Making thawed universal donor plasma available rapidly for massively bleeding trauma patients: experience from the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial.

BACKGROUND: The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request. STUDY DESIGN AND METHODS: At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines. RESULTS: Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared. CONCLUSION: Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study.

A paradigm shift in trauma resuscitation: evaluation of evolving massive transfusion practices.

IMPORTANCE: The evolution of damage control strategies has led to significant changes in the use of resuscitation after traumatic injury. OBJECTIVE: To evaluate changes in the administration of fluids and blood products, hypothesizing that a reduction in crystalloid volume and a reduced red blood cell (RBC) to fresh frozen plasma (FFP) ratio over the last 7 years would correlate with better resuscitation outcomes. DESIGN: Observational prospective cohort study. SETTING: Urban level I trauma center. PARTICIPANTS: A total of 174 trauma patients receiving a massive transfusion (>10 units of RBCs in 24 hours) or requiring the activation of the institutional massive transfusion protocol from February 2005 to June 2011. EXPOSURE: Patients had to either receive a massive transfusion or require the activation of the institutional massive transfusion protocol. MAIN OUTCOMES AND MEASURES: In-hospital mortality. RESULTS: The mean (SD) Injury Severity Score was 28.4 (16.2), the mean (SD) base deficit was -9.8 (6.3), and median international normalized ratio was 1.3 (interquartile range, 1.2-1.6); the mortality rate was 40.8%. Patients received a median of 6.1 L of crystalloid, 13 units of RBCs, 10 units of FFP, and 1 unit of platelets over 24 hours, with a mean RBC:FFP ratio of 1.58:1. The mean 24-hour crystalloid infusion volume and number of the total blood product units given in the first 24 hours decreased significantly over the study period (P < .05). The RBC:FFP ratio decreased from a peak of 1.84:1 in 2007 to 1.55:1 in 2011 (P = .20). Injury severity and mortality remained stable over the study period. When adjusted for age and injury characteristics using Cox regression, each decrease of 0.1 achieved in the massive transfusion protocol's RBC:FFP ratio was associated with a 5.6% reduction in mortality (P = .005). CONCLUSIONS AND RELEVANCE: There has been a shift toward a reduced crystalloid volume and the recreation of whole blood from component products in resuscitation. These changes are associated with markedly improved outcomes and a new paradigm in the resuscitation of severely injured patients.

Diminished need for folate measurements among indigent populations in the post folic acid supplementation era.

CONTEXT: The mandated fortification of processed grains with folic acid in the United States and Canada in 1998 was intended to reduce the incidence of neural tube defects in pregnant women. The incidence of folate deficiency in most populations has declined dramatically since then. OBJECTIVE: To determine the rate of folate deficiency in a cohort of indigent patients, a population among those at highest risk for folate deficiency. DESIGN: Using data from 3 years (1997, 2000, and 2004), we examined results of laboratory tests for red blood cell folate ordered at 3 hospitals that predominately service the needs of indigent patients. Folate concentration cutoffs were 160 ng/mL (363.6 nmol/L) and 94 ng/mL (213 nmol/L). RESULTS: Using a red blood cell folate cutoff concentration of 160 ng/mL (363.6 nmol/L), the combined incidence of folate deficiency decreased from 4.8% in 1997 to 0.6% in 2004. At a cutoff of 94 ng/mL (213 nmol/L), the incidence went from 0.98% to 0.09% in 1997 and 2004, respectively. Even when the folate concentration was found to be low, the majority of these subjects did not have macrocytosis. CONCLUSIONS: These data suggest that folate deficiency has become a rare event in the United States, and the utility of routine folate measurements for patients with anemia and/or increased mean corpuscular volume are difficult to justify.

Intermittent low-level viremia in very early primary HIV-1 infection.

