Search

The article discusses a study conducted by Bougie and colleagues on the association between transfusion of ABO nonidentical platelets and mortality. The study analyzed data from the REDSIII study, which is the largest dataset on this topic. The authors found that ABO nonidentical transfusions were associated with increased mortality for certain disease cohorts, such as patients with hematologic malignancies or intracerebral hemorrhage. However, the authors raise some questions about the methodology used in the study and suggest further analysis to clarify the relationship between ABO nonidentical platelets and mortality. The authors also emphasize the need to consider ABO nonidentical red cells and plasma in future studies to fully understand the potential associations with mortality. [Extracted from the article]

Real-world utilization of 4-factor prothrombin complex concentrate (4F-PCC) and plasma for the management of oral anticoagulant (OAC)-associated bleeding in US trauma hospitals was described. This is amulticenter, retrospective chart review evaluating the use of 4F-PCC and plasma in OAC reversal across medical specialties. Physicians completed a survey and extracted data from 3 to 5 patient charts. Variables of interest included medical specialty, urgency, and bleed type. Two hundred and thirty-five physicians completed the survey, and 861 patient charts were included in the study. 4F-PCC was commonly used in life-threatening or emergent indications, whereas plasma was used in emergent and urgent indications. Plasma was used mostly for patients on warfarin (53% vs 47% 4F-PCC) and 4F-PCC for those on apixaban (82% vs 18% plasma) and rivaroxaban (77% vs 23% plasma). This retrospective analysis showed that 4F-PCC was predominantly used for OAC reversal despite available specific reversal agents for some of the OAC. Although it is not recommended by any reversal guidelines, plasma is still used for OAC reversal. Plasma should be avoided in the management of OAC-associated bleeding. [ABSTRACT FROM AUTHOR]

Objectives: Thromboelastography (TEG) measures whole blood coagulation kinetics in real time and is useful in guiding blood product transfusion. At our institution, providers have immediate remote access to TEG results. However, some critical values are occasionally missed. Our patient blood management program implemented a critical TEG value callback system to improve patient management and blood product utilization.Methods: This retrospective, observational study assessed the data of trauma and critical care patients preimplementation (n = 20) and postimplementation (n = 100) of the callback system. Provider responses to callbacks and changes in TEG parameters after subsequent testing were compared between the two groups.Results: In response to callbacks, 42% provided appropriate management and 42% ordered a repeat TEG vs 28% and 33% in the historical group (P < .0001 and P = .0002, respectively). Following callback, 90% of the TEG parameters in the study group showed an improvement vs 57% in the control group (P = .011).Conclusions: The increase in appropriate management and the improvement in TEG parameters upon repeat testing in the study group compared to the control group demonstrate the efficacy of the TEG callback system. Further studies are needed to evaluate the callback system effect on patient outcome. [ABSTRACT FROM AUTHOR]

The article discusses the detrimental impact of ABO nonidentical platelet transfusions on premature newborns, highlighting increased mortality and complications. Topics discussed include the inflammatory and prothrombotic effects of platelet transfusions, the importance of using ABO identical blood components, and recommendations for more conservative platelet transfusion practices.

Background: Platelet transfusion carries risk of transfusion‐transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion‐related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion. Study design: An open label, sequential cohort study of transfusion‐dependent hematology‐oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment‐emergent assisted mechanical ventilation (TEAMV) by non‐inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri‐transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality. Results: By modified intent‐to‐treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non‐inferior to CPC for TEAMV (treatment difference −1.7%, 95% CI: (−3.3% to −0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p =.039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p =.151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p =.256); and allergic TR were significantly less with PRPC (p =.006). PC and RBC use were not increased with PRPC. Discussion: PRPC demonstrated reduced TEAMV with no excess treatment‐related pulmonary morbidity. [ABSTRACT FROM AUTHOR]

Background: Solvent/detergent‐treated, pooled plasma (SDP) is approved for use in orthotopic liver transplantation (OLT) and thrombotic thrombocytopenic purpura (TTP) patients; however, studies evaluating safety and effectiveness of SDP in these populations are limited. Methods: This prospective study included two cohorts: OLT patients (n = 40) who received either SDP (n = 20) or FFP (control group) (n = 20), and TTP patients (n = 20) who received either SDP (n = 10) or FFP (control group) (n = 10) throughout hospitalization. Medical, laboratory, and blood bank records were retroactively assessed for both cohorts for differences in clinical outcomes, laboratory values, and transfusion data from admission to discharge. Results: In the OLT cohort, significant changes in AST and ALP were observed in the control group as compared to SDP (p <.05 each), and creatinine levels improved significantly in the SDP group as compared to the control group (p <.05) from admission to discharge. In the TTP cohort, platelet counts were significantly improved within the control and SDP groups from admission to discharge, but there were no significant differences between groups (p =.31). LDH levels improved between admission and discharge for both groups (70% decrease in the control group, p <.001, and 80% decrease in the SDP group, p =.001). There were no significant differences detected in clinical outcomes in either cohort. Conclusions: As evidenced by the lack of adverse events in either cohort and similar clinical outcomes, we conclude that SDP is comparable in safety and effectiveness to FFP in OLT and TTP patients. Further studies are needed to evaluate the potential for improved safety with SDP. [ABSTRACT FROM AUTHOR]

