Evaluation of the risks of anticoagulation therapy following experimental craniotomy in the rat

Abstract

The risk of hemorrhagic complications with anticoagulation therapy in patients following intracranial surgery has prevented investigation of the potential use of heparin in the early postoperative period. The authors have evaluated the safety of anticoagulation therapy following experimental craniotomy in male Holtzman rats. The dose and schedule of heparin administration, which elevated and maintained the activated partial thromboplastin time (APTT) within the therapeutic range of 1 1/2 to 3 X control APTT, was alternating doses of 400 and 500 IU/kg injected subcutaneously every 6 hours. This schedule was initiated 2, 4, 7, 10, and 14 days after craniotomy and was continued for 72 hours thereafter. The results demonstrated that the incidence of intracerebral hemorrhage declined as the postoperative interval prior to initiation of anticoagulation increased. If anticoagulation therapy was initiated during the first 7 postoperative days, the risk of intracerebral hemorrhage was high (mean 14.7%): however, if an additional 3 to 7 days elapsed prior to initiation of anticoagulation, the incidence of intracerebral hemorrhage dropped significantly (mean 0%) (p less than 0.05). These results suggest that anticoagulation therapy can be safely initiated 10 to 14 days after craniotomy.

Anticoagulation for Hypercoagulable Patients Associated with Complications after Large Cranioplasty Reconstruction

“…28,49,50 Fortunately, we experienced only one case of a postoperative deep venous thrombosis in a patient with Ehlers-Danlos syndrome (type IV) on a long-term regimen of Coumadin, which was stopped 6 days before surgery. In contrast, our analysis reveals that continuation or early postoperative use of therapeutic anticoagulant not only is associated with an increased short-term risk of bleeding 22,28,46,[50][51][52] but may also be associated with overall complications, including infection and wound dehiscence. Therefore, a successful balance between these two opposing considerations is essential for safe and effective management of patients who undergo reconstructive cranioplasty-especially in the setting of nonautologous custom cranial implants.…”

Postoperative venous thromboembolism and brain tumors: part I. Clinical profile

“…Anecdotal experiences suggest that anticoagulation may be safe as early as 24 hours after craniotomy. However, experimental data in rats suggest an increased risk of intracerebral hemorrhage if anticoagulation therapy is initiated during the first 7 postoperative days [24]. Placement of a vena cava umbrella, on the other hand, carries a low risk when properly performed, but it does not help reduce the occurrence or sequelae of lower extremity thrombophlebitis [23,25,26].…”

Intermittent Pneumatic Compression Stocking Prophylaxis Against Deep Venous Thrombosis in Anterior Cervical Spinal Surgery

“…In a Holtzman rat model, full heparinization was initiated 2, 4, 7, 10, and 14 days, and continued for 3 days, following craniotomy. 29 Within 7 days of surgery, the risk of intracranial bleeding was high (14.7%) but dropped to 0% when administered 10 and 14 days after surgery. Clinically, full anticoagulation therapy is often contraindicated in neurosurgical patients within the first 10 postoperative days 30,31 as even mini-heparin and low-dose heparin regimens pose an increased risk of major postoperative hemorrhage (0.7%-4%).…”