Cost-Effectiveness of Thrombopoietin Mimetics in Patients with Thrombocytopenia: A Systematic Review.

OBJECTIVES: Thrombopoietin (TPO) mimetics are a potential alternative to platelet transfusion to minimize blood loss in patients with thrombocytopenia. This systematic review aimed to evaluate the cost-effectiveness of TPO mimetics, compared with not using TPO mimetics, in adult patients with thrombocytopenia. METHODS: Eight databases and registries were searched for full economic evaluations (EEs) and randomized controlled trials (RCTs). Incremental cost-effectiveness ratios (ICERs) were synthesized as cost per quality-adjusted life year gained (QALY) or as cost per health outcome (e.g. bleeding event avoided). Included studies were critically appraised using the Philips reporting checklist. RESULTS: Eighteen evaluations from nine different countries were included, evaluating the cost-effectiveness of TPO mimetics compared with no TPO, watch-and-rescue therapy, the standard of care, rituximab, splenectomy or platelet transfusion. ICERs varied from a dominant strategy (i.e. cost-saving and more effective), to an incremental cost per QALY/health outcome of EUR 25,000-50,000, EUR 75,000-750,000 and EUR > 1 million, to a dominated strategy (cost-increasing and less effective). Few evaluations (n = 2, 10%) addressed the four principal types of uncertainty (methodological, structural, heterogeneity and parameter). Parameter uncertainty was most frequently reported (80%), followed by heterogeneity (45%), structural uncertainty (43%) and methodological uncertainty (28%). CONCLUSIONS: Cost-effectiveness of TPO mimetics in adult patients with thrombocytopenia ranged from a dominant strategy to a significant incremental cost per QALY/health outcome or a strategy that is clinically inferior and has increased costs. Future validation and tackling the uncertainty of these models with country-specific cost data and up-to-date efficacy and safety data are needed to increase the generalizability.

A prospective multi-faceted interventional study of blood bank technologist screening of red blood cell transfusion orders: The START study.

BACKGROUND: Transfusion of red blood cells (RBC) is a common procedure, which when prescribed inappropriately can result in adverse patient outcomes. This study sought to determine the impact of a multi-faceted intervention on unnecessary RBC transfusions at hospitals with a baseline appropriateness below 90%. STUDY DESIGN AND METHODS: A prospective medical chart audit of RBC transfusions was conducted across 15 hospitals. For each site, 10 RBCs per month transfused to inpatients were audited for a 5-month pre- and 10-month post-intervention period, with each transfusion adjudicated for appropriateness based on pre-set criteria. Hospitals with appropriateness rates below 90% underwent a 3-month intervention which included: adoption of standardized RBC guidelines, staff education, and prospective transfusion order screening by blood bank technologists. Proportions of RBC transfusions adjudicated as appropriate and the total number of RBC units transfused per month in the pre- and post-intervention period were examined. RESULTS: Over the 15-month audit period, at the 13 hospital sites with a baseline appropriateness below 90%, 1950 patients were audited of which 81.2% were adjudicated as appropriate. Proportions of appropriateness and single-unit orders increased from 73.5% to 85% and 46.2% to 68.2%, respectively from pre- to post-intervention (P < .0001). Pre- and post-transfusion hemoglobin levels and the total number of RBCs transfused decreased from baseline (P < .05). The median pre-transfusion hemoglobin decreased from a baseline of 72.0 g/L to 69.0 g/L in the post-intervention period (P < .0001). RBC transfusions per acute inpatient days decreased significantly in intervention hospitals, but not in control hospitals (P < .001). The intervention had no impact on patient length of stay, need for intensive care support, or in-hospital mortality. CONCLUSION: This multifaceted intervention demonstrated a marked improvement in RBC transfusion appropriateness and reduced overall RBC utilization without impacts on patient safety.

Albumin 5% Versus Crystalloids for Fluid Resuscitation in Children After Cardiac Surgery.

OBJECTIVES: To determine the clinical benefit of using colloids versus crystalloids for volume resuscitation in children admitted after cardiac surgery. DESIGN: Retrospective pre-/postintervention cohort study. SETTING: Stollery Children's Hospital tertiary care pediatric cardiac ICU. PATIENTS: Children admitted to the pediatric cardiac ICU after cardiac surgery. INTERVENTIONS: Fluid resuscitation policy change in which crystalloids replaced albumin 5% as the primary fluid strategy for resuscitation after cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Children who underwent cardiac surgery in the 6 months prior to the policy change (5% albumin group) were compared with children admitted during the 6 months after (crystalloid group). Demographic, perioperative, and outcome variables (fluid intake days 1-4 postoperative, vasoactive therapy, blood products, time to negative fluid balance, renal replacement therapies, mechanical ventilation, pediatric cardiac ICU, and length of stay) were collected. Data were analyzed using linear and logistic multivariate analysis. The study included 360 children. There was no association between fluid group and fluid intake (mL/kg) on day 1 postoperatively (coefficient, 2.84; 95% CI, 5.37-11.05; p = 0.497). However, crystalloid group was associated with significantly less fluid intake on day 2 (coefficient, -12.8; 95% CI, -22.0 to -3.65; p = 0.006), day 3 (coefficient, -14.9; 95% CI, -24.3 to -5.57; p = 0.002), and on the first 48 hours postoperative (coefficient, 10.1; 95% CI, -27.9 to -1.29; p = 0.032). Pediatric cardiac ICU stay (coefficient, -1.29; 95% CI, -2.50 to -0.08; p = 0.036) was shorter for the crystalloid group. There were no significant differences in the time to negative balance, need for renal replacement therapy, mechanical ventilation days, hospital stay, or pediatric cardiac ICU survival. CONCLUSIONS: In our study, the use of albumin 5% for resuscitation after cardiac surgery was not associated with less fluid intake but rather the opposite. Albumin administration did not provide measured clinical benefit while exposing children to side effects and generating higher costs to the healthcare system.

