Inflammation-triggered thrombotic thrombocytopenic purpura: A case series highlighting diagnostic pitfalls and atypical presentations Free

Background

Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy marked by thrombocytopenia, microangiopathic hemolytic anemia (MAHA), neurologic symptoms, renal dysfunction, and fever. While idiopathic in most cases, systemic inflammatory states may trigger secondary TTP through endothelial injury and cytokine-mediated ADAMTS13 inhibition. We present two rare cases of TTP triggered by acute inflammatory conditions—cholecystitis and pancreatitis—with diagnostic challenges and atypical presentations.Methods/Case Summaries

Case 1:

A 74-year-old male with type 2 diabetes and cholelithiasis presented with right-sided chest pain. Initial labs showed Hb 13.5 g/dL, platelets 106 × 10⁹/L, and troponin 430 ng/L. Over the next few days, he developed progressive thrombocytopenia (nadir 22 × 10⁹/L), fever, acute kidney injury, and altered mentation. Peripheral smear revealed schistocytes. ADAMTS13 activity was within normal range. TTP was diagnosed clinically and treated with IV methylprednisolone and plasmapheresis, leading to full hematologic recovery.

Case 2:

A 38-year-old male with alcohol use disorder presented with acute pancreatitis following abdominal trauma. On day 2, thrombocytopenia (73 × 10³/µL) and rising bilirubin developed. By day 3, platelets dropped to 21 × 10³/µL, Hb to 11.9 g/dL, and LDH exceeded 15,000 U/L. Peripheral smear confirmed schistocytes. Coombs test was negative. TTP was diagnosed and treated with IV steroids and 7 sessions of plasmapheresis, resulting in platelet normalization (268 × 10³/µL) and resolution of hemolysis and organ dysfunction.Discussion

These cases illustrate the diagnostic difficulty of inflammation-triggered TTP. Neither patient initially met the classical diagnostic criteria of ADAMTS13 <10%, but both had clinical features consistent with TTP and showed rapid improvement with plasmapheresis. Acute pancreatitis and cholecystitis likely contributed to transient endothelial dysfunction and cytokine-driven vWF dysregulation. These findings underscore the importance of maintaining clinical vigilance and acting promptly despite incomplete laboratory confirmation.Conclusion

TTP should be considered in patients with acute inflammatory conditions who develop thrombocytopenia and MAHA, even in the absence of severely reduced ADAMTS13 levels. Early recognition and treatment can be lifesaving. These cases support the notion that inflammation alone can precipitate clinically significant TTP-like syndromes and challenge the over-reliance on ADAMTS13 for diagnosis.