Early Plasma Transfusion Research Articles

ASSOCIATION BETWEEN PLASMA TRANSFUSION AND IN-HOSPITAL MORTALITY IN CRITICALLY ILL PATIENTS WITH SEPSIS-INDUCED COAGULOPATHY.

Background: Plasma is commonly used in patients with coagulopathy; however, its role in patients with sepsis-induced coagulopathy (SIC) is unclear. This study aimed to evaluate the effect of plasma transfusion on the prognosis of patients with SIC. Methods: Data were collected from the Medical Information Mart for Intensive Care IV database. Multivariable logistic regression analysis was used to determine the association between plasma transfusion and the incidence of in-hospital mortality, pulmonary embolism, and lower extremity deep vein thrombosis in critically ill patients with SIC. Propensity score matching (PSM) and propensity score-based inverse probability of treatment weighting (IPTW) models were used to ensure the robustness of our findings. Furthermore, the nonparametric relationship between in-hospital mortality and plasma transfusion volume was analyzed using restricted cubic spline. Subgroups analyses were performed for age, sex, Charlson score, Sequential Organ Failure Assessment score, SIC score, and with hemorrhage. Results: A total of 8,747 patients with SIC were enrolled: of them, 1874 were in the plasma infusion group, and 6,873 were in the no plasma infusion group. Compared with the no plasma infusion group, the plasma infusion group had higher in-hospital mortality (odds ratio [OR], 1.4411; 95% confidence interval [CI], 1.2280-1.6897, P < 0.05), and the results were robust after PSM (OR, 1.3227; 95% CI, 1.1152-1.5697; P < 0.05) and IPTW (OR, 1.1541; 95% CI, 1.0738-1.2404; P < 0.05). Similar results were also observed in different subgroups. However, because of conflicting results after PSM and IPTW, we were unable to definitively link plasma transfusion with pulmonary embolism and deep vein thrombosis. Compared with the no early plasma transfusion group (≥12 h), the in-hospital mortality rate was lower in the early plasma transfusion group (<12 h) (OR, 0.5426; 95% CI, 0.4398-0.6844; P < 0.05). The restricted cubic spline analysis indicated that increased plasma transfusion was associated with increased in-hospital mortality in patients with SIC. Conclusion: Plasma transfusion increases in-hospital mortality in patients with SIC, and the mortality rate increases with the amount of plasma transfusion. Patients with SIC who received early plasma infusion had lower in-hospital mortality than those who received no early plasma transfusion.

Evaluation of the Potential for Improvement of Clinical Outcomes in Trauma Patients with Massive Hemorrhage by Maintaining a High Plasma-to-Red Blood Cell Ratio during the First Hour of Hospitalization.

Several reports indicate that early plasma transfusion may promote survival and reduce the incidence of traumatic coagulopathy in situations of massive bleeding. Consequently, it is recommended to maintain a plasma and RBC transfusion ratio between 1 : 1 and 1 : 2 at the start of admission. This retrospective study examined the effect of an early high plasma : RBC ratio on mortality rates by adopting a massive transfusion protocol (MTP) that forced an early and rapid issue of plasma products. Patients who received massive transfusions at a single trauma center between January 2014 and May 2020 were included in the study. A new protocol was established in January 2020, wherein a fixed amount of plasma was issued following MTP activation. Patients who underwent massive transfusions before and after the adoption of the new protocol were compared. In total, 1059 patients met the inclusion criteria. Fifty-one patients who underwent MTP were propensity score-matched with the patients who received a nonprotocolized massive transfusion. The MTP group had a higher plasma : RBC ratio at 1 h (0.8 vs. 0.2) and 4 h of hospitalization (1.1 vs. 0.6), with no significant between-group difference in the plasma : RBC ratio at 24 h of hospitalization. The MTP group had a lower 24 h mortality rate than the control group. There was no significant difference in the 30-day mortality. Using MTP to achieve a high plasma : RBC ratio in the early period of hospitalization appeared to affect 24-hour mortality; however, 30-day mortality did not change.

