Timing for deep vein thrombosis chemoprophylaxis in traumatic brain injury: an evidence-based review

Hiba Abdel-Aziz, C Michael Dunham, Rema J Malik, Barbara M Hileman

Multiple studies have addressed deep vein thrombosis chemoprophylaxis timing in traumatic brain injuries. However, a precise time for safe and effective chemoprophylaxis is uncertain according to experts. A comprehensive literature review on brain injuries was performed to delineate temporal proportions for 1) spontaneous intracranial hemorrhage (ICH) progression, 2) post-chemoprophylaxis ICH expansion, and 3) post-chemoprophylaxis deep vein thrombosis. Twenty-three publications were found including more than 5,000 patients. Spontaneous ICH expansion at 24 hours was 14.8% in 1,437 patients from chemoprophylaxis studies and 29.9% in 1,257 patients not in chemoprophylaxis studies (P < 0.0001). With low-risk ICH (n = 136), 99% of spontaneous ICH expansion occurred within 48 hours. In moderate or high-risk ICH (n = 109), 18% of spontaneous ICH expansion occurred after day 3. If patients with pre-chemoprophylaxis ICH expansion are included, the post-chemoprophylaxis ICH expansion proportion was 5.6% in 1,258 patients with chemoprophylaxis on days 1 to 3 and was 1.5% in 401 with chemoprophylaxis after day 3 (P = 0.0116). If patients with pre-chemoprophylaxis ICH expansion were excluded, the post-chemoprophylaxis ICH expansion proportion was 3.1% in 1,570 patients with chemoprophylaxis on days 1 to 3 and was 2.8% in 582 with chemoprophylaxis after day 3 (P = 0.7769). In diffuse axonal injury (n = 188), the post-chemoprophylaxis ICH expansion proportion was 1.6% with chemoprophylaxis after day 3. The deep vein thrombosis proportions were as follows: chemoprophylaxis on days 1 to 3, 2.6% in 2,384 patients; chemoprophylaxis on days 4 or 5, 2.2% in 831; and chemoprophylaxis on day 8, 14.1% in 99 (P < 0.0001). Spontaneous ICH expansion proportions at 24 hours substantially vary between chemoprophylaxis and non-chemoprophylaxis studies. Chemoprophylaxis should not be given within 3 days of injury for moderate-risk or high-risk ICH. Chemoprophylaxis is reasonable when low-risk patients have not developed ICH expansion within 48 hours post-injury. Chemoprophylaxis is also acceptable after day 3, when low-risk patients develop ICH expansion within 48 hours post-injury. In diffuse axonal injury patients who have not developed ICH within 72 hours, chemoprophylaxis is reasonable. Deep vein thrombosis proportions significantly increase when chemoprophylaxis is withheld for greater than 7 days.