Rapid detection of platelet inhibition and dysfunction in traumatic brain injury: A prospective observational study.

BACKGROUND: Rapid platelet function testing is frequently used to determine platelet function in patients with traumatic intracranial hemorrhage (tICH). Accuracy and clinical significance of decreased platelet response detected by these tests is not well understood. We sought to determine whether VerifyNow and whole blood aggregometry (WBA) can detect poor platelet response and to elucidate its clinical significance for tICH patients. METHODS: We prospectively enrolled patients with isolated tICH between 2018 and 2020. Demographics, medical history, injury characteristics, and patient outcomes were recorded. Platelet function was determined by VerifyNow and WBA testing at the time of arrival to the trauma bay and 6 hours later. RESULTS: A total of 221 patients were enrolled, including 111 patients on no antiplatelet medication, 78 on aspirin, 6 on clopidogrel, and 26 on aspirin and clopidogrel. In the trauma bay, 29.7% and 67.7% of patients on no antiplatelet medication had poor platelet response on VerifyNow and WBA, respectively. Among patients on aspirin, 72.2% and 82.2% had platelet dysfunction on VerifyNow and WBA. Among patients on clopidogrel, 67.9% and 88.9% had platelet dysfunction on VerifyNow and WBA. Patients with nonresponsive platelets had similar in-hospital mortality (3 [3.0%] vs. 6 [6.3%], p = 0.324), tICH progression (26 [27.1%] vs. 24 [26.1%], p = 0.877), intensive care unit admission rates (34 [34.3%] vs. 38 [40.0%), p = 0.415), and length of stay (3 [interquartile range, 2-8] vs. 3.2 [interquartile range, 2-7], p = 0.818) to those with responsive platelets. Platelet transfusion did not improve platelet response or patient outcomes. CONCLUSION: Rapid platelet function testing detects a highly prevalent poor platelet response among patients with tICH, irrespective of antiplatelet medication use. VerifyNow correlated fairly with whole blood aggregometry among patients with tICH and platelet responsiveness detectable by these tests did not correlate with clinical outcomes. In addition, our results suggest that platelet transfusion may not improve clinical outcomes in patients with tICH. LEVEL OF EVIDENCE: Diagnostic tests, level II.

Eastern Association for the Surgery of Trauma Multicenter Trial: Comparison of pre-injury antithrombotic use and reversal strategies among severe traumatic brain injury patients.

BACKGROUND: Trauma teams are often faced with patients on antithrombotic (AT) drugs, which is challenging when bleeding occurs. We sought to compare the effects of different AT medications on head injury severity and hypothesized that AT reversal would not improve mortality in severe traumatic brain injury (TBI) patients. METHODS: An Eastern Association for the Surgery of Trauma-sponsored prospective, multicentered, observational study of 15 trauma centers was performed. Patient demographics, injury burden, comorbidities, AT agents, and reversal attempts were collected. Outcomes of interest were head injury severity and in-hospital mortality. RESULTS: Analysis was performed on 2,793 patients. The majority of patients were on aspirin (acetylsalicylic acid [ASA], 46.1%). Patients on a platelet chemoreceptor blocker (P2Y12) had the highest mean Injury Severity Score (9.1 ± 8.1). Patients taking P2Y12 inhibitors ± ASA, and ASA-warfarin had the highest head Abbreviated Injury Scale (AIS) mean (1.2 ± 1.6). On risk-adjusted analysis, warfarin-ASA was associated with a higher head AIS (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.34-4.42) after controlling for Injury Severity Score, Charlson Comorbidity Index, initial Glasgow Coma Scale score, and initial systolic blood pressure. Among patients with severe TBI (head AIS score, ≥3) on antiplatelet therapy, reversal with desmopressin (DDAVP) and/or platelet transfusion did not improve survival (82.9% reversal vs. 90.4% none, p = 0.30). In severe TBI patients taking Xa inhibitors who received prothrombin complex concentrate, survival was not improved (84.6% reversal vs. 84.6% none, p = 0.68). With risk adjustment as described previously, mortality was not improved with reversal attempts (antiplatelet agents: OR 0.83; 85% CI, 0.12-5.9 [p = 0.85]; Xa inhibitors: OR, 0.76; 95% CI, 0.12-4.64; p = 0.77). CONCLUSION: Reversal attempts appear to confer no mortality benefit in severe TBI patients on antiplatelet agents or Xa inhibitors. Combination therapy was associated with severity of head injury among patients taking preinjury AT therapy, with ASA-warfarin possessing the greatest risk. LEVEL OF EVIDENCE: Prognostic, level II.