Efficacy of early transfusion of convalescent plasma with high-titer SARS-CoV-2 neutralizing antibodies in hospitalized patients with COVID-19.

BackgroundDespite most controlled trials have shown no measurable benefit of COVID‐19 convalescent plasma (CCP) in patients with COVID‐19, some studies suggest that early administration of CCP with high‐titer anti‐SARS‐CoV‐2 can be beneficial in selected patients. We investigated the efficacy of early administration of high‐titer CCP to patients with COVID‐19 who required hospitalization,Study design and methodsObservational, propensity score (PS) matched case–control study of COVID‐19 patients treated with CCP within 72 h of hospital admission and untreated controls from August 2020 to February 2021. All CCP donations had a Euroimmun anti‐SARS‐CoV‐2 sample‐to‐cutoff ratio ≥3. PS matching was based on prognostic factors and presented features with high‐standardized differences between the treated and control groups. The primary endpoint was mortality within 30 days of diagnosis.ResultsA total of 1604 patients were analyzed, 261 of whom received CCP, most (82%) within 24 h after admission. Median age was 67 years (interquartile range: 56–79), and 953 (60%) were men. Presenting factors independently associated with higher 30‐day mortality were increased age, cardiac disease, hypoxemic respiratory failure, renal failure, and plasma d‐dimer >700 ng/ml.After PS matching, transfusion of CCP was associated with a significant reduction in the 30‐day mortality rate (odds ratio [OR]; 0.94, 95% confidence interval [CI]: 0.91–0.98; p = .001) that extended to the 60th day after COVID‐19 diagnosis (OR: 0.95; 95% CI: 0.92–0.99; p = .01).ConclusionOur results suggest that CCP can still be helpful in selected patients with COVID‐19 and call for further studies before withdrawing CCP from the COVID‐19 therapeutic armamentarium.

Retention of hemostatic and immunological properties of frozen plasma and COVID-19 convalescent apheresis fresh-frozen plasma produced and freeze-dried in Canada.

Randomized clinical trial data show that early plasma transfusion may save lives among trauma patients. Supplying plasma in remote environments is logistically challenging. Freeze-dried plasma (FDP) offers a possible solution. A Terumo BCT plasma freeze-drying system was evaluated. We compared pooled frozen plasma (FP) units with derived Terumo BCT FDP (TFDP) units and pooled COVID-19 convalescent apheresis fresh-frozen plasma (CC-AFFP) with derived CC-TFDP units. Parameters measured were: coagulation factors (F) II; V; VII; VIII; IX; XI; XIII; fibrinogen; Proteins C (PC) and S (PS); antithrombin (AT); α2 -antiplasmin (α2 AP); ADAMTS13; von Willebrand Factor (vWF); thrombin-antithrombin (TAT); D-dimer; activated complement factors 3 (C3a) and 5 (C5a); pH; osmolality; prothrombin time (PT); and activated partial thromboplastin time (aPTT). Antibodies to SARS-CoV-2 in CC-AFFP and CC-TFDP units were compared by plaque reduction assays and viral protein immunoassays. Most parameters were unchanged in TFDP versus FP or differed ≤15%. Mean aPTT, PT, C3a, and pH were elevated 5.9%, 6.9%, 64%, and 0.28 units, respectively, versus FP. CC-TFDP showed no loss of SARS-CoV-2 neutralization titer versus CC-AFFP and no mean signal loss in most pools by viral protein immunoassays. Changes in protein activities or clotting times arising from freeze-drying were <15%. Although C3a levels in TFDP were elevated, they were less than literature values for transfusable plasma. SARS-CoV-2-neutralizing antibody titers and viral protein binding levels were largely unaffected by freeze-drying. In vitro characteristics of TFDP or CC-TFDP were comparable to their originating plasma, making future clinical studies appropriate.

