Pär I. Johansson
Continued hemorrhage remains a major contributor to mortality in massively transfused (MT) patients of whom many develop coagulopathy (1). The complexity of treating MT patients may result in a suboptimal transfusion therapy further contributing to the poor outcome (2,3). Classically, blood banks have focused on providing compatible blood products of the highest possible quality to meet the requests from the clinicians, relying on that the clinicians' knowledge of existing transfusion guidelines which results in optimal transfusion therapy for bleeding patients (4). These guidelines, however, advocate early administration of crystalloids and colloids, and administration of FFP and platelets only when a whole blood volume or more has been substituted, which may compromise hemostatic ability further in the most severely bleeding patients (5,6). Furthermore, these guidelines base their recommendations on when to administer plasma and platelets on the result of conventional coagulation assays such as activated partial thromboplastin time (APTT) and prothrombin time (PT) despite that these assays poorly correlate with clinically relevant coagulopathies (7-10). Instead, employing a cell-based whole blood assay such as thrombelastography (TEG) will provide quantitative information of the entire haemostatic process and, thereby, a profile of the haemostatic changes occurring during coagulation (11,12). Furthermore, the TEG® data are described quantitatively to provide for a dynamic velocity profile of changes in blood elasticity and therefore may better guide how patients presenting with massive bleeding should be treated with blood products (13,14,15,16). Based on this assumption, TEG was implemented as routine analysis in the blood bank and displayed bedside in the trauma centre, operation theatres, or in the intensive care units (iCU). We therefore evaluated whether the blood bank could improve its service for the clinician and, ultimately, for the patient thereby affecting the outcome for these complex patients. Furthermore, we investigated whether a revised and more proactive transfusion strategy for the MT patients improves outcome. Lastly, how best to monitor the treatment of these MT patients?
The blood bank introduced monitoring the delivery of blood products and contacted the clinician provided when a patient received >10 red blood cells (RBC), but no fresh frozen plasma (FFP) or when >20 RBC+FFP were delivered but no platelets, suggesting that administration of FFP and/or platelet concentrates (PC) should be considered For MT patients, a transfusion package encompassing 5 units of RBC, 5 units of FFP and 2 units of PC were introduced to be administered in parallel and consecutively until the patient either demonstrated hemostasis or expired. A cell-based assay, the TEG® analysis, was implemented in the blood bank, and the results displayed bedside in the trauma center, operating rooms and intensive care units for diagnosis and treatment of coagulopathy by the anesthesiologists who had been trained and certified in the use of TEG by the blood bank. Furthermore, an expert in transfusion medicine and TEG® in the blood bank was on call 24/7 as a back-up .
These interventions were introduced in 2004 and, hence, MT patients treated in 2003 were compared to those treated after the interventions treated in 2005. To evaluate the transfusion packages in a more standardized setting patients undergoing surgery for a ruptured abdominal aortic aneurysm (rAAA) was investigated. Transfusion packages was administered intraoperatively to patients operated for a rAAA during a 12-month period and their survival was compared to controls, transfused according to current guidelines, 24 months prior to the intervention (18).
Introducing real-time monitoring and transfusion packages reduced the population of suboptimally transfused MT patients from 6% in 2003 to less than 2% in 2005, p<0.01. In regard to patients operated for a rAAA the intervention group, as planned, received more PC 4 (2-16) vs. 0 (0-3) units and FFP 11 (2-42) vs. 7 (0-46) units, p<0.05 respectively, during surgery than the control group and had a higher platelet count (155 vs. 69 x109/L, p < 0.001) and shorter APTT upon arrival at the ICU (39 vs. 44 s, p < 0.001). Blood product transfusion requirements in the ICU were lower in the intervention group for RBC 2 (0-30) vs. 6 (0-54) units, for FFP 2 (0-12) vs. 4 (0-32) units and for PC 0 (0-4) vs. 1 (0-6) units, p<0.05 for all comparisons when compared with the control group. Importantly, the 30-day survival in the intervention group was higher (66%) compared to that of the control group (44%), p=0.02. Survival was related to platelet count upon arrival at the ICU and it was 30% in patients with a platelet count <50 x109/L, 45% in those with a platelet count between 50-100 x109/L compared to 69% in patients having a platelet count >100 x109/L .
The TEG® analysis demonstrated a 97% predictability for a surgical cause of bleeding in 35 postoperative patients with ongoing transfusion requirements and a normal TEG® . In trauma patients, 10% of the hemodynamically unstable patients had fibrinolysis as the major cause of bleeding upon arrival, identified by TEG® alone, whereas 45% were hypercoagulable. In complex cardiac surgery, TEG® alone, were able to identify coagulopathies, other than anticoagulation by heparin, in patients on ECMO or cardiopulmonary bypass and correction of such a coagulopathy was life saving (19).
The blood bank has become an integrated element in the treatment of MT patients by introducing real-time monitoring, transfusion packages and TEG® as to identify the type of coagulopathy in actively bleeding patients. These results supports that suboptimal transfusion therapy can be prevented by the use of transfusion packages and also that early and aggressive administration with plasma and platelets improves coagulation competence in massively bleeding patients.
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