An Audit of Thrombophilia Testing in Patients with Ischemic Stroke or Transient Ischemic Attack: The Futility of Testing.

OBJECTIVES: Many patients admitted with an ischemic stroke or transient ischemic attack (TIA) undergo thrombophilia testing. There is limited evidence to support this practice. We examined the effect of thrombophilia testing on management of patients admitted with an ischemic stroke or TIA. MATERIALS AND METHODS: In this retrospective observational single-center study, we identified patients who were admitted with stroke or TIA and underwent thrombophilia testing over a 45-month period. We reviewed their electronic medical records to assess whether testing affected clinical management, defined as anticoagulation treatment by the time of discharge due to a positive test result. Secondary endpoints included potential misdiagnosis due to false positive results and cost of testing. RESULTS: Testing was performed in 143 patients with a stroke or TIA. Forty-four patients (31%) had at least 1 positive test result. The most common positive tests were an elevated factor VIII activity (18% of patients tested) and decreased protein S activity (11% of patients tested). Both of these tests are subject to acute phase effects. Testing altered clinical management in only 1 patient (1% of total patients tested). Thirty-three patients (75%) have the potential for carrying a misdiagnosis due to a positive test that was never repeated for confirmation or repeated too soon after the initial positive test. The annual cost of testing was approximately $62,000. CONCLUSIONS: Thrombophilia testing in the acute inpatient setting rarely impacted the clinical management of patients admitted with a stroke or TIA. By avoiding thrombophilia testing, both the potential for misdiagnosis and health care costs can be reduced. Therefore, we have discontinued thrombophilia testing in in-patients with a diagnosis of stroke.

A case of autoimmune severe acquired von Willebrand syndrome (type 3-like).

Von Willebrand disease (VWD) is the most common congenital bleeding disorder and is due to quantitative or qualitative defects of von Willebrand factor (VWF). Acquired defects of VWF, termed acquired von Willebrand syndrome (AVWS), are due to a host of different mechanisms. Autoantibody-mediated AVWS may be associated with lymphoproliferative or immunological disorders, such as systemic lupus erythematosus (SLE). A large majority of AVWS cases are type 1 or type 2A-like and patients tend to have a mild to moderate bleeding tendency. We report a case of severe autoimmune AVWS in a woman with SLE who presented with clinical and laboratory features of type 3 VWD (undetectable VWF antigen, ristocetin cofactor activity, and VWF multimers). A mixing study demonstrated an inhibitor to VWF (6BU/mL). Her bleeds were managed with antifibrinolytics, recombinant activated factor VII, and activated prothrombin complex concentrate. She was initially treated with steroids and intravenous immunoglobulin therapy. However, her bleeding symptoms continued until she was treated with rituximab, and her VWF parameters normalized. She relapsed two years later due to non-compliance with her immunosuppressive medications and expired another two years later secondary to complications of sepsis and uremic pericarditis. This case emphasizes the importance of aggressive initial therapy of SLE to reduce secondary complications, frequent patient monitoring, and continued treatment of the underlying autoimmune disorder in patients with AVWS.

Ischemic stroke in a patient with moderate to severe inherited factor VII deficiency.

Thrombosis is known to occur in patients with rare inherited bleeding disorders, usually in the presence of a thrombotic risk factor such as surgery and/or factor replacement therapy, but sometimes spontaneously. We present the case of a 72-year-old African American male diagnosed with congenital factor VII (FVII) deficiency after presenting with ischemic stroke, presumably embolic, in the setting of atherosclerotic carotid artery stenosis. The patient had an international normalized ratio (INR) of 2.0 at presentation, with FVII activity of 6% and normal Extem clotting time in rotational thromboelastometry. He was treated with aspirin (325 mg daily) and clopidogrel (75 mg daily) with no additional bleeding or thrombotic complications throughout his admission. This case provides further evidence that moderate to severe FVII deficiency does not protect against thrombosis.