Review Question - QID 108426

The most likely diagnosis for this patient is von Willebrand disease, which is caused by deficient or defective von Willebrand factor (vWF). Since vWF is also responsible for protecting factor VIII from degradation, this patient would also likely have decreased levels of factor VIII, which contributes to this patient's bleeding diathesis.

Hematomas obtained after minor trauma and a history of bruising and bleeding establish that this question is dealing with a bleeding disorder. Bleeding disorders can be divided into platelet disorders, coagulation cascade disorders, and mixed disorders. Notice that this patient has aspects of both mucosal bleeding characteristic of platelet disorders (epistaxis) as well as deep bleeding characteristic of coagulation disorders (bruising/hematoma) suggesting a mixed disorder. This suspicion is confirmed by the increased bleeding time (a platelet assay) and the elevated PTT with a normal PT (suggests an isolated defect in the intrinsic coagulation cascade). On Step 1 this combination of findings is nearly pathognomonic of von Willebrand disease, a diagnosis that is supported by the administration of desmopressin and an injunction against aspirin. The platelet assay abnormalities result from low levels of vWF, which normally functions to promote platelet adhesion through binding GP1b. As ristocetin depends on vWF to function, this defect explains why the ristocetin cofactor assay is abnormal in this patient. The coagulation defects result because vWF normally stabilizes circulating factor VIII thus decreased vWF leads to decreased levels of factor VIII.

Incorrect Answers:
Answer 1: A decreased platelet count is found in many disorders with mucosal and petechial bleeding. Examples include idiopathic thrombocytopenic purpura and heparin-induced thrombocytopenia. These disorders, however, would present with isolated defects in platelet labs such as bleeding time and ristocetin cofactor assays without affecting coagulation labs such as PT and PTT. The platelet count is normal in von Willeband disease.

Answer 3: Decreased levels of factor IX would be found in hemophilia B. This disorder would present with deep bleeding as well as an increased PTT but would not affect platelet function assays. In addition, the treatment for hemophilia is administration of the missing factor, which is not seen in this case.

Answer 4: Abnormal activity of ADAMTS13 is characteristic of thrombotic thrombocytopenic purpura (TTP). Since ADAMTS13 is responsible for cleavage of vWF multimers, a defect in this function leads to formation of platelet adhesions in microthrombi. The classic presentation is fever, hemolytic anemia, thrombocytopenia, renal dysfunction, and neurologic abnormalities. Schistocytes are seen in peripheral blood smears. Technically, in this patient, ADAMTS13 activity would be decreased since there would be less vWF to act upon, but this does not contribute to the underlying disease process as this question asks.

Answer 5: Decreased plasma fibrinogen is found in acute disseminated intravascular coagulation (DIC). DIC has many etiologies but they all lead to the formation of intravascular thrombi and associated generalized bleeding due to consumption of coagulation markers. DIC's features include increased PT, increased PTT, increased bleeding time, and decreased number of platelets.

Bullet Summary:
Von Willebrand disease is the only disorder tested on Step 1 with an isolated increase in PTT associated with an increased bleeding time. The increased PTT is due to destabilization of factor VIII in this disorder because factor VIII is usually carried by vWF in circulation.