The Effect of Ex Vivo Factor XIII Supplementation on Clot Formation in Blood Samples From Cardiac and Scoliosis Surgery Patients.

Excessive perioperative bleeding remains a substantial problem. Factor XIII (FXIII) contributes to clot stability, and it has therefore been suggested that supplementation with FXIII concentrate may improve perioperative hemostasis. We evaluated the effects of increasing doses of FXIII, alone or in combination with fibrinogen or platelet concentrate, in blood samples from 2 considerably different groups of surgical patients: cardiac and scoliosis surgery patients. Whole-blood samples were collected immediately after operation from cardiac and scoliosis surgery patients. The samples were supplemented with 3 clinically relevant doses of FXIII concentrate (+20%, +40%, and +60%), alone or in combination with a fixed dose of fibrinogen concentrate (+1.0 g/L) or fresh apheresis platelets (+92 × 109/L). Clot formation was assessed with rotational thromboelastometry (ROTEM). When the highest dose of FXIII concentrate was added, EXTEM clotting time was shortened by 10% in both cardiac and scoliosis surgery patients (95% confidence intervals: 2.4%-17% and 3.3%-17%, respectively), and FIBTEM maximum clot firmness was increased by 25% (9.3%-41%) in cardiac patients, relative to baseline. When fibrinogen was added, the dose-dependent effect of FXIII on clot stability was maintained, but the total effect was markedly greater than with FXIII alone, +150% (100%-200%) and +160% (130%-200%) for the highest FXIII dose in cardiac and scoliosis patients, respectively. Ex vivo supplementation with clinically relevant doses of FXIII improved clot formation moderately in blood samples from cardiac and scoliosis surgery patients, both alone and when given in combination with fibrinogen or platelet concentrate.

Preoperative plasma fibrinogen concentration, factor XIII activity, perioperative bleeding, and transfusions in elective orthopaedic surgery: A prospective observational study.

BACKGROUND: Major orthopaedic surgery involves a calculated risk of bleeding. In other groups of surgical patients, low preoperative plasma fibrinogen concentration and factor XIII (FXIII) activity have been associated with an elevated risk of bleeding. In the present study we investigated the association between preoperative fibrinogen plasma concentration and FXIII activity on bleeding and transfusion requirements in patients undergoing a spinal fusion procedure or hip or knee arthroplasty. METHODS: Two hundred and forty-five adult patients undergoing spine fusion surgery (n=52), total unilateral primary hip arthroplasty (n=114), or total knee arthroplasty (n=79) were included in a prospective observational study. Blood samples were collected <24h before surgery and analysed for fibrinogen concentration and FXIII activity. Intraoperative and postoperative bleeding volume and transfusion requirements were recorded. RESULTS: Spinal fusion surgery patients with a low preoperative fibrinogen concentration (≤2.5g/L) had a greater total perioperative median bleeding volume than patients with fibrinogen>2.5g/L (2430 (400-6560) mL vs. 1390 (400-7420) mL, p=0.029). No significant association between low fibrinogen levels and perioperative bleeding volume was observed for arthroplasty patients. There was no association between low fibrinogen levels and transfusion requirements in any of the groups. Low FXIII activity was not significantly associated with bleeding volume and transfusion requirements in any group. CONCLUSION: Measurement of preoperative fibrinogen plasma concentration can identify spinal fusion patients with an increased risk of excessive perioperative bleeding. Measurement of FXIII activity cannot identify orthopaedic patients with elevated risk of bleeding.

Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study.

BACKGROUND: There is a high prevalence of blood product transfusions in orthopedic surgery. The reported prevalence of red blood cell transfusions in unselected patients undergoing hip or knee replacement varies between 21% and 70%. We determined current blood loss and transfusion prevalence in total hip and knee arthroplasty when tranexamic acid was used as a routine prophylaxis, and further investigated potential predictors for excessive blood loss and transfusion requirement. METHODS/MATERIALS: In total, 193 consecutive patients undergoing unilateral hip (n = 114) or knee arthroplasty (n = 79) were included in a prospective observational study. Estimated perioperative blood loss was calculated and transfusions of allogeneic blood products registered and related to patient characteristics and perioperative variables. RESULTS: Overall transfusion rate was 16% (18% in hip patients and 11% in knee patients, p = 0.19). Median estimated blood loss was significantly higher in hip patients (984 vs 789 mL, p < 0.001). Preoperative hemoglobin concentration was the only independent predictor of red blood cell transfusion in hip patients while low hemoglobin concentration, body mass index, and operation time were independent predictors for red blood cell transfusion in knee patients. CONCLUSIONS: The prevalence of red blood cell transfusion was lower than previously reported in unselected total hip or knee arthroplasty patients. Routine use of tranexamic acid may have contributed. Low preoperative hemoglobin levels, low body mass index, and long operation increase the risk for red blood cell transfusion.

Preoperative fibrinogen plasma concentration is associated with perioperative bleeding and transfusion requirements in scoliosis surgery.

STUDY DESIGN: Prospective observational study. OBJECTIVE: To investigate the potential association between fibrinogen, bleeding, and transfusion requirements after scoliosis surgery. SUMMARY OF BACKGROUND DATA: Bleeding complications during and after orthopedic surgery are associated with increased morbidity and mortality. Early identification of patients with increased risk of excessive bleeding offers the possibility to initiate countermeasures. Fibrinogen is a key protein in the coagulation cascade, and thus a potential biomarker for bleeding risk. METHODS: A total of 82 otherwise healthy patients (mean age: 15 ± 3 years, 85% girls) undergoing surgery for adolescent idiopathic scoliosis were included in the study. Patient variables (age, gender, operation time, and thrombosis prophylaxis), preoperative laboratory variables (hemoglobin, platelet count, activated partial thromboplastin time [aPTT], prothrombin time [PT], and fibrinogen), peroperative and postoperative bleeding volume, and transfusions were registered. Correlations between laboratory variables and bleeding volume were calculated with Pearson test. Patient variables and laboratory variables were compared with Student t test between patients with bleeding volume in the upper quartile ("bleeders") and the remaining patients, and between patients with extensive transfusion (defined as >2 U of packed red cells) and no or limited transfusions (≤ 2 U). RESULTS: Mean fibrinogen concentration was 3.0 ± 0.7 g/L (range, 1.3- 4.9). Mean total perioperative bleeding volume was 1552 ± 1019 mL (range, 100-5800 mL). Total bleeding volume correlated significantly with preoperative fibrinogen concentration (r = -0.31, P = 0.005) but neither with platelet count, aPTT, nor PT (P = 0.61, 0.46, and 0.57, respectively). Bleeders had significantly lower preoperative fibrinogen plasma concentration (2.6 ± 0.6 vs. 3.1 ± 0.6 g/L, P = 0.002). Of total, 16% (13/82) of the patients were transfused with >2 U of packed red cells. Patients with extensive transfusions had significantly lower preoperative fibrinogen plasma concentration (2.5 ± 0.7 vs. 3.1 ± 0.6 g/L, P = 0.002), while preoperative platelet count, aPTT, and PT did not differ. CONCLUSION: The results indicate that preoperative fibrinogen concentration is a limiting factor for postoperative hemostasis during and after scoliosis surgery. Preoperative measurement of fibrinogen concentration provides more information about bleeding volume and transfusion requirements than standard screening tests.