Case Presentation: A 54-year-old female presented to the Emergency Department (ED) with acute onset right leg weakness. Her medical history included recurrent cryptogenic strokes, fibromuscular dysplasia (FMD) involving the bilateral internal carotid arteries (ICAs), thrombocytopenia presumed to be immune thrombocytopenic purpura, and heterozygous Factor V Leiden and prothrombin G20210A gene mutations. Initial physical exam revealed a broad-based, unsteady gait with normal strength in the bilateral upper and lower extremities. Labs were notable for new normocytic anemia (hemoglobin 11.4 g/dL), acute on chronic thrombocytopenia (platelets 49 ×10^9/L), and a stage I acute kidney injury. Peripheral smear showed thrombocytopenia with occasional large platelets and rare schistocytes. LDH was elevated (540 U/L), and haptoglobin was undetectable. Computed tomography angiography of the head and neck demonstrated stable FMD of the bilateral ICAs. MRI brain showed multifocal acute ischemic strokes involving the right cerebellum, left frontoparietal region, and right parietal lobe. Given embolic appearance of the infarcts, the patient underwent transesophageal echocardiogram, which demonstrated an 8×13 mm echodense mass on the mitral valve, possibly reflective of non-bacterial thrombotic endocarditis as serial blood cultures were negative. Although the mitral valve vegetation was initially thought the probable embolic source for her strokes, thrombotic microangiopathy was also considered. Her PLASMIC score (1) was 5, indicating intermediate risk of severe ADAMTS13 deficiency. ADAMTS13 activity was < 5% with presence of ADAMTS13 inhibitor (1.8 Bethesda Units), diagnostic of autoimmune thrombotic thrombocytopenic purpura (TTP). The patient underwent six sessions of therapeutic plasma exchange (PLEX) and subsequently received rituximab with complete resolution of her thrombocytopenia and improvement in ADAMTS13 activity to 65% two months after hospital discharge.
Discussion: Autoimmune TTP classically presents with a pentad of microangiopathic hemolysis, thrombocytopenia, neurologic symptoms, renal dysfunction, and fever. However, less than 7% of cases in the ED present with the full pentad (2), so a high index of suspicion must be maintained in all patients presenting with thrombocytopenia and evidence of MAHA. These patients should be risk-stratified with the PLASMIC Score, and PLEX should be emergently initiated for patients with a score ≥6. Although there may be alternative etiologies for ischemic stroke, as in our patient who had a mitral valve vegetation, FMD, and hereditary thrombophilia, it is imperative for hospitalists to consider autoimmune TTP in their differential to avoid missing this potentially fatal condition. For our patient, although she had worsening thrombocytopenia during previous strokes, it is unknown whether those infarcts are attributable to TTP as hemolysis work-up and ADAMTS13 activity assay were not performed at the time.
Conclusions: This unusual case of a patient with recurrent cryptogenic ischemic strokes who was found to have autoimmune TTP demonstrates the need for hospitalists to consider TTP as a differential diagnosis in patients presenting with acute neurologic deficits, thrombocytopenia, and evidence of microangiopathic hemolysis. These patients should be risk stratified with the PLASMIC score for possible emergent PLEX, even if another probable cause of their clinical presentation has been identified.