Early Transfusion of Convalescent Plasma Improves the Clinical Outcome in Severe SARS-CoV2 Infection.

IntroductionPlasma harvested from convalescent COVID-19 patients (CCP) has been applied as first-line therapy in the early phase of the SARS-CoV2 pandemic through clinical studies using various protocols.MethodsWe present data from a cohort of 267 hospitalized severe COVID-19 patients who received CCP. No transfusion-related complications were reported, indicating the overall safety of CCP therapy.ResultsPatients who eventually died from COVID-19 received CCP significantly later (3.95 versus 5.22 days after hospital admission) and had higher interleukin 6 (IL-6) levels (28.9 pg/ml versus 102.5 pg/ml) than those who survived. In addition, CCP transfusion caused a significant reduction in the overall inflammatory status of the patients regardless of the severity of disease or outcome, as evidenced by decreasing C-reactive protein, IL6 and ferritin levels.ConclusionWe conclude that CCP transfusion is a safe and effective supplementary treatment modality for hospitalized COVID-19 patients characterized by better expected outcome if applied as early as possible. We also observed that IL-6 may be a suitable laboratory parameter for patient selection and monitoring of CCP therapy effectiveness.

Evaluation of the hemostatic capacity of methylene blue-treated liquid (not frozen) plasma stored up 14 days at 2° to 6°C.

Early plasma transfusion for management of bleeding, particularly trauma, is associated with better outcomes. Improving the availability/safety of plasma transfusion for patients is essential for transfusion services. The aim of this study is to evaluate the hemostatic capacity of methylene-blue (MB) liquid (not frozen) plasma over time. Twenty whole blood-derived plasma units collected from male donors were separated and processed within 18 h of collection. Individual plasmas were treated with MB and stored in liquid status at 2-6°C for 14 days. A range of coagulation assays, including thrombin generation, rotational thromboelastometry (ROTEM), and Thrombodynamics were tested at different time-points, together with bacterial growth. Apart from Factor (F)XII, other coagulation factors (fibrinogen, FV, FVIII, FXI) reduced significantly after MB treatment, with levels remaining stable except for FVIII afterward. By day 14, most clotting factors were >0.7IU/ml, apart from FVIII. There was a disproportionate decrease in Protein S (PS) activity compared to free PS antigen and by day 14 its value was ~50%. There was no significant difference in maximum clot formation (ROTEM) and clot-density (Thrombodynamics) over time. Endogenous thrombin potential (Thrombin-Generation), clot-size, and velocity index (Thrombodynamics) decreased significantly over time consistent with clotting factor reduction. There was no bacterial growth. MB-treated liquid plasma stored at 2-6°C can be used for up to 14 days: the long shelf-life, the liquid status, and the MB treatment will improve its availability for management of bleeding as well as providing a safe component from pathogens.

Re-introducing whole blood for transfusion: considerations for blood providers.

Whole blood is the original blood preparation but disappeared from the blood bank inventories in the 1980s following the advent of component therapy. In the early 2000s, both military and civilian practice called for changes in the transfusion support for massive haemorrhage. The 'clear fluid' policy was abandoned and replaced by early balanced transfusion of platelets, plasma and red cells. Whole blood is an attractive alternative to multi-component therapy, which offers reduced hemodilution, lower donor exposure and simplified logistics. However, the potential for wider re-introduction of whole blood requires re-evaluation of haemolysins, storage conditions and shelf-life, the need for leucocyte depletion/ pathogen reduction and inventory management for blood providers. This review addresses these questions and calls for research to define the optimal whole blood product and the indications for its use.

Trauma-Induced Coagulopathy and Massive Bleeding: Current Hemostatic Concepts and Treatment Strategies.

