Cocaine-Induced Thrombotic Microangiopathy (TMA)
Definition and Pathophysiology
Thrombotic microangiopathy (TMA) in the context of cocaine use is a rare but serious complication characterized by microvascular injury, endothelial damage, and microthrombi formation leading to microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury—often presenting as hemolytic-uremic syndrome. 1, 2, 3
The pathogenesis involves multiple mechanisms:
- Cocaine-mediated endothelial injury through direct vasoconstriction and vascular damage, which triggers the cascade of microvascular thrombosis 1, 3
- Platelet activation and procoagulant effects of cocaine, increasing thromboxane A2 production and platelet aggregation 4, 2
- Complement activation, specifically through the alternative pathway (evidenced by reduced C3 with normal C4 levels), which may predispose certain cocaine users to TMA development 5
- Malignant hypertension as a frequent precipitating factor, with cocaine-induced severe hypertension causing additional endothelial damage and fibrinoid necrosis 1, 3
Clinical Presentation
The classic triad includes:
- Microangiopathic hemolytic anemia with severe anemia (hemoglobin can drop to 1.8 g/dL), schistocytes on peripheral smear, elevated LDH, and low haptoglobin 2, 6
- Thrombocytopenia from platelet consumption in microthrombi 2, 6
- Acute kidney injury requiring dialysis in many cases, with renal biopsy showing thrombotic microangiopathy, fibrinoid necrosis of arterioles, and glomerular tuft involvement 1, 3
Diagnostic Considerations
ADAMTS13 activity is typically normal in cocaine-induced TMA, distinguishing it from idiopathic thrombotic thrombocytopenic purpura (TTP). 6
Key diagnostic features on renal biopsy:
- Thrombotic microangiopathy with fibrinoid necrosis of arterioles 1, 3
- Glomerular tuft necrosis and capillary thrombosis 3
- Patchy renal cortical necrosis in severe cases 2
Management Approach
Unlike idiopathic TTP, cocaine-induced TMA may not require therapeutic plasma exchange (TPE) and can improve with supportive care alone once cocaine use is discontinued. 6
Treatment priorities:
- Immediate cessation of cocaine use is the cornerstone of management 1, 3
- Blood pressure control using benzodiazepines as first-line for hypertensive urgency, followed by calcium channel blockers or phentolamine if needed 7
- Avoid beta-blockers due to risk of unopposed alpha-adrenergic stimulation causing further vasoconstriction 4, 7
- Supportive care including dialysis for acute kidney injury as needed 1, 3
- Consider stopping TPE if ADAMTS13 activity returns normal, as the condition may resolve without plasma exchange 6
Critical Pitfalls
- Cocaine-induced TMA is extremely rare despite widespread cocaine use, suggesting other predisposing factors (such as complement dysregulation) may be necessary for development 5
- Do not assume all cases of MAHA with thrombocytopenia in cocaine users are TTP—check ADAMTS13 activity before committing to prolonged TPE therapy 6
- Screen for malignant hypertension as it frequently coexists with cocaine-induced TMA and requires specific management 1, 3
- Rhabdomyolysis can coexist and contribute to acute kidney injury, but TMA represents a distinct pathophysiologic process requiring different recognition 1