Acquired Thrombotic Thrombocytopenic Purpura with a Poor Response to Treatment can be an Initial Manifestation of Occult Signet Ring Cell Carcinoma and other Malignancies.

Abstract

Introduction: Acquired thrombotic thrombocytopenic purpura (aTTP) is a severe microangiopathic hemolytic anemia (MAHA) characterized by profound ADAMTS13 deficiency. MAHA can also manifest as a paraneoplastic syndrome, particularly in advanced malignancies, with cancer-associated MAHA (CA-MAHA) linked to signet ring cell carcinoma being exceptionally rare.

Case description: We present the case of a 42-year-old Arab male who initially presented with classic features of aTTP, including severe MAHA, profound thrombocytopenia, and renal and neurological dysfunction, confirmed by an ADAMTS13 activity level of 6%. Despite standard TTP therapy including plasma exchange, his atypical response and rapid deterioration prompted further investigation, leading to the diagnosis of aggressive, metastatic signet ring cell carcinoma. Tragically, he passed away less than a week after first presentation.

Conclusion: This case underscores the critical importance of maintaining a high index of suspicion for occult malignancies in patients with atypical thrombotic microangiopathy presentations, especially those with an incomplete response to conventional TTP therapies. It emphasizes the need for comprehensive diagnostic workup and a multidisciplinary approach to manage these complex and often fatal conditions, as early identification of underlying cancer is crucial for guiding appropriate, often tumour-directed, therapy and improving patient outcomes.

Learning points: An atypical response to standard thrombotic thrombocytopenic purpura therapy warrants immediate investigation for alternate diagnoses.Underlying malignancy should be actively considered in patients presenting with thrombotic microangiopathy, particularly in cases with atypical features, poor response to standard therapy, or rapid clinical deterioration.