Hemorrhage after trauma remains a significant cause of preventable death. Trauma-induced coagulopathy (TIC) at the time of hospital admission is associated with an impaired outcome. Rather than a universal phenotype, TIC represents a complex hemostatic disorder, and standard coagulation tests are not designed to adequately reflect the complexity of TIC. Viscoelastic testing (VET) has gained increasing interest for the characterization of TIC because it provides a more comprehensive depiction of the coagulation process. Thus, VET has been established as a point-of-care-available hemostatic monitoring tool in many trauma centers. Damage-control resuscitation and early administration of tranexamic acid provide the basis for treating TIC. To improve survival, ratio-driven massive transfusion protocols favoring early and high-dose plasma transfusion have been implemented in many trauma centers around the world. Although plasma contains all coagulation factors and inhibitors, only high-volume plasma transfusion allows for adequate substitution of lacking coagulation proteins. However, high-volume plasma transfusion has been associated with several relevant risks. In some European trauma facilities, a more individualized hemostatic therapy concept has been implemented. The hemostatic profile of the bleeding patient is evaluated by VET. Subsequently, goal-directed hemostatic therapy is primarily based on coagulation factor concentrates such as fibrinogen concentrate or prothrombin complex concentrate. However, a clear difference in survival benefit between these two treatment strategies has not yet been shown. This concise review aims to summarize current evidence for different diagnostic and therapeutic strategies in patients with TIC.

Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes: A Post Hoc Analysis of the PAMPer and COMBAT Clinical Trials

Current guidelines emphasize early plasma transfusion and balanced transfusion in trauma patients with hemorrhagic shock. There have been 2 recent randomized control trials, the Prehospital Air Medical Plasma (PAMPer) trial and the Control of Major Bleeding After Trauma (COMBAT) trial, that took a closer look at initiating plasma transfusion even earlier - in the prehospital setting. These trials had contradicting results as the PAMPer trial showed improved survival and the COMBAT trial showed no benefit.

Current state of whole blood transfusion for civilian trauma resuscitation.

Whole blood (WB) is rapidly emerging as the treatment modality of choice for the initial resuscitation of civilian trauma patients across the United States. The reemergence of WB has been rapid and driven in part by recognition of the importance of early plasma transfusion in the resuscitation process. The study was designed as a critical analysis of the available literature on WB transfusion in civilian trauma patients. Studies were included if they reported on transfusion of cold-stored WB used in a civilian setting and measured safety, feasibility, or a direct clinical outcome. Examination of the available literature supports the feasibility and safety of WB used in treatment of civilian trauma patients. The evidence regarding clinical outcomes, particularly with direct comparison to equivalent doses of component therapy, is more limited. The literature is predominantly descriptive and retrospective in nature and limited by the heterogeneity of clinical WB protocols being used. Based on this limited data set, there are limited conclusions that can be used to definitely support or refute the clinical superiority of WB to component therapy. Current literature supports the safety and feasibility of WB, but prospective randomized trials comparing WB to component therapy are needed to provide the definitive evidence on this topic.

Indications for early plasma transfusion and its optimal use following trauma.

This study aimed to evaluate the effect of plasma transfusion before urgent hemostasis initiation on in-hospital mortality in hemodynamically unstable patients with severe trauma. This retrospective observational study of patients admitted to hospital between January 2011 and January 2019 grouped patients according to whether plasma transfusion was initiated before (Before group) or after (After group) hemostasis initiation. Patients with severe trauma who were unable to wait for plasma transfusion and had started hemostasis before the plasma infusion were excluded. We used multivariable logistic regression analysis to determine the effect of plasma transfusion before the initiation of urgent hemostasis on in-hospital mortality. We included 47 and 73 patients in the Before and After groups, respectively. Blunt trauma was more common, and the D-dimer levels and Injury Severity Score were significantly higher in the Before group than in the After group (median D-dimer, 57.5 versus 38.1μg/mL; P=0.040; median Injury Severity Score, 50 versus 34; P<0.001). Plasma given before hemostasis initiation was associated with significantly lower in-hospital mortality (adjusted odds ratio, 0.27; 95% confidence interval, 0.078-0.900; P=0.033) in contrast with the total plasma volume given in the first 6 or 24h. Plasma transfusion before hemostasis initiation could be an important factor for improving outcomes in hemodynamically unstable patients with blunt trauma, high D-dimer levels, or a high Injury Severity Score.