Background: Patients receiving anticoagulant therapies, such as vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs), commonly experience gastrointestinal (GI) bleeding as a complication and may require anticoagulant reversal prior to endoscopic treatment. Anticoagulant reversal agents include prothrombin complex concentrates (PCCs; including 3 or 4 coagulation factors), plasma, vitamin K, and target-specific DOAC reversal agents (e.g., idarucizumab and andexanet alfa). Aim: To review current US, as well as international, guidelines for anticoagulant reversal agents in patients on VKAs or DOACs presenting with GI bleeding prior to endoscopy, guideline-based management of coagulation defects, timing of endoscopy, and recommendations for resumption of anticoagulant therapy following hemostasis. Supporting clinical data were also reviewed. Methods: This is a narrative review, based on PubMed and Internet searches reporting GI guidelines and supporting clinical data. Results: GI-specific guidelines state that use of reversal agents should be considered in patients with life-threatening GI bleeding. For VKA patients presenting with an international normalized ratio > 2.5, guidelines recommend PCCs (specifically 4F-PCC), as they may exhibit greater efficacy/safety compared with fresh frozen plasma in reversal of VKA-associated GI bleeding. For DOAC patients, most guidelines recommend targeted specific reversal agents in the setting of GI bleeding; however, PCCs (primarily 4F-PCC) are often listed as another option. Resumption of anticoagulant therapy following cessation of GI bleeding is also recommended to reduce risks of future thromboembolic complications. Conclusions: The utility of anticoagulant reversal agents in GI bleeding is recognized in guidelines; however, such agents should be reserved for use in truly life-threatening scenarios. [ABSTRACT FROM AUTHOR]

Background: Anemia is an independent risk factor for hospitalization, readmission, prolonged length of stay (LOS), diminished quality of life, and mortality. A multidisciplinary program was implemented to manage anemia preoperatively as a patient blood management (PBM) initiative. Methods and Materials: From March 2016 to August 2018, 240 patients were screened for anemia during their preoperative cardiovascular visit. About 52/240 (22%) were found to be anemic and met out inclusion criteria. Also, 45/52 (87%) had iron deficiency anemia and 7 (13%) had anemia without iron deficiency. A similar historical cohort of patients undergoing elective cardiovascular surgery with hemoglobin (Hb) < 12 g/dl from September 2014 to February /2016 (n = 52) served as control group. The primary outcome was perioperative red blood cell (RBC) transfusion. Secondary outcomes were date‐of‐surgery Hb, intensive care unit (ICU) and hospital LOS, complication rates, and transfusion cost. Results: The two most common treatments were IV iron ± folate (n = 36/45; 80%) and oral iron (n = 9/45; 20%). As compared to historical patients, study patients had significantly higher day‐of‐surgery Hb (10.6 ± 1.4 vs. 9.8 ± 1.3 g/dl, p <.001), lower utilization of RBC transfusion (0.86 ± 1.4 vs. 2.78 ± 2.4, p <.001), fewer days in the ICU (2.1 ± 2.0 vs. 4.0 ± 3.5, p =.002), and shorter total LOS (6.9 ± 4.8 vs. 12.9 ± 6.8, p <.0001). Study patients also showed lower overall complication rates (p <.0001). Analysis of RBC acquisition cost and transfusion cost also showed significant saving of 69% ($293 vs. $945 and $656 vs. $2116, respectively). Conclusion: When corrected for type of procedures and surgeon, our pilot anemia program in elective cardiovascular surgeries showed higher day‐of‐surgery Hb and significant reduction in RBC transfusion rates, ICU and hospital LOS, and overall complication rates. See editorial on page 2519–2521, in this issue [ABSTRACT FROM AUTHOR]

Cell saver blood is typically washed with normal saline (NS); however, recent studies have reported decreased red blood cell hemolysis and increased platelet function when a more physiologic washing solution, such as Plasma-Lyte A (PL-A) is used. We evaluated the in vitro and in vivo effects of NS compared to PL-A as washing solutions for cell saver blood in pediatric cardiac surgery. Cell saver blood was re-infused for up to 24 hours post-collection. Laboratory and clinical data were collected from infants receiving cell saver washed with either NS (n 5 20) or PL-A (n 5 21). Compositions of the cell saver blood were compared between groups at 5 in vitro time points and in vivo patient blood at 24 hours post-bypass. Although there were differences in in vitro laboratory values between groups; 24 hours post-bypass, in vivo results were similar. Our data supports 24-hour reinfusion of cell saver washed with either NS versus PL-A in pediatric cardiac surgery patients, and provides data on the differences in cell saver composition to guide future studies. [ABSTRACT FROM AUTHOR]

