RBC Requirements Research Articles

Transfusion Burden in Allogeneic Hematopoietic Stem Cell Transplantation over Time: Experience from a Single Institution.

Transfusion plays a main role in supportive treatment for patients who receive an allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we compare the transfusion requirements of patients undergoing different modalities of HSCT according to different time periods. The objective is to assess the evolution of HSCT transfusion requirements over time, from a single institution. The clinical charts and transfusion records of patients who underwent HSCT of different modalities at La Fe University Hospital during a twelve-year period were reviewed (2009-2020). For analysis, we divided the overall time into three periods: 1 from 2009 to 2012, 2 from 2013 to 2016 and 3 from 2017 to 2020. The study included 855 consecutive adult HSCT: 358 HLA-matched related donors (MRD), 134 HLA-matched unrelated donors (MUD), 223 umbilical cord blood transplantation (UCBT) and 140 haploidentical transplants (Haplo-HSCT). There were no significant differences in RBC and PLT requirements or transfusion independence among the three time periods for MUD and Haplo-HSCT. However, the transfusion burden increased significantly for MRD HSCT during the 2017-2020 period. despite HSCT modalities having evolved and changed over time, overall transfusion requirements have not significantly decreased and continue to be a cornerstone of transplantation-supportive care.

Red Blood Cell Alloimmunization in Sickle Cell Disease: Advantage of Ethnic Heritage between Donors and Patients in Jeddah, Saudi Arabia

Abstract Introduction/Objective Red blood cell (RBC) transfusion is frequently required for patients with sickle cell disease (SCD). Development of alloantibodies in these patients complicates the blood bank process needed to identify these antibodies and to find compatible RBC units. The rate of alloimmunization has been reported as high as 47% in one study and 34.2% in another study from Eastern region of Saudi Arabia. The purpose of this study was to determine incidence and rate of RBC alloimmunization in the Saudi population in the Western region in SCD. Methods/Case Report A retrospective analysis of the immunohematological and transfusion history of a total of 161 SCD patients was reviewed, of which there 95 males and 66 females. All patients had erythrocytapheresis, ranging from one to 24 full red cell exchange sessions. A total of 490 red cell exchanges were performed and 4,914 units of blood were used. Extended compatibility to RhCcEe and K antigen was performed. Patient who developed alloimmunization to any of RhCcEe and K antigen were matched for Kidd, Duffy and MSN antigens for subsequent RBC requirements. Results (if a Case Study enter NA) The RBC alloimmunization incidence was 18% with a rate of 0.6 antibodies per 100 RBC transfusions. Alloimmunization in females was significantly higher than in the patients. Eighteen (11.2%) female patients demonstrated antibodies as compared to eleven (6.8%) male patients. Twelve patients (7.4%) had a history of at least one alloantibody and 17 (10.6%) had more than one. Antibodies found were directed against E (7.4%), K (5.6%), and D, C, c, S, M, Lea, Jk a, Chido/Rodgers, Fy a. Seven (4.3%) patients also had warm autoantibodies. Conclusion RBC alloimmunization incidence and rate in our study was lower to those reported in less heterogeneous population of donors and patients. Nonetheless, RBC alloimmunization still occurs in patients with SCD, often due to Rh variants or lack of consistency in the application of prophylactic antigen matching between institutions. Therefore, we believe that this rate can still be further reduced if all centers in the region establish transfusion programs to include at least RhCcEe and K phenotypic compatibility and communication mechanisms between major treating centers and transfusion centers in smaller cities to minimize the risks of exposing the patient to different RhCcEe and K phenotype and of developing RBC alloimmunization.

Bloody Transplants! Impact of Prior Sternotomy on Transfusion Rate in Heart Transplantation

