ADAMTS13 Deficiency and Obesity as Risk Factors for Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease caused by dysfunction or absence of ADAMTS13 (A Disintegrin And Metalloproteinase with ThromboSpondin type one motif, member 13), which cleaves prothrombotic ultralarge von Willebrand factor multimers (UL-VWF), thereby preventing the formation of platelet-rich microthrombi that block capillaries and arterioles, which leads to organ failure and death. Concerning the Oklahoma TTP-HUS registry, the annual incidence of TTP is 4 to 11 cases/million. This rare disease is mainly characterized by severe thrombocytopenia and microangiopathic hemolytic anemia, but other symptoms like fever and neurological dysfunctions are also observed (1). Acute TTP episodes are often triggered by secondary events like pregnancy, alcohol abuse, infections or surgery (2). A positive correlation was established between ADAMTS13 levels and body mass index (BMI) in humans (3). This is in agreement with higher expression levels of ADAMTS13 observed in livers of obese mice (4). Therefore, obesity would not be expected to be a risk factor for TTP, since it is associated with higher levels of the VWF-cleaving protease ADAMTS13. Moreover, ADAMTS13 has anti-inflammatory properties (5), whereas obesity is a state of low-grade chronic inflammation (6). Nevertheless, it was suggested that obesity might be a trigger for acute TTP episodes in humans, regardless of their initial ADAMTS13 activity levels. Indeed, in patients with a BMI > 30, obesity was identified as a potential inducer of acute TTP (7). Furthermore, in a population of TTP patients, more than 25% was found to be morbidly obese (BMI > 40) (8). We have addressed this apparent paradox by using a TTP model in obese Adamts13 deficient mice.

Publication year:2017

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