Dynamics of Platelet Counts in Major Trauma: The Impact of Haemostatic Resuscitation and Effects of Platelet Transfusion—A Sub-Study of the Randomized Controlled RETIC Trial

Abstract

Although platelets play a central role in haemostasis, the dynamics of platelet counts during haemostatic resuscitation, the response to platelet transfusion, and effects on clinical outcome are poorly described for trauma patients. As a sub-study of the already published randomized controlled RETIC Study “Reversal of Trauma-induced Coagulopathy using First-line Coagulation Factor Concentrates or Fresh-Frozen Plasma” trial, we here analysed whether the type of first-line haemostatic resuscitation influences the frequency of platelet transfusion and determined the effects of platelet transfusion in coagulopathic patients with major trauma. Patients randomly received first-line plasma (FFP) or coagulation factor concentrates (CFC), mainly fibrinogen concentrate. In both groups, platelets were transfused to maintain platelet counts between 50 and 100 × 109/L. Transfusion rates were significantly higher in the FFP (n = 44) vs. CFC (n = 50) group (FFP 47.7% vs. CFC 26%); p = 0.0335. Logistic regression analysis adjusted for the stratification variables injury severity score (ISS) and brain injury confirmed that first-line FFP therapy increases the odds for platelet transfusion (odds ratio (OR) 5.79 (1.89 to 20.62), p = 0.0036) and this effect was larger than a 16-point increase in ISS (OR 4.33 (2.17 to 9.74), p = 0.0001). In conclusion, early fibrinogen supplementation exerted a platelet-saving effect while platelet transfusions did not substantially improve platelet count and might contribute to poor clinical outcome.

The European guideline on management of major bleeding and coagulopathy following trauma: sixth edition

“…While a low platelet count has been consistently associated with both morbidity and mortality in trauma patients, the threshold and timing of platelet transfusion remains controversial [ 6 ]. Although the platelet count at admission was found to be a biomarker for trauma severity and predictive of outcome, including bleeding intensity and transfusion requirements [ 262 ], platelet counts are frequently within the normal range at hospital admission, but may decrease sharply in the following 1–2 h of haemostatic resuscitation and decline continuously thereafter, suggesting an important role for the treatment administered [ 310 ].…”

First-Line Administration of Fibrinogen Concentrate in the Bleeding Trauma Patient: Searching for Effective Dosages and Optimal Post-Treatment Levels Limiting Massive Transfusion—Further Results of the RETIC Study

“…In an in vitro study questioning the optimal level of fibrinogen, Bollinger and co-workers found that only fibrinogen levels above 200 mg•dL −1 enhance total clot formation [26]. Previously published results from the RETIC study confirmed that early achievement of fibrinogen levels above 200 mg•dL −1 not only normalized FibA10, but also total clot firmness, reduced the rate of MT significantly, and reduced platelet count decline and the need for platelet transfusion [21,22].…”

“…However, fibrinogen is at least a contributing factor and also one, which can be influenced by therapy. Moreover, early achievement of fibrinogen levels above 200 mg•dL −1 exerts a platelet saving effect and platelets further augment stable clot formation and limitation of blood loss [22].…”

“…Post randomization, six patients were excluded (erroneously inclusion, protocol deviation with loss of follow up), leaving data of 44 patients in the FFP group and 50 patients in the CFC group for final modified intent-to-treat analysis. First results have been previously published [21,22].…”

Platelet Transfusion and Outcomes After Massive Transfusion Protocol Activation for Major Trauma: A Retrospective Cohort Study

“…Recently, a substudy of the randomized, controlled RETIC trial has shown that platelet transfusion did not substantially improve platelet counts and that, after adjusting for injury severity, transfusion of platelets was associated with poor clinical outcomes. 30 However, the authors did conclude that there is no evidence of a causal relationship between platelet transfusion and poor outcomes and that platelet transfusion is more likely to be a surrogate marker of severe injury and massive bleeding, both of which are associated with mortality.…”