Serial samples from source plasma donors with confirmed new HIV infection were investigated for low-level viremia (LLV) (ie, < 100 genome copies [cp]/mL) at time points preceding the period of steadily rising viremia above 100 cp/mL (ramp-up viremia). Fifteen of 44 plasma donor panels previously studied for the dynamics of HIV viremia during primary infection contained 70 samples with undetectable HIV-1 RNA by quantitative polymerase chain reaction (PCR). On retesting with a sensitive qualitative reverse transcriptase PCR assay (95% detection at 4 cp/mL), we identified LLV in 13 of 15 panels and 23 of 69 retested samples. In 6 panels, a total of 11 samples (1-3 per panel) were consistent with LLV before ramp-up viremia. These samples preceded the first sample with >100 cp/mL HIV by 9 to 25 days (median = 18 days) and were separated from the latter by at least 1 sample with undetectable viremia by the qualitative PCR assay. We conclude that LLV is not uncommon during the very early period of primary HIV infection preceding ramp-up viremia. It is not known if blood is infectious during this period; however, given the low viral concentrations and transient nature of the observed viremic "blips," the risk of infectivity can be assumed to be small.

Clinically relevant differences in prothrombin time and INR values related to blood sample collection in plastic vs glass tubes.

We compared prothrombin times (PTs) and international normalized ratios (INRs) for blood samples drawn into plastic vs glass collection tubes. We collected 60 venous blood samples into 4.5-mL glass and 2 plastic tubes (2.7 and 3.5 mL). An additional 153 samples, including 63 from warfarin-anticoagulated patients, were collected only in glass and 2.7-mL plastic tubes. The PTs and INRs were determined following routine laboratory procedures. A subset of 35 frozen aliquot samples was analyzed with a different instrument-reagent combination. The PTs and INRs for samples in plastic tubes were significantly lower than for samples in glass tubes. The mean INR differences increased with INR magnitude from approximately -0.1 (INR, 1.5) to -0.7 (INR, 4.5). Of the plastic tube INRs, 50% were more than 10% lower than INRs from samples collected in glass tubes. Therapeutic monitoring based on plastic-tube INRs could result in higher doses of warfarin.

Emerging infections in transfusion medicine.

The risk of transfusion-transmitted infectious diseases (TTIDs) has declined dramatically in high-income nations over the past 2 decades, primarily because of extraordinary success in preventing HIV and other established transfusion-transmitted viruses from entering the blood supply. Despite this achievement, TTIDs remain a public health concern, and attention is refocusing on new and emerging pathogens, such as West Nile virus, infectious proteins (the presumed cause of variant Creutzfeldt-Jakob disease), and other transmissible organisms such as bacteria and parasites. In this article the authors concentrate on this heterogeneous group of infectious agents, describe individual pathogens and the risks they pose to transfusion recipients, and comment on existing and evolving procedures that are designed to protect the blood supply from this threat.

Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection.

OBJECTIVES: The characterization of primary HIV infection by the analysis of serial plasma samples from newly infected persons using multiple standard viral assays. DESIGN: A retrospective study involving two sets of archived samples from HIV-infected plasma donors. (A) 435 samples from 51 donors detected by anti-HIV enzyme immunoassays donated during 1984-1994; (B) 145 specimens from 44 donors detected by p24 antigen screening donated during 1996-1998. SETTING: Two US plasma products companies. MAIN OUTCOME MEASURES: The timepoints of appearance of HIV-1 markers and viral load concentrations during primary HIV infection. RESULTS: The pattern of sequential emergence of viral markers in the 'A' panels was highly consistent, allowing the definition and estimation of the duration of six sequential stages. From the 'B' panels, the viral load at p24 antigen seroconversion was estimated by regression analysis at 10 000 copies/ml (95% CI 2000-93 000) and the HIV replication rate at 0.35 log copies/ml/day, corresponding to a doubling time in the preseroconversion phase of 20.5 h (95% CI 18.2-23.4 h). Consequently, an RNA test with 50 copies/ml sensitivity would detect HIV infection approximately 7 days before a p24 antigen test, and 12 days before a sensitive anti-HIV test. CONCLUSION: The sequential emergence of assay reactivity allows the classification of primary HIV-1 infection into distinct laboratory stages, which may facilitate the diagnosis of recent infection and stratification of patients enrolled in clinical trials. Quantitative analysis of preseroconversion replication rates of HIV is useful for projecting the yield and predictive value of assays targeting primary HIV infection.