Platelet dysfunction in patients with traumatic intracranial hemorrhage: Do desmopressin and platelet therapy help or harm?

BACKGROUND: Pre-injury anti-platelet use has been associated with increased risk of progression of traumatic intracranial hemorrhage (TICH) and worse outcomes. VerifyNow® assays assess platelet inhibition due to aspirin/clopidogrel. This study assesses the outcomes of patients with TICH and platelet dysfunction treated with desmopressin and/or platelets. METHODS: We performed a retrospective chart review of patients with mild TICH at a level 1 trauma center 1/1/2013-6/1/2016. Patients with documented platelet dysfunction who received desmopressin and/or platelets were compared to those who were untreated. Primary outcomes were progression of TICH and neurologic outcomes at discharge. RESULTS: Of 565 patients with a mild TICH, 200 patients had evidence of platelet dysfunction (a positive VerifyNow® assay). Patients had similar baseline demographics, injury characteristics, and rate of TICH progression; but patients who received desmopressin and/or platelets had worse Glasgow Outcomes Score at discharge. CONCLUSION: Treatment of patients with mild TICH and platelet dysfunction with desmopressin and/or platelets did not affect TICH progression but correlated with worse neurologic status at discharge.

Transfusion practices for pediatric oncology and hematopoietic stem cell transplantation patients: Data from the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III (REDS-III).

BACKGROUND: To evaluate transfusion practices in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients. STUDY DESIGN AND METHODS: This is a multicenter retrospective study of children with oncologic diagnoses treated from 2013 to 2016 at hospitals participating in the National Heart Lung and Blood Institute Recipient Epidemiology and Donor Evaluation Study-III. Transfusion practices were evaluated by diagnosis codes and pre-transfusion laboratory values. RESULTS: A total of 4766 inpatient encounters of oncology and HSCT patients were evaluated, with 39.3% (95% confidence interval [CI]: 37.9%-40.7%) involving a transfusion. Red blood cells (RBCs) were the most commonly transfused component (32.4%; 95% CI: 31.1%-33.8%), followed by platelets (22.7%; 95% CI: 21.5%-23.9%). Patients in the 1 to <6 years of range were most likely to be transfused and HSCT, acute myeloid leukemia, and aplastic anemia were the diagnoses most often associated with transfusion. The median hemoglobin (Hb) prior to RBC transfusion was 7.5 g/dl (10-90th percentile: 6.4-8.8 g/dl), with 45.7% of transfusions being given at 7 to <8 g/dl. The median platelet count prior to platelet transfusion was 20 × 109 /L (10-90th percentile: 8-51 × 109 /L), and 37.9% of transfusions were given at platelet count of >20-50 × 109 /L. The median international normalized ratio (INR) prior to plasma transfusion was 1.7 (10-90th percentile: 1.3-2.7), and 36.3% of plasma transfusions were given at an INR between 1.4 and 1.7. DISCUSSION: Transfusion of blood components is common in hospitalized pediatric oncology/HSCT patients. Relatively high pre-transfusion Hb and platelet values and relatively low INR values prior to transfusion across the studied diagnoses highlight the need for additional studies in this population.

Platelet to erythrocyte transfusion ratio and mortality in massively transfused trauma patients. A systematic review and meta-analysis.