Incremental value of the bone marrow trephine biopsy in detecting residual leukemia following treatment for Acute Myeloid Leukemia.

Most guidelines suggest that only the bone marrow aspirate (BMA) is necessary to assess residual disease following intensive chemotherapy for Acute Myeloid Leukemia (AML) with the bone marrow trephine biopsy (BMTB) recommended in cases of a poor quality BMA. We performed a retrospective study evaluating this in a cohort of patients receiving intensive chemotherapy for AML. Residual disease was assessed by morphological examination of the BMA and BMTB±immunohistochemistry. Of the 647 marrows 32.6% were interim marrows performed prior to peripheral count recovery, 41.7% were end of induction (EOI) marrows and the remaining were 'other marrows'. The BMA and BMTB findings were concordant in 92.8% of cases. The BMTB led to a change in diagnosis from 'no leukemia' to 'residual leukemia' in 5.2% of interim, 3.7% of EOI and 2.4% of 'other' marrows. The BMA alone had a sensitivity of 86.8% in detecting residual leukemia and of 82.3%, 82.5% and 94.2% for interim, EOI and 'other marrows', respectively. Despite the high concordance between the BMA and the BMTB the poor sensitivity of the BMA in detecting residual leukemia, particularly at EOI, may lead to an overestimation of the complete remission rates which may have therapeutic and clinical trial implications.

Cryoprecipitate use in 25 Canadian hospitals: commonly used outside of the published guidelines.

BACKGROUND: Canadian Blood Services' disposition reports suggested considerable variation in cryoprecipitate use and prompted this national audit. STUDY DESIGN AND METHODS: Thirty-one institutions were invited to participate in a 2-month audit. Patient information and relevant laboratory and transfusion data were collected. Cryoprecipitate transfusions were categorized as appropriate if a fibrinogen level (taken 6 hr before/after transfusion) was not more than 1.0 g per L and inappropriate if the pretransfusion fibrinogen level was more than 1.0 g per L and posttransfusion fibrinogen level was more than 1.0 g per L or not performed. Appropriateness was categorized as undetermined if the pretransfusion fibrinogen level was not performed and the posttransfusion fibrinogen level was more than 1.0 g per L or not performed. RESULTS: Overall, 25 of 31 invited hospitals agreed to participate. A total of 4370 units of cryoprecipitate were transfused in 603 events to 453 patients representing 62 percent of cryoprecipitate issued to hospitals during the time period. Comparison of the number of units of cryoprecipitate per 100 units of red blood cells (RBCs) transfused by each institution showed significant variation in practice (mean, 9 per 100 RBCs; range, 2 to 27 units). The single most common indication for cryoprecipitate was cardiac surgery (45.4% of events). Overall, 24 percent of cryoprecipitate transfusions were considered to be appropriate (pretransfusion fibrinogen level

Viability of AS-3 and SAG-M red cells stored in plastic syringes for pediatric transfusion.

BACKGROUND: Pediatric patients may require small-volume transfusions necessitating splitting of red cell (RBC) units. This process usually involves temporary storage of aliquots in pediatric blood bags or, in some cases, plastic syringes, until they are transfused. While many studies have been published on the efficacy of storage in blood bags, there is little evidence to show that RBCs are safe and effective for transfusion after separation into plastic syringe aliquots. STUDY DESIGN AND METHODS: Donor RBC units, stored in either SAG-M (n = 10) or AS-3 additive (n = 11), were split into transfer bags and plastic syringes and stored at either 4 degrees C or room temperature (RT). Half of the aliquots were also irradiated at 25 Gy. RBCs were monitored after 0, 4, and 24 hours of storage with the following variables to assess cellular function and viability: adenosine triphosphate, percent hemolysis, hematocrit, pH, lactate dehydrogenase, extracellular potassium, sodium, and RBC indices. RESULTS: There was no difference found between irradiated and nonirradiated aliquots or aliquots stored in the refrigerator versus those stored at RT. Significant differences between aliquots stored in approved transfer bags and those stored in syringes were not identified. CONCLUSIONS: Irradiation and storage of aliquoted RBCs demonstrated expected but not significant changes in the in vitro variables. Storage for up to 24 hours in syringes does not have a greater detrimental effect on RBCs than storage in transfer bags, making products stored in either container safe for transfusion to pediatric patients.

