Yulia Lin

Cryoprecipitate: The Current State of Knowledge

Cryoprecipitate is a diverse product containing factor VIII, von Willebrand factor, fibrinogen, fibronectin, factor XIII, and platelet microparticles. The role of this complex product in the management of hemostasis has not been well studied (excluding patients with factor VIII deficiency). There are insufficient data to determine the clinical setting where this product might be clinically efficacious despite its widespread use in multiple different clinical scenarios. The best method of pooling before transfusion has also not been thoroughly investigated to determine the optimal infusion strategy (intralaboratory vs bedside). The most common current indication for the use of this product is hypofibrinogenemia in the setting of massive hemorrhage. There are insufficient data in the literature to determine the efficacy, safety, and dosage in this patient population. Despite 45 years of the use of this product, we still have a lot to learn regarding the optimal use of cryoprecipitate.

Clinical review: Fresh frozen plasma in massive bleedings - more questions than answers.

Fresh frozen plasma (FFP) is indicated for the management of massive bleedings. Recent audits suggest physician knowledge of FFP is inadequate and half of the FFP transfused in critical care is inappropriate. Trauma is among the largest consumers of FFP. Current trauma resuscitation guidelines recommend FFP to correct coagulopathy only after diagnosed by laboratory tests, often when overt dilutional coagulopathy already exists. The evidence supporting these guidelines is limited and bleeding remains a major cause of trauma-related death. Recent studies demonstrated that coagulopathy occurs early in trauma. A novel early formula-driven haemostatic resuscitation proposes addressing coagulopathy early in massive bleedings with FFP at a near 1:1 ratio with red blood cells. Recent retrospective reports suggest such strategy significantly reduces mortality, and its use is gradually expanding to nontraumatic bleedings in critical care. The supporting studies, however, have bias limiting the interpretation of the results. Furthermore, logistical considerations including need for immediately available universal donor AB plasma, short life after thawing, potential waste and transfusion-associated complications have challenged its implementation. The present review focuses on FFP transfusion in massive bleeding and critically appraises the evidence on formula-driven resuscitation, providing resources to allow clinicians to develop informed opinion, given the current deficient and conflicting evidence.

Proceedings of a Consensus Conference: Pathogen Inactivation—Making Decisions About New Technologies

Significant progress has been made in reducing the risk of pathogen transmission to transfusion recipients. Nonetheless, there remains a continuing risk of transmission of viruses, bacteria, protozoa, and prions to recipients. These include many of the viruses for which specific screening tests exist as well as pathogens for which testing is currently not being done, including various species of bacteria, babesiosis, variant Creutzfeld-Jacob disease, hepatitis A virus, human herpes virus 8, chikungunya virus, Chagas disease, and malaria. Pathogen inactivation (PI) technologies potentially provide an additional way to protect the blood supply from emerging agents and also provide additional protection against both known and as-yet-unidentified agents. However, the impact of PI on product quality and recipient safety remains to be determined. The purpose of this consensus conference was to bring together international experts in an effort to consider the following issues with respect to PI: implementation criteria; licensing requirements; blood service and clinical issues; risk management issues; cost-benefit impact; and research requirements. These proceedings are provided to make available to the transfusion medicine community the considerable amount of important information presented at this consensus conference.

Effect of a fixed-ratio (1:1:1) transfusion protocol versus laboratory-results–guided transfusion in patients with severe trauma: a randomized feasibility trial

Background: Hemorrhage coupled with coagulopathy remains the leading cause of preventable in-hospital deaths among trauma patients. Use of a transfusion protocol with a predefined ratio of 1:1:1 (1 each of red blood cells [RBC], frozen plasma [FP] and platelets) has been associated with improved survival in retrospective studies in military and civilian settings, but such a protocol has its challenges and may increase the risk of respiratory complications. We conducted a randomized controlled trial to assess the feasibility of a 1:1:1 transfusion protocol and its effect on mortality and complications among patients with severe trauma. Methods: We included 78 patients seen in a tertiary trauma centre between July 2009 and October 2011 who had hypotension and bleeding and were expected to need massive transfusion (≥ 10 RBC units in 24 h). We randomly assigned them to either the fixed-ratio (1:1:1) transfusion protocol (n = 40) or to a laboratory-results–guided transfusion protocol (control; n = 38). The primary outcome, feasibility, was assessed in terms of blood product ratios and plasma wastage. Safety was measured based on 28-day mortality and survival free of acute respiratory distress syndrome. Results: Overall, a transfusion ratio of 1:1:1 was achieved in 57% (21/37) of patients in the fixed-ratio group, as compared with 6% (2/32) in the control group. A ratio of 1:1 (RBC:FP) was achieved in 73% (27/37) in the fixed-ratio group and 22% (7/32) in the control group. Plasma wastage was higher with the intervention protocol (22% [86/390] of FP units v. 10% [30/289] in the control group). The 28-day mortality and number of days free of acute respiratory distress syndrome were statistically similar between the groups. Interpretation: The fixed-ratio transfusion protocol was feasible in our study, but it was associated with increased plasma wastage. Larger randomized trials are needed to evaluate the efficacy of such a protocol in trauma care. Trial registration: ClinicalTrials.gov, no. NCT00945542

