The potential role of complements in cocaine-induced thrombotic microangiopathy

Abstract

Thrombotic microangiopathy (TMA) is a rare disorder characterized by microvascular injury and occlusion resulting in tissue ischemia and dysfunction. TMA occurs in a variety of settings including cocaine use. Although cocaine is widely used in the United States, cocaine-associated TMA is only rarely reported. Therefore, other factors may predispose cocaine users to the development of TMA. Emerging evidence indicates that cocaine activates complements. Therefore, complement activation may contribute to the development of cocaine-induced TMA. Here, we report a cocaine user who presented with renal failure. Renal biopsy demonstrated TMA. Laboratory tests revealed reduced serum complement C3 and normal complement C4 levels indicative of alternative complement activation. We postulate that complement activation is involved in the pathogenesis of cocaine-induced TMA.

Acute kidney injury secondary to thrombotic microangiopathy associated with idiopathic hypereosinophilic syndrome: a case report and review of the literature

“…TMA is a life-threatening syndrome of systemic microvascular occlusions and is characterized by sudden or gradual onset of thrombocytopenia, microangiopathic hemolytic anemia, and renal or other end-organ damage [22]. It has been associated with diverse diseases and syndromes, such as systemic infections, cancer, pregnancy complications (for example, preeclampsia, eclampsia, HELLP [hemolysis, elevated liver enzymes, low platelet count] syndrome), autoimmune disorders (for example, systemic lupus erythematosus, systemic sclerosis, antiphospholipid syndrome), hematopoietic stem cell or organ transplant, severe hypertension, and cocaine-induced [22, 23]. Liapis et al first reported two cases of TMA associated with idiopathic HES, along with a third case of myeloproliferative variant of HES in association with TMA [3] (Table 5).…”

Cocaine‐associated atypical haemolytic uraemic syndrome in a genetically susceptible individual

“…Cocaine is known to cause direct endothelial dysfunction and promote coagulation by activating platelets, increasing levels of von Willebrand factor and fibrinogen . Cocaine has been reported to cause TMA, either with or without concomitant hypertension . The patient described had evidence of longstanding hypertension on echocardiogram, and chronic kidney disease (left ventricular hypertrophy and moderate chronic tubulointerstitial damage on biopsy).…”

“…Cocaine is a commonly abused stimulant drug that comes in the form of either a hydrochloride salt that is inhaled, or as a free base crystal that is smoked . Cocaine is known to cause direct endothelial dysfunction and promote coagulation by activating platelets, increasing levels of von Willebrand factor and fibrinogen . Cocaine has been reported to cause TMA, either with or without concomitant hypertension .…”

Cocaine-Induced Four-Extremity Ischemia Caused by a Hypercoagulable State

“…Our patient’s blood culture was positive for S. epidermidis bacteremia and this, in combination with her chronic cocaine use, may explain the extensive ischemia that she developed. Another theory was proposed by Dejman et al which suggested that complement activation in a patient with reduced level of serum complement C3 and normal C4 may contribute to the development of cocaine-induced thrombotic microangiopathy [ 18 ].…”