<h3>Purpose</h3> Ventricular Assist device (VAD) patients are at higher risk of bleeding at the time of heart transplant. Moreover, the quantity of packed red cells (RBC) received during the first 24 hours postoperatively correlates with increased mortality. Whether this is related to surgical issues or due to the anticoagulation associated with VADs is unknown. <h3>Methods</h3> Operative transfusion requirements and demographics data was obtained from our hospital cardiothoracic database for all patients who underwent heart transplantation between 2006 and 2020. Patients were divided into three groups - No previous sternotomy (NPS), VAD explant (VE) and Previous (non-VAD) Sternotomy (PS). Biventricular VAD, total artificial heart explants and multi-organ transplants were excluded. <h3>Results</h3> 428 patients were included in the analysis. Median age was 54 years (IQR 43-61), 131 patients were female (31%), median eGFR was 78ml/min/1.73m2 (IQR 54-95). 236 patients (54.2%) were in the NPS group, 133 (31.1%) in the VE group and 62 patients (14.6%) in the PS group. There was a strong association between blood transfusion and re-do sternotomy (both VE and PS groups) (p<0.001), but no difference between the VE and PS groups. A lower mean eGFR (<78ml/min/1.73m2) was associated with higher transfusion requirement (P<0.001). <h3>Conclusion</h3> Sternotomy patients (with or without VAD explant) demonstrated a higher RBC transfusion requirement compared to clean skin and these patients tended to have a lower renal function post-operatively. The lack of difference in RBC requirement between VE and PS patients suggest that anticoagulated VAD patients who have received Vitamin K do not necessarily have higher bleeding risk than other re-do sternotomy patients.

Comparison of transfusion requirements in adult patients undergoing Haploidentical or single-unit umbilical cord blood stem cell transplantation.

Umbilical cord blood transplantation (UCBT) and haploidentical hematopoietic stem cell transplantation (haplo-HSCT) modalities have been developed to offset the lack of matched donors. In this study, we compare the transfusion requirements of patients undergoing UCBT and haplo-HSCT in a single institution with the aim of providing additional information for clinicians to choose the most adequate alternative graft for HSCT. The study reviewed 67 and 46 patients undergoing UCBT and haplo-HSCT, respectively. There were no significant differences for RBC and PLT requirements according to the transplantation modality. Median time to RBC transfusion independence was 35 and 25.5days in patients who received an UCBT and haplo-HSCT, respectively (P=0.38), while median time to platelet transfusion independence was 31days for UCBT patients and 23 for haplo-HSCT patients (P<0.001). Days until neutrophils>0.5×109 /L were the only variable that significantly influenced RBC and PLT requirements for both transplantation modalities. Cumulative incidence of RBC and PLT transfusion independence at 90days after transplantation was similar for both UCBT and haplo-HSCT. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy. Both transplantation platforms require prolonged and intensive supportive RBC and PLT transfusion therapy.

Early acute kidney injury after liver transplantation in patients with normal preoperative renal function

Acute kidney injury (AKI) commonly occurs in patients after liver transplantation (LT). However, few studies have focused on AKI and its correlation with clinical outcomes under the Kidney Disease Improving Global Outcomes (KDIGO) criteria. This study aimed to identity the incidence, risk factors, and impacts of early AKI on outcomes in LT recipients with normal preoperative renal function, according to the KDIGO criteria. Clinical and laboratory data of 227 patients with normal preoperative renal function who underwent LT from January 2011 to January 2015 were retrospectively analyzed. During the first week after LT, 106 patients (46.7%) developed AKI based on the KDIGO criteria. A multivariate analysis revealed that BMI of > 25, prolonged inferior vena cava clamping, prolonged cold ischemia time, and post-operative RBC requirements > 10 units were independent risk factors for AKI after LT. The area under the receiver operating characteristic curve for the predictive ability of AKI under these risk factors was 0.748. The occurrence of AKI was associated with longer mechanical ventilation time and post-operative ICU stay, increased post-operative 30-day mortality and decreased long-term patient survival. Even in patients with normal preoperative renal function, AKI was a frequent complication in LT recipients and had both negative short- or long-term effects on patient outcomes, also the severity of AKI had a dose-response relationship with worse outcomes. Patients with BMI > 25, prolonged inferior vena cava clamping, prolonged cold ischemia time, or post-operative RBC requirement > 10 units should be pay particular attention, which may assist in achieving better clinical outcomes.