Association of Prehospital Plasma Transfusion With Survival in Trauma Patients With Hemorrhagic Shock When Transport Times Are Longer Than 20 Minutes

Both military and civilian clinical practice guidelines include early plasma transfusion to achieve a plasma to red cell ratio approaching 1:1 to 1:2. However, it was not known how early plasma should be given for optimal benefit. Two recent randomized clinical trials were published, with apparently contradictory results. The Prehospital Air Medical Plasma (PAMPer) clinical trial showed a nearly 30% reduction in mortality with plasma transfusion in the prehospital environment, while the Control of Major Bleeding After Trauma (COMBAT) clinical trial showed no survival improvement. To facilitate a post hoc combined analysis of the COMBAT and PAMPer trials to examine questions that could not be answered by either clinical trial alone. We hypothesized that prehospital transport time influenced the effects of prehospital plasma on 28-day mortality. A total of 626 patients in the 2 clinical trials were included. Patients with trauma and hemorrhagic shock were randomly assigned to receive either standard care or 2 U of thawed plasma followed by standard care in the prehospital environment. Data analysis was performed between September 2018 and January 2019. Prehospital transfusion of 2 U of plasma compared with crystalloid-based resuscitation. The main outcome was 28-day mortality. In this post hoc analysis of 626 patients (467 men [74.6%] and 159 women [25.4%]; median [interquartile range] age, 42 [27-57] years) who had trauma with hemorrhagic shock, a Cox regression analysis showed a significant overall survival benefit for plasma (hazard ratio [HR], 0.65; 95% CI, 0.47-0.90; P = .01) after adjustment for injury severity, age, and clinical trial cohort (COMBAT or PAMPer). A significant association with prehospital transport time was detected (from arrival on scene to arrival at the trauma center). Increased mortality was observed in patients in the standard care group when prehospital transport was longer than 20 minutes (HR, 2.12; 95% CI, 1.05-4.30; P = .04), while increased mortality was not observed in patients in the prehospital plasma group (HR, 0.78; 95% CI, 0.40-1.51; P = .46). No serious adverse events were associated with prehospital plasma transfusion. These data suggest that prehospital plasma is associated with a survival benefit when transport times are longer than 20 minutes and that the benefit-risk ratio is favorable for use of prehospital plasma. ClinicalTrials.gov identifiers: NCT01838863 (COMBAT) and NCT01818427 (PAMPer).

Association of Timing of Plasma Transfusion With Adverse Maternal Outcomes in Women With Persistent Postpartum Hemorrhage

Early plasma transfusion for women with severe postpartum hemorrhage (PPH) is recommended to prevent coagulopathy. However, there is no comparative, quantitative evidence on the association of early plasma transfusion with maternal outcomes. To compare the incidence of adverse maternal outcomes among women who received plasma during the first 60 minutes of persistent PPH vs women who did not receive plasma for similarly severe persistent PPH. This multicenter cohort study used a consecutive sample of women with persistent PPH, defined as PPH refractory to first-line measures to control bleeding, between January 1, 2011, and January 1, 2013. Time-dependent propensity score matching was used to select women who received plasma during the first 60 minutes of persistent PPH and match each of them with a woman who had shown the same severity and received the same treatment of PPH but who had not received plasma at the moment of matching. Transfusions were not guided by coagulation tests. Statistical analysis was performed from June 2018 to June 2019. Transfusion of plasma during the first 60 minutes of persistent PPH vs no or later plasma transfusion. Incidence of adverse maternal outcomes, defined as a composite of death, hysterectomy, or arterial embolization. This study included 1216 women (mean [SD] age, 31.6 [5.0] years) with persistent PPH, of whom 932 (76.6%) delivered vaginally and 780 (64.1%) had PPH caused by uterine atony. Seven women (0.6%) died because of PPH, 62 women (5.1%) had a hysterectomy, and 159 women (13.1%) had arterial embolizations. Among women who received plasma during the first 60 minutes of persistent PPH, 114 women could be matched with a comparable woman who had not received plasma at the moment of matching. The incidence of adverse maternal outcomes was similar between the women, with adverse outcomes recorded in 24 women (21.2%) who received early plasma transfusion and 23 women (19.9%) who did not receive early plasma transfusion (odds ratio, 1.09; 95% CI, 0.57-2.09). Results of sensitivity analyses were comparable to the primary results. In this cohort study, initiation of plasma transfusion during the first 60 minutes of persistent PPH was not associated with adverse maternal outcomes compared with no or later plasma transfusion, independent of severity of PPH.

