Mazyar Javidroozi

What is really dangerous: anaemia or transfusion?

Summary While complex physiological mechanisms exist to regulate and optimize tissue oxygenation under various conditions, clinical and experimental evidence indicates that anaemia, unchecked, is associated with organ injury and unfavourable outcomes. More data (especially from human studies) are needed to answer questions regarding the optimal approaches to the treatment of acute and chronic anaemia. Meantime, allogeneic blood transfusions remain the most common treatment, particularly in surgical/trauma patients and those with moderate-to-severe anaemia. Clinical studies emphasize the paradox that both anaemia and transfusion are associated with organ injury and increased morbidity and mortality across a wide span of disease states and surgical interventions. Further characterization of the mechanisms of injury is needed to appropriately balance these risks and to develop novel treatment strategies that will improve patient outcomes. Here, we present the current understanding of the physiological mechanisms of tissue oxygen delivery, utilization, adaptation, and survival in the face of anaemia and current evidence on the independent (and often, synergistic) deleterious impact of anaemia and transfusion on patient outcomes. The risks of anaemia and transfusion in the light of substantial variations in transfusion practices, increasing costs, shrinking pool of donated resources, and ambiguity about actual clinical benefits of banked allogeneic blood demand better management strategies targeted at improving patient outcomes.

Appropriateness of allogeneic red blood cell transfusion: the international consensus conference on transfusion outcomes.

An international multidisciplinary panel of 15 experts reviewed 494 published articles and used the RAND/UCLA Appropriateness Method to determine the appropriateness of allogeneic red blood cell (RBC) transfusion based on its expected impact on outcomes of stable nonbleeding patients in 450 typical inpatient medical, surgical, or trauma scenarios. Panelists rated allogeneic RBC transfusion as appropriate in 53 of the scenarios (11.8%), inappropriate in 267 (59.3%), and uncertain in 130 (28.9%). Red blood cell transfusion was most often rated appropriate (81%) in scenarios featuring patients with hemoglobin (Hb) level 7.9 g/dL or less, associated comorbidities, and age older than 65 years. Red blood cell transfusion was rated inappropriate in all scenarios featuring patients with Hb level 10 g/dL or more and in 71.3% of scenarios featuring patients with Hb level 8 to 9.9 g/dL. Conversely, no scenario with patients Hb level of 8 g/dL or more was rated as appropriate. Nearly one third of all scenarios were rated uncertain, indicating the need for more research. The observation that allogeneic RBC transfusions were rated as either inappropriate or uncertain in most scenarios in this study supports a more judicious transfusion strategy. In addition, the large number of scenarios in which RBC transfusions were rated as uncertain can serve as a road map to identify areas in need of further investigation.

When blood is not an option: factors affecting survival after the use of a hemoglobin-based oxygen carrier in 54 patients with life-threatening anemia.

BACKGROUND: In consenting Jehovahs Witness patients and others for whom blood is contraindicated or not available, hemoglobin-based oxygen carrier (HBOC)-201 may enable survival in acutely anemic patients while underlying conditions are treated. METHODS: Survival factors were identified in a multicenter, unblinded series of severely anemic “compassionate use” patients receiving available standard treatment plus consultant-supported HBOC-201 administration by novice users. Predictors of outcome were sought and compared between survivors and nonsurvivors. A compound variable, hemoglobin-duration deficit product was used to describe the interactive clinical effects of severity and duration of anemia. Mortality, correlations between patient characteristics, and survival to hospital discharge were determined from patient records. RESULTS: Fifty-four patients (median age 50 years) with life-threatening anemia (median hemoglobin concentration at time of request = 4 g/dL) received 60 to 300 g HBOC-201. Twenty-three patients (41.8%) were discharged. Intraoperative blood loss (45%), malignancy (18%), and acute hemolysis (13%) were the prevailing reasons for anemia. Time from onset of anemia (≤8 g/dL) to HBOC-201 infusion was shorter for survivors than nonsurvivors (3.2 vs 4.4 days, P = 0.027). Mean hemoglobin levels before HBOC-201 infusion in survivors and nonsurvivors were 4.5 and 3.8 g/dL, respectively (P = 0.120). No serious adverse event was attributed to HBOC-201. The hemoglobin-duration deficit product separated survivors from nonsurvivors. Cancer and renal disease were associated with nonsurvival. CONCLUSION: Earlier, compared with later, administration by inexperienced users of HBOC-201 to patients with anemia was associated with improved chances of survival of acutely bleeding and hemolyzing patients. Survival was more likely if the duration and magnitude of low hemoglobin was minimized before treatment with HBOC-201.

