Marilyn F.M. Johnston

The variability of transfusion practice in coronary artery bypass surgery. Transfusion Medicine Academic Award Group.

We audited 540 patients undergoing elective first-time coronary artery bypass grafts at 18 institutions. The purposes of the study were to describe the variability in transfusions among institutions and to determine factors that may account for variability. Mean homologous red blood cell use per patient was 2.9(+/- 0.1) U (institutional range, 0.4 to 6.3 U). One hundred seventy-seven patients (32%) received plasma (institutional range, 0% to 97%), and 119 (22%) received platelets (institutional range, 0% to 80%). After controlling for patient and surgical practice variables, transfusion practice factors still accounted for variation in red blood cell transfusions. Variation in patients receiving plasma and platelet transfusions among institutions was determined in part by prophylactic transfusions. We conclude that blood component usage for coronary artery bypass grafts differs widely among institutions. The variability in use of these components is accounted for in part by unnecessary transfusions in otherwise routine, uncomplicated coronary artery bypass graft procedures.

Guidelines for transfusion support in patients undergoing coronary artery bypass grafting

We have reviewed the impact of evolving issues in coronary artery bypass grafting (CABG) on transfusion support for these patients. Issues include increased awareness of transfusion risks, reappraisal of traditional indicators triggering transfusion, and evolving alternatives to homologous blood transfusion such as autologous blood and pharmacologic therapy. These issues have been prompted by programs, such as the National Institutes of Health Consensus Conferences, to provide physicians with guidelines for appropriate use of blood components. However, evidence suggests that transfusion practice in coronary artery bypass grafting procedures remains variable and does not take into account the results of recently published clinical studies. We have therefore developed guidelines and recommendations for transfusion support in patients undergoing coronary artery bypass grafting. In summary, they are the following. 1. Institutions with coronary artery bypass grafting programs should establish a multidisciplinary approach to use a combination of interventions designed to minimize homologous blood exposure. 2. Prophylactic transfusion of plasma and platelets are of no benefit and therefore carry an unnecessary risk to the patient. 3. Special request products such as designated blood donation from first-degree relatives should not be used because of the risk of transfusion-associated graft versus host disease. 4. For support of intravascular volume, crystalloids or colloids should be used because they do not have the potential to transmit infection.

A phase III trial of recombinant human erythropoietin therapy in nonanemic orthopedic patients subjected to aggressive removal of blood for autologous use: dose, response, toxicity, and efficacy

BACKGROUND: Previous clinical trials have shown that the use of recombinant human erythropoietin (EPO) can facilitate autologous blood donation and reduce allogeneic blood transfusions in autologous blood donors who are anemic at first donation. However, the role of EPO therapy in nonanemic patients remains undefined. To identify this role, a randomized, controlled, multicenter dose‐escalation trial was conducted in patients whose initial hematocrit was > 39 percent (0.39).

The effect of recombinant human erythropoietin on the efficacy of autologous blood donation in patients with low hematocrits: a multicenter, randomized, double-blind, controlled trial.

Background: This randomized controlled study was undertaken to determine the effect of recombinant human erythropoietin (rHuEPO) on erythropoiesis, autologous blood collection, and allogeneic transfusion risk in elective surgery patients with low baseline hematocrits.

Transfusions of granulocyte-colony-stimulating factor-mobilized granulocyte components to allogeneic transplant recipients: analysis of kinetics and factors determining posttransfusion neutrophil and platelet counts.

BACKGROUND: Granulocyte‐colony‐stimulating factor (G‐CSF) is a safe and effective agent for mobilization of neutrophils in normal donors, consistently resulting in cell yields per leukapheresis (LA) procedure that are superior to those with other agents. LA components also contain platelets, whose clinical relevance is unknown. STUDY DESIGN AND METHODS: This study describes the kinetics of and analyzes the factors determining the ANC and platelet count increments seen with each of three transfusions of granulocytes collected from HLA‐matched sibling donors receiving G‐CSF (n=10; maximum of 3 LA procedures/donor). The transfusions were given to recipients (n=10) on alternate days beginning. Day 1 after allogeneic bone marrow transplant (BMT). RESULTS: Significant, sustained increments in the recipient ANCs were observed after the transfusion of G‐CSF‐mobilized LA components. The mean peak posttransfusion increments in the ANCs were 1195, 729, and 631 per microL with transfusion of donor LA components on Days 1, 3, and 5, respectively. The length of time that the mean posttransfusion ANC was at or above the baseline (pretransfusion) value was 25 to 37 hours, depending on the post‐BMT day when the component was administered. No consistent relationship was observed between LA component granulocyte dose, baseline recipient ANC, or temperature elevation and post‐transfusion ANC increments. Large numbers of platelets (mean, 2.55 × 10(11)) were present in LA components, and this resulted in significant increments from baseline in the mean platelet count 1 hour after LA component transfusions. Between Days 1 and 7, the duration of severe neutropenia was shorter and the percentage of patients requiring nondonor platelet transfusions was less in study patients who received LA component transfusions than in a similar historical control group who did not. CONCLUSION: The transfusion of G‐CSF‐mobilized, HLA‐matched LA components to allogeneic BMT recipients resulted in significant and sustained increments in the ANC and the platelet count. Within the range examined, a relationship between neutrophil dose and an increment in the ANC was not demonstrated.

