An Atypical Case of Thrombotic Microangiopathy Secondary to Acute Pancreatitis

Learning Objective 1: Recognize acute pancreatitis as a cause of secondary thrombotic microangiopathy

Case: An 18-year-old male with cerebral palsy, chronic colitis and leucine-sensitive hypoglycemia presented with one day of abdominal pain, vomiting and diarrhea. On exam, he was tachycardic, hypertensive and had diffuse abdominal tenderness and periorbital edema. Initial work up revealed WBC 14.9 K/uL, platelets 446 K/uL and hemoglobin 17.7g/dL consistent with hemoconcentration in the setting of hypovolemia. Initial chemistries were unremarkable with a creatinine of 0.71mg/dL, consistent with his baseline creatinine. Lipase was elevated to 349U/L and an abdominal CT with contrast demonstrated peripancreatic fluid. Clostridium difficile PCR testing of the stool was negative. The patient was admitted to the general pediatric floor and started on IV fluids for management of acute pancreatitis. On hospital day 2, the platelet count decreased to 93K/uL. Over the course of the next few days, the platelet count and hemoglobin continued to decrease. Peripheral blood smear showed evidence of hemolysis with schistocytes (not seen on initial blood smear), along with a low haptoglobin (68%) and plasmapheresis was not started. Meanwhile, his creatinine stabilized and began to downtrend, and his platelet count also improved. His hemoglobin stabilized around 7g/dL (after transfusion), his platelet count returned to normal limits, and his creatinine decreased to 1.2mg/dL. Ecluzimab treatment was not initiated given his clinical improvement. His proteinuria resolved. Further workup for atypical HUS was performed during the hospitalization. His C3 was initially low at 54mg/dL (RR 88-203mg/dL) and later improved to normal range by discharge. The CD46, factor I level, factor B level and factor H were relatively unremarkable. An atypical HUS genetic panel was equivocal. Over the course of the next year and a half, the patient was admitted on multiple occasions for treatment of acute pancreatitis and Clostridium difficile colitis without further episodes of thrombotic microangiopathy. His most recent urinalysis did not demonstrate proteinuria and his creatinine most recently was 0.63mg/dL.

Discussion: We present a patient with acute pancreatitis who later developed features of thrombotic microangiopathy (TMA). TMAs are defined by vessel wall injury of arterioles and capillaries causing microvascular thrombosis. These changes lead to the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia and end-organ damage, most commonly renal insufficiency and/or neurologic symptoms. As in the case above, determining the underlying etiology of TMAs is often challenging. The most common TMA syndromes include thrombotic thrombocytopenic purpura (TTP), caused by ADAMTS13 deficiency and hemolytic-uremic syndrome (HUS), mediated by Shiga toxin-producing bacteria such as E. coli O157:H7. These primary causes were ruled out. A diagnostic workup for atypical HUS, TMA caused by unregulated alternative complement pathway activation remained equivocal as well. TMAs can also be secondary to other systemic disorders including, but not limited to, preeclampsia/HELLP, malignant hypertension, malignancies and systemic rheumatologic disorders. In addition to providing supportive care, TMAs have different therapeutic management strategies obviating the importance of determining the underlying etiology. Acute pancreatitis is a well-known complication of various TMA syndromes; however, acute pancreatitis has less commonly been known to precipitate a secondary TMA. The proposed pathogenesis includes the release of cytokines such as IL-1 and TNF-a, leading to endothelial damage. Given the timeline of symptoms and presentation, it is likely that the preceding pancreatitis led to the development of a secondary TMA. His TMA syndrome resolved with supportive care alone, further supporting the diagnosis of secondary TMA from pancreatitis. Nevertheless, he will continue to require close renal function and hematologic monitoring, both routinely and during any future inflammatory illness.