Objectives: RBCs are known to undergo deleterious changes during storage, known as storage lesions, which have been shown to result in decreased oxygen-carrying capacity. However, there is inadequate literature describing the effects of stored RBC allogeneic transfusion on oxygen parameters in vivo. The oxygen standard parameters were retrospectively assessed before and after RBC transfusion.Methods: Patients who received 1 RBC transfusion were assessed for hemoglobin (Hb) levels, peripheral capillary oxygen saturation (Spo2), and partial pressure of arterial oxygen (Pao2) from 12 hours before and 24 hours after transfusion.Results: In total, 78 patients who were monitored by Spo2 and 28 patients monitored by Pao2 were included in this analysis. Following RBC transfusion, Hb levels increased significantly (P < .001); however, there was a significant decrease in both Spo2 and Pao2 within 24 hours after transfusion (P = .04 and P = .003, respectively), indicating lower tissue oxygenation and lower soluble oxygen level.Conclusions: This single-center, retrospective study revealed evidence of significantly decreased oxygenation and tissue perfusion after single-unit RBC transfusion, despite corrected Hb levels. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been renewed interest in whole blood (WB) transfusion, particularly in damage control resuscitation, in part due to the ability to provide the adequate ratio of blood components in a single transfusion. However, there is insufficient evidence to suggest that WB units maintain their haemostatic function during storage, which could compromise their quality and efficacy if transfused. Here, we evaluate the in vitro haemostatic function of stored WB units over a 28‐day refrigeration period. Methods: Standard WB units were collected from healthy volunteers and stored at 4°C for 28 days. Samples were collected from each unit on several days throughout the storage period and tested for complete blood count (CBC), WB aggregation, clot kinetics as measured by thromboelastography (TEG), closure time and plasma‐free haemoglobin. Results: Throughout the storage period, there were gradual, significant decreases in platelet count and function, including WB aggregation in response to collagen (P < 0·05) and closure time with epinephrine (P < 0·0005). Plasma‐free haemoglobin increased substantially (by 163%) throughout the storage period. However, TEG results remained relatively stable for 3 weeks, indicating possible preservation of haemostatic function during that time. Conclusion: This study shows that clot kinetics (as measured by TEG) in WB units stored at 4°C are preserved for up to 21 days. However, high levels of free haemoglobin raise concern for the potential risks of transfusing stored WB. Clinical studies are required to evaluate optimal storage times and outcomes of patients resuscitated with WB as compared to blood components. [ABSTRACT FROM AUTHOR]

Platelet-transfusion refractoriness (PTR) is common in patients with hematological malignancies. The etiology of immune PTR is typically human leukocyte antigen (HLA) antibodies (Abs) from pregnancy or previous transfusion. Herein, we report PTR in the setting of induction chemotherapy for acute myelogenous leukemia (AML) from Abs against CD36/glycoprotein (GP)IV. A 66-year-old African American woman presented with anemia and thrombocytopenia. She was found to have transfusion-dependent AML, and a 7 + 3 regimen (7 days of standard-dose cytarabine and 3 days of an anthracycline antibiotic or an anthracenedione, most often daunorubicin) was initiated. The patient developed profound thrombocytopenia, with platelet nadir of 0 by day 13. The results of HLA antibody screening were negative. However, the results of a screening test for platelet-specific antibodies screen showed Abs against cluster of differentiation (CD)36. The platelets of the patient lacked expression of CD36, and DNA analysis showed mutations in the CD36 gene. HLA Ab–mediated PTR is common in patients with hematological malignancies. However, once HLA Abs are excluded, other less-frequent Abs should be considered, particularly in patient populations of Asian, African, or Middle Eastern descent. [ABSTRACT FROM AUTHOR]

Background: Platelet transfusion is associated with logistical problems with the national storage guidelines of platelets. This results in decreased function in vivo as a result of the platelet storage lesion, and complications such as allergic or hemolytic reactions and thrombosis. We evaluated a new, freshly prepared platelet modified lysate (PML) product designed to be more procoagulant than fresh and stored platelets.Methods: Fresh platelets were concentrated, sonicated, and centrifuged to produce PML. Samples of both washed and unwashed PML were evaluated for particle size, concentration, and activity, and then tested for clot kinetics and thrombin generation. PML samples were also stored at various temperatures for durations up to 6 months and evaluated for clot kinetics and thrombin generation throughout.Results: PML showed significantly higher concentration of platelet microparticles, increased procoagulant properties, and increased thrombin generation as compared to fresh and stored platelets. In addition, PML maintained its clot kinetics over a 6-month storage period with variable storage conditions.Conclusions: The newly proposed PML product is more procoagulant, stable, and has additional potential applications than currently available platelet products. Further studies will be performed to assess its functions in vivo and to assess thrombotic potential. [ABSTRACT FROM AUTHOR]

Rivaroxaban (Xarelto; Johnson & Johnson Services, Inc) is a direct oral anticoagulant (DOAC) that works by directly inhibiting the active site of factor Xa (FXa). Rivaroxaban is metabolized and cleared via the kidney and liver. The results of various studies have shown that patients with severe renal impairment should receive reduced dosages of rivaroxaban or another anticoagulant due to impaired clearance. Although it is not required, monitoring rivaroxaban is useful in some conditions; however, the assays required for such monitoring are not readily available. Herein, we present a case of a 68-year-old Caucasian male patient who was receiving rivaroxaban (20 mg/day) for atrial flutter and had mild renal impairment. The patient was found to have increased effect of rivaroxaban due to further impairment of renal clearance caused by several renally cleared medications. This case highlights the importance of closely examining the renal function of and medication list for a patient before starting DOACs such as rivaroxaban. [ABSTRACT FROM AUTHOR]

The main clinical distinction between post-transfusion purpura (PTP) and idiopathic thrombocytopenic purpura (ITP) is the sudden development of severe thrombocytopenia in the days after transfusion. Herein, we report the case of a 53-year-old Caucasian woman who developed multiple myeloma (MM) after peripheral blood-stem-cell transplant (PBSCT), along with severe thrombocytopenia (with a nadir of 1 × 109/L); she also experienced severe adverse events after each platelet transfusion, including the first one. These reactions were absent with any other transfused blood products. The results of an human leukocyte antigen (HLA) class-1 panel reactive antibody assay were 0%, and the results of a platelet-antibody screening assay were positive for HLA class-1 antibodies and glycoprotein (Gp)IIb/IIIa antibodies. Her platelet count reached 42 × 109 per L on day 50, after rituximab on day 22 and daratumumab on day 29. Her clinical scenario was most consistent with the course of PTP. [ABSTRACT FROM AUTHOR]

