Abstract
Abstract Background:
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening autoimmune disorder characterized by thrombocytopenia, microangiopathic hemolytic anemia, neurological deficits, sometimes accompanied by fever, and renal impairment. While classic diagnostic criteria emphasize hemolysis, emerging evidence suggests that TTP can present atypically, particularly in the context of cerebrovascular events and without overt laboratory evidence of hemolysis.
Case Description: Case 1 At the University of Maryland Medical Center, we recently encountered a 63-year-old Black female with a history of multiple cerebrovascular accidents (CVAs) and previously diagnosed Immune thrombocytopenia with platelets of 101 x 10^9/L who presented with left-sided weakness and numbness. Initial labs revealed a hemoglobin level of 9.5 g/dl and platelet count: 32 × 10^9/L, without significant hemolysis (reticulocyte count, indirect bilirubin, and haptoglobin levels were all within normal limits). ADAMTS13 activity was <5%, confirming a diagnosis of TTP. The patient was initiated on therapeutic plasma exchange and received steroids, caplacizumab and rituximab, resulting in partial improvement of her neurological symptoms and normalization of ADAMTS13 activity.
Case 2 A 67-year-old Black female with a past medical history of three prior CVAs and possible antiphospholipid syndrome presented with right-sided weakness, slurred speech, and left gaze deviation. Lab work revealed a hemoglobin of 10 g/dl, platelets of 91 x 10^9/L, haptoglobin of 70mg/dl, and total bilirubin of 0.3mg/dl. Reticulocyte count was 2.0%. All were within or near normal ranges, suggestting an absence of hemolysis. CT imaging showed occlusion of the left MCA and MRI showed multiple acute embolic infarcts in the bilateral frontal and temporal lobes as well as the left occipital lobe. Records from her prior admission to another hospital 8 months earlier show that she presented with aphasia, and had a platelet count of 76 x 10^9/L. An ADAMTS13 level sent later in the admission was 20, but she was not treated for TTP.
Retrospective Review: A retrospective review was conducted at the University of Maryland Medical Center, encompassing 126 patients with suspected thrombotic thrombocytopenic purpura (TTP) and documented ADAMTS13 activity levels <20% from the year 2000 to the present. Among these cases, only two patients—those described in this report—presented without laboratory evidence of hemolysis, with the exception of a patient who was noted to have thrombocytopenia in a routine follow up visit. Both individuals were Black females who exhibited acute neurological symptoms consistent with cerebrovascular events. Laboratory evaluations in both cases revealed thrombocytopenia in the presence of normal haptoglobin and bilirubin levels, indicating an absence of microangiopathic hemolytic anemia. Both patients were treated with therapeutic plasma exchange and corticosteroids with clinical improvement. In addition, the index patient received rituximab and caplacizumab. .
Conclusion: This case series underscores a diagnostically challenging subset of TTP in which patients present with acute neurological deficits and thrombocytopenia, but without laboratory evidence of hemolysis. These atypical presentations may delay diagnosis and management. Clinicians should maintain a high index of suspicion for TTP in similar clinical scenarios. Early measurement of ADAMTS13 activity is essential and should be considered in the initial diagnostic evaluation of patients presenting with unexplained thrombocytopenia and neurological symptoms, regardless of hemolytic marker status, to facilitate prompt initiation of life-saving therapies.
