Objective To investigate the effectiveness and safety of low molecular weight heparin combined with aspirin for perioperative prophylactic anticoagulation in patients with lower extremity fracture after splenectomy. MethodsThe clinical data of 50 patients with splenic rupture combined with lower extremity fracture between January 2009 and June 2022 were retrospectively analyzed. All patients were given enoxaparin sodium at 48 hours after splenectomy, and stopped at 24 hours before fracture surgery. After fracture surgery, the patients were divided into aspirin group (group A, 15 cases), low molecular weight heparin group (group B, 16 cases), and low molecular weight heparin combined with aspirin group (group C, 19 cases) according to different anticoagulation regimens. The treatment course was 28 days. There was no significant difference in gender, age, body mass index, cause of injury, fracture site, time from injury to operation, complications, and other general data between groups (P>0.05). The occurrence of venous thromboembolism (VTE) was observed; hemoglobin (Hb), platelet (PLT), D-D dimer, and fibrinogen degradation product (FDP) were recorded before operation and at 1, 3, and 7 days after operation, and the effect of anticoagulation regimen on coagulation function was observed. The incidences of wound complications and bleeding related complications were recorded, and the total perioperative blood loss, hidden blood loss, and overt blood loss were calculated. Results The incidences of VTE in groups A, B, and C were 13.33% (2/15), 12.50% (2/16), and 5.26% (1/19), respectively, and there was no significant difference between groups (χ2=0.770, P=0.680). There was no portal vein thrombosis and no VTE-related death in the 3 groups. There was no significant difference in the levels of Hb, PLT, D-D dimer, and FDP between groups before and after operation (P>0.05); and there was no significant difference in total perioperative blood loss, hidden blood loss, and overt blood loss between groups (P>0.05). No local skin necrosis was found in all patients. In group A, 1 case occurred redness and swelling of incision; in group B, 1 case had incision discharge, redness, and swelling, and 1 case had fat liquefaction; in group C, 1 case had repeated incision exudation accompanied by local tissue redness and swelling, and 1 case had local hematoma. The incidences of adverse incision in groups A, B, and C were 6.66% (1/15), 12.50% (2/16), and 11.76% (2/19), respectively, with no significant difference (χ2=0.302, P=0.860). There were 4 cases of bleeding related complications, including 1 case of incision ecchymosis in groups A and B respectively, with the incidence of 6.66% and 6.25%, respectively; there was 1 case of incision hematoma and 1 case of bleeding in group C, with the incidence of 11.76%; showing no significant difference in the incidence of bleeding related complications between groups (χ2=0.268, P=0.875). Conclusion Perioperative combined use of low molecular weight heparin and aspirin for prevention of anticoagulation in patients with splenic rupture and lower extremity fracture can effectively prevent the occurrence of VTE without increasing the incidence of complications, which is an effective and safe treatment method. However, whether the incidence of VTE can be reduced needs to be further studied by expanding the sample size.