Objectives: To provide an overview of the clot viscoelastic testing technology and to describe its utility in guiding blood product transfusions.Methods: A case scenario will be discussed as well as interpretation of thromboelastography (TEG) tracings. In addition, literature examining the utility of viscoelastic testing in guiding patient management and blood product transfusions will be reviewed.Results: TEG/rotational thromboelastometry (ROTEM) is useful in evaluating clot kinetics in trauma and acutely bleeding patients. TEG/ROTEM parameters are reflective of values measured using standard coagulation assays; however, TEG/ROTEM parameters are more rapidly available and more costly. TEG and ROTEM are used in three main settings: cardiac surgery, liver transplantation, and trauma to assess global hemostasis and administration of blood products.Conclusions: TEG/ROTEM can be helpful in guiding resuscitation and blood product transfusion. Several studies have demonstrated a reduction in transfusion of blood components with TEG/ROTEM; however, other studies have suggested that TEG/ROTEM is not clinically effective in guiding transfusion. [ABSTRACT FROM AUTHOR]

Introduction: Heparin‐induced thrombocytopenia (HIT) is a potentially life‐threatening adverse reaction of heparin. Laboratory evaluation of HIT is often not available within a reasonable time. We evaluated the HemosIL® HIT‐Ab(PF4‐H) (Instrumentation Laboratory), a rapid, on‐demand, fully automated, latex immunoturbidimetric assay (LIA). Materials and methods: Following determination of the LIA's reference interval and cutoff values, a multicenter study was conducted between March 2013 and June 2015. Plasma samples of HIT‐suspected patients (n = 632) were collected and evaluated by LIA on the ACL TOP® Family systems (Instrumentation Laboratory), enzyme‐linked immunosorbent assays (EIA), and serotonin release assay (SRA). Patient characteristics, medical conditions, comorbidities, laboratory results, and medications were collected via medical chart review. The pretest clinical probability of HIT was also calculated for each patient. Results: Based on the 95% reference interval for healthy donors and HIT‐negative patients, a LIA value ≥1.0 U/mL was interpreted positive. The overall agreement of LIA versus EIA and SRA results were 90% (95% CI 88%‐92%) and 79% (95% CI 75%‐82%), respectively. The negative predictive value for LIA and EIA was comparable (87%) with SRA. The positive and negative percent agreements with the clinical probability were 89% (95% CI 69%‐97%) and 86% (95% CI 83%‐89%), respectively, with a negative predictive value of 99.6% (95% CI 98%‐100%). Discussion: Overall, the LIA results were comparable to those of EIA and SRA. This fully automated assay with a remarkable short analytical turnaround time of <20 minutes can be performed on‐demand, which would greatly facilitate more prompt management of HIT. [ABSTRACT FROM AUTHOR]

Introduction: Chorionic cysts of the chorion laeve, fetal chorionic plate, septum, and free membranes have been associated with placental hypoxia, but they have no clear clinical significance. Although immunohistochemistry has identified fibronectin and collagen IV in cyst fluid, the contents have yet to be fully characterized. Methods: Placental chorionic cysts (N = 10) were sampled by fluid extraction and hemotoxylin and eosin-stained sections. Amniotic fluid samples (N = 8) were obtained from pregnant women who had cytogenetic evaluation. The content of the cysts was tested for thrombogenicity using thromboelastography. The cyst content was tested by Luminex multiplex and ELISA assays and for known prothrombotic and proinflammatory factors. Results: We identified cysts, especially those in the chorionic plate, adjacent to intervillous thrombi with apparent cyst rupture. Thromboelastography revealed a significantly shorter R time compared to whole blood control samples. Concentration of creatinine, α-fetoprotein, and surfactant D in the cyst fluid differed significantly from amniotic fluid. Cyst fluids had a significantly higher expression of all prothrombotic and some proinflammatory factors. Discussion: Our data provide the first evidence that chorionic cyst fluid is prothrombotic and different from amniotic fluid. The association of ruptured cysts with adjacent thrombi and the prothrombotic properties of cyst fluid suggest a causal relationship; however, further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Relationships between red blood cell (RBC) transfusion, circulating cell-free heme, and clinical outcomes in critically ill transfusion recipients are incompletely understood. The goal of this study was to determine whether total plasma heme increases after RBC transfusion and predicts mortality in critically ill patients.Study Design and Methods: This was a prospective cohort study of 111 consecutive medical intensive care patients requiring RBC transfusion. Cell-free heme was measured in RBC units before transfusion and in the patients' plasma before and after transfusion.Results: Total plasma heme levels increased in response to transfusion, from a median (interquartile range [IQR]) of 35 (26-76) μmol/L to 47 (35-73) μmol/L (p < 0.001). Posttransfusion total plasma heme was higher in nonsurvivors (54 [35-136] μmol/L) versus survivors (44 [31-65] μmol/L, p = 0.03). Posttransfusion total plasma heme predicted hospital mortality (odds ratio [95% confidence interval] per quartile increase in posttransfusion plasma heme, 1.76 [1.17-2.66]; p = 0.007). Posttransfusion total plasma heme was not correlated with RBC unit storage duration and weakly correlated with RBC unit cell-free heme concentration.Conclusions: Total plasma heme concentration increases in critically ill patients after RBC transfusion and is independently associated with mortality. This transfusion-associated increase in total plasma heme is not fully explained by RBC unit storage age or cell-free heme content. Additional studies are warranted to define mechanisms of transfusion-related plasma heme accumulation and test prevention strategies. [ABSTRACT FROM AUTHOR]