Open abdomen in liver transplantation

IntroductionDamage control laparotomy with vacuum assisted closure (VAC) is used for selective cases in trauma. In liver transplantation, VAC has also been applied for management of intra-operative hemorrhage. The primary objective was to evaluate peri-operative blood loss and blood product utilization in VAC compared to primary abdominal closure (PAC) at the index transplant operation. MethodsRetrospective review of all adults undergoing deceased donor liver transplantation (2007–2011) at a single center tertiary care institution. Results201 deceased donor liver transplantations were performed, with 167 PAC and 34 VAC cases. Intra-operative blood loss (4.4L vs 10.7L), cell saver return (1399 ml vs 3998 ml), FFP (7.6U vs 15.9U) and PLT requirements (8.5U vs 18.3U), were all significantly elevated in VAC compared to PAC. VAC patients had significantly increased RBC, FFP, PLT, and total volume requirements during initial ICU admission. 30 PAC cases required on demand laparotomy and most commonly for post-operative bleeding. ConclusionIn liver transplantation, application of VAC secondary to massive intra-operative exsanguination was safely utilized. Further evaluation is required to identify long-term morbidity and mortality.

Optimal Timing of Initiation of Thromboprophylaxis after Nonoperative Blunt Spinal Trauma: A Propensity-Matched Analysis

Patients with spinal trauma have the highest risk of a venous thromboembolism. Although anticoagulation is recommended, its optimal timing is not well-defined. We aimed to assess the impact of early initiation of thromboprophylaxis in spinal trauma patients who were managed nonoperatively. A 2-year (2013 to 2014) analysis of all isolated spinal trauma patients managed nonoperatively who received thromboprophylaxis in the American College of Surgeons Trauma Quality Improvement Program. Patients were divided into 2 groups based on timing of initiation of thromboprophylaxis: early (<48 hours) and late (≥48 hours), and were matched in a 1:1 ratio using propensity score matching for demographic characteristics, admission vitals, injury severity, level of spine injury, and type of prophylaxis. Outcomes were prevalence of deep venous thrombosis (DVT) and pulmonary embolism, packed RBC requirement, and mortality. We included 20,106 patients, of which 8,552 (early, n= 4,276; late, n= 4,276) were matched. Matched groups were similar in demographic characteristics, vital and injury parameters, and type of prophylaxis. Patients in the early group were less likely to have DVT (1.7% vs 7.6%; p < 0.001) or pulmonary embolism (0.8% vs 2.2%; p < 0.001) develop compared with the late group. In addition, there was no difference in packed RBC requirement (p= 0.61) and mortality (p= 0.49). Patients who received unfractionated heparin had a similar rate of DVT (p= 0.26) and pulmonary embolism (p= 0.35) compared with those who received low-molecular-weight heparin. In patients with nonoperative spinal trauma, early initiation of thromboprophylaxis is associated with decreased rates of DVT and pulmonary embolism. In addition, we did not find any association between the type of pharmacologic agents and venous thromboembolism rates. Additional prospective clinical trials should be undertaken to define guidelines for the timing of initiation of thromboprophylaxis.

ABO incompatibility does not influence transfusion requirements in patients undergoing single-unit umbilical cord blood transplantation.

Hematopoietic stem cell transplantation is usually performed without considering the ABO compatibility between donor and recipient. There are few studies analyzing ABO matching impact on transfusion outcome of umbilical cord blood transplantation (UCBT) recipients. The aim of this study was to analyze factors influencing transfusion outcome, highlighting the ABO matching between donor and recipient. This study has reviewed data from 318 patients who underwent single unit UCBT at la Fe University Hospital from January 2000 to December 2014. There were no differences between RBC and platelet (PLT) requirements or RBC and PLT transfusion independence according to ABO matching between donor and recipient. RBC and PLT requirements were statistically correlated (ρ=0,841, P<0.001). A total of 170 and 188 patients achieved RBC and PLT independence, respectively, within 180 days after UCBT. Persistence of recipient isoagglutinins was detected in 6.8% of patients with major ABO incompatibility at median of 176 days (103-269) after UCBT. Autoimmune haemolytic anemia was diagnosed in 15 patients, 12 of them due to cold antibodies. In conclusion, ABO matching has not influenced transfusion requirements of patients undergoing UCBT.

