Causes of Non-Traumatic Epidural Hematoma
Non-traumatic epidural hematoma (EDH) occurs primarily due to coagulopathy from anticoagulant or antiplatelet medications, bleeding disorders, vascular malformations of the dura mater, infectious disease, and hemorrhagic tumors. 1
Primary Etiologic Categories
Medication-Induced Coagulopathy
Anticoagulant therapy is the most clinically significant cause of non-traumatic EDH in contemporary practice:
Warfarin (vitamin K antagonists) causes spontaneous intracranial hemorrhages including epidural hematomas, with patients experiencing more severe consequences than those not anticoagulated 2. The FDA label for warfarin documents major bleeding complications occurring at rates of 2.1-4.6 events per 100 patient-years depending on INR intensity 3.
Direct oral anticoagulants (DOACs) including dabigatran, apixaban, and rivaroxaban are associated with spontaneous epidural hematomas, though guidelines note that intracranial hemorrhage prognosis may not be worse than with warfarin 2.
Heparin therapy (both unfractionated and low molecular weight heparin) carries boxed FDA warnings about spinal/epidural hematoma risk that could result in long-term paralysis 2, 4. Cases have been documented even when anticoagulation is within therapeutic range 5.
Antiplatelet agents represent an underappreciated but significant risk:
Aspirin (acetylsalicylic acid) causes epidural hematomas through aspirin-induced bleeding disorder and prolonged bleeding time 6. Multiple case reports document spinal epidural hematomas from excessive aspirin ingestion 6, 7.
Clopidogrel and other antiplatelet agents carry similar bleeding risks to anticoagulants and should not be considered safer 8.
Drug Interactions
Polypharmacy with warfarin dramatically increases bleeding risk:
Concurrent use of warfarin with aspirin, NSAIDs (diclofenac), statins (atorvastatin), fibrates (fenofibrate), SSRIs (citalopram), and antipsychotics (quetiapine) can precipitate spontaneous epidural hematoma even when INR remains in therapeutic range (2.2-2.4) 5.
Drug interactions with warfarin are common and high suspicion is essential in any patient on anticoagulants who develops spinal pain with neurological deficits 5.
Hematologic Disorders
Inherited and acquired bleeding disorders cause non-traumatic EDH:
Hemophilia and other congenital coagulation factor deficiencies are established causes 1.
Thrombocytopenia from any cause, including systemic lupus erythematosus with marked platelet reduction, precipitates spontaneous epidural bleeding 7.
Sickle cell disease has been implicated as a causative factor 1.
Vascular Malformations
Arteriovenous malformations of the dura mater can rupture spontaneously causing epidural hematoma 1, 7.
These vascular anomalies should be suspected particularly in younger patients without other risk factors 1.
Infectious Etiologies
Infectious disease represents one of the most common causes of non-traumatic spontaneous acute epidural hematoma historically 1.
The mechanism involves erosion of dural vessels by infectious processes 1.
Neoplastic Causes
Hemorrhagic tumors involving the dura or skull can bleed spontaneously into the epidural space 1.
Metastatic disease with vascular tumors should be considered in the differential 1.
Iatrogenic and Procedural Causes
Epidural catheter-related hematomas occur even when guidelines are followed:
Epidural hematoma can develop after epidural catheter removal despite adherence to American Society of Regional Anesthesia (ASRA) timing guidelines for antithrombotic therapy 9.
The risk exists both during placement and removal of epidural catheters in patients receiving any anticoagulation 9.
Medical Comorbidities
Open heart surgery and hemodialysis have been implicated as causative factors, likely through transient coagulopathy 1.
Systemic lupus erythematosus increases risk through multiple mechanisms including thrombocytopenia and vasculitis 1, 7.
Critical Clinical Pearls
Key distinguishing features from traumatic EDH:
Non-traumatic EDH presents with local or referred spinal pain associated with neurological deficits in the absence of trauma history 5.
Spinal epidural hematomas are more common than cranial in the non-traumatic setting, particularly in anticoagulated patients 6, 5, 7.
The American College of Cardiology classifies epidural hematomas as critical site bleeds that compromise organ function and may necessitate surgical procedures for hemostasis 2.
Common pitfall: Assuming therapeutic INR range provides safety—most reported cases of warfarin-associated spontaneous epidural hematoma occurred with INR in the recommended therapeutic range of 2.0-3.0 5.