The effect of anticoagulation therapy on perioperative bleeding risk in patients undergoing heart transplantation
Background: Oral anticoagulation therapy for the prevention of thromboembolic complications of atrial fibrillation in patients awaiting heart transplantation (HTx) traditionally includes warfarin, and in the last few years it increasingly includes dabigatran. Anticoagulation must be reversed before the surgery. The possibility of rapid reversal of the anticoagulant effect of dabigatran with idarucizumab seems to represent an advantage (1). A comparison of bleeding complications between these two strategies has not been completely investigated.
Patients and Methods: We did a retrospective analysis of bleeding complications during and immediately after HTx performed in University Hospital Center Zagreb in 15 patients divided into 3 groups: patients who were on warfarin prior to HTx, patients who were on dabigatran prior to HTx, and control patients without indication for anticoagulation therapy. Patients were mutually paired to eliminate the influence of other risk factors including age, gender, etiology of heart failure, renal function, as well as whether surgery was primary or after previous sternotomy. For the comparison of bleeding complications we measured the utilization of blood products (red blood cells, platelets, fibrinogen, fresh frozen plasma (FFP), prothrombin complex (PC) and the amount of thoracic drainage within the first 24 hours after the HTx.
Results: There was no significant difference in the utilization of blood products as well as the amount of 24h thoracic drainage between these three groups (Table 1). Only 2/5 patients in the warfarin group were within the therapeutic INR range (2 pts below and 1 pts above the range). 24h thoracic drainage, FFP and PC consumption correlated with pretransplant INR (Table 2).
TABLE 1 Comparison of different demographic and clinical characteristics, and crucial pretransplant/posttransplant laboratory findings between patient groups stratified according to anticoagulant use.
| Therapy groups: | No anticoagulation
(n=5) | Warfarin
(n=5) | Dabigatran
(n=5) | p-value |
|---|
| Male gender, N (%) | 4 (80) | 4 (80) | 4 (80) | 1.000 |
| Age at the time of HTx [y] (IQR) | 53 (53-57) | 59 (46-60) | 62 (46-63) | 0.756 |
| Ischemic CMP, N (%) | 1 (20) | 1 (20) | 1 (20) | 1.000 |
| Resternotomy, N (%) | 1 (20) | 1 (20) | 1 (20) | 1.000 |
| eGFR [mL/min/1,73m2] (IQR) | 71 (66-84) | 65 (53-71) | 65 (50-76) | 0.423 |
| Erythrocyte concentrate [mL] (IQR) | 260 (0-1510) | 250 (250-1020) | 550 (470-730) | 0.755 |
| FFP [mL] (IQR) | 1020 (910-1060) | 1310 (1240-1380) | 1060 (1030-1150) | 0.385 |
| Platelet concentrate [doses] (IQR) | 8 (6-8) | 8 (8-8) | 5 (0-10) | 0.919 |
| Fibrinogen [g] (IQR) | 2 (2-3) | 2 (2-2) | 2 (2-4) | 0.698 |
| Prothrombin complex [IU] (IQR) | 0 (0-0) | 0 (0-2500) | 0 (0-0) | 0.117 |
| Thymoglobulin (IQR) | 24 (22-24) | 26 (24-29) | 28 (24-30) | 0.363 |
| Thoracic drainage within the first 24h [mL] (IQR) | 400 (300-700) | 450 (400-550) | 600 (450-650) | 0.643 |
| Hemoglobin before HTx [g/L] (IQR) | 139 (137-146) | 125 (121-160) | 142 (138-149) | 0.756 |
| Platelets before HTx [10E9/L] (IQR) | 205 (200-260) | 282 (270-292) | 188 (174-202) | 0.102 |
| PT-INR before HTx (IQR) | 0.96 (0.92-1.15) | 2.40 (1.18-2.41) | 1.09 (1.06-1.13) | 0.230 |
| APTT before HTx [s] (IQR) | 24.60 (23.25-26.40) | 36.9 (27.7-37.5) | 31.3 (28.9-47.3) | 0.079 |
| Fibrinogen before HTx [g/L] (IQR) | 3.75 (3.35-4.15) | 4.20 (3.40-5.70) | 3.85 (3.70-4.95) | 0.693 |
| Hemoglobin 1st day after HTx [g/L] (IQR) | 101 (93-111) | 107 (95-112) | 96 (95-100) | 0.485 |
| Platelets 1st day after HTx [10E9/L] (IQR) | 113 (94-163) | 135 (129-171) | 98 (92-131) | 0.330 |
| PT-INR 1st day after HTx (IQR) | 1.02 (0.99-1.09) | 1.22 (1.03-1.43) | 1.18 (1.10-1.23) | 0.259 |
| APTT 1st day after HTx [s] (IQR) | 25.7 (24.6-27.4) | 27.7 (23.9-28.4) | 25.4 (24.6-25.9) | 0.635 |
| Fibrinogen 1st day after HTx [g/L] (IQR) | 4.50 (3.80-6.70) | 3.50 (3.40-3.70) | 3.4 (3.0-3.4) | 0.068 |
| Hemoglobin 7th day after HTx [g/L] (IQR) | 102 (96-111) | 100 (92-101) | 88 (88-92) | 0.150 |
| Platelets 7th day after HTx [10E9/L] (IQR) | 117 (97-193) | 112 (104-154) | 93 (73-108) | 0.228 |
| PT-INR 7th day after HTx (IQR) | 1.00 (0.98-1.02) | 1.01 (0.95-1.12) | 1.08 (1.06-1.11) | 0.203 |
| APTT 7th day after HTx [s] (IQR) | 20.5 (19.1-21.0) | 22.8 (21.3-23.3) | 21.7 (21.1-22.2) | 0.172 |
| Fibrinogen 7th day after HTx [g/L] (IQR) | 2.3 (2.2-3.3) | 3.4 (2.9-5.2) | 3.5 (2.3-3.5) | 0.438 |
| HTx – Heart Transplant; CMP – cardiomyopathy; eGFR – estimated Glomerular filtration rate; FFP– Fresh Frozen Plazma; PT-INR – Prothrombin Time – International Normalized Ratio; APTT – Activated Partial Thromboplastin Time. |
TABLE 2 Potential predictors of periprocedural bleeding in the observed heart transplant patient population.
| Correlation Pair | Spearman ρ | Correlation Significance |
|---|
| Total Chest Output in 24h & Pretransplant PT-INR | 0.645 | 0.009* |
| Packed Red Blood Cell Transfusion Volume & Ischemic Etiology of Heart Failure | 0.543 | 0.036* |
| Fresh Frozen Plasma Transfusion Volume & Pretransplant PT-INR | 0.661 | 0.007* |
| Platelet Transfusion Volume & Ischemic Etiology of Heart Failure | 0.583 | 0.022* |
| Prothrombin Complex Concentrate Transfusion & Pretransplant PT-INR | 0.592 | 0.020* |
PT-INR – Prothrombin Time – International Normalized Ratio
* P < 0.05 |
Conclusion: Although there was no difference in the consumption of blood products and 24h thoracic drainage between patients who were on warfarin or dabigatran anticoagulation before HTx, it should be noted that the majority of patients on warfarin were not within the therapeutic INR range, and it was precisely the elevated INR that significantly correlated with the consumption of blood products and 24h thoracic drainage. It is necessary to conduct a study on a larger number of patients in order to find out whether the pre-HTx use of warfarin is equally safe and effective as the use of dabigatran, in terms of the perioperative bleeding.
