(P-HC-3) A Case of Immune-mediated Thrombotic Thrombocytopenic Purpura with Atypical Clinical Presentation and Low PLASMIC Score due to Non-neutralizing Anti-ADAMTS13 Autoantibodies

Background/Case Studies: Thrombotic thrombocytopenic purpura (TTP) is a life-threatening microvascular thrombotic condition due to ADAMST13 (AT13) deficiency. As AT13 activity is often not readily available, TTP diagnosis heavily relied on presence of the classic pentad/tirade and more recently the PLASMIC score (PS). We hereby describe a case of immune mediated TTP (iTTP) with an atypical clinical presentation including a low PS.

Study

Design/Methods: A 41 year old G1P1 female presented to the emergency department with 2 weeks of fatigue and headaches. She has a remote history of treated hyperparathyroidism and papillary thyroid carcinoma, and non-insulin dependent diabetes mellitus and started taking semaglutide 2 weeks prior. She was found to be anemic (11.6g/dL) and thrombocytopenic (73K/uL) with a mildly elevated LDH (322U/L N: 87-225). Peripheral blood smear did not demonstrate increased schistocytes. Head CT scan however identified multiple small foci of acute ischemia. PS at presentation was 4 (0% likelihood) strongly against diagnosis of TTP. Unexpectedly, locally performed AT13 activity was undetectable. Therefore, daily therapeutic plasma exchange (TPE) was initiated in combination with high dose corticosteroids.

Results/Findings: Subsequent AT13 neutralizing inhibitor workup was negative but additional testing was positive for non-neutralizing autoantibody (NNAA) at 13U/mL (< =11) confirming iTTP. The patient required a total of 6 daily TPE resulting in a stabilized platelet count at 207K/uL and AT13 activity at 44%. The patient was discharged home on corticosteroid.

Conclusions: This abstract describes a case of iTTP caused by NNAA. Patient’s atypical clinical presentation with mild symptoms and low PS may suggest a pathophysiology of gradual depletion of AT13 enzymes vs. the typical acute and rapid AT13 activity neutralization. This case illustrates both the limitations of PLASMIC score as the primary diagnostic tool and the laboratory challenges of identifying a NNAA.