Pre-Trauma Center Red Blood Cell Transfusion Is Associated with Improved Early Outcomes in Air Medical Trauma Patients

Hemorrhage is the leading cause of survivable death in trauma and resuscitation strategies including early RBC transfusion have reduced this. Pre-trauma center (PTC) RBC transfusion is growing and preliminary evidence suggests improved outcomes. The study objective was to evaluate the association of PTC RBC transfusion with outcomes in air medical trauma patients. We conducted a retrospective cohort study of trauma patients transported by helicopter to a Level I trauma center from 2007 to 2012. Patients receiving PTC RBC transfusion were matched to control patients (receiving no PTC RBC transfusion during transport) in a 1:2 ratio using a propensity score based on prehospital variables. Conditional logistic regression and mixed-effects linear regression were used to determine the association of PTC RBC transfusion with outcomes. Subgroup analysis was performed for scene transport patients. Two-hundred and forty treatment patients were matched to 480 control patients receiving no PTC RBC transfusion. Pre-trauma center RBC transfusion was associated with increased odds of 24-hour survival (adjusted odds ratio [AOR] = 4.92; 95% CI, 1.51-16.04; p = 0.01), lower odds of shock (AOR = 0.28; 95% CI, 0.09-0.85; p = 0.03), and lower 24-hour RBC requirement (Coefficient -3.6 RBC units; 95% CI, -7.0 to -0.2; p = 0.04). Among matched scene patients, PTC RBC was also associated with increased odds of 24-hour survival (AOR = 6.31; 95% CI, 1.88-21.14; p < 0.01), lower odds of shock (AOR = 0.24; 95% CI, 0.07-0.80; p = 0.02), and lower 24-hour RBC requirement (Coefficient -4.5 RBC units; 95% CI, -8.3 to -0.7; p = 0.02). Pre-trauma center RBC was associated with an increased probability of 24-hour survival, decreased risk of shock, and lower 24-hour RBC requirement. Pre-trauma center RBC appears beneficial in severely injured air medical trauma patients and prospective study is warranted as PTC RBC transfusion becomes more readily available.

Discontinuing washed red cell transfusions in thalassaemia patients

<h3>Aim</h3> To assess if thalassaemia patients previously transfused with washed red cells (WRC) can effectively be transitioned to leucodepleted RBC (LDRC) with leucodepletion standard and RBC plasma content low. <h3>Methods</h3> An audit was conducted from June 2009 at POWH of 20 thalassaemia patients previously receiving WRC before and after changing to LDRCs. Transfusion reactions, RBC requirement and Hb pre-transfusion were documented for six episodes around the introduction of LDRC. NSW Blood Service WRC supply data before and after this change in policy at POWH is reported. <h3>Results</h3> Reactions were only noted in a small number of patients transitioned to LDRC. In most cases reactions did not require reins-tituting WRC. In 2/20 patients WRC use was reinstituted. Changes in RBC requirement and haemoglobin levels were not apparent. In the 2008-2009 financial year, a total of 2708 washed units were supplied in NSW and following the wider adoption of this policy, 811 washed units were supplied in the 2012-2013 financial year. <h3>Discussion</h3> Thalassaemia patients on WRC can be successfully transitioned to leucodepleted RBC. The transition appears safe and the subsequent rate of reactions appears low. This change in transfusion practice may save costs and also simplify the logistics of regular blood transfusion in this patient group.

Use of Activated Recombinant Factor VII in Severe Bleeding – Evidence for Efficacy and Safety in Trauma, Postpartum Hemorrhage, Cardiac Surgery, and Gastrointestinal Bleeding

Background: Uncontrolled bleeding continues to be a major cause of mortality in trauma, cardiac surgery, postpartum hemorrhage and liver failure. The aim of this paper is to assess the evidence supporting the efficacy of activated recombinant factor VII (rFVIIa) administration in these settings. Methods: Electronic literature search. Results: Numerous retrospective trials have mostly shown a decrease in blood transfusion requirements with no increase in thromboembolic events (TEE), but major limitations in trial design make generalization difficult. In most retrospective reports rFVIIa has been administered as a last-ditch attempt to control bleeding, when acidosis, hypothermia and coagulation factor depletion may not allow optimal rFVIIa effect. Prospective randomized controlled trials have not shown any effect of rFVIIa on mortality or TEE, although some have shown a reduction in RBC requirement. Conclusion: Stipulated transfusion protocols in prospective trials have reduced anticipated mortality among controls and make future trials for mortality effect unlikely in view of large sample size requirements. Establishment of these protocols and rapid hemostasis are likely to have greater benefits than administration of a single agent.

