Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing

Lokhandwala, Parvez M.; O'Neal, Adrian; Patel, Eshan U.; Brunker, Patricia A. R.; Gehrie, Eric A.; Zheng, Gang; Kickler, Thomas S.; Ness, Paul M.; Tobian, Aaron A.R.

doi:10.1111/trf.14550

Cited by 13 publications

(21 citation statements)

References 21 publications

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“…Cryoprecipitate is not intended to replace FVIII or vWF in critical bleeding; nevertheless, we characterized these factors as well. As previously reported, FVIII levels decline precipitously after thawing, and vWF increases over the first 24 hours before declining at a much slower rate . vWF activity was better maintained in refrigerated cryoprecipitate.…”

Section: Discussionsupporting

confidence: 82%

“…Since cryoprecipitate is now primarily used for fibrinogen replacement in critical bleeding, the current guidelines may be overly restrictive and may contribute to decreased or delayed utilization and product waste. Previously published work has demonstrated that fibrinogen concentration is maintained in cryoprecipitate stored at room temperatures for up to 5 days . Recently, Green and colleagues showed that the function of fibrinogen, as measured by thrombin potential and ROTEM, in thawed cryoprecipitate stored at room temperature for 72 hours did not differ significantly from baseline …”

Section: Discussionmentioning

confidence: 97%

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Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures

et al. 2019

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BACKGROUND Cryoprecipitate's shelf life is limited due to concerns over decreased clotting factor activity and contamination with extended storage. Hemostatic characteristics of thawed cryoprecipitate stored up to 35 days at refrigerated and room temperatures were assessed. STUDY DESIGN AND METHODS Pooled cryoprecipitate was thawed and aliquoted for storage at 1–6°C or 21–24°C. Samples were tested immediately after thawing and at 4 h, 24 h, 72 h, and weekly for 35 days. At each time point fibrinogen, factor VIII (FVIII), and von Willebrand factor (vWF) were assessed. Thrombin generation and rotational thromboelastometry (ROTEM) were also performed. Further, packed red cells, platelet concentrates, frozen plasma, and stored cryoprecipitate were combined (1:1:1:1) to simulate massive transfusion and analyzed by ROTEM. Day 35 samples were cultured for bacterial contamination. RESULTS Precipitation was observed in refrigerated samples; however, these aggregates were easily resuspended upon warming in a 37°C water bath. No significant changes were observed in fibrinogen concentration or ROTEM at either temperature. FVIII and vWF declined significantly during storage. vWF, clot time, and thrombin generation were significantly better preserved with refrigeration. With simulated massive transfusion, fibrinogen function remained at or above the established range for whole blood at both storage temperatures. Bacterial contamination was not observed in cold stored or room temperature cryoprecipitate. CONCLUSION The fibrinogen concentration and function of cryoprecipitate at extended storage durations are adequate for fibrinogen replacement in critical bleeding. These results support extension of the shelf life of cryoprecipitate when used for fibrinogen replacement.

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 97%

Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures

et al. 2019

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“…We also observed prolonged APTT in the plasma collected from mice immediately after the hypothermia treatment, regardless of the presence or absence of splenic tissue where the platelets were being activated, indicating that the hypothermia itself inhibited the intrinsic pathway of the coagulation cascade. Some in vitro studies have shown that cold storage of plasma results in the reduction of coagulation factors . However, the impact of body temperature reduction on each coagulation factor needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Hypothermia‐induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model