BACKGROUND: Platelet transfusion during major hemorrhage is important and often embedded in massive transfusion protocols. However, the optimal ratio of platelets to erythrocytes (platelet-rich plasma [PLT]/red blood cell [RBC] ratio) remains unclear. We hypothesized that high PLT/RBC ratios, as compared with low PLT/RBC ratios, are associated with improved survival in patients requiring massive transfusion. METHODS: Four databases (Pubmed, CINAHL, EMBASE, and Cochrane) were systematically screened for literatures published until January 21, 2021, to determine the effect of PLT/RBC ratio on the primary outcome measure mortality at 1 hour to 6 hours and 24 hours and at 28 days to 30 days. Studies comparing various PLT/RBC ratios were included in the meta-analysis. Secondary outcomes included intensive care unit length of stay and in-hospital length of stay and total blood component use. The study protocol was registered in PROSPERO under number CRD42020165648. RESULTS: The search identified a total of 8903 records. After removing the duplicates and second screening of title, abstract, and full text, a total of 59 articles were included in the analysis. Of these articles, 12 were included in the meta-analysis. Mortality at 1 hour to 6 hours, 24 hours, and 28 days to 30 days was significantly lower for high PLT/RBC ratios as compared with low PLT/RBC ratios. CONCLUSION: Higher PLT/RBC ratios are associated with significantly lower 1-hour to 6-hour, 24-hour, 28-day to 30-day mortalities as compared with lower PLT/RBC ratios. The optimal PLT/RBC ratio for massive transfusion in trauma patients is approximately 1:1. LEVEL OF EVIDENCE: Systematic review and meta-analysis, therapeutic Level III.

How do we implement pathogen reduction technology, while maintaining an adequate platelet inventory for our patients?

Despite the significantly reduced infectious disease risk through robust and sensitive laboratory assays, comprehensive donor screening and good manufacturing practices, new and emerging infectious agents and bacterial contamination continue to pose a threat to the blood supply. Pathogen Reduction (PR) technology is an option to mitigate the risk of platelet transfusion transmitted infections. Here we describe our structure and strategies to implement PR technology. Pre-implementation and phased approach implementation processes from our hospital-based donor center, components processing laboratory, transfusion service, clinicians, nursing, and patient perspectives are described. Communication and reassessment of collection settings occurred between the donor center and components processing laboratory (CPL). During Phase 1, CPL consistently processed approximately 56% of monthly apheresis platelets (AP) collections by PR and the remaining 44% as conventional platelets (CP). Phase 2 increased the amount of AP undergoing PR from 56% to approximately 78%. A phased implementation and maintenance of a dual inventory may provide flexibility to blood collection, blood manufacturing, and transfusion service processes. Our dual inventory of PR and CP allows our transfusion service a readily available platelet inventory. A collaborative hospital-based donor center, component processing laboratory, and transfusion service are essential to the productivity and maintenance of the dual platelet inventory.

Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation in children: Single-centre experience.

Delayed recovery of thrombocytopenia is a well-known complication after allogeneic HSCT. Eltrombopag (ELT), a thrombopoietin receptor agonist (TRAs), induces platelet maturation and release. Mostly conducted in adults, some of the previous studies have shown that ELT seems to enhance platelet recovery for post-allogeneic HSCT thrombocytopenia, appears efficacious, and offers transfusion independence. To evaluate the safety and efficacy of ELT in pediatric patients with prolonged isolated thrombocytopenia (PIT) or secondary failure of platelet recovery (SFPR) after alloHSCT. Retrospective analysis of childhood patients who received treatment with ELT for persistent thrombocytopenia after alloHSCT between May 2016 and August 2019. We evaluated the safety and efficacy of ELT in 18 childhood patients with PIT or SFPR after alloHSCT. Eltrombopag (50 mg/d) treatment was started in all patients, above 6 years of age and 20 kg weight, who had thrombocytopenia despite neutrophil engraftment on the 30th day of HSCT. Our objective was to decrease the need for platelet transfusion and have a platelet count of more than 50 000/µL. The overall response rate was 77.7%. The median time to achieve a platelet level above 30 000/µL and 50 000/µL was 21 and 44 days, respectively. In four patients, platelet count never reached 30 000/mm3 . In two patients, the treatment was discontinued due to grade 3 hepatotoxicity. Our study supports the efficacy and relative safety of ELT use for the treatment of PIT and SFPR seen after alloHSCT in children.

Platelet Transfusion After Traumatic Intracranial Hemorrhage in Patients on Antiplatelet Agents.

