Can Rhabdomyolysis Cause Elevated D-dimer?
Yes, rhabdomyolysis can cause elevated D-dimer levels, primarily through the development of disseminated intravascular coagulation (DIC), which is a recognized complication of severe rhabdomyolysis. 1
Mechanism of D-dimer Elevation in Rhabdomyolysis
The pathophysiological connection occurs through the following pathway:
Rhabdomyolysis triggers systemic coagulation activation when severe muscle necrosis releases intracellular contents (myoglobin, creatine phosphokinase, electrolytes, and proteins) into the circulation, which can activate the coagulation cascade. 1
DIC develops as a complication of fulminant rhabdomyolysis, characterized by widespread activation of coagulation and subsequent fibrinolysis, leading to markedly elevated D-dimer levels. 1, 2
D-dimer specifically indicates crosslinked fibrin breakdown, which occurs when plasmin cleaves the fibrin mesh formed during DIC, releasing D-dimer fragments into circulation. 3
Clinical Context and Severity
The likelihood and degree of D-dimer elevation depends on rhabdomyolysis severity:
Mild rhabdomyolysis (isolated creatine kinase elevation without systemic complications) is unlikely to cause significant D-dimer elevation. 4, 5
Severe/fulminant rhabdomyolysis with systemic complications including acute renal failure, metabolic acidosis, hypovolemic shock, and DIC will produce elevated D-dimer levels. 1, 6
DIC is specifically listed as one of the major life-threatening complications of rhabdomyolysis that requires early recognition and treatment. 1, 5
Differential Diagnosis Considerations
When encountering elevated D-dimer in a patient with suspected or confirmed rhabdomyolysis:
Assess for DIC by checking complete blood count (platelet count), coagulation studies (PT, APTT), and fibrinogen levels alongside the D-dimer. 2
Consider alternative thrombotic causes including venous thromboembolism (VTE), as immobilized patients with rhabdomyolysis may develop DVT/PE independently. 7, 8
Evaluate for sepsis, which commonly coexists with rhabdomyolysis (particularly in drug/toxin-induced cases) and independently causes D-dimer elevation through systemic coagulation activation. 7, 4
Critical Clinical Pitfalls
Do not assume D-dimer elevation is solely from rhabdomyolysis without excluding VTE, especially if the patient has been immobilized or has additional risk factors for thrombosis. 7
Extremely elevated D-dimer levels (>5000 μg/L) in rhabdomyolysis patients should prompt aggressive evaluation for DIC, sepsis, or concurrent VTE, as 89% of patients with this degree of elevation have VTE, sepsis, and/or cancer. 9
Monitor for evolving DIC in severe rhabdomyolysis by tracking serial platelet counts, fibrinogen levels, and coagulation parameters, not just D-dimer alone. 2
Prognostic Implications
D-dimer elevation in rhabdomyolysis signals systemic complications and warrants intensive monitoring for acute renal failure, electrolyte abnormalities, and hemodynamic instability. 1, 5
The presence of DIC (confirmed by elevated D-dimer plus thrombocytopenia, prolonged PT/APTT, and low fibrinogen) indicates severe disease requiring aggressive supportive care and treatment of the underlying cause. 2