Background: Normal saline has been the fluid of choice for resuscitation, rehydration and fluid replacement during plasma or red cell exchange/cytapheresis. There are increased concerns about its clinical effects and data showing it causes more haemolysis in vitro than buffered solutions such as Plasma‐Lyte A. Methods: We investigated whether normal saline or Plasma‐Lyte A was associated with greater haemolysis during hours of in vitro incubation with both normal red cells and samples from patients with sickle cell anaemia. Results: Sickle red cells haemolysed more than normal red cells did in both crystalloid solutions. The results of 24‐hour exposure to saline were particularly striking (median of 163 mg/dl (IQ range 105–247) for sickle red cells vs. 53 (48–92) for normal red cells (P < 0·0001). In patient samples containing variable quantities of haemoglobin S red cells, increased haemoglobin S was associated with increased haemolysis. This effect was greater for normal saline than Plasma‐Lyte A (P = 0·12). Conclusions: These in vitro models demonstrate that short‐term ex vivo exposure of sickle red cells to normal saline leads to greater haemolysis than short‐term exposure of normal red cells, and this effect is exacerbated by normal saline. Whether use of normal saline causes increased haemolysis in vivo is unknown. Given recent evidence that normal saline increases renal failure and mortality in critically ill patients, further studies are urgently needed. [ABSTRACT FROM AUTHOR]

Background: Vitamin K is reported to begin reversing warfarin within 6 to 12 hours, but this may occur sooner. We sought to determine the rate of international normalized ratio (INR) reversal following vitamin K and relationships with dose, route, and baseline INR.Methods: We evaluated adult patients receiving vitamin K monotherapy for warfarin reversal. Post-vitamin K INRs through 48 hours were collected. Relationships between vitamin K dose and route and baseline INR on rate of reversal and complete reversal (INR < 1.5) were evaluated. Assessment was performed graphically using scatter plots with a line of best fit and a counting process model to determine variables associated with achieving complete reversal.Results: A total of 469 post-vitamin K INRs from 235 patients were included. Time to first INR follow-up after vitamin K administration averaged 10.5 ± 4.2 hours. A significant decrease was detected in INR values in comparison to the baseline INR (3.0 ± 1.9 vs. 4.7 ± 2.2; p < 0.01). Rapid and steady INR change began immediately after vitamin K administration (0-4 hr). A high vitamin K dose and intravenous route were associated with rapid INR change and complete reversal (Vitamin K 10 mg [hazard ratio, 2.4; 95% confidence interval, 1.4-4.2] and IV route [hazard ratio, 1.8; 95% confidence interval, 1.3-2.6]); however, overall complete reversal at 24 and 48 hours was low (14.5% and 41.7%, respectively). Higher baseline INR was associated with rapid INR change and lower baseline INR with complete reversal.Conclusion: Vitamin K alone starts to reverse warfarin immediately. High vitamin K doses and intravenous route are associated with faster INR reversal. Baseline INR also influences rate of correction and frequency of achieving complete reversal. [ABSTRACT FROM AUTHOR]

Objectives: To provide an overview of the complexities associated with the human leukocyte antigen (HLA)-mediated platelet refractoriness. HLA antibody detection technologies and limitations associated with methodologies are discussed.Methods: A case scenario and review of relevant literature describing platelet refractoriness are presented, followed by a discussion of HLA antibody testing.Results: Following diagnosis of HLA-mediated refractoriness, a decision is made regarding the approach to obtain the appropriate platelets. The panel reactive antibodies (PRA) % of the patient, HLA typing, and limitations of the HLA testing should be taken into account when deciding which type of product would be the best option for a given patient.Conclusions: Following confirmation and review of HLA antibody testing, platelets are ordered based upon the PRA% and approach employed, HLA-matched platelets, antigen restricted platelets, or cross-matched platelets. The platelets are transfused and a posttransfusion increment count is monitored to determine transfusion success. [ABSTRACT FROM AUTHOR]

There have been rare reports of patients with simultaneous HIT and APS.12-15 More alarming are the reports of false-positive HIT tests in thrombocytopenic patients with aPL, resulting in unwarranted changes in anti-coagulation and increased risk of thrombosis. Thromb Res. 1991; 62 (1-2): 23 - 9. 14 Auger W, Permpikul P, Moser K. Lupus anticoagulant, heparin use, and thrombocytopenia in patients with chronic thromboembo-Tromboendarterektomi lic pulmonary hypertension: a preliminary report. Keywords: lupus anticoagulant; antiphospholipid syndrome; heparin induced thrombocytopenia; thrombocytopenia; heparin EN lupus anticoagulant antiphospholipid syndrome heparin induced thrombocytopenia thrombocytopenia heparin 211 213 3 07/01/21 20210701 NES 210701 The prothrombotic, antibody-mediated reaction to heparin therapy known as heparin-induced thrombocytopenia (HIT) requires both laboratory testing and clinical evaluation for diagnosis, though the latter is subjective and can be challenging in certain clinical scenarios. Lupus anticoagulant, antiphospholipid syndrome, heparin induced thrombocytopenia, thrombocytopenia, heparin. [Extracted from the article]