The Implications of Prompt Corrective Action for Insurance Firms

S. 40, the National Insurance Act of 2007, requires the development of a system of Prompt Corrective Action (PCA) for federally chartered insurers. This paper discusses the issues associated with developing a system of PCA and makes recommendations regarding its structure. First, the paper considers the historical motivation for the development of PCA in banking and insurance. Second, the paper provides an overview of PCA in banking and reviews the evidence regarding the extent to which banking regulators rely on PCA and its effects on FDIC costs. Third, the paper provides an overview of the risk-based capital requirements in insurance, and compares those requirements with PCA in banking. Fourth, the paper considers the banking requirements related to Least Cost Resolution (LCR) and related language in S. 40. The paper concludes that PCA requirements should be included in any Optional Federal Charter (OFC) legislation, and that NAIC RBC requirements provide a good initial structure. Second, the paper concludes that other regulatory authority giving the Commissioner discretion to intervene beyond PCA is essential in any OFC system. S. 40 would benefit from the inclusion of a provision requiring review of costly insolvencies and transparency with respect to the results of that review and the costs of resolving insolvent insurers. Finally, S. 40 provides a clear objective for resolving insolvencies, a positive change from current insurance laws, but the appropriateness of the objective is dependent on the continued existence of the current guaranty fund system.

Treatment of MDS Related Transfusion-Dependent Anemia with Epoetin alfa: A Meta-Analysis Perspective.

Background: Regular transfusion dependence is seen in almost every MDS patient (pt) during the natural course of disease. Due to deleterious sequelae of chronic transfusions, including iron-overload, alloimmunization, and infections, delaying transfusion dependence or attainment of transfusion-independence are important MDS treatment goals. The role of epoetin alfa (EPO) is well established for anemia treatment prior to transfusion dependence, although its utility in transfusion-dependent pts is not well understood. The present meta-analysis was conducted to assess the efficacy of EPO in achieving transfusion independence in transfusion-dependent MDS pts.Methods: Data was extracted from studies from PubMed, ASCO and ASH proceedings from 1990–2006 in transfusion-dependent MDS pts treated with EPO±G/GM-CSF. Studies using International Working Group (IWG) response and IWG-like criteria with EPO±G/GM-CSF were compared with EPO monotherapy studies not using IWG criteria (Non-IWG). Pooled estimates of erythroid response (ER) rates were calculated using random-effects models. Where only pre-therapy values were available, values for post-therapy reductions in RBC requirements (units/month) were imputed based on response criteria stated in the study.Results: Included were 578 evaluable transfusion-dependent pts representing 58% of the total study population in 25 studies. All studies collectively showed significant treatment effects from baseline (BL) as evidenced by a mean overall ER rate of 34.5% and a mean proportion of pts achieving complete transfusion independence of 23.3% with EPO±G/GM-CSF (p<.001 for both). A significant decrease was observed in mean RBC units/month after treatment (2.55 pre-therapy vs 1.96 post-therapy,p=.0002,n=17 studies). IWG studies showed numerically higher ER rates and lower transfusion requirements than Non-IWG studies (Table) (p>.05). Among IWG studies, EPO monotherapy as compared to EPO±G/GM-CSF, showed comparable ER rates (41.6% vs 36.4%,p=.643), a comparable proportion of pts achieving transfusion-independence (28.8% vs 24.8%,p=0.705), and a greater reduction in RBC units/month (34.3% vs 10.4%,p=0.339). Additionally, EPO monotherapy IWG studies showed dose response with significantly higher overall ER rates in pts receiving 60-80,000 units/week vs 30-40,000 units/week (45.3% vs 30.8%,p=.041). Multivariate regression did not yield significant association of any BL study characteristics with overall ER rate.Conclusion: Findings from this meta-analysis showed EPO±G/GM-CSF treatment is effective in reducing transfusion requirements in transfusion-dependent MDS pts. Identification of predictors of EPO response in this population may offer significant clinical benefit to this subset.Study GroupNon-IWG StudiesIWG StudiesIWG StudiesEPOMonotherapyEPOMonotherapyEPO +G/GM-CSFNo. of studies (evaluable pts)12(268)7(195)6(115)BL sEPO levels, mU/mL (Mean±SD)687.2±684.7374.3±72.2288±172.1BL Hb, g/dL (Mean±SD)8.5±0.67.9±0.48.1±0.4Initial weekly dose of EPO, Units (Mean±SD)48,310±41,34549,326±22,75234,789±12,083Mean monthly pre-therapy RBC Units2.712.372.33Pooled ER rate, % (95%CI)27.8(20.4–35.2)41.6(24.5–58.6)36.4(22.5–50.2)Post-therapy transfusion-independent pts, % (95%CI)17.9(10.9–24.9)28.8(12.6–45.1)24.8(11.8–37.8)Mean post-therapy reduction in RBC units/month, % (Median)17.3(17.1)34.3(24.7)10.4(11.5)

