The use of cryopreserved platelets in a trauma‐induced hemorrhage model

Abstract

Background Cryopreserved platelet products can be stored for years and are mainly used in military settings. Following thawing, cryopreserved platelets are activated, resulting in faster clot formation but reduced aggregation in vitro, rendering their efficacy in bleeding unknown. Also, concerns remain on the safety of these products. The aim was to investigate the efficacy and safety of cryopreserved platelets in a rat model of traumatic hemorrhage. Study Design and Methods After 1 hour of shock, rats (n = 13/group) were randomized to receive a balanced transfusion pack (1:1:1 red blood cell:plasma:platelet) made from syngeneic rat blood, containing either liquid stored platelets or cryopreserved platelets. Primary outcome was the transfusion volume required to obtain a mean arterial pressure (MAP) of 60 mmHg. Secondary outcomes were coagulation as assessed by thromboelastometry (ROTEM®) and organ failure as assessed by biochemistry and histopathology. Results The transfusion volume to obtain a MAP of 60 mmHg was lower in animals receiving cryopreserved platelets (5.4 [4.1‐7.1] mL/kg) compared to those receiving liquid stored platelets (7.5 [6.4‐8.5] mL/kg, p < 0.05). ROTEM® clotting times were shorter (45 [41‐48] vs. 49 [45‐53]sec, p < 0.05), while maximum clot firmness was slightly lower (68 [67‐68] vs. 69 [69‐71]mm, p < 0.01). Organ failure was similar in both groups. Conclusions Use of cryopreserved platelets required less transfusion volume to reach a targeted MAP compared to liquid stored platelets, while organ injury was similar. These results provide a rationale for clinical trials with cryopreserved platelets in (traumatic) bleeding.

The haemostatic effect of deep-frozen platelets versus room temperature-stored platelets in the treatment of surgical bleeding: MAFOD—study protocol for a randomized controlled non-inferiority trial

“…An animal study including rats with traumatic haemorrhage who were subsequently transfused with DTC showed reduced blood component use compared to RSP to reach and maintain a mean arterial pressure of 60 mmHg [ 11 , 12 ]. In thrombocytopenic patients, the use of cryopreserved platelets appears to be safe and effective, and also in trauma [ 12 ], cardiopulmonary surgery [ 9 ] or thrombocytopenia [ 10 , 14 ], the outcome of treatment with frozen platelets was similar to room-stored platelet transfusion. Despite this fact, high-quality evidence from randomized clinical trials for the efficacy of DTC in acute bleeding is still lacking.…”

“…Retrospective data from missions from the NLAF show that increased DTC and plasma use as a result of the implementation of an MTP resulted in a significant improvement in chances of survival during armed conflict [ 7 ]. However, in this setting, no RSP were available to provide evidence of an improved haemostatic potential of DTC in the treatment of acute bleeding, as has been suggested by the above-mentioned rat study [ 12 ] and one cardiopulmonary bypass surgery study [ 9 ]. We believe that DTCs provide a suitable and potentially better alternative to RSP in the treatment of bleeding patients.…”

“…These differences are likely due to platelet activation and release of platelet-derived microparticles after the thaw [ 11 ]. The use of DTCs in several clinical studies has not led to effectivity or safety issues in trauma [ 12 ], thrombocytopenic [ 11 , 13 ] or cardiopulmonary bypass [ 9 ] patients and in rats [ 12 ]. In the currently introduced multi-centre, single-blinded, randomized controlled non-inferiority trial, the objective is to compare the haemostatic effects of DTCs with the currently predominantly used RSPs in the treatment of surgical bleeding and to show that DTCs have at least similar haemostatic effects as compared to RSP.…”

Proteomics: A Tool to Study Platelet Function

“…The clearance occurs through triggered surface up-regulation of neuraminidases, which perform the vWF-receptor complex’s desialylation, specifically, the GPIbα subunit leading to GPIbα-clustering and rapid platelet clearance by liver phagocytes [ 154 , 187 , 188 ]. Although cryopreservation slows down the metabolism, reduces the risk of bacterial contamination, and is therefore proposed as a prominent alternative to the current storage standard at 22 °C, its application is still under debate since the freeze-thawing-induced activation of platelets may promote the risk of thromboembolic events [ 189 ]. Wang et al compared the proteomic signature of platelets stored at 22 °C, 10 °C, and −80 °C and concluded that different conditions caused different PSLs.…”

The haemostatic effect of deep-frozen platelets versus room temperature stored platelets in the treatment of surgical bleeding. MAFOD: study protocol for a randomized controlled non-inferiority trial

“…(8-10) These differences are likely due to platelet activation and release of platelet derived micro particles after thaw. (11) The use of DTCs in several clinical studies has not led to effectivity or safety issues in trauma (12), thrombocytopenic (11,13) or cardiopulmonary bypass (9) patients and in in rats. (12) In the current introduced multi-centre, single blinded, randomized controlled non-inferiority trial, the objective is to compare the haemostatic effects of DTCs with the currently predominantly used RSPs in the treatment of surgical bleeding and to show that DTCs have at least similar haemostatic effects as compared to RSP.…”