Comparing TEM to conventional assays in sepsis and non-sepsis patients, Brenner et al8 suggested that TEM-generated lysis index could be useful to delineate sepsis and postoperative inflammation, and identify patients at high risk for DIC. Viscoelastic hemostatic assays (VHA) such as thromboelastography (TEG) and rotational thromboelastometry (ROTEM or TEM), which assess whole blood clot kinetics, have shown significant potential for the diagnosis of DIC SP [ sp .2 In this systematic review, we assessed VHA role in predicting sepsis-induced DIC. Keywords: disseminated intravascular coagulation; rotational thromboelastometry; sepsis; thromboelastography; thromboelastometry; viscoelastic hemostatic assay EN disseminated intravascular coagulation rotational thromboelastometry sepsis thromboelastography thromboelastometry viscoelastic hemostatic assay 873 875 3 05/10/21 20210601 NES 210601 SIGNIFICANCE STATEMENT Disseminated intravascular coagulation (DIC) is a clinical phenomenon that occurs in up to one third of patients with severe sepsis, and of these patients, the mortality rate can be as high as 50%. Efficacy of viscoelastic hemostatic assay testing in patients with sepsis-induced disseminated intravascular coagulation. [Extracted from the article]

Objectives: Washing cellular blood products is accepted to ameliorate repeated severe allergic reactions but is associated with RBC hemolysis and suboptimal platelet function. We compared in vitro hemolysis and platelet function in blood components after washing with Plasma-Lyte A (PL-A) vs normal saline (NS).Methods: RBC (n = 14) were washed/resuspended in NS or PL-A. Free hemoglobin and heme were determined at 0, 24, 48, and 72 hours. Platelet concentrates (PCs; n = 21) were washed with NS or PL-A and resuspended in same washing solution (n = 13) or ABO-identical plasma (n = 8). Platelet aggregation and spreading were evaluated.Results: The 24-hour free hemoglobin and heme levels were higher in NS (P < .05). Improved platelet function was observed in PL-A-washed PCs (P < .001).Discussion: PL-A showed less RBC hemolysis and better platelet function than NS. Whether such differences would occur in vivo is unknown. [ABSTRACT FROM AUTHOR]

Background: There are data suggesting that free hemoglobin (Hb), heme, and iron contribute to infection, thrombosis, multiorgan failure, and death in critically ill patients. These outcomes may be mitigated by haptoglobin.Study Design and Methods: 164 consecutively treated children undergoing surgery for congenital heart disease were evaluated for associations between free Hb and haptoglobin and clinical outcomes, physiologic metrics, and biomarkers of inflammation RESULTS: Higher perioperative free Hb levels (and lower haptoglobin levels) were associated with mortality, nosocomial infection, thrombosis, hours of intubation and inotropes, increased interleukin-6, peak serum lactate levels, and lower nadir mean arterial pressures. The median free Hb in patients without infection (30 mg/dL; 29 interquartile range [IQR], 24-52 mg/dL) was lower than in those who became infected (39 mg/dL; IQR, 33-88 mg/ 31 dL; p = 0.0046). The median mechanical ventilation requirements were 19 (IQR, 7-72) hours in patients with higher levels of haptoglobin versus 48 (IQR, 18-144) hours in patients with lower levels (p = 0.0047). Transfusion dose, bypass duration, and complexity of surgery were all significantly correlated with Hb levels and haptoglobin levels. Multivariate analyses demonstrated that these variables were independently and significantly associated with outcomes.Conclusions: Elevated pre- and postoperative levels of free Hb and decreased levels of haptoglobin were associated with adverse clinical outcomes, inflammation, and unfavorable physiologic metrics. Transfusion, RACHS score, and duration of bypass were associated with increased free Hb and decreased haptoglobin. Further investigation of the role of hemolysis and haptoglobin as potential mediators or markers of outcomes is warranted. [ABSTRACT FROM AUTHOR]

Oxidation reduction potential (ORP) or Redox is the ratio of activity between oxidizers and reducers. Oxidative stress (OS) can cause cellular injury and death, and is important in the regulation of immune response to injury or disease. In the present study, we investigated changes in the redox system as a function of cardiopulmonary bypass (CPB) in pediatric patients. 664 plasma samples were collected from 162 pediatric patients having cardiac surgery of various CPB times. Lower ORP values at 12 h post-CPB were associated with poor survival rate (mean ± SD 167 ± 20 vs. 138 ± 19, p = 0.005) and higher rate of thrombotic complications (153 ± 21 vs. 168 ± 20, p < 0.008). Similarly, patients who developed infections had lower ORP values at 6 h (149 ± 19 vs. 160 ± 22, p = 0.02) and 12 h (156 ± 17 vs. 168 ± 21, p = 0.004) post-CPB. Patients that developed any post-operative complication also had lower 6 h (149 ± 17 vs. 161 ± 23, p = 0.002) and 12 h (157 ± 18 vs. 170 ± 21, p = 0.0007) post-CPB ORP values. Free hemoglobin and IL-6, IL-10, and CRP were not associated with ORP levels. However, higher haptoglobin levels preoperatively were protective against decreases in ORP. Decreased ORP is a marker for poor outcome and predictive of post-operative thrombosis, infection, and other complications in critically ill pediatric cardiac surgery patients. These results suggest that redox imbalance and OS may contribute to the risk of complications and poor outcome in pediatric CBP patients. Haptoglobin may be a marker for increased resilience to OS in this population. [ABSTRACT FROM AUTHOR]