Study on the Role of Recombinant Factor VIIa in the Management of Intractable Blood Loss in Patients without Inherited Bleeding Disorder in a UK District General Hospital.

Introduction: Recombinant Factor VIIa (rFVIIa) was developed in early 1990s. Since its license for use in haemophilia with inhibitors, there has been a rationale for use in the management of intractable blood loss in a wide array of clinical situations in patients without an inherited bleeding disorder such as cardiac and general surgery, acute gastrointestinal bleeding and trauma. Little data exists regarding rFVIIa use in such scenarios in the United Kingdom District General Hospitals particularly as access to rFVIIa is not universal.Aim :We aimed to survey rFVIIa use in a UK District General Hospital with a large cardiothoracic unit to study indications for use, dosing, efficacy, safety profile, cost implications, whether adequate optimisation of coagulation profile occured prior to use in addition to the effect of rFVIIa use on blood product requirement, charting patient outcome at 24 hours and 7 days post dosing.Methods: Retrospective review of consecutive patients receiving rFVIIa from April 2004 to April 2006 at our instituion. Data was obtained from blood bank records with information stored on an audit database. Adequate optimisation of coagulation profile was defined as achieving platelet count > 20 × 109 /L, PT <1.5, APTT 30–45 secs and Fibrinogen >1 pre factorVIIa use; appropriate dose for Factor VIIa defined as 90 micrograms/kg except patients requiring warfarin reversal where 15–20 microgram/kg has been shown to be effective.Results: 26 patients (Median age 63.5 years; 62% male) received rFVIIa during the study period. Indicaions for use were: 65% (17/26) during cardiac surgery; 23% (6/26) during general surgery; 8% (2/26) for acute GI bleed and 4% (1/26) for trauma cases. Optimisation of coagulation profile was not performed in 62% of cases due to PT>1.5; in 58% of cases APTT>45s with Fibrinogen <1 in 3% of cases prior to administration. Median dose used was 8.4 mg; 54% (14/26) received an inappropriate dosage of rFVIIa with 12 due to excessive dosage and 2 receieving sub-optimal dosage. No adverse effects were noted in 96% of cases; only 1 patient with subclavian vein thrombosis was reported 10 days post use. 65%, 31% and 4% of patients received 1, 2 and 3 doses of rFVIIa respectively. Significant differences were noted between pre and post dosing RBC (8.5u v 2.0u; 95% CI = 2.78 8.76; p = 0.001), FFP (7u v 0u; 95% CI = 2.73 7.95; p<0.001) and Platelet (2u v 0.5u; 95% CI= 0.7–2.4; p=0.001) requirement but not in cryoprecipitate use (2u v 0u; p=0.195; see table). The difference between mean blood loss pre and post Factor VIIa use was also significant (472.75 v 105.41 mls/hr; 95% CI = 187.62 547.055 ; p=0.001). The total expenditure on Factor VIIa during the study period was £124,755 of which £22,912 amounted to excess dosing. All cause mortality at 24 hours and 7 days post Factor VIIa use was 7.7% and 23.1% respectively with 11.1% discharged from hospital by 7 days.Conclusion: This study demonstrates rFVIIa is safe and effective in promoting haemostasis and decreasing transfusion requirements in intractable bleeding post cardiac surgery and a variety of other causes. We recommend attention to optimization of coagulation prior to administration as the combination of persistent thrombocytopenia and exhaustion of coagulation factors may result in resistance to rFVIIa therapy. Appropriate dosing is of paramount importance in all cases.Blood product requirement pre and post Factor VIIa useRBCFFPPlateletCryoPre8.5722Post200.50

Azacytidine in the Management of Myelodysplastic Syndrome: A Single Institutional Retrospective Review of Responses and Tolerability.