BACKGROUND: With an aging population, the number of patients on antiplatelet medications and traumatic brain injury (TBI) is increasing. Our study aimed to evaluate the role of platelet transfusion on outcomes after traumatic intracranial bleeding (IB) in these patients. METHODS: We analyzed our prospectively maintained TBI database from 2014 to 2016. We included all isolated TBI patients with an IB, who were on preinjury antiplatelet agents and excluded patients taking anticoagulants. Outcome measures included the progression of IB, neurosurgical intervention, and mortality. Regression analysis was performed. RESULTS: A total of 343 patients met the inclusion criteria. Mean age was 58 ± 11 y, 58% were men, and median injury severity score was 15 (10-24). Distribution of antiplatelet agents was as follows: aspirin (60%) and clopidogrel (35%). Overall, 74% patients received platelet transfusion after admission with a median number of two platelet units. After controlling for confounders, patients who received one unit of pooled platelets had no difference in progression of IB (odds ratio [OR]: 0.98, [0.6-1.9], P = 0.41), need for neurosurgical intervention (OR: 1.09, [0.7-2.5], P = 0.53), and mortality (OR: 0.84, [0.6-1.8], P = 0.51). However, patients who received two units of pooled platelets had lower rate of progression of IB (OR: 0.69, [0.4-0.8], P = 0.02), the need for neurosurgical intervention (OR: 0.81, [0.3-0.9], P = 0.03), and mortality (OR: 0.84, [0.5-0.9], P = 0.04). Both groups were compared with those who did not receive platelet transfusion. CONCLUSIONS: The use of two units of platelet may decrease the risk of IB progression, neurosurgical intervention, and mortality in patients on preinjury antiplatelet agents and TBI. Further studies should focus on developing protocols for platelet transfusion to improve outcomes in these patients. LEVEL OF EVIDENCE: Level III prognostic.

The current state of the platelet supply in the US and proposed options to decrease the risk of critical shortages.

Due to circumstances such as increased demand and an aging donor pool, the likelihood of critical platelet shortages is increasing. The platelet supply could be improved through the expansion of the donor pool, the identification and sustained utilization of high-quality donors, and changes in component processing and storage that result in a longer platelet shelf-life. Refrigerated platelets, stored at 1° to 6°C, have the potential to improve patient safety by decreasing the risk of bacterial contamination while concurrently allowing for a longer storage period (eg, 14 days) and improved hemostatic effectiveness in actively bleeding patients. An approach utilizing remuneration of apheresis platelet donors combined with pathogen reduction of the platelet components could be used as a means to increase the donor pool and identify and sustain safe, reliable, high-quality donors. Remuneration might provide an incentive for underutilized populations (eg, individuals <30 years old) to enter the apheresis platelet donor population resulting in a significant expansion of the platelet donor pool. Over time, approaches such as the use of refrigerated platelets, platelet donor remuneration, and the application of pathogen reduction technology, might serve to attract a large, reliable, and safe donor base that provides platelet collections with high yields, longer shelf-lives and, excellent hemostatic function.

Fecal blood loss: A quantitative method of evaluating hemostasis in patients with thrombocytopenia.

BACKGROUND: The purpose of our studies was to determine if fecal blood loss can provide a quantitative measure of bleeding at platelet counts of 20 000/µL or less in patients with hypoproliferative thrombocytopenia and to document the effects of different prophylactic platelet transfusion triggers on fecal blood loss. METHODS AND MATERIALS: Patients had an aliquot of their autologous red blood cells (RBCs) labeled with 51 Cr. Following reinjection of their radiolabeled RBCs, all feces and a daily blood sample were collected to determine fecal blood loss per day. Three different studies were performed in patients with thrombocytopenia: The first was in patients with thrombocytopenia with aplastic anemia who were not receiving platelet transfusions, and the other two trials involved thrombocytopenic patients with cancer who were receiving prophylactic platelet transfusions at platelet transfusion triggers of 5000/µL, 10 000/µL, or 20 000/µL. RESULTS: In patients with thrombocytopenia not receiving platelet transfusions, fecal blood loss does not increase substantially until platelet counts are 5000/µL or less. When platelet transfusions are given prophylactically to patients with cancer with chemotherapy-induced thrombocytopenia at platelet counts of 5000/µL or less, fecal blood loss and red cell transfusion requirements are the same as those for patients transfused prophylactically at higher transfusion triggers of 10 000 platelets/µL or 20 000 platelets/µL. However, the total number of platelet transfusions needed increases significantly, and the duration of the patient's thrombocytopenia tends to be longer at the higher platelet transfusion thresholds. CONCLUSION: A prophylactic platelet transfusion threshold of 5000/µL or greater is sufficient to maintain hemostasis in patients with thrombocytopenia.