Horioka

Tanaka

Isozaki

et al. 2019

Journal of Thrombosis and Haemostasis

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BackgroundHypothermia, either therapeutically induced or accidental (ie, an involuntary decrease in core body temperature to <35°C), results in hemostatic disorders. However, it remains unclear whether hypothermia enhances or inhibits coagulation, especially in severe hypothermia. The present study evaluated the thrombocytic and hemostatic changes in hypothermic mice.MethodsC57Bl/6 mice were placed at an ambient temperature of −20°C under general anesthesia. When the rectal temperature decreased to 15°C, 10 mice were immediately euthanized, while another 10 mice were rewarmed, kept in normal conditions for 24 hours, and then euthanized. These treatments were also performed in 20 splenectomized mice.ResultsThe hypothermic mice had adhesion of CD62P‐positive platelets with high expression of von Willebrand factor (vWF) in their spleens, while the status of the peripheral platelets was unchanged. Furthermore, the plasma levels of platelet factor 4 (PF4) and pro‐platelet basic protein (PPBP), which are biomarkers for platelet degranulation, were significantly higher in hypothermic mice than in control mice, indicating that hypothermia activated the platelets in the splenic pool. Thus, we analyzed these biomarkers in asplenic mice. There was no increase in either PF4 or PPBP in splenectomized hypothermic mice. Additionally, the plasma D‐dimer elevation and microthrombosis were caused in rewarmed mice, but not in asplenic rewarmed mice.ConclusionsOur results indicate that hypothermia leads to platelet activation in the spleen via the upregulation of vWF, and this activation causes hypercoagulability after rewarming.

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“…Hemostatic properties and fibrinogen levels of thawed cryoprecipitate held at ambient temperature (18–24°C) are preserved up to 120 hours . The stability of thromboelastometry clot firmness has also been demonstrated in thawed pooled cryoprecipitate units held at room temperature for up to 72 hours .…”

Section: Discussionmentioning

confidence: 96%

“…Prolonged shelf life of cryoprecipitate for up to 5 days after thawing has shown no significant decrease in factor content . The main impediment to the use of cryoprecipitate for longer than 6 hours after thawing is the risk of bacterial contamination in a product stored at room temperature.…”

mentioning

confidence: 99%

Efficacy of a new pathogen‐reduced cryoprecipitate stored 5 days after thawing to correct dilutional coagulopathy in vitro

et al. 2019

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BACKGROUND Fibrinogen supplementation during bleeding restores clot strength and hemostasis. Cryoprecipitate, a concentrated source of fibrinogen, has prolonged preparation time for thawing, a short shelf life resulting in frequent wastage, and infectious disease risk. This in vitro study investigated the efficacy of a new pathogen‐reduced cryoprecipitate thawed and stored at room temperature for 5 days (PR Cryo) to treat dilutional hypofibrinogenemia, compared to immediately thawed standard cryoprecipitate (Cryo) or fibrinogen concentrate (FC). STUDY DESIGN AND METHODS Ten phlebotomy specimens from healthy volunteers were diluted 1:1 with crystalloid and supplemented with PR Cryo and Cryo (at a dose replicating transfusion of two pooled doses [10 units]) and FC at a dose replicating 50 mg/kg. Changes in clot firmness (thromboelastometry) and in coagulation factor activity were assessed at baseline, after dilution, and after supplementation. RESULTS Clinical dosing was used, as described above, and consequently the FC dose contained 24% and 36% more fibrinogen versus PR Cryo and Cryo, respectively. At baseline, subjects had a median FIBTEM maximum clot firmness of 13.5 mm, versus 6.5 mm after 50% dilution (p = 0.005). After supplementation with PR Cryo, a median FIBTEM maximum clot firmness of 13 mm was observed versus 9.0 mm for Cryo (p = 0.005) or 16.5 mm for FC (p = 0.005). Median factor XIII was higher after PR Cryo (64.8%) versus Cryo (48.3%) (p = 0.005). Fibrinogen activity was higher after FC (269.0 mg/dL) versus PR Cryo (187.0 mg/dL; p = 0.005) or Cryo (193.5 mg/dL; p = 0.005); the difference between PR Cryo and Cryo supplementation (p = 0.445) was not significant. CONCLUSION PR Cryo used 5 days after thawing effectively restores clot strength after in vitro dilution.

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Hemostatic profile and safety of pooled cryoprecipitate up to 120 hours after thawing

Abstract: Extended cryoprecipitate storage at ambient temperature did not affect fibrinogen levels over 120 hours. Sterility of products held at ambient temperature for an extended period of time could be assessed by secondary culture.

Cited by 13 publications

References 21 publications

Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures

Hemostatic characteristics of thawed, pooled cryoprecipitate stored for 35 days at refrigerated and room temperatures

Hypothermia‐induced activation of the splenic platelet pool as a risk factor for thrombotic disease in a mouse model

Efficacy of a new pathogen‐reduced cryoprecipitate stored 5 days after thawing to correct dilutional coagulopathy in vitro

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