Malignancy-associated Thrombotic Thrombocytopenic Purpura: A Case of Diagnostic Challenges and Therapeutic Strategies

Document Type

Conference Proceeding

Publication Date

5-1-2025

Publication Title

Am J Respir Crit Care Med

Keywords

bilirubin, creatinine, haptoglobin, hemoglobin, lactate dehydrogenase, von Willebrand factor cleaving proteinase, acquired thrombotic thrombocytopenic purpura, adult, anemia, anorexia, bone scintiscanning, case report, clinical article, conference abstract, diagnosis, drug therapy, dyspnea, fatigue, female, heart arrest, hemolytic anemia, high anion gap metabolic acidosis, human, intubation, kidney failure, kidney function, metamyelocyte, metastatic breast cancer, monocyte, muscle weakness, myelofibrosis, oral drug administration, physical examination, plasmapheresis, remission, respiratory acidosis, respiratory failure, tachycardia, therapy, thrombocytopenia, thrombotic thrombocytopenic purpura

Abstract

Introduction: Thrombotic Thrombocytopenic Purpura (TTP) is a rare life-threatening condition that is imperative to recognize early as the estimated mortality is 10 - 20% despite therapy. Here we describe a 47-year-old female with metastatic breast cancer who acquired TTP. Case: A 47-yearold woman with angioinvasive ductal carcinoma diagnosed three weeks prior presented with rapidly progressive weakness, fatigue, tachycardia, dyspnea, and anorexia. Her physical exam was unremarkable except for lethargic appearance. She had thrombocytopenia with 22,000 platelets and hemoglobin of 12.9 g/dL; nucleated red blood cells, atypical lymphocytes, metamyelocytes, myelocytes, basophils, and monocytes were elevated. She had a high anion gap metabolic acidosis with elevated creatinine, increased LDH and bilirubin, and low haptoglobin levels. Peripheral smear reduced suspicion of TTP due to few scattered schistocytes. Worsening thrombocytopenia was accompanied by worsening metabolic and respiratory acidosis, anemia, and further deterioration in renal function. Plasmapheresis was initiated following identification of high-density schistocytes on peripheral smear, suggestive of TTP. Despite this, she rapidly deteriorated with subsequent respiratory failure, intubation, and cardiac arrest. Postmortem ADAMTS13 level was 40.7%, suggestive of acquired TTP. Discussion: In cancer patients there are two primary etiologies of TTP: 1) chemotherapy, 2) malignancy itself. In the case of malignancy driven TTP, it is suspected that bone marrow invasion and secondary myelofibrosis play crucial roles. In the presented case, labs suggested bone marrow invasion, and nuclear medicine bone scan showed increased radiotracer uptake in the proximal humeri, distal femora, right sacrum, and proximal left tibia. Hemolytic anemia, renal failure, thrombocytopenia, and schistocytes on peripheral smear raised concern for TTP.Plasmapheresis remains the cornerstone of therapy for TTP. Despite intervention the mortality for cancer patients who develop TTP remains high. One study reports 75% mortality for cancer patients treated with plasmapheresis without chemotherapy due to high rates of TTP recurrence; average survival was 1 month. One patient had remission of TTP and survived 31 months when chemotherapy and plasmapheresis were combined.TTP remains diagnostically challenging due to ADAMTS13 levels requiring several days to result. It requires high clinical suspicion due to high mortality despite therapy. The PLASMIC score and peripheral smear can assist with risk stratification. However, several cases report TTP despite absence of schistocytes, while others report presence of schistocytes without TTP. Therefore, the full clinical picture is imperative when evaluating patients for TTP, particularly in cancer patients where symptoms of metastatic disease and TTP may overlap.

Volume

211

Issue

Supplement 1

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