HCV viral load in anti-HCV-reactive donors and infectivity for their recipients.

BACKGROUND: An attempt has been made to determine the minimum level of HCV nucleic acid in donors associated with infection of recipients. This is important for considerations about assay sensitivity, use of minipool versus single-donation testing, and continued use of serologic testing. STUDY DESIGN AND METHODS: A total of 5387 specimens from the Transfusion-Transmitted Viruses Study in the 1970s were screened for antibody to HCV (anti-HCV). The outcome in recipients of seroreactive donations was examined for viremia and seroconversion. Present techniques for both groups included third-generation EIA, RIBA, quantitative RT-PCR assay, and transcription-mediated amplification (TMA) assay. RESULTS: A total of 156 recipients of components from 180 anti-HCV-reactive donors were identified. One-hundred seven of these were HCV-naïve before transfusion and received a single, confirmed seropositive unit; 94 (88%) became infected. Eighty-five recipients had donors whose HCV RNA level was quantifiable by RT-PCR (range, 182-3,310,000 copies/mL). Eighty-three (98%) seroconverted. Of the remaining 22, a total of 10 received units positive for HCV RNA detected only by TMA; all 10 recipients seroconverted. Of the remaining 12 recipients of anti-HCV+, TMA-negative units, 1 recipient seroconverted. CONCLUSIONS: High rates of transmission were seen at all levels of viremia, and one donor transmitted with undetectable levels in the TMA assay. Current HCV RNA testing will therefore not interdict all infectious units, even with single-donation testing, and serologic screening must be continued.

Comparative sensitivity of HBV NATs and HBsAg assays for detection of acute HBV infection.

BACKGROUND: A study was designed to estimate relative analytic sensitivity and window-period (WP) closure and to project incremental yield of newer HBsAg tests, pooled-sample NAT, and single-sample NAT, compared to currently licensed HBsAg tests. STUDY DESIGN AND METHODS: HBV DNA and HBsAg test results for 23 HBV seroconversion (SC) panels were first analyzed to construct a model of primary HBV viremia. One-hundred representative samples were then selected from 10 panels and coded with 28 analytical controls. All 128 samples were tested by seven HBsAg tests and by four pooled-sample and three single-sample NAT assay formats. Results were analyzed to obtain differential times to HBV detection and combined with HBV incidence rates to project comparative yields. RESULTS: HBV doubling time during the ramp-up phase was estimated at 2.56 days. HBsAg concentrations at cutoff for new tests ranged from 0.07 to 0.12 ng per mL, compared with 0.13 to 0.62 ng per mL for licensed tests. Estimated viral load at cutoff ranged from 102 to 267 IU per mL for new tests and from 363 to 1069 IU per mL for licensed tests. HBsAg tests detected 31 to 63 percent of early ramp-up phase samples in the 100-member seroconversion panel study, while pooled-sample NAT detected 55 to 71 percent and single-sample NAT, 82 to 99 percent. Compared with currently licensed HBsAg assays, newer HBsAg assays would reduce the WP by 2 to 9 days; pooled-sample NAT would reduce the WP by 9 to 11 days; and single-sample NAT would reduce the WP by 25 to 36 days. CONCLUSION: Newer HBsAg tests would be expected to detect an additional 15 to 21 infected units per 107 donations, compared to licensed HBsAg tests. Sensitivity, WP closure, and yield projections for newer HBsAg assays and pooled-sample NAT are comparable. Single-sample NAT would increase yield by 13 to 15 units per 107 donations over pooled-sample NAT and newer HBsAg assays and by 35 to 50 units per 107 donations over currently licensed HBsAg assays.