Twenty two patients (pts) with primary or therapy-related MDS were treated with 5-azayctidine (AZA) at the Kellogg Cancer Care Centers (KCCC) from July 2004–May 2006. We retrospectively reviewed all consecutive patients with myelodysplastic syndrome treated at the KCCC who received this agent. Charts were reviewed for response, time to response, duration of response and rate of hospitalization with complications of therapy or disease during AZA therapy. Treated patients had Refractory Anemia with Excess Blasts-type 1 (RAEB-1, n=6), RAEB type-2 (RAEB-2, n=3), Chronic Myelomonocytic Leukemia (CMMoL, n=4) or Refractory anemia (RA, n=6). Median age at study entry was 80 yrs (range, 58–95). Patients were treated with azacytidine 75mg/m2 daily for seven consecutive days or five days followed by a two day break and an additional two days of treatment. Patients were treated until best response and treatment frequency was decreased to every 6–8 weeks once a response had occurred.Responses were as follows: Complete response (CR) with normalization of cytopenias, marrow dysplasia and blasts (as defined in IWG criteria by Cheson et al) occurred in 2 pts (9%). Complete hematologic response (CHR) meeting all of the peripheral blood criteria but without a confirmation bone marrow performed was noted in 4 pts (18%) while hematologic improvement (HE) major (>2 gm rise in Hgb) occurred in 1 pt (5%) and HE minor (1–2 gm rise in Hgb or 50% decrease in RBC requirements) occurred in 2 pts (9%). Thus, a response using the IWG criteria was seen in 9/22 pts yielding an overall response rate of 41%. The median time to response was 3 cycles (range, 1–4). The median duration of response was 8 months (range, 3–18+). Responses are ongoing in 4/9 of the responders. One of the complete response patients had a complex karyotype (5q-, 7q-, del (18p)) that was not present on follow-up marrow after response was noted. Though treatment related cytopenias did occur frequently in the first two cycles of therapy, there were no treatment related hospitalizations for neutropenic patients in this consecutive cohort of patients and no deaths due to therapy. Azacytidine is a well tolerated agent with responses occurring with a significant rate and duration in MDS.

Red cell requirements for intensive care units adhering to evidence-based transfusion guidelines.

Anemia commonly complicates critical illness. Restrictive transfusion triggers are appropriate in this setting, but no large studies have measured red cell (RBC) requirements for intensive care patients when evidence-based transfusion guidelines are followed consistently. Data were recorded daily for 1023 of 1042 sequential admissions to 10 intensive care units (ICUs) over 100 days. The sample comprised 44 percent of all ICU admissions in Scotland during this period. RBC transfusions and the occurrence of clinically significant hemorrhage were recorded for every ICU day. Transfusion episodes were classified as either associated with or not associated with hemorrhage. Measures of RBC use were derived for the cohort and for Scotland with national audit data. A total of 39.5 percent (95% confidence interval [CI], 36.5%-42.5%) of admissions received transfusions. Eighteen percent of admissions received at least one transfusion associated with hemorrhage and 26 percent received at least one transfusion not associated with hemorrhage. The median (interquartile range) transfusion trigger in the absence of hemorrhage was 78 (73-78) g/L. The overall mean RBC use was 1.87 (95% CI, 1.79-1.96) units per admission or 0.34 (95% CI, 0.33-0.36) units per ICU-day. Forty-seven percent of RBCs administered were not associated with clinically significant hemorrhage. Mean RBC requirements for intensive care in Scotland were estimated to be 3950 (95% CI, 3780-4140) per million-adult-population per year. This represented 7 to 8 percent of the Scottish blood supply. Despite evidence-based transfusion practice, 40 percent of ICU patients receive transfusions, which account for 7 to 8 percent of the national blood supply.

