Epoetin alfa. A bloodless approach for the treatment of perioperative anemia

Under normal physiologic conditions the level of circulating red blood cells is regulated precisely by the glycoprotein erythropoietin. In major elective surgery, patients who are participating in preoperative autologous blood donation or who are anemic may not have the capacity to manufacture sufficient red blood cells in response to increases in endogenous erythropoietin that is sufficient to avoid perioperative allogeneic blood transfusion. In these patients pharmacologic doses of recombinant human erythropoietin (Epoetin alfa) have been shown to accelerate erythropoiesis, thereby increasing preoperative red blood cell production, hematocrit level, and hemoglobin concentration and reducing exposure to allogeneic blood transfusion. In four large multicenter studies, 869 patients undergoing major elective surgery were treated with a daily regimen (300 or 100 IU/kg x 14 or 15 doses) or a weekly regimen (600 IU/kg x 4 doses) of subcutaneous Epoetin alfa beginning either 2 or 3 weeks before surgery, respectively. Although all Epoetin alfa regimens were effective at accelerating erythropoiesis and increasing red blood cell production, the weekly regimen was the most patient friendly, cost effective regimen for treating preoperative anemia and minimizing patient risk of allogeneic blood transfusion.     

Additive effect of beraprost on pulmonary vasodilation by inhaled nitric oxide in children with pulmonary hypertension

Using a prospective audit, we have evaluated the efficacy of an integrated autotransfusion regimen which comprised predepositing and intra- and postoperative blood salvage in major orthopaedic surgery. We examined prospectively the records of 1785 patients (1198 females, 5867 males, mean age 62 (range 16-90) yr, preoperative haemoglobin concentration 13.4 (SD 1.4) g dl-1) undergoing total hip arthroplasty (THA, 1229 patients), THA after removal of internal fixation devices (RFD + THA, 18 patients), total knee arthroplasty (TKA, 263 patients), revision surgery of the hip (HR cup + stem revision, 197 patients; cup revision, 53 patients; stem revision, 16 patients) and total knee revision (TKR, nine patients). We estimated that the number of predonations (MSBOS = maximum surgery blood order schedule) was 2 u. for THA, TKA and TKR, and 3 u. for partial or total hip revision and total hip arthroplasty with fixation removal. We found that it was possible to obtain the MSBOS in 1597 patients (89.5%). Homologous red blood cell (HRBC) transfusions were carried out in 131 patients (7.3%). We found that the need to use HRBC was significantly associated with failure to meet the number of MSBOS, female sex, lower preoperative haemoglobin concentration, use of calcium heparin for antithrombosis prophylaxis, more extensive surgery, higher ASA rating and co-existing diseases such as coronary artery disease.     

A retrospective audit of blood loss in total hip joint replacement surgery at Middlemore Hospital

AIMS: To quantify the level of inappropriate red cell transfusion in primary and complex hip replacement surgery. METHODS: Data extraction was by retrospective review of patients records. Calculation of total red cell volume loss was by use of pre and postoperative (day 7) haematocrit levels, patient weight and number of units transfused. Transfusion was accepted as justified only if instituted for a 30% red cell volume loss or loss sufficient to drop the haematocrit below 0.28. RESULTS: Of 104 patients having primary hip joint replacement, 58 were transfused with a total of 157 units of red cells; 37 (24%) of these units were given inappropriately. Of 38 patients having complex hip replacement operations, 32 were transfused with a total of 139 units of red cells; 12 (9%) of these were given inappropriately. CONCLUSIONS: Inappropriate transfusion occurs in hip replacement surgery. A concurrent audit of red cell usage is required to better define the magnitude of the problem. Two unit transfusion is commonly given when one unit would have been sufficient.     

Blood conservation in hip trauma

Patients with hip or pelvic fractures experience significant blood loss as a result of the fracture and from the surgery that subsequently is performed. The emergent and unplanned nature of fracture surgery precludes the use of preoperative blood donation and the optimization of chronic medical problems. Blood transfusion frequently is required to maintain adequate tissue O2 delivery in these injured patients. However, the administration of allogeneic blood causes other problems, including a well documented increase in the risk of infectious complications. Perioperative measures to minimize blood loss such as hypotensive anesthesia and red blood cell salvage are important, but often are inadequate to prevent the need for blood transfusion. Recently, erythropoietin therapy has been shown to stimulate hematopoiesis in patients with hip fractures. The authors discuss their experience with blood loss management in these patients with hip injuries, including aggressive Fe replacement therapy and the use of recombinant human erythropoietin.     

