Pancreatitis Preceding Acute Episodes of Thrombotic Thrombocytopenic Purpura: Report of Five Patients with a Systematic Review of Published Reports.

Thrombotic thrombocytopenic purpura (TTP) is a syndrome with multiple recognized etiologies, associated conditions, and risk factors but the events that may precipitate acute episodes are unclear. Patients may have undetectable ADAMTS13 activity without evidence for TTP until a precipitating condition, such as pregnancy, infection, or surgery, occurs. These clinical observations are similar to experimental observations on transgenic mice with absent ADAMTS13 in which a TTP-like condition only occurred when an additional stimulus, Shiga toxin or collagen/thrombin, was administered. Also patients may have acute episodes of typical TTP without apparent ADAMTS13 deficiency. We report 5 patients (Table) who had the onset of an acute episode of TTP 1–13 days following the onset of pancreatitis. Three patients are from The Oklahoma TTP-HUS Registry, a series of 360 consecutive patients with TTP, 1/1/1989 – 6/30/2006. Two patients are from Northwestern University. In each patient there was an apparent etiology for the pancreatitis: bile duct obstruction in patients 1, 4 and 5 and alcoholism in patients 2 and 3. There was no evidence for TTP when the pancreatitis was diagnosed. In patients 1 and 2, the pancreatitis was clearly resolving when the TTP occurred. ADAMTS13 was measured in patients 2–5 and was severely deficient with a high-titer inhibitor in patients 3 and 5. Patient 5 had a recurrent episode of pancreatitis that was also followed by an acute episode of TTP.

A systematic review of published case reports identified 16 additional patients who had TTP following pancreatitis. Seven patients were alcoholic; 5 patients had gallbladder disease. Coagulation tests were reported in 12 patients and all were normal. Recurrent TTP following a recurrence of pancreatitis was reported in 3 of the 16 patients. Our 5 patients and the 16 previously reported patients all recovered from TTP.

CONCLUSION: Pancreatitis, a disorder that results in an intense systemic inflammatory response, may provoke acute episodes of TTP. Inflammatory cytokines may precipitate acute episodes of TTP by stimulating endothelial cell release of ultralarge von Willebrand factor multimers and inhibiting the cleavage of these multimers by ADAMTS13.