A 77-Year-Old Man with a Prolonged Activated Partial Thromboplastin Time

A 77-year-old man was admitted to another hospital because of increasing dyspnea and edema of the lower limbs. The patient reported a loss of appetite and a flu-like illness 4 weeks previously. He was on various medications for heart failure, including metoprolol, ramipril, spironolactone, torasemide, metformin, and digoxin. For chronic atrial fibrillation, the patient had received dabigatran (75 mg twice per day) for 12 months; dabigatran is a direct thrombin inhibitor that has recently been cleared by the US Food and Drug Administration for the prevention of stroke in patients with atrial fibrillation.Five days before admission, the patient discontinued dabigatran on his own after recognizing a fresh hematoma on the right hip, easy bruising, and a conjunctival hemorrhage of the right eye. Routine laboratory investigations on admission revealed a prolonged activated partial thromboplastin time (aPTT)3 of 69 s (reference interval, 25–35 s) and a slightly prolonged prothrombin time (PT). Initially, these laboratory findings and the ecchymosis were attributed to the previous anticoagulant intake.The patient's other symptoms were felt to be due to exacerbation of congestive heart failure, and these symptoms resolved with optimization of his diuretic therapy. He developed fresh hematomas, however. Because the aPTT remained prolonged 2 days after admission (a total of 7 days after the last dabigatran intake), clotting factor activities were quantified. Clotting factor VIII activity was below the detection limit (<5 IU/dL; reference interval, 70–150 IU/dL), and the activity of factor XII was slightly reduced (53 IU/dL, reference interval, 70–150 IU/dL). Subsequently, the patient was referred to our clinic for further evaluation. QUESTIONS TO CONSIDER1. Which differential diagnoses should be considered when aPTT prolongation is detected?2. To what extent do new anticoagulants, such as direct thrombin inhibitors, affect standard coagulation tests?3. What techniques should be used to evaluate the cause of a prolonged aPTT?On …