From bloodless surgery to patient blood management.

Safety and efficacy concerns of allogeneic blood transfusions and their impact on patient outcomes and associated staggering costs and restricted supply have fueled the quest for other modalities and strategies to reduce use of blood components. Patient blood management focuses on multidisciplinary and multimodal preventive measures to reduce or obviate the need for transfusions and ultimately to improve the clinical outcomes of patients. Patient blood management strategies can be applied at every stage of care to surgical and nonsurgical patients, and they generally fall under one of these three categories (the so-called pillars of blood management): optimizing hematopoiesis and appropriate management of anemia, minimizing bleeding and blood loss, and harnessing and optimizing physiological tolerance of anemia through employing all available modalities while treatment is initiated. Several tools and modalities are available to address each of these pillars. Examples include hematinic agents, systemic and topical hemostatic agents, autotransfusion, and blood-sparing perfusion and surgical techniques. Additionally, changes in practice of clinicians (e.g., adherence to restrictive, evidence-based transfusion strategies with emphasis on physiologic indications for transfusion, minimization of iatrogenic blood loss, and adequate planning) play an important role in patient blood management. Emerging evidence supports that appropriate use of these strategies as part of a multimodal program is a safe and effective way of reducing allogeneic transfusions and improving patient outcomes.

An update on mortality and morbidity in patients with very low postoperative hemoglobin levels who decline blood transfusion (CME)

Severely anemic patients for whom blood transfusion is not an option provide highly valuable information on risks of anemia and alternative management strategies.

Iron Deficiency Anemia—Bridging the Knowledge and Practice Gap

Despite its high prevalence, anemia often does not receive proper clinical attention, and detection, evaluation, and management of iron deficiency anemia and iron-restricted erythropoiesis can possibly be an unmet medical need. A multidisciplinary panel of clinicians with expertise in anemia management convened and reviewed recent published data on prevalence, etiology, and health implications of anemia as well as current therapeutic options and available guidelines on management of anemia across various patient populations and made recommendations on the detection, diagnostic approach, and management of anemia. The available evidence confirms that the prevalence of anemia is high across all populations, especially in hospitalized patients. Anemia is associated with worse clinical outcomes including longer length of hospital stay, diminished quality of life, and increased risk of morbidity and mortality, and it is a modifiable risk factor of allogeneic blood transfusion with its own inherent risks. Iron deficiency is usually present in anemic patients. An algorithm for detection and management of anemia was discussed, which incorporated iron study (with primary emphasis on transferrin saturation), serum creatinine and glomerular filtration rate, and vitamin B12 and folic acid measurements. Management strategies included iron therapy (oral or intravenous), erythropoiesis-stimulating agents, and referral as needed.

A new perspective on best transfusion practices.

More than a decade has passed since the publication of the results of the Transfusion Requirements in Critical Care (TRICC) trial, supporting the restriction of red blood cell (RBC) transfusions in the gravest patients1. Since then, some reports are indicative of improvements in transfusion practices (mostly as regards reduced haemoglobin [Hb] thresholds at which patients are transfused2–4). Nonetheless, the overall use of allogeneic RBC transfusions in clinical practice remains relatively high and still varies widely among many centres and practitioners5–7. The latest data from the U.S. Department of Health and Human Services indicate that over 14.6 million units of RBC or whole blood were transfused in the USA in 2006, which is a 3.3% increase from the previous report8. Similarly, the Agency for Healthcare Research and Quality (AHRQ) reported that in 2007, blood transfusions were given in one in every ten hospital admissions in which a procedure was performed; this is a 140% increase from 1997, making transfusion the fastest growing common procedure in hospitals in the USA9. Allogeneic blood transfusions have historically been linked with a myriad of risks and complications. Some risks (e.g. transfusion reactions and transmission of pathogens) have been largely mitigated through advancements in blood banking (e.g. screening for antibodies and markers of infective agents), although these risks are not likely to ever be completely eliminated10,11. Some other risks and complications (e.g. immunomodulation and transfusion-related acute lung injury [TRALI]) appear to have more subtle and elusive aetiologies and are more difficult to tackle11. The presence of leukocytes, residual plasma, and the effects of blood storage have been investigated as possible causes of harmful consequences of banked allogeneic blood12–15. Notably, a number of clinical trials on the effects of storage age of blood on patients’ outcomes are underway: the results of these trials could substantially change the transfusion practice landscape, if they demonstrate that the currently accepted shelf-life of banked blood is too long and should be revised16–19. The other potential threat to safe, readily available transfusions is the aging population which could result in more recipients and fewer donors, putting more pressure on the less than 10% margin that currently exists between the number of collected and transfused blood units8. Finally, direct and indirect costs associated with transfusion have been rising steadily20, providing another motivation for improving transfusion practices.