Erythropoietin therapy in the perioperative setting

Recombinant human erythropoietin has been approved for use in patients undergoing autologous donation in Japan, Europe, and Canada since 1993, 1994, and 1996, respectively, and for perisurgical adjuvant therapy without autologous donation in Canada and the United States since 1996. Early clinical trials of erythropoietin therapy in the setting of autologous donation have provided important information regarding clinical safety, erythropoietin dose, and erythropoietic response. Later trials of perisurgical erythropoietin therapy without autologous donation provided data on efficacy (reduced allogeneic blood exposure) that led to approval of erythropoietin in patients undergoing surgery. However, the erythropoietin doses (300 U/kg subcutaneous x14 days) used in these trials, and their subsequent inclusion in labeling for the use of this product, are costly and tedious to administer. A recent study reported that a weekly regimen of erythropoietin (600 U/kg) for 4 weeks is less costly but just as effective at reducing allogeneic blood exposure in elective orthopaedic surgery. The most cost effective regimen that has been shown to minimize allogeneic exposure is preoperative erythropoietin therapy (600 U/kg subcutaneous weekly x2 and 300 U/kg subcutaneous on day of surgery) coupled with acute normovolemic hemodilution in patients undergoing radical retropubic prostatectomy. A similar regimen of erythropoietin therapy in patients undergoing coronary artery bypass grafting (2500 U/kg subcutaneous in divided doses for 2 weeks preoperatively) coupled with hemodilution also was effective. Low dose erythropoietin therapy coupled with acute normovolemic hemodilution ultimately may be shown to be cost equivalent to the predonation of three autologous blood units before elective surgery.     

Acute normovolemic hemodilution can replace preoperative autologous blood donation as a standard of care for autologous blood procurement in radical prostatectomy

Predonation of autologous blood (PAD) is a standard of care for patients undergoing radical prostatectomy, but recent studies have shown that PAD is not cost-effective. Acute normovolemic hemodilution (ANH) is an alternative autologous blood procurement technique that is much less costly than PAD. We compared the efficacy and costs of ANH alone to ANH combined with PAD. Two hundred-fifty patients who predonated fewer than 3 units of autologous blood before radical prostatectomy underwent ANH to a target hematocrit of 28%. Perioperative hematocrit levels, transfusion outcomes and costs, and postoperative outcomes were compared for patients who predonated 0, 1, or 2 units of blood before surgery. A computer model was used to estimate the savings in red blood cells (RBC) associated with each autologous intervention. ANH alone resulted in a 21% allogeneic transfusion rate and contributed a mean net savings of 112 mL RBC in blood conservation (equivalent to 0.6 unit of blood). The addition of 1 or 2 units of PAD reduced allogeneic exposure rates to 6% or 0%, respectively. Overall, patients who predonated blood had a mean net loss of 198 mL of RBC (equivalent to 1 blood unit), due to both an absence in compensatory erythropoiesis and to the wastage of 60% of the blood units donated. Patients who underwent ANH alone had a 60% reduction in mean total transfusion costs ($103 +/- $102) compared with patients who predeposited 2 units of autologous blood in addition to ANH ($269 +/- $11, P < 0.05). We conclude that ANH can replace PAD as an autologous blood option because it is less costly and equally effective. A combination of ANH and PAD can further decrease allogeneic blood exposure, but it increases transfusion costs and wastage. IMPLICATIONS: A patient's own blood can be obtained for use in surgery by predonation or acute normovolemic hemodilution on the day of surgery. Both blood collection techniques decrease the need for blood bank transfusions, but acute normovolemic hemodilution is less expensive and more convenient for patients.     