Introduction. To investigate the impact of a 4-factor prothrombin complex concentrate (4F-PCC [Beriplex®/Kcentra®]) versus plasma on “time to procedure” in patients with acute/severe gastrointestinal bleeding requiring rapid vitamin K antagonist (VKA) reversal prior to invasive procedure. Methods. A post hoc analysis of two phase III trials of 4F-PCC versus plasma in patients with acute/severe gastrointestinal bleeding. The treatment arms were compared for study treatment volume, infusion times, and time from start of study treatment to procedure. Results. Analysis included 42 patients (plasma, n=20; 4F-PCC, n=22). Median (interquartile range) infusion time was significantly shorter for the 4F-PCC group than for the plasma group (16 [13, 26] min versus 210 [149, 393] min; P<0.0001). Median infusion volumes were significantly smaller (103 [80, 130] mL versus 870 [748, 1001] mL; P<0.0001) and median time from study treatment initiation to first procedure was significantly shorter in the 4F-PCC group than in the plasma group (17.5 [12.8, 22.8] versus 23.9 [18.5, 62.0] h; P=0.037). Conclusions. In this analysis of patients with acute/severe gastrointestinal bleeding requiring urgent VKA reversal prior to an invasive procedure, 4F-PCC (compared with plasma) was associated with smaller infusion volumes, shorter infusion times, and reduced time to procedure. [ABSTRACT FROM AUTHOR]

Objectives Clinicians often need to rapidly reverse vitamin K antagonists ( VKAs) in the setting of major hemorrhage or urgent need for surgery. Little is known about the safety profile of the traditional reversal agent, plasma, or the newly approved agent, four-factor prothrombin complex concentrate (4F- PCC), in a randomized setting. This is an integrated analysis of safety data from two clinical trials that evaluated 4F- PCC versus plasma for the treatment of patients requiring rapid VKA reversal for acute major bleeding or prior to an urgent surgical/invasive procedure. Methods This descriptive analysis comprised adverse event ( AE) data from two phase IIIb, randomized, controlled trials. The bleeding and surgical studies were performed across 36 and 33 sites, respectively, in nine countries, with the integrated analysis comprising 388 patients (4F- PCC, n = 191; plasma, n = 197) aged ≥ 18 years, who required VKA reversal due to major bleeding or prior to an urgent surgical/invasive procedure. Patients received either 4F- PCC, containing nonactivated factors II, VII, IX, and X and proteins C and S (Beriplex/Kcentra, CSL Behring) or plasma, both dosed according to baseline international normalized ratio and body weight. Patients were also to receive vitamin K1. AEs and serious AEs ( SAEs) were assessed up to days 10 and 45, respectively. Results The proportion of patients with AEs (4F- PCC, 115/191 [60.2%]; plasma, 124/197 [62.9%]) and SAEs (4F- PCC, 54/191 [28.3%]; plasma, 49/197 [24.9%]) was similar between groups. The proportion of patients with thromboembolic events was also similar between groups (4F- PCC, 14/191 [7.3%]; plasma, 14/197 [7.1%]). There were 13 (6.8%) deaths in the 4F- PCC group and 13 (6.6%) in the plasma group. Fluid overload events occurred in more patients in the plasma group than the 4F- PCC group (25 [12.7%] and 9 [4.7%], respectively). Conclusions These safety data represent the largest controlled assessment of a 4F- PCC to date. For patients requiring urgent VKA reversal, 4F- PCC had a safety profile similar to that of plasma ( AEs, SAEs, thromboembolic events, and deaths), but was associated with fewer fluid overload events. [ABSTRACT FROM AUTHOR]

Stored platelets undergo biochemical, structural and functional changes that lead to decreased efficacy and safety of platelet transfusions. Not only do platelets acquire markers of activation during storage, but they also fail to respond normally to agonists post-storage. We hypothesized that resveratrol, a cardioprotective antioxidant, could act as a novel platelet storage additive to safely prevent unwanted platelet activation during storage, while simultaneously preserving normal haemostatic function. Human platelets treated with resveratrol and stored for 5 d released less thromboxane B2 and prostaglandin E2 compared to control platelets. Resveratrol preserved the ability of platelets to aggregate, spread and respond to thrombin, suggesting an improved ability to activate post-storage. Utilizing an in vitro model of transfusion and thromboelastography, clot strength was improved with resveratrol treatment compared to conventionally stored platelets. The mechanism of resveratrol's beneficial actions on stored platelets was partly mediated through decreased platelet apoptosis in storage, resulting in a longer half-life following transfusion. Lastly, an in vivo mouse model of transfusion demonstrated that stored platelets are prothrombotic and that resveratrol delayed vessel occlusion time to a level similar to transfusion with fresh platelets. We show resveratrol has a dual ability to reduce unwanted platelet activation during storage, while preserving critical haemostatic function. [ABSTRACT FROM AUTHOR]