Transfusion-Associated Hyperkalemia

The supernatant potassium concentration [K+] of red blood cell (RBC) units is frequently much higher than normal human plasma potassium levels, especially in units nearing the end of their storage life. Clinical hyperkalemia resulting from RBC transfusions has been recognized as a transfusion complication for decades, and there have been reported cardiac arrests attributed to transfusion-associated hyperkalemia. This review summarizes the evidence surrounding RBC [K+] levels, effects of irradiation and washing on [K+], the evidence for clinical hyperkalemia and cardiac arrests resulting from transfusion, predictors of post-transfusion hyperkalemia, and their preventative strategies. Key points include: (a) the [K+] (in mmol/L) increases linearly and is approximately equal to the number of days of RBC unit storage; (b) irradiation causes a rapid increase in [K+]; (c) there is potentially sufficient potassium in the supernatant of current RBC preparations to lead to hyperkalemia with large transfusion volumes; (d) any rise in patient potassium after transfusion is usually transient due to the redistribution of the potassium load; (e) transfusion-associated hyperkalemic cardiac arrests probably do occur, although it is difficult to prove this fact conclusively; and (f) promising strategies to combat transfusion-associated hyperkalemia include RBC washing, the use of in-line potassium filters, and the use of traditional treatments for hyperkalemia such as the use of insulin.

Transfusion-related acute lung injury prevention measures and their impact at Canadian Blood Services

BACKGROUND: Blood operators have taken measures to reduce transfusion‐related acute lung injury (TRALI). We classified suspected TRALI cases reported to Canadian Blood Services from 2001 to 2009 and assessed the impact of TRALI reduction measures.

A Retrospective Review of Patient Factors, Transfusion Practices, and Outcomes in Patients With Transfusion-Associated Circulatory Overload

Transfusion-associated circulatory overload (TACO) is a common yet underrecognized and underreported complication of transfusion associated with significant morbidity and mortality. The objective of this study was to examine patient and transfusion characteristics in a cohort of TACO cases. A retrospective medical record review of 100 consecutive TACO episodes reported at 2 academic centers was performed. Information related to demographics, medical history, radiologic and echocardiographic investigations, infusion practices, reaction features, management, and outcome were collected. Ninety-eight cases were accessible for review. A history of congestive heart failure (41%), renal dysfunction (44%), and age more than 70 years (56%) were common in TACO patients. Suboptimal fluid status management and inappropriate infusion practices were often seen (eg, verbal orders, double red cell transfusions, rapid infusion rates, lack or improper timing of preemptive diuretics). The median volume of blood ordered was 500 mL, and the median volume of crystalloid or colloid (preceding 24 hours) was 2200 mL. A physician order specifying the infusion rate was documented in 50% of transfusion orders. Preemptive diuretics were ordered in only 29% of cases, most commonly introduced midway or after the transfusion at a dose of furosemide 20 mg intravenously. After TACO, 18% of patients required transfer to the intensive care unit, 8% suffered a major complication, and 2% died. Suboptimal ordering and infusion practices may be contributing to the high incidence and severity of TACO. Research in TACO prevention strategies, such as slow rates of infusion and preemptive diuretics, is warranted.

A systematic review of transfusion-associated graft-versus-host disease.

Transfusion-associated graft-versus-host disease (TA-GVHD) is a rare complication of blood transfusion. The clinicolaboratory features of TA-GVHD and the relative contributions of recipient and component factors remain poorly understood. We conducted a systematic review of TA-GVHD reports. The HLA relationship between donor and recipient was classified as D = 0 when no donor antigens were foreign to the recipient vs D ≥ 1 when ≥1 donor antigen disparity occurred. We identified 348 unique cases. Criteria for component irradiation were met in 48.9% of cases (34.5% immune-compromised, 14.4% related-donor), although nonirradiated components were transfused in the vast majority of these (97.6%). Components were typically whole blood and red cells. When reported, component storage duration was ≤10 days in 94%, and 23 (6.6%) were leukoreduced (10 bedside, 2 prestorage, and 11 unknown). Among 84 cases with HLA data available, the category of D = 0 was present in 60 patients (71%) at either HLA class I or II loci and was more common among recipients without traditional indications for component irradiation. These data challenge the historic emphasis on host immune defects in the pathogenesis of TA-GVHD. The dominant mechanism of TA-GVHD in both immunocompetent and compromised hosts is exposure to viable donor lymphocytes not recognized as foreign by, but able to respond against, the recipient.

The evidence for the use of recombinant factor VIIa in massive bleeding: revision of the transfusion policy framework

In 2006, the Canadian National Advisory Committee on Blood and Blood Products (NAC) developed a transfusion policy framework for the use of off‐label recombinant factor VIIa (rFVIIa) in massive bleeding. Because the number of randomised controlled trials has doubled, the NAC undertook a review of the policy framework in 2011. On the basis of the review of 29 randomised controlled trials, there remains little evidence to support the routine use of rFVIIa in massive bleeding. Mortality benefits have not been demonstrated. Contrarily, an increase in arterial thromboembolic events has been observed with the use of off‐label rFVIIa. Given the absence of evidence of benefit and with evidence of the risk of harm, the NAC recommends that recombinant VIIa no longer be used for the off‐label indications of prevention and treatment of bleeding in patients without haemophilia.

Cryoprecipitate transfusion: assessing appropriateness and dosing in trauma.

Background: Originally developed for patients with congenital factor VIII deficiency, cryoprecipitate is currently largely used for acquired hypofibrinogenemia in the context of bleeding. However, scant evidence supports this indication and cryoprecipitate is commonly used outside guidelines. In trauma, the appropriate cryoprecipitate dose and its impact on plasma fibrinogen levels are unclear.