Avatrombopag and lusutrombopag for thrombocytopenia in people with chronic liver disease needing an elective procedure: a systematic review and cost-effectiveness analysis.

BACKGROUND: There have been no licensed treatment options in the UK for treating thrombocytopenia in people with chronic liver disease requiring surgery. Established management largely involves platelet transfusion prior to the procedure or as rescue therapy for bleeding due to the procedure. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of two thrombopoietin receptor agonists, avatrombopag (Doptelet®; Dova Pharmaceuticals, Durham, NC, USA) and lusutrombopag (Mulpleta®; Shionogi Inc., London, UK), in addition to established clinical management compared with established clinical management (no thrombopoietin receptor agonist) in the licensed populations. DESIGN: Systematic review and cost-effectiveness analysis. SETTING: Secondary care. PARTICIPANTS: Severe thrombocytopenia (platelet count of < 50,000/µl) in people with chronic liver disease requiring surgery. INTERVENTIONS: Lusutrombopag 3 mg and avatrombopag (60 mg if the baseline platelet count is < 40,000/µl and 40 mg if it is 40,000-< 50,000/µl). MAIN OUTCOME MEASURES: Risk of platelet transfusion and rescue therapy or risk of rescue therapy only. REVIEW METHODS: Systematic review including meta-analysis. English-language and non-English-language articles were obtained from several databases including MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials, all searched from inception to 29 May 2019. ECONOMIC EVALUATION: Model-based cost-effectiveness analysis. RESULTS: From a comprehensive search retrieving 11,305 records, six studies were included. Analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy or rescue therapy only, and mostly with a statistically significant difference (i.e. 95% confidence intervals not overlapping the point of no difference). However, only avatrombopag seemed to be superior to no thrombopoietin receptor agonist in reducing the risk of rescue therapy, although far fewer patients in the lusutrombopag trials than in the avatrombopag trials received rescue therapy. When assessing the cost-effectiveness of lusutrombopag and avatrombopag, it was found that, despite the success of these in avoiding platelet transfusions prior to surgery, the additional long-term gain in quality-adjusted life-years was very small. No thrombopoietin receptor agonist was clearly cheaper than both lusutrombopag and avatrombopag, as the cost savings from avoiding platelet transfusions were more than offset by the drug cost. The probabilistic sensitivity analysis showed that, for all thresholds below £100,000, no thrombopoietin receptor agonist had 100% probability of being cost-effective. LIMITATIONS: Some of the rescue therapy data for lusutrombopag were not available. There were inconsistencies in the avatrombopag data. From the cost-effectiveness point of view, there were several additional important gaps in the evidence required, including the lack of a price for avatrombopag. CONCLUSIONS: Avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy, but they were not cost-effective given the lack of benefit and increase in cost. FUTURE WORK: A head-to-head trial is warranted. STUDY REGISTRATION: This study is registered as PROSPERO CRD42019125311. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 51. See the NIHR Journals Library website for further project information.