In vitro evaluation of a novel system for monitoring surgical hemoglobin loss

BACKGROUND:Accurate measurement of intraoperative blood loss is an important clinical variable in managing fluid resuscitation and avoiding unnecessary transfusion of blood products. In this study, we measured surgical blood loss using a tablet computer programmed with a unique algorithm modeled after facial recognition technology. The aim of the study was to assess the accuracy and performance of the system on surgical laparotomy sponges in vitro. METHODS:Whole blood samples of premeasured hemoglobin (Hb) and volume were reconstituted from units of human packed red blood cells and plasma and distributed across surgical laparotomy sponges. Normal saline was added to simulate the presence of varying levels of hemodilution and/or irrigation use. Soaked sponges from 4 different manufacturers were scanned using the Triton System with Feature Extraction Technology (Gauss Surgical, Inc., Palo Alto, CA) under 3 different ambient light conditions in an operating room. Accuracy of Hb loss measurement was evaluated relative to the premeasured values using linear regression and Bland-Altman analysis. Correlations between studied variables and measurement bias were analyzed using nonparametric tests. RESULTS:The overall mean percent error for measure of Hb loss for the Triton System was 12.3% (95% confidence interval [CI], 8.2%−16.4%). A strong positive linear correlation between the premeasured and actual Hb masses was noted across the full range of intraoperative lighting conditions, including (A) high (r = 0.95 [95% CI, 0.93–0.96]), (B) medium (r = 0.94 [95% CI, 0.93–0.96]), and (C) low (r = 0.90 [95% CI, 0.87–0.93]) mean ambient light intensity. Bland-Altman analysis revealed a bias of 0.01 g [95% CI, −0.03 to 0.06 g] of Hb per sponge between the 2 measures. The corresponding lower and upper limits of agreement were −1.16 g (95% CI, −1.21 to −1.12 g) per sponge and 1.19 g (95% CI, 1.15–1.24 g) per sponge, respectively. Measurement bias of estimated blood loss and Hb mass using the new system were not associated with the volume of saline used to reconstitute the samples (P = 0.506 and P = 0.469, respectively), suggesting that the system is robust under a wide range of sponge saturation conditions. CONCLUSIONS:Mobile blood loss monitoring using the Triton system is accurate in assessing Hb mass on surgical sponges across a range of ambient light conditions, sponge saturation, saline contamination, and initial blood Hb. Utilization of this tool could significantly improve the accuracy of blood loss estimates.

Strategies to reduce the use of blood products: a US perspective

Purpose of review To describe the recent developments in the strategies to reduce allogeneic blood transfusions with emphasis on the impact on clinical outcomes. Recent findings Concerns over the safety, efficacy, and supply of allogeneic blood continue to necessitate its judicious use as the standard of care. Patient blood management is emerging as a multidisciplinary, multimodality strategy to address anemia and decrease bleeding with the goal of reduced transfusions and improved patient outcomes. Common risk factors for transfusion include anemia, blood loss, and inappropriate transfusion decisions. Several approaches are available to mitigate these. Recent data continue to support the effectiveness of various hematinics, hemostatic agents and devices, as well as intermittent discontinuation of anticoagulant therapy. Use of autotransfusion techniques, particularly cell salvage, is the other strategy with accumulating data supporting its safety and efficacy. Finally, implementation of evidence-based transfusion guidelines will help to target allogeneic blood to those patients who are likely to benefit from it and thus reduce or eliminate unnecessary exposure to blood. Summary Patient blood management is the timely use of safe and effective medical and surgical techniques designed to prevent anemia and decrease bleeding in an effort to improve patient outcome.

Postoperative blood loss and transfusion associated with use of Hextend in cardiac surgery patients at a blood conservation center

BACKGROUND: Hydroxyethyl starch (HES) solutions are readily available colloids, but their widespread use is shadowed by controversies surrounding their effects on bleeding. This retrospective study was conducted to evaluate the relationship between Hextend (HEX; Hospira, Inc.) doses of 1 to 20 mL/kg and allogeneic transfusion and 24‐hour chest tube drainage (CTD) in cardiac surgeries at a blood conservation center.