The need for dried plasma - a national issue.

Recent studies have demonstrated that early transfusion of plasma or RBCs improves survival in patients with severe trauma and hemorrhagic shock. Time to initiate transfusion is the critical factor. It is essential that transfusion begin in the prehospital environment when transport times are longer than approximately 15 to 20 minutes. Unfortunately, logistic constraints severely limit the use of blood products in the prehospital setting, especially in military, remote civilian, and mass disaster circumstances, where the need can be most acute. US military requirements for logistically supportable blood products are projected to increase dramatically in future conflicts. Although dried plasma products have been available and safely used in a number of countries for over 20 years, there is no dried plasma product commercially available in the United States. A US Food and Drug Administration-approved dried plasma is urgently needed. Considering the US military, disaster preparedness, and remote civilian trauma perspectives, this is an urgent national health care issue.

Use of French lyophilized plasma transfusion in severe trauma patients is associated with an early plasma transfusion and early transfusion ratio improvement.

Early transfusion of high ratio of fresh frozen plasma (FFP) and red blood cells (RBC) is associated with mortality reduction. However, time to reach high ratio is limited by the need to thaw the FFP. French lyophilized plasma (FLYP) used by French army and available in military teaching hospital does not need to be thawed and is immediately available. We hypothesize that the use of FLYP may reduce time to reach a plasma/RBC ratio of 1:1. A retrospective study performed in a Level 1 trauma center between January 2012 and December 2015. Severe trauma patients who received 2 U of RBC in the emergency room were included and assigned to two groups according to first plasma transfused: FLYP group and FFP group. Forty-three severe trauma patients in the FLYP group and 29 in the FFP group were included. The time until first plasma transfusion was shorter in the FLYP group than in the FFP group, respectively 15 min (10-25) versus 95 min (70-145) (p < 0.0001). Time until a 1:1 ratio was shorter in the FLYP group than in the FFP group. There were significantly fewer cases of massive transfusion in the FLYP group than in the FFP group with respectively 7% vs. 45% (p < 0.0001). The use of FLYP provided significantly faster plasma transfusions than the use of FFP as well as a plasma and RBC ratio superior to 1:2 that was reached more rapidly in severe trauma patients. These results may explain the less frequent need for massive transfusion in the patients who received FLYP. These positive results should be confirmed by a prospective and randomized evaluation. Therapeutic, level IV.