Thrombocytopenia, which is a reduction in platelet numbers in the blood, is a common complication of chronic liver disease. It increases the risk of bleeding during procedures including liver biopsy and transplantation. It can delay or prevent procedures, leading to illness and death. Established treatment largely involves platelet transfusion before the procedure or as rescue therapy for bleeding. This report aims to systematically review the clinical effectiveness and estimate the cost-effectiveness of the first two recently licensed treatments, thrombopoietin receptor agonists avatrombopag (Doptelet^®; Dova Pharmaceuticals, Durham, NC, USA) (60 mg if platelet count is < 40,000/µl and 40 mg if platelet count is 40,000­< 50,000/µl) and lusutrombopag (Mulpleta^®; Shionogi Inc., London, UK) (3 mg if platelet count is < 50,000/µl), compared with established treatment. From a comprehensive search, six studies were included. Clinical effectiveness analysis showed that avatrombopag and lusutrombopag were superior to no thrombopoietin receptor agonist in avoiding both platelet transfusion and rescue therapy. Only avatrombopag seemed superior to no thrombopoietin receptor agonist in reducing rescue therapy alone. Cost-effectiveness analysis found that lusutrombopag and avatrombopag were more expensive than no thrombopoietin receptor agonist over a lifetime, as the savings from avoiding platelet transfusions were exceeded by the drug cost, and without long-term health benefits. The probabilistic sensitivity analysis, which examined the effect of uncertainty, showed that no thrombopoietin receptor agonist had 100% probability of being cost-effective. Uncertainty about the price of avatrombopag and the content and costs of platelet transfusions and the potential under-reporting of use to estimate platelet transfusion-specific mortality had the greatest impact on results. If the price of avatrombopag was (confidential information has been removed) below the price of lusutrombopag, avatrombopag would become cost saving in the 40,000­< 50,000/µl subgroup. However, although in some scenarios avatrombopag costs could decrease in the 40,000­< 50,000/µl subgroup to around 10% more than the cost of no thrombopoietin receptor agonist, there would be negligible health benefits and the incremental cost-effectiveness ratios would remain very high, meaning that lusutrombopag and avatrombopag would still not be considered cost-effective.

Epidemiology of Hemostatic Transfusions in Children Supported by Extracorporeal Membrane Oxygenation.

OBJECTIVE: To evaluate the epidemiology of hemostatic transfusions (plasma, platelet, and cryoprecipitate) in children supported by extracorporeal membrane oxygenation. DESIGN: Secondary analysis of a large observational cohort study. SETTING: Eight pediatric institutions within the Eunice Kennedy Shriver National Institute of Child Health and Human Development's Collaborative Pediatric Critical Care Research Network. PATIENTS: Critically ill children supported by extracorporeal membrane oxygenation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Extracorporeal membrane oxygenation was used in the care of 514 consecutive children. Platelets were transfused on 68% of extracorporeal membrane oxygenation days, plasma on 34% of the days on extracorporeal membrane oxygenation, and cryoprecipitate on 14%. Only 24% of the days on extracorporeal membrane oxygenation were free of any hemostatic transfusions. Daily platelet transfusion dose was independently associated with chest tube output (p < 0.001), other bleeding requiring RBC transfusion (p = 0.03), and daily set platelet goal (p = 0.009), but not with total platelet count (p = 0.75). Daily plasma transfusion dose was independently associated with chest tube output (p < 0.001), other bleeding requiring RBC transfusion (p = 0.01), activated clotting time (p = 0.001), and antithrombin levels (p = 0.02), but not with international normalized ratio (p = 0.99) or activated partial thromboplastin time (p = 0.29). Daily cryoprecipitate transfusion dose was independently associated with younger age (p = 0.009), but not with chest tube bleeding (p = 0.18), other bleeding requiring RBC transfusion (p = 0.75), fibrinogen level (p = 0.67), or daily fibrinogen goal (p = 0.81). CONCLUSIONS: Platelets were transfused on two third of the days on extracorporeal membrane oxygenation, plasma on one third, and cryoprecipitate on one sixth of the days. Although most hemostatic transfusions were independently associated with bleeding, they were not independently associated with the majority of hemostatic testing. Further studies are warranted to evaluate the appropriateness of these transfusion strategies.

Blood component use in critical care in patients with COVID-19 infection: a single-centre experience.

There has been a significant surge in admissions to critical care during the coronavirus disease 2019 (COVID-19) pandemic. At present, the demands on blood components have not been described. We reviewed their use during the first 6 weeks of the outbreak from 3 March 2020 in a tertiary-level critical care department providing venovenous extracorporeal membrane oxygenation (vv-ECMO). A total of 265 patients were reviewed, with 235 not requiring ECMO and 30 requiring vv-ECMO. In total, 50 patients required blood components during their critical care admission. Red cell concentrates were the most frequently transfused component in COVID-19-infected patients with higher rates of use during vv-ECMO. The use of fresh frozen plasma, cryoprecipitate and platelet transfusions was low in a period prior to the use of convalescent plasma.

