Increased fibrinolysis increases bleeding in orthopedic patients receiving prophylactic fondaparinux

Abstract

We evaluated hemostatic markers in patients who underwent major orthopedic surgery, including total hip and total knee arthroplasty, and were treated for the prophylaxis of deep vein thrombosis (DVT) with or without fondaparinux (anti-Xa group, n = 98 and without anti-Xa group, n = 20). The frequency of DVT was significantly higher in the without anti-Xa group than in the anti-Xa group, but the reduction of hemoglobin and fibrinolytic marker levels was significantly lower in the without anti-Xa group than in the anti-Xa group. Eighteen patients in the anti-Xa group showed a reduction in hemoglobin of more than 2 g/dl, and those individuals were considered to be the increased bleeding (IB) group. The concentration of fibrinolytic markers in the anti-Xa group was significantly higher in the IB group than in the non-IB group. There were also no significant differences in the levels of anti-Xa activity, plasminogen activator inhibitor-I, soluble fibrin and antithrombin between the IB and non-IB groups. In conclusion, elevated fibrinolysis induced by increased bleeding may lead to further increases in bleeding in patients receiving thromboprophylaxis with fondaparinux following major orthopedic surgery.

Perioperative Factors and Their Effect on the Fibrinolytic System in Arthroplasty Patients

“…2,4,5 Increased fibrinolytic activity in TKA and THA patients has also been associated with increased bleeding amount. 6,7 One of the main components of the fibrinolytic system is plasminogen activator inhibitor 1 (PAI-1), which is synthesized from endothelium, liver, and adipose tissue. 8 The PAI-1 inhibits tissue plasminogen activator (tPA), thereby inhibiting its activator effect on inactive plasminogen to active plasmin, which degrades fibrin.…”

Monitoring of hemostatic abnormalities in major orthopedic surgery patients treated with edoxaban by APTT waveform

“…These patients received 30 mg of edoxaban by oral administration once a day for 14 days beginning 24 hours after the discontinuation of lumbar anesthesia. Of these 99 patients, 12 exhibited DVT, and 25 had MB, defined as a reduction in the hemoglobin level by > 2 g/dL compared with that at Day 1 or a hemoglobin level < 7 g/dL (Table ). The APTT assay was performed in plasma from 30 healthy volunteers (HVs; 10 females and 20 males; age, 21 years; 20‐24 years) and 22 patients treated with warfarin (16 females and 6 males; 63.0 years; 54.5‐71.3 years) and compared with the findings in plasma from patients treated with edoxaban.…”

“…Massive bleeding (MB) due to withdrawal of anticoagulants is sometimes observed in these patients, although these drugs are generally considered to induce little bleeding. While the above drugs are usually difficult to monitor by routine coagulation tests, anti‐Xa assays have recently been developed to monitor LMWH and oral anti‐Xa inhibitors . However, the anti‐Xa assay is not a routine assay and is more expensive than assays for activated partial thromboplastin time (APTT) or prothrombin time (PT).…”

Evaluation of Factor Xa-Specific Chromogenic Substrate Assays and the Determination of Pharmacokinetics of Fondaparinux

“…The above results confirmed that both assays were capable of reproducibly measuring the anti-Xa activity within a clinically relevant range. 16,17 As for the intra-individual variability, patients who underwent lower intestinal surgery and received 2.5 mg of FPX daily demonstrated a gradual but significant increase in anti-Xa activity. In terms of inter-individual variability, the plasma levels of anti-Xa activity showed a significant negative correlation with body weight and with BMI.…”