The term “spontaneous acute SDH” has been used rather indiscriminately in the literature. Some authors[22,23] use the term strictly to refer to subdural hematomas caused by the rupture of a cortical vessel that does not involve a cerebral aneurysm, arterio-venous malformation, tumor, metastasis, or blood dyscrasias. Other authors[7,13,19,24,33,34] have used the term based simply on the absence of a traumatic history. We prefer to use the term according to the latter definition. Head trauma was not an immediate factor in the development of SDH in either of the authors’ patients. Patient 1 was recovering from a decompressive craniectomy that had occurred 3 weeks earlier. There was no history of any trauma for the second patient. Aggravating cofactors existing in these two patients included self-medication with a platelet inhibitor in the second patient. No cerebrovascular abnormality was observed in either case during surgery.

Both the patients experienced a spontaneous acute SDH after recently taking fondaparinux for VTE prophylaxis. There has been one report of an SDH resulting from a fall while a patient was taking fondaparinux.[10] Another report linked a large spontaneous retroperitoneal hematoma to this pharmacologic agent.[15] To our knowledge, our report presents the first instances of spontaneous acute SDH most likely attributed to fondaparinux. The second patient had also been taking aspirin, but the influence of this on the development of spontaneous hemorrhage cannot be fully assessed. However, the recent introduction of fondaparinux in this patient's drug regimen suggested that this drug was the trigger, either as an independent factor or in a combined mechanism with aspirin.

Fondaparinux acts as a selective AT-III dependent inhibitor of activated factor Xa.[8] The drug is approved by the Food and Drug Administration for VTE prophylaxis after hip fracture surgery, total hip replacement, total knee replacement, and major abdominal surgery.[8] Moreover, it is approved for the initial management of deep venous thrombosis (DVT) and pulmonary embolism.[8] However, the drug is contraindicated in patients with renal failure (creatinine clearance <30 ml/min), body weight <50 kg, active major bleeding, and bacterial endocarditis.

Although its safety has been shown in previous studies when compared to low-molecular-weight heparin (LMWH), a black box warning has been issued for its use near the neural axis, describing the potential for development of epidural hematomas. During the Phase III trials of fondaparinux, the patients who underwent surgical procedures involving brain and spine in the last 3 months were excluded from the study. There is no specific antidote available to counteract the effects of fondaparinux. However, in cases of severe bleeding, the anticoagulant effect can be reversed with fresh frozen plasma or recombinant factor VIIa.

The occurrences of spontaneous hematomas and the subsequent re-hemorrhage in our second patient echo the potential risks of major bleeding while taking medications for pharmacologic VTE prophylaxis. Unfortunately, no controlled trials have focused on VTE prophylaxis for the neurosurgical population. Established in 2004, the present guidelines for neurosurgical procedures were extrapolated from data for general surgery and orthopedic surgery; the recommendations embraced multimodal prophylaxis with mechanical methods, which could be enhanced by either LMWH or unfractionated heparin (UFH).[11,16] There are no guidelines for the use of fondaparinux in neurosurgery. Since that time, several articles[2,12] have emerged stressing the increased risk of intracranial hemorrhage for patients receiving LMWH prophylaxis compared with the patients receiving mechanical modalities. Surprisingly, a meta-analysis by Collen et al.[11] suggested that mechanical modalities (i.e., intermittent compression devices) may be as effective as heparin therapy in the neurosurgical population without the hemorrhagic risks. This is contrary to popular belief that pharmacologic therapy is considered superior for prevention of thromboembolism.[11]