these are also negative and there is still high suspicion, they recommend using a ristocetin cofactor assay (the gold standard) to confirm the diagnosis.

Kujovich et al. report on the prevalence of menorrhagia with vWD. They state that 60-95% of women with vWD present with menorrhagia as a chief complaint. Similarly, they report that 5-20% of the women suffering from menorrhagia have vWD. Lastly, a recent survey showed that while 91% of hematologists were able identify menorrhagia as an indicator of vWD, only 4% of gynecologists were able to do so.

Illustration A shows the coagulation cascade.

Incorrect Answers:

Answer 1: Factor V leiden predisposes people to hypercoagulability and present with normal PT, PTT and INR.
Answer 2 and 3: Hemophilia A and Hemophilia B affect coagulation factors 8 and 9, respectively. They results in a prolonged PTT without change in PT, but this is unlikely in this patient because they are inherited in a X-linked recessive fashion and without a history in her father, the patient would not exhibit signs of hemophilia as a female.
Answer 5: Antiphospholipid antibody syndrome can occur with or without symptoms of lupus erythematous and can lead to the coagulation study findings as noted in this question, or with even more prolonged PT/INR. She does exhibit any symptoms of lupus and denies previous medical history making this diagnosis less likely.