Indium-labeled white blood cells apheresed from donors receiving G-CSF localize to sites of inflammation when infused into allogeneic bone marrow transplant recipients

G-CSF administration to normal donors results in granulocyte apheresis yields generally greater than those observed with other neutrophil mobilizing agents. In vitro, neutrophils cultured with G-CSF exhibit prolonged survival; however, the random migration of neutrophils exposed to this agent is inhibited. Although transfused neutrophils mobilized with agents other than G-CSF migrate to sites of inflammation or infection in vivo, this has yet to be demonstrated with infusion of G-CSF-mobilized neutrophils into neutropenic human subjects. Five neutropenic allogeneic bone marrow transplant (BMT) patients each received a fresh infusion of G-CSF-mobilized indium-labeled irradiated white blood cells (WBC) apheresed from HLA-matched normal donors on day +5 post-transplant. Localization of activity on delayed scintigraphic images of indium-labeled WBC scans to sites of tissue damage (oral/nasopharynx in two patients with mucositis and terminal ileum/cecum in one with diarrhea) occurred, and supports the hypothesis that G-CSF-mobilized HLA-matched donor neutrophils which have been irradiated are functional after infusion into neutropenic recipients.

Improving the efficacy of preoperative autologous blood donation in patients with low hematocrit: A randomized, double-blind, controlled trial of recombinant human erythropoietin

The effects of therapy with recombinant human erythropoietin (Epoetin alfa) on erythropoiesis, preoperative autologous blood donation, and risk of exposure to allogeneic blood were evaluated in 204 patients scheduled to undergo elective orthopedic surgery. Study protocol required patients to have a baseline hematocrit < or = 39% and surgery scheduled 25-35 days in advance. Patients were randomized to two equal groups and were seen at study centers every 3-4 days within the 21-day trial period. At each visit, phlebotomy(< or = 450 mL) was performed if the hematocrit was > or = 33%, and Epoetin alfa (600 U/kg) or placebo was administered intravenously. A total of 173 patients were assessable; 31% of placebo recipients and 20% of Epoetin alfa recipients required allogeneic transfusion (p = 0.09). Logistic regression modeling showed that the risk of allogeneic transfusion was reduced by Epoetin alfa (p = 0.025). When patients receiving > 6 units of blood (necessitating allogeneic units) were excluded from analysis, 29% of placebo recipients and 14% of Epoetin alfa recipients were exposed to allogeneic blood (p = 0.015). Epoetin alfa recipients predonated more autologous units than did placebo recipients (4.5 vs 3.0 units, respectively; p < 0.001), and their production of red blood cells increased significantly more over baseline production values (668 vs 353 mL, respectively; p < 0.05). These results demonstrate that administration of Epoetin alfa stimulates erythropoiesis, allows predonation of more units of autologous blood, and reduces the risk of exposure to allogeneic blood. Optimal dosing regimens and surgical patients most likely to benefit fro Epoetin alfa therapy must be established.

Erythropoietin response to anaemia is not altered by surgery or recombinant human erythropoietin therapy

Summary. Recombinant human erythropoietin (EPO) therapy has been shown to increase red blood cell (RBC) production and facilitate autologous blood donation before elective surgery. However, recent reports have suggested that surgery and/or EPO therapy may suppress endogenous erythropoietin secretion in response to anaemia. We therefore analysed the haemoglobin/erythropoietin relationship preoperatively and postoperatively in 71 autologous blood donors subjected to aggressive phlebotomy and six treatments with either EPO (150U/kg, n=16, 300U/kg, n=18, or 600 U/kg, n=19) or placebo (n=18). Using data from the three prepoerative study visit, the linear relationship between log erythropoietin and haemoglobin was determined for each of the 18 placebo patients. We found no significant differences in the slopes of the relationships in this group during aggressive phlebotomy. Furthermore, there was no evidence of a significant difference in the erythropoietin level recorded postoperatively for each patient to that predicted from the patients postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. Similarly, for each of the EPO‐treated groups, there was no evidence of a significant difference when comparing the recorded erythropoietin level to that predicted from each patients postoperative haemoglobin level, based on the haemoglobin/log erythropoietin relationship preoperatively. We conclude that preoperative recombinant human erythropoietin therapy and/or surgery do not adversely affect the postoperative erythropoietin response to anaemia.

Detection of Cold Hemagglutination in a Blood Cardioplegia Unit Before Systemic Cooling of a Patient With Unsuspected Cold Agglutinin Disease

A case is described in which hemagglutination occurred intraoperatively in cold blood flushed through the blood cardioplegia delivery system from a patient with unsuspected cold agglutinin disease. On initiating cardiopulmonary bypass and then selectively cooling the perfusate in the blood cardioplegia delivery system before inducing systemic cooling, it is possible to check for cold agglutination. Routine use of this technique may be worthwhile to detect cold agglutination in vitro before systemic cooling is begun in the rare patient with unsuspected cold agglutinins.

Transfusion therapy in emergency medicine

Volume replacement is critical to the resuscitation of the hemorrhaging patient, but this usually can be accomplished quickly and safely with crystalloid and/or colloid solutions. Red cells should be used in addition to asanguinous fluids in the treatment of tissue hypoxia due to anemia. The need for whole blood as opposed to packed red blood cells is controversial. However, plasma should not be used as a volume expander, and its use to supplement coagulation factors during the massive transfusion of red cells should be guided by laboratory tests that document a coagulopathy. Similarly, platelet transfusions are indicated to correct documented thrombocytopenia or platelet dysfunction, and routine prophylaxis after fixed volumes of red cells results is unwarranted. Many anticipated complications of massive transfusions, including hemostatic abnormalities, acid-base imbalances, hyperkalemia, and hypocalcemia, are uncommon or of limited clinical significance. The risks of immune hemolysis and transfusion-transmitted diseases, on the other hand, are significant, and argue for judicious use of blood components. In emergencies in which blood is required immediately before compatibility testing can be completed, O-negative uncrossmatched blood can be requested. Careful blood specimen collection and patient identification prior to transfusion are critical. Practices that emphasize blood conservation, including the use of autologous salvaged blood, are always to the patients advantage.