Failure of prophylactic intravenous immunoglobulin to prevent sensitization to cryopreserved allograft tissue used in congenital cardiac surgery.

OBJECTIVE: Cryopreserved allograft tissue used in the Norwood procedure for infants with hypoplastic left heart syndrome causes profound immunologic sensitization, which may complicate future transplantation. Intravenous immunoglobulin has been shown to reduce sensitization after it has developed, allowing successful transplantation. The purpose of this pilot trial was to determine whether intravenous immunoglobulin given before and after the procedure could prevent sensitization to cryopreserved allograft patches used in the initial repair of hypoplastic left heart syndrome. METHODS: Intravenous immunoglobulin (2 g/kg) was given preoperatively, 3 weeks postoperatively, and 4 months postoperatively to 7 infants undergoing the Norwood procedure. Panel-reactive antibodies were measured with flow cytometry preoperatively and at 1, 4, 6, and 12 months postoperatively and compared with values from a contemporary cohort of 12 infants undergoing the Norwood procedure who did not receive intravenous immunoglobulin. RESULTS: The groups were well matched for length and weight at time of surgery. Control infants were somewhat younger than the cohort receiving intravenous immunoglobulin (8 +/- 5 vs 17 +/- 14 days, P = .021). There were no differences in transfusion requirements. There was no difference in the degree of sensitization between control and intravenous immunoglobulin groups at 1 month (class I panel-reactive antibodies 20% +/- 30% vs 4% +/- 9%, P = .443, class II panel-reactive antibodies 17% +/- 27% vs 20% +/- 17%, P = .400), 4 months (class I panel-reactive antibodies 62% +/- 40% vs 73% +/- 41%, P = .813, class II panel-reactive antibodies 49% +/- 42% vs 54% +/- 41%, P = .706), and 12 months (class I panel-reactive antibodies 49% +/- 42% vs 58% +/- 39%, P = .686, class II panel-reactive antibodies 44% +/- 36% vs 49% +/- 42%, P = .651). CONCLUSION: Despite studies showing intravenous immunoglobulin to reduce sensitization, we were unable to demonstrate that intravenous immunoglobulin prevented sensitization after exposure to allograft tissue in neonates undergoing congenital cardiac surgery.

Guidelines on the use of intravenous immune globulin for hematologic conditions.

Canada's per capita use of intravenous immune globulin (IVIG) grew by approximately 115% between 1998 and 2006, making Canada one of the world's highest per capita users of IVIG. It is believed that most of this growth is attributable to off-label usage. To help ensure IVIG use is in keeping with an evidence-based approach to the practice of medicine, the National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services convened a panel of national experts to develop an evidence-based practice guideline on the use of IVIG for hematologic conditions. The mandate of the expert panel was to review evidence regarding use of IVIG for 18 hematologic conditions and formulate recommendations on IVIG use for each. A panel of 13 clinical experts and 1 expert in practice guideline development met to review the evidence and reach consensus on the recommendations for the use of IVIG. The primary sources used by the panel were 3 recent evidence-based reviews. Recommendations were based on interpretation of the available evidence and where evidence was lacking, consensus of expert clinical opinion. A draft of the practice guideline was circulated to hematologists in Canada for feedback. The results of this process were reviewed by the expert panel, and modifications to the draft guideline were made where appropriate. This practice guideline will provide the NAC with a basis for making recommendations to provincial and territorial health ministries regarding IVIG use management. Specific recommendations for routine use of IVIG were made for 7 conditions including acquired red cell aplasia; acquired hypogammaglobulinemia (secondary to malignancy); fetal-neonatal alloimmune thrombocytopenia; hemolytic disease of the newborn; HIV-associated thrombocytopenia; idiopathic thrombocytopenic purpura; and posttransfusion purpura. Intravenous immune globulin was not recommended for use, except under certain life-threatening circumstances, for 8 conditions including acquired hemophilia; acquired von Willebrand disease; autoimmune hemolytic anemia; autoimmune neutropenia; hemolytic transfusion reaction; hemolytic transfusion reaction associated with sickle cell disease; hemolytic uremic syndrome/thrombotic thrombocytopenic purpura; and viral-associated hemophagocytic syndrome. Intravenous immune globulin was not recommended for 2 conditions (aplastic anemia and hematopoietic stem cell transplantation) and was contraindicated for 1 condition (heparin-induced thrombocytopenia). For most hematologic conditions reviewed by the expert panel, routine use of IVIG was not recommended. Development and dissemination of evidence-based guidelines may help to facilitate appropriate use of IVIG.