Superimposed Hypercoagulable and Hypocoagulable States: Elevated Von Willebrand Factor (vWF) Levels Secondary to Polycystic Ovary Syndrome Masking Von Willebrand Disease

Von Willebrand Disease (vWD) is the most common inherited bleeding diathesis and can present with easy bruising, cutaneous bleeding, prolonged bleeding from mucosal surfaces after surgical procedures, and menorrhagia. However, laboratory confirmation of vWD can be challenging, as vWF and Factor VIII are acute-phase reactants, and levels will be elevated in inflammation, stress, physical activity, estrogen therapy, and hyperthyroidism.

Polycystic Ovary Syndrome (PCOS) induces a state of both chronic inflammation and hyperestrogenism. PCOS is further characterized by a prothrombotic state, with elevated circulating levels of vWF, fibrinogen, and PAI-1. The precise origin of PCOS-induced hypercoagulability is yet to be elucidated but is most likely multifactorial, with insulin resistance, hyperestrogenism, hyperandrogenism, LH excess, age, and BMI imparting varying degrees of influence and synergism.

We present a case of a morbidly obese 23 year-old female with PCOS presenting with menorrhagia. She has a history of prolonged bleeding after surgical procedures and was self-referred due to concern for bleeding risk during an upcoming dental extraction. Laboratory evaluation revealed she was blood group A positive with a normal PT and aPTT. Evaluation for vWD was within normal limits, with vWF antigen of 84% (55-200%), vWF activity of 68% (55-200%), Factor VIII activity assay of 75% (55-200%), and normal vWF multimers. Factor IX assay was significantly elevated at 218% (60-150%). Thromboelastography (TEG) showed elevated MA and G, consistent with platelet hypercoagulability and increased clot strength.

Subsequent review of remote external records determined that the patient had a previous evaluation for a bleeding disorder at age three following prolonged bleeding after tonsillectomy. At that time, she had a prolonged aPTT of 36.1 sec (21.0-31.0 sec) that corrected after mixing study to 29.9 sec. vWF antigen and ristocetin cofactor levels were both low. Factors VIII, IX, XI, and XII were within normal limits. The patient was diagnosed with type I von Willebrand disease at that time.

PCOS is a hypercoagulable state associated with hyperestrogenism and elevated vWF levels, which may lead to a false negative workup for vWD. In this case, a patient with PCOS and a remote diagnosis of type I vWD had elevation of vWF levels into the normal range on current laboratory studies. The patient's current laboratory studies are consistent with a hypercoagulable state with an elevated Factor IX level and do not reflect the underlying bleeding diathesis. Management of such patients with coexisting hypercoagulable and hypocoagulable states, particularly perioperatively, may be complex.