Bacterial contamination and septic transfusion reaction rates associated with platelet components before and after introduction of primary culture: experience at a US Academic Medical Center 1991 through 2017.

BACKGROUND: The high incidence of septic transfusion reactions (STRs) led to testing being mandated by AABB from 2004. This was implemented by primary culture of single-donor apheresis platelets (APs) from 2004 and prestorage pooled platelets (PSPPs) from 2007. STUDY DESIGN/METHODS: Platelet (PLT) aliquots were cultured at issue and transfusion reactions evaluated at our hospital. Bacterial contamination and STR rates (shown as rates per million transfusions in Results) were evaluated before and after introduction of primary culture by blood centers that used a microbial detection system (BacT/ALERT, bioMerieux) or enhanced bacterial detection system (eBDS, Haemonetics). RESULTS: A total of 28,457 PLTs were cultured during pre-primary culture periods (44.7% APs; 55.3% at-issue pooled PLTs [AIPPs]) and 97,595 during post-primary culture periods (79.3% APs; 20.7% PSPPs). Forty-three contaminated units were identified in preculture and 34 in postculture periods (rates, 1511 vs. 348; p < 0.0001). Contamination rates of APs were significantly lower than AIPPs in the preculture (393 vs. 2415; p < 0.0001) but not postculture period compared to PSPPs (387 vs. 198; p = 0.9). STR rates (79 vs. 90; p = 0.98) were unchanged with APs but decreased considerably with pooled PLTs (826 vs. 50; p = 0.0006). Contamination (299 vs. 324; p = 0.84) and STR rates (25 vs. 116; p = 0.22) were similar for PLTs tested by BacT/ALERT and eBDS primary culture methods. A change in donor skin preparation method in 2012 was associated with decreased contamination and STR rates. CONCLUSION: Primary culture significantly reduced bacterial contamination and STR associated with pooled but not AP PLTs. Measures such as secondary testing near time of use or pathogen reduction are needed to further reduce STRs.

Evolution of perioperative blood transfusion practice after coronary artery bypass grafting in the past two decades.

BACKGROUND AND AIM OF THE STUDY: Transfusion of blood products after coronary artery bypass grafting (CABG) is associated with increased morbidity and mortality. We evaluated the perioperative use of blood products in patients undergoing CABG in our institution over the past two decades. METHODS: The study included 18 992 patients who underwent isolated CABG at our hospital between 1998 and 2017. Baseline characteristics of patients and the number of perioperative transfusions during their hospital stay (including red blood cells [RBCs], platelets, and fresh frozen plasma [FFP]) were assessed. Logistic regression models were used to identify risk factors for perioperative transfusion. RESULTS: The rates of perioperative RBC transfusion decreased for all patients undergoing isolated CABG (52.1% in 1998 vs 18.6% in 2017) in our institution. The mean number of transfused RBC units was significantly higher in women than in men (1.57 ± 2.2 vs 0.68 ± 1.84; P < .005); this difference remained significant over the years. After adjusting the results for other risk factors, female sex was a significant independent risk factor for perioperative RBC transfusion. The platelet transfusion rate increased over the past two decades (1.4% in 1998 vs 9.7% in 2017). The number of FFP transfusions remained unchanged. CONCLUSIONS: Over the past two decades, we observed a decrease in the incidence of perioperative RBC transfusions in patients undergoing isolated CABG, whereas platelet transfusions increased. Female sex was an independent predictor of perioperative RBC transfusion.

Cost-effectiveness evaluation of the PROPPR trial transfusion protocols.

BACKGROUND: There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period. STUDY DESIGN AND METHODS: International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments. RESULTS: The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained. CONCLUSION: The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths.

Pre-infusion single-dose mesenchymal stem cells promote platelet engraftment and decrease severe acute graft versus host disease without relapse in haploidentical peripheral blood stem cell transplantation.

