A 32-year-old Caucasian woman experiences three episodes of deep venous thrombosis in a six year period. She has a history of pulmonary embolism as well. The patient's partial thromboplastin time (PTT) is within normal limits, and remains unchanged when activated protein C is added to her plasma. The most likely cause of this patient's problem is:

Question

A 32-year-old Caucasian woman experiences three episodes of deep venous thrombosis in a six year period.  She has a history of pulmonary embolism as well.  The patient's partial thromboplastin time (PTT) is within normal limits, and remains unchanged when activated protein C is added to her plasma.  The most likely cause of this patient's problem is:

Quizplus · Accepted Answer

This is a young patient with recurrent deep venous thromboses, features indicative of a hypercoagulable state. Inherited causes of hypercoagulability must be considered in all patients under age 50 who present with thromboses in the absence of any obvious explanation for an acquired prothrombotic state. The patient's plasma is resistant to the normally antithrombotic effects of activated protein C. Thus, the most likely diagnosis is a mutation in the factor V gene, which renders factor Va resistant to inactivation by activated protein C. Approximately 2-15% of Caucasians carry a specific factor V mutation, the Leiden mutation. The factor V Leiden mutation and mutations in the prothrombin gene are the most common inherited causes of hypercoagulability. Activated protein C resistance (factor V Leiden mutation) is detected in approximately 20% (range 12-40%) of patients with abnormal venous thromboses. (Choice A) Antiphospholipid antibody syndrome is a common immune cause of hypercoagulability. This condition is defined by the presence of antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies) plus one or more of the following: venous thromboembolism, arterial thromboembolism, or frequent fetal loss. Unlike the patient in the vignette, patients with antiphospholipid antibody syndrome typically have a prolonged baseline aPTT. Lupus anticoagulants are the most common cause of aPTT prolongation. (Choice B) Folic acid deficiency can cause hyperhomocysteinemia, which is a prothrombotic state. However, activated protein C resistance is not seen with this condition. (Choice D) Endovascular infections and/or systemic inflammatory states may affect vascular endothelial cells in a way that favors thrombosis. However, infection and inflammatory mediators do not directly promote activated protein C resistance in the aPTT coagulation test. (Choice E) A paraneoplastic syndrome of hypercoagulability may be seen in some patients with cancer, especially patients with adenocarcinomas of the pancreas, colon, or lung. The mechanism of cancer-induced hypercoagulability is thought to involve release of procoagulant tumor products. Vascular stasis due to obstruction of blood flow by the tumor, patient immobility, hepatic involvement and dysfunction, sepsis, and advanced age may also contribute to the tendency toward thrombosis in cancer patients. None of these mechanisms/factors directly promotes activated protein C resistance in the aPTT coagulation test. Educational Objective: Inherited causes of hypercoagulability should be considered in patients younger than age 50 who present with thrombosis and no obvious explanation for an acquired prothrombotic state. The factor V Leiden mutation, which causes factor Va resistance to inactivation by activated protein C, may account for approximately 20% of cases of atypical venous thrombosis.

A 32-Year-Old Caucasian Woman Experiences Three Episodes of Deep Venous