N‐Methyl‐3,4‐methylendioxymethamphetamine (MDMA)‐related coagulopathy and rhabdomyolysis: A case series and literature review

Abstract

Coagulation changes, thrombosis, and hemorrhage have been described in patients following N‐methyl‐3,4‐methylenedioxymethylamphetamine (MDMA) intoxication who subsequently developed serotonin syndrome and rhabdomyolysis. The clinical features and mechanism of this remain poorly described. We describe 5 sequential cases admitted to critical care due to severe recreational MDMA toxicity where coagulopathy occurred, and discuss key clinical issues. All patients presented with hyperpyrexia then developed subsequent rhabdomyolysis accompanied by a coagulopathy within 24 hours of presentation. This included a severe thrombocytopenia, prolonged coagulation times, grossly elevated D‐dimer levels, and hypofibrogenemia. Multiorgan dysfunction was seen in all patients, including stroke in one patient and major hemorrhage in another. In 2 cases, low‐dose low‐molecular‐weight heparin was used early after presentation, with no significant bleeding complications. Blood products usage was high but variable between the patients with lower use in those who received low‐molecular‐weight heparin early. Other treatments included intravascular therapeutic cooling, renal replacement therapy with large filter pores and cyprohepatidine. Current evidence suggests that in this group, rhabdomyolysis with subsequent myosin release may be a profound activator of coagulation leading to disseminated intravascular coagulation. Myosin‐activated coagulation seems a potential cause of MDMA‐related coagulopathy in the setting of rhabdomyolysis and serotonin syndrome. Further studies are needed to validate this and explore the use of low‐molecular‐weight heparin to reduce the clinical effects of this coagulopathy.

Drug-induced Hyperthermic Syndromes in Psychiatry

“…Drugs with adrenergic stimulating properties including amphetamines, cocaine (“crack”), 3,4-methylenedioxymethamphetamine (MDMA or “ecstasy”), other methamphetamine analogs (“ice”) and cathinones (“bath salts”) continue to be synthesized, sold and abused [ 3 ]. The clinical presentation of sympathomimetic intoxication consists of sweating, hypertension, tachycardia, dilated and reactive pupils, agitation, delirium, psychosis, tremors, rhabdomyolysis and hyperthermia which can progress to arrhythmias, shock, renal failure, myocardial infarction, stroke, coagulation disorders and death [ 47 ]. Hyperthermia and rhabdomyolysis result from impaired heat dissipation and ischemia due to vasoconstriction, compounded by increased heat production from agitation or seizures.…”

“…While MDMA has only one tenth the adrenergic stimulant effect of amphetamine, toxicity has also been attributed to serotonin toxicity leading to SS, as MDMA releases and inhibits reuptake of serotonin [ 47 ]. Hyperthermic deaths attributable to MDMA used as a “club” drug have been associated with hot settings during “rave” dance parties, implying that stimulant-driven exertional heatstroke may also play a role in its toxicity [ 48 ].…”

Time-Dependent Molecular Changes Following MDMA-Induced Nephrotoxicity

“…There is evidence of renal-related adverse effects, such as hyponatremia and acute kidney injury (AKI), linked to MDMA consumption. AKI is often a complication of acute health issues including malignant hypertension (3), hyperthermia, multi-organ failure, rhabdomyolysis, and disseminated intravascular coagulation (DIC) (4)(5)(6)(7)(8). Additionally, post-mortem findings from a case of chronic renal failure following oral ecstasy ingestion revealed necrotizing vasculitis in a renal biopsy, suggesting a direct nephrotoxic effect of MDMA (9).…”