BACKGROUND: Mesenchymal stem cells (MSCs) may be used to treat steroid-refractory graft versus host disease (GVHD). However, the effects of MSCs in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) have not been confirmed in randomized studies. METHODS: We conducted a randomized clinical study to investigate the effects of pre-infusion (1 × 106 cells/kg) MSCs on hematopoietic recovery, Epstein-Barr and cytomegalovirus infection, GVHD, and relapse in patients undergoing haplo-PBSCT. Fifty patients with acute leukemia or myelodysplastic syndrome were randomly divided into an MSC group administered 1 × 106 MSCs/kg 4 to 6 hours before infusion of peripheral stem cells and a control group without MSCs. RESULTS: Mean platelet engraftment time was significantly faster in the MSC compared with the control group (12.28 vs 13.29 days). The mean neutrophil engraftment time was comparable in both groups (10.76 ± 2.40 vs. 10.29 ± 1.72 days). Grade II or above acute GVHD was significantly decreased in the MSC compared with the control group (12% vs. 36%). There were no significant differences in relapse rate or overall survival between the groups. CONCLUSION: These results suggest that pre-infusion single-dose MSCs promote platelet engraftment and decrease severe acute GVHD without increasing relapse rate.

Financial analysis of large-volume delayed sampling to reduce bacterial contamination of platelets.

BACKGROUND: Effective and financially viable mitigation approaches are needed to reduce bacterial contamination of platelets in the US. Expected costs of large-volume delayed sampling (LVDS), which would be performed by a blood center prior to shipment to a hospital, were compared to those of pathogen reduction (PR), point-of-release testing (PORt), and secondary bacterial culture (SBC). METHODS: Using a Markov-based decision-tree model, the financial and clinical impact of implementing all variants of LVDS, PR, PORt, and SBC described in FDA guidance were evaluated from a hospital perspective. Hospitals were assumed to acquire leukoreduced apheresis platelets, with LVDS adding $30 per unit. Monte Carlo simulations were run to estimate the direct medical costs for platelet acquisition, testing, transfusion, and possible complications associated with each approach. Input parameters, including test sensitivity and specificity, were drawn from existing literature and costs (2018US$) were based on a hospital perspective. A one-way sensitivity analysis varied the assumed additional cost of LVDS. RESULTS: Under an approach of LVDS (7-day), the total cost per transfused unit is $735.78, which falls between estimates for SBC (7-day) and PORt. Assuming 20,000 transfusions each year, LVDS would cost $14.72 million annually. Per-unit LVDS costs would need to be less than $22.32 to be cheaper per transfusion than all other strategies, less than $32.02 to be cheaper than SBC (7-day), and less than $196.19 to be cheaper than PR (5-day). CONCLUSIONS: LVDS is an effective and cost-competitive approach, assuming additional costs to blood centers and associated charges to hospitals are modest.

Bacterial contamination rate of platelet components by primary culture: a systematic review and meta-analysis.

BACKGROUND: Platelets have the highest bacterial contamination risk of all blood components, and septic transfusion reactions remain a problem. A good estimate of contamination rates could provide information about residual risk and inform optimal testing strategies. We performed a systematic review and meta-analysis of platelet contamination rates by primary culture. STUDY DESIGN AND METHODS: A literature search in December 2019 identified articles on platelet contamination rates using primary culture. We used meta-analysis to estimate the overall rate of contamination and meta-regression to identify heterogeneity. We studied the following sources of heterogeneity: collection method, sample volume, positivity criteria, and study date. Contamination rate estimates were obtained for apheresis (AP), platelet rich plasma (PRP), and buffy coat (BC) collection methods. RESULTS: The search identified 6102 studies, and 22 were included for meta-analysis. Among these 22 studies, there were 21 AP cohorts (4,072,022 components), 4 PRP cohorts (138,869 components), and 15 BC cohorts (1,474,679 components). The overall mean contamination rate per 1000 components was 0.51 (95% CI: 0.38-0.67) including AP (0.23, 95% CI: 0.18-0.28), PRP, (0.38, 95% CI: 0.15-0.70), and BC (1.12, 95% CI: 0.51-1.96). There was considerable variability within each collection method. Sample volume, positivity criteria, and publication year were significant sources of heterogeneity. CONCLUSION: The bacterial contamination rate of platelets by primary culture is 1 in 1961. AP and PRP components showed a lower contamination rate than BC components. There is clinically significant between-study variability for each method. Larger sample volumes increased sensitivity, and bacterial contamination rates have decreased over time.