Damage Control Resuscitation: Restarting the Machinery of Life

Resuscitation of the patients suffering major haemorrhage has seen a marked change in mind-set in the current millennium. This article contains a perspective on the history of shock, the detrimental effects of the traditional sequential resuscitation reactive approach of using clear fluids for volume expansion followed by blood and component therapy, and the current philosophy of the early proactive transfusion of red blood cells, plasma, and platelets in a recommended ratio. The debate concerning pharmacological intervention for fibrinolysis and percutaneous mechanical control of haemorrhage will be discussed. Although the initial goal should be to achieve a ratio of 1:1:1 for packed red blood cells, plasma, and platelets, thromboelastometry is an essential point of care tool to determine the need for and effect of component therapy. This point of care tool is superior to the traditional laboratory assessment of coagulation. The use of tranexamic acid has come into question with the discovery of fibrinolytic shutdown and the detrimental effects on physiological fibrinolysis. The benefit of mechanical control of haemorrhage using percutaneous aortic occlusion is debatable. Major haemorrhage remains the commonest potentially correctable cause of early in-hospital death following major trauma. Minimising the use of clear resuscitative fluids and the early use of blood and component therapy is essential to maximise oxygen delivery, reverse the oxygen deficit and debt, and correct the coagulopathy of trauma and shock. The optimal ratio remains elusive but should be guided by thromboelastometry which will also dictate the need for antifibrinolytic therapy. The benefit and extent of permissive hypotension in those with ongoing haemorrhage until surgical control of haemorrhage can be obtained is unclear. The use of endovascular balloon occlusion of the aorta is controversial. Throughout resuscitation and damage control surgery, hypothermia must be corrected by core rewarming. Commensurate with damage control resuscitation is damage control surgery, the two being complementary for maximal benefit.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage

Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P=.08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage.

Plasma Transfusion: History, Current Realities, and Novel Improvements.

Traumatic hemorrhage is the leading cause of preventable death after trauma. Early transfusion of plasma and balanced transfusion have been shown to optimize survival, mitigate the acute coagulopathy of trauma, and restore the endothelial glycocalyx. There are a myriad of plasma formulations available worldwide, including fresh frozen plasma, thawed plasma, liquid plasma, plasma frozen within 24 h, and lyophilized plasma (LP). Significant equipoise exists in the literature regarding the optimal plasma formulation. LP is a freeze-dried formulation that was originally developed in the 1930s and used by the American and British military in World War II. It was subsequently discontinued due to risk of disease transmission from pooled donors. Recently, there has been a significant amount of research focusing on optimizing reconstitution of LP. Findings show that sterile water buffered with ascorbic acid results in decreased blood loss with suppression of systemic inflammation. We are now beginning to realize the creation of a plasma-derived formulation that rapidly produces the associated benefits without logistical or safety constraints. This review will highlight the history of plasma, detail the various types of plasma formulations currently available, their pathophysiological effects, impacts of storage on coagulation factors in vitro and in vivo, novel concepts, and future directions.

Dried plasma: state of the science and recent developments.

The early transfusion of plasma is important to ensure optimal survival of patients with traumatic hemorrhage. In military and remote or austere civilian settings, it may be impossible to move patients to hospital facilities within the first few hours of injury. A dried plasma product with reduced logistical requirements is needed to enable plasma transfusion where medically needed, instead of only where freezers and other equipment are available. First developed in the 1930s, pooled lyophilized plasma was widely used by British and American forces in WWII and the Korean War. Historical dried plasma products solved the logistical problem but were abandoned because of disease transmission. Modern methods to improve blood safety have made it possible to produce safe and effective dried plasma. Dried plasma products are available in France, Germany, South Africa, and a limited number of other countries. However, no product is available in the US. Promising products are in development that employ different methods of drying, pathogen reduction, pooling, packaging, and other approaches. Although challenges exist, the in vitro and in vivo data suggest that these products have great potential to be safe and effective. The history, state of the science, and recent developments in dried plasma are reviewed.

Medical Advances in the Treatment of Postpartum Hemorrhage

Postpartum hemorrhage (PPH) is a leading cause of maternal mortality worldwide. Recent advances in the management of severe bleeding for trauma patients may provide insight into PPH management, but must be applied with caution considering the significant differences between trauma and obstetric patients. In this review, we summarized evidence for current management strategies for patients with major obstetric hemorrhage, including (1) rapid laboratory assessment of coagulopathy, (2) early transfusion of plasma and high plasma-to-red blood cell transfusion ratios in massive PPH, and (3) use of tranexamic acid and fibrinogen concentrates in the setting of PPH complicated by coagulopathy.