A Study on The RBC Requirements for P/L Insurer Insolvencies

A Study on The RBC Requirements for P/L Insurer Insolvencies

Physiological and clinical implications of proANP(1–98) circulating levels in the perioperative phase of liver transplantation

Background: ProANP(1–126), the prohormone synthesized and secreted by atrial myocites, generates an ANP peptide family, the main forms of which are proANP(1–30), proANP(31–67), proANP(1–98) and proANP(99–126). These molecular circulating forms are involved in hemodynamic and electrolyte homeostasis. In cirrhotic patients, volume homeostasis is almost impaired due to abnormal sodium retention, which results in ascites formation and hemodynamic changes, including high cardiac output and low systemic vascular resistance. During liver transplantation, in the anhepatic phase, hemodynamic instability may occur because of decreased venous return due to surgical manipulation of inferior vena cava, considerable blood loss or cross-clamping. Moreover, marked hemodynamic instability is often observed at the reperfusion of the graft. Aims: The aims of present study are to investigate the changes of ANP during the perioperative phases of Orthotopic Liver Transplantation (OLTx) in end-stage cirrhotic patients. Patients and methods: From July to September 1999, 11 cirrhotic patients undergoing to OLTx were included in the study: seven males and four females (average age 46±10.4 years) affected by post-alcoholic cirrhosis [Hypertension 15 (1990) 9], post-hepatitis cirrhosis [D.G. Gardner, M.C. Lapointe, B. Kovacic-Milivojevic, C.F. Deschepper, Molecular analisys and regulation of the atrial natriuretic factor gene, in: A.D. Struphers (Ed.), Frontiers in Farmacology and Therapeutics: Atrial Natriuretic Factor, Blackwell, Oxford, England, 1991, pp. 1–22], Wilson disease [Life Sci. 28 (1981) 89] and policistic disease [Life Sci. 28 (1981) 89], autoimmune cirrhosis [Life Sci. 28 (1981) 89]. In each patient, a hemodynamic assessment was achieved using a Swan–Ganz catheter. Periferical venous samples were performed during and immediately after OLTx for the determination of ANP(1–98) and other biohumoral parameters. Results: Basal (I) Anesthetic induction (II) Anhepatic phase (III) 30 min from reperfusion (IV) 2 h from reperfusion (V) 24 h (VI) 7 days (VII) ANP 4830±1161 3945±883 3466±510 4559±479 5291±554 9811±2703 8785±2532 Mean ANP(1–98) (pmol/ml mean±SD) basal levels resulted higher than that recorded in the group of healthy subjects. A significant correlation between 24-h post-reperfusion ANP and intra-operative RBC and RIS requirement was found ( p<0.05). The basal values resulted significantly higher than that observed at phase II° ( p<0.04) and lower than that at phase VI° ( p<0.05); the anesthetic induction values were significantly lower than that observed at phase VI° ( p<0.03). Conclusions: ANP(1–98) values may represent a useful marker of hemodynamic derangements during and after OLTx. Further clinical correlations will need a larger patient basis.

7179 Use of argon plasma coagulation (apc) in gastrointestinal angiectasia in an infant.

Background:APC is an alternative to conventional diathermy and ND:YAG laser for hemostasis of large surface bleeding. Features of benefit for small children include limitation of maximum penetration to a tissue depth of 3mm and no tissue vaporization, reducing the risk of perforation, and ease of application through small flexible endoscopes (2.2 mm channel). Case report: A nine month old male infant presented with melena, anemia and thrombocytopenia. Melena was not decreased by platelet infusions. Upper endoscopy revealed diffuse angioma in the stomach with bleeding but none in the duodenum or esophagus. Scattered bleeding lesions were seen in the colon. Epinephrine (1:1000) injections in the stomach, controlled bleeding briefly (24hrs) on 4 occasions.The 5th injection was complicated by tachyarrhythmia, hypertension and increased bleeding.e-aminocaproic acid, steroids and somatostatin were ineffective. Bleeding worsened over 2 months up to an RBC requirement of 30 cc/kg/day.The number of gastric lesions increased, especially in the fundus.APC was performed under general anesthesia with a Pentax EG2901 endoscope. A flexible APC probe was passed through the instrument channel to within 3-5 mm from the lesion. Argon flow at 0.7-0.9 l/min and coagulation current adjusted between 40-50 watts power with small bursts was sufficient for hemostasis and ablation of nonbleeding angiectasias. Melena stopped for 10-12 days following the procedure which was repeated on 5 occasions at 14 day intervals. New lesions were noted at successive endoscopies until treatment with interferona-2b reduced the appearance of new lesions.Complications included passage of a mild electric current once while the baby was being touched during the procedure and scar formation at the site of a fundic ulcer resulting from repeated ablation.Conclusion:Argon plasma coagulation is safe and effective in the management of multiple mucosal bleeding lesions in the GI tract in infants.