Acquired Thrombotic Thrombocytopenic Purpura and Acute Pancreatitis: Variable and Reciprocal Pathophysiologic Relationships

INTRODUCTION

Acquired thrombotic thrombocytopenic purpura (TTP) is an aggressive thrombotic microangiopathy (TMA). Central to the pathophysiology is loss of ADAMTS 13 activity, due to inhibitors in the acquired form, allowing circulating ulVWF multimers to activate platelets and produce organ damage from microvascular thromboses. Autopsy studies find frequent pancreatic involvement, but clinically evident acute pancreatitis (AP) is infrequently reported. The relationship of TTP and AP may be variable and complex, with either capable of precipitating, exacerbating or mimicking the other. More so than other organ systems, the pancreas has immense potential for cytokine production and proteolytic enzyme release. This characteristic may contribute to the reciprocal fueling, and thus severity, of TTP in association with pancreatitis.

METHODS

We generated a descriptive, retrospective case series, querying the Methodist Environmental for Translational Enhancement and Outcomes Research database, a system that integrates Houston Methodist Hospital patient data into a single, comprehensive warehouse. We included all patients in whom TTP and AP were diagnosed during the same hospitalization between 2006 and 2016. Baseline demographics, laboratory values, time between onset of TTP and AP, complications, treatment, as well as short term morbidity and mortality were analyzed.

RESULTS

Twelve patients were identified as having TTP and AP in the same hospitalization. Demographics, onset intervals, and laboratory values of all patients are summarized in Table 1. Four patients had likely TTP induced AP with time to AP onset between 3 to 28 days, while eight patients had concurrent TTP and AP at initial presentation. All patients had elevated LDH levels with a range of 1575 U/L to 28,342 U/L and decreased platelet counts with a range of 5 k/µL to 59 k/µL. In the seven cases where ADAMTS13 measurements were performed prior to plasma exchenge (PEX), levels were below 5%. With the exception of case 5 in whom mild disseminated intravascular coagulation may have played a role in addition to TTP, no alternative etiologies were identified for the induction of the AP or the TMA.

Gastrointestinal (GI) symptoms were observed in 91% of the patients, with severe cases exhibiting ischemic colitis and GI bleeds. Eighty-one percent experienced neurological symptoms, of which 80% were considered major (coma, stroke seizures, or transient focal abnormalities) and the remaining minor (transient headache or confusion). Occurring more often than in TTP patient without AP, significant renal manifestations were seen in 81% (44% progressing to renal failure requiring dialysis), and acute coronary syndromes were experienced by 50%. All patient received fresh frozen plasma, PEX, and glucocorticoids for their TTP. However, 67% of the patients had refractory TTP, of which two thirds required the addition of rituximab. With the exception of two patients who expired secondary to cardiac arrests, all others achieved normalization of their platelets by discharge. Details of the organ involvements, treatments, and complications are summarized in Table 2.

CONCLUSION

We describe twelve patients with clinically evident acute pancreatitis in association with TTP. Compared to the severely ADAMTS13 deficient (<10%) patients reported in other studies, our patients suffered significantly worse organ involvement (George, 2010). Pancreatic cytokine release observed in other studies may have contributed to ADAMTS13 depletion, contributing to the phenotypic severity (Reiter et al, 2003; Bernardo et al, 2004; Mannucci et al, 2004; Swisher et al, 2007; Morioka et al, 2008). A review of literature also revealed the role of pancreatitis in nitric oxide depletion and complement activation, which may augment micro-thrombi formation and fuel TTP propagation. Whereas the relationship between TTP and other organ systems may be one of cause and effect, the relationship between AP and TTP may be one of reciprocal fueling. As such, early appreciation and treatment of pancreatitis might significantly decrease the severity of TTP and improve patient outcomes.

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