Platelets perform a vital role in hemostasis and their role in inflammation is becoming increasingly evident. Blood transfusion is the most common procedure performed in hospitals and platelet transfusions comprise a significant proportion. Over the past few decades, retrospective studies and randomized clinical trials have demonstrated that blood transfusion is more harmful than previously thought and is associated with numerous complications, such as transfusion-associated lung injury, transfusionassociated cardiac overload, transfusion-associated immune modulation, and infectious diseases such as human immunodeficiency virus, hepatitis C virus, and hepatitis B virus. Recent data suggest an association between platelet transfusion and thrombosis. This review will highlight the mechanistic issues that may be relevant to the epidemiologic associations of platelet transfusion with thrombosis and mortality in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Plasma is commonly used for vitamin K antagonist (VKA) reversal, but observational studies suggest that it is associated with transfusion-related adverse reactions (e.g., volume overload). However, this issue has not previously been addressed in a randomized controlled trial (RCT).Study Design and Methods: Factors associated with volume overload were examined using data from two Phase IIIb RCTs comparing plasma with four-factor prothrombin complex concentrate (4F-PCC, Beriplex/Kcentra, CSL Behring) for urgent VKA reversal. VKA-treated patients with major bleeding (NCT00708435) or requiring an urgent surgical or invasive procedure (NCT00803101) were randomly assigned (1:1) to receive either plasma or 4F-PCC, concomitant with vitamin K. Adverse events (AEs) and serious AEs were prospectively captured up to Day 10 and 45, respectively. Volume overload predictors were evaluated on a univariate and multivariate basis.Results: A total of 388 patients (4F-PCC, n = 191; plasma, n = 197) were enrolled. Volume overload occurred in 34 (9%) patients (4F-PCC, n = 9; plasma, n = 25). In univariate analyses, use of plasma (vs. 4F-PCC), use of nonstudy plasma and/or platelets, race, history of congestive heart failure (CHF), and history of renal disease were associated with volume overload. In multivariate analyses, use of plasma (vs. 4F-PCC), history of CHF, and history of renal disease were independent volume overload predictors. In an additional analysis restricted to volume overload events recorded up to Day 7, only use of plasma (vs. 4F-PCC) was an independent volume overload predictor.Conclusions: After adjusting for other potential risk factors, plasma use was independently associated with a greater risk of volume overload than 4F-PCC in patients requiring urgent VKA reversal. [ABSTRACT FROM AUTHOR]

Platelet transfusion has been a vital therapeutic approach in patients with hematologic malignancies for close to half a century. Randomized trials show that prophylactic platelet transfusions mitigate bleeding in patients with acutemyeloid leukemia. However, even with prophylactic transfusions, as many as 75% of patients, experience hemorrhage. While platelet transfusion efficacy is modest, questions and concerns have arisen about the risks of platelet transfusion therapy. The acknowledged serious risks of platelet transfusion include viral transmission, bacterial sepsis, and acute lung injury. Less serious adverse effects include allergic and non-hemolytic febrile reactions. Rare hemolytic reactions have occurred due to a common policy of transfusing without regard to ABO type. In the last decade or so, new concerns have arisen; platelet-derived lipids are implicated in transfusion-related acute lung injury after transfusion. With the recognition that platelets are immune cells came the discoveries that supernatant IL-6, IL-27 sCD40L, and OX40L are closely linked to febrile reactions and sCD40L with acute lung injury. Platelet transfusions are pro-inflammatory, and may be pro-thrombotic. Anti-A and anti-B can bind to incompatible recipient or donor platelets and soluble antigens, impair hemostasis and thus increase bleeding. Finally, stored platelet supernatants contain biological mediators such as VEGF and TGF-b1 that may compromise the host versus tumor response. This is particularly of concern in patients receiving many platelet transfusions, as for acute leukemia. New evidence suggests that removing stored supernatant will improve clinical outcomes. This new view of platelets as pro-inflammatory and immunomodulatory agents suggests that innovative approaches to improving platelet storage and pre-transfusion manipulations to reduce toxicity could substantially improve the efficacy and safety of this long-employed therapy. [ABSTRACT FROM AUTHOR]

Background Stored red blood cells ( RBCs) release hemoglobin ( Hb) that leads to oxidative damage, which may contribute to thrombosis in susceptible transfusion recipients. Oxidative stress stimulates the generation of a new class of lipid mediators called F2-isoprostanes ( F2- IsoPs) and isofurans ( IsoFs) that influence cellular behavior. This study investigated RBC-derived F2- IsoPs and IsoFs during storage and their influence on human platelets ( PLTs). Study Design and Methods F2- IsoP and IsoF levels in RBC supernatants were measured by mass spectrometry during storage and after washing. The effects of stored supernatants, cell-free Hb, or a key F2- IsoP, 8-iso-prostaglandin F2α ( PGF2α), on PLT function were examined in vitro. Results F2- IsoPs, IsoFs, and Hb accumulated in stored RBC supernatants. Prestorage leukoreduction reduced supernatant F2- IsoPs and IsoFs levels, which increased again over storage time. Stored RBC supernatants and 8-iso- PGF2α induced PLT activation marker CD62 P ( P-selectin) expression and prothrombotic thromboxane A2 release. Cell-free Hb did not alter PLT mediator release, but did inhibit PLT spreading. Poststorage RBC washing reduced F2- IsoP and IsoF levels up to 24 hours. Conclusions F2- IsoPs and IsoFs are produced by stored RBCs and induce adverse effects on PLT function in vitro, supporting a potential novel role for bioactive lipids in adverse transfusion outcomes. F2- IsoP and IsoF levels could be useful biomarkers for determining the suitability of blood components for transfusion. A novel finding is that cell-free Hb inhibits PLT spreading and could adversely influence wound healing. Poststorage RBC washing minimizes harmful lipid mediators, and its use could potentially reduce transfusion complications. [ABSTRACT FROM AUTHOR]