Giving both enoxaparin and dextran increases the need for transfusion in revision hip arthroplasty

OBJECTIVE: To find out if the need for transfusion was increased by volume substitution with dextran 70 in patients receiving prophylaxis against thrombosis with low molecular weight heparin. DESIGN: Open randomised controlled trial. SETTING: University hospital, Sweden. SUBJECTS: 40 patients undergoing revision hip arthroplasty. INTERVENTIONS: Enoxaparin 40 mg was given daily. Intraoperative normovolaemia was maintained with albumin (n = 20) or dextran 70 (n = 20). Intraoperative autotransfusion was used. Packed cell volume was kept above 0.29, if necessary with homologous blood. MAIN OUTCOME MEASURES: External blood loss, red cell balance. RESULTS: Dextran patients received 0.64 (0.2) g/kg of dextran (mean (SD)) and required more (p < 0.05) homologous blood (3.8 (2.4) units) than those receiving albumin (2.3 (1.6) units). The initial and final packed cell volumes were similar (0.40 and 0.32 compared with 0.41 and 0.32, respectively). The calculated loss of red cells was larger in the dextran group (1401 (511) compared with 1077 (374); p < 0.05). CONCLUSION: The combination of enoxaparin and dextran appreciably increased the need for transfusion compared with enoxaparin alone.     

Transfusion management in pediatric and adolescent scoliosis surgery. Efficacy of autologous blood

STUDY DESIGN: A retrospective review of consecutive pediatric and adolescent patients who required posterior spinal fusion to correct scoliosis. OBJECTIVES: To 1) measure the participation of pediatric patients in predeposit programs for autologous and directed blood donation 2) to assess the success of autologous predonation in preventing allogeneic blood use, 3) to determine whether transfusion indications differed between patients who received allogeneic blood and those who received autologous blood, and 4) to assess factors that predict transfusion requirements during scoliosis surgery. SUMMARY OF BACKGROUND DATA: Authors of recent studies in adults have questioned whether transfusion of autologous blood is a cost-effective therapy when compared with the less-expensive alternative--transfusion of allogeneic blood. In children, the efficacy of autologous blood has not been assessed in a large population of surgical patients. In adults, the frequency of patient participation, the success of autologous donors in avoiding allogeneic transfusion, and the proportion of collected autologous units used during the perioperative period are measures used to establish the efficacy of autologous predonation programs. METHODS: Hospital and clinic records for each patient who underwent posterior spinal fusion from September 1, 1989 through September 1, 1994 were reviewed. Blood bank consultation, autologous donation records, anesthesia records, surgical reports, and hospital records were reviewed. Seventy percent of patients (164 of 243) participated in autologous donation. RESULTS: More than 90% of autologous donors successfully avoided receiving allogeneic blood. Patients with idiopathic scoliosis (n = 168) were more likely to participate in autologous donation (n = 144) and to avoid allogeneic blood (n = 135). Patients with neurologic causes of scoliosis more commonly used allogeneic or directed donation (56 of 75 patients). Nineteen patients with neuromuscular causes of scoliosis participated in autologous donation, but more than one half of this group (10 of 19 patients) required allogeneic blood in addition to autologous units. CONCLUSIONS: Using measures of efficacy similar to those reported in studies of adults, autologous blood was found to be more effective in meeting the transfusion needs of pediatric patients who required posterior spinal fusion than in meeting those needs in adult surgical patients in previous studies.     

Genetic therapy for transplant vascular sclerosis

Red blood cells are still transfused inappropriately in spite of recent media attention and public awareness about the risks of blood products. A prospective audit was conducted to determine the avoidable blood transfusion rates in the elective perioperative setting utilising the guidelines issued by the American College of Physicians (ACP). Of 82 consecutive adult patients who were admitted for major elective surgery over a 3-month period, 28 were transfused a total of 94 units of homologous SAG-M blood, of which 50 (53%) were inappropriate as recommended by the ACP guidelines. Violations of the guidelines were perioperative transfusion in bleeding patients who were haemodynamically stable (31%) and transfusion in asymptomatic, stable patients solely to attain a haemoglobin level above 10 g% (22%). There is a need for objective, easily adaptable and widely disseminated consensus guidelines to the indications for red blood cell transfusion.     

Predictors of transfusion risk in elective knee surgery

Two hundred seventy-nine patients undergoing primary unilateral total knee replacement and 280 patients undergoing primary bilateral total knee replacements were reviewed retrospectively. Patients' height, weight, hemoglobin level before donation, hemoglobin level before surgery, autologous donation, number and type of transfusions whether autologous or allogeneic, and hemoglobin at discharge were collected from hospital and clinic records. The average drop in hemoglobin was 3.85 g/dL in the group of patients undergoing unilateral total knee replacement and 5.42 g/dL in the group of patients undergoing bilateral total knee replacements. The preoperative hemoglobin and blood volume seemed to be very strong, statistically significant predictors of transfusion risk in single and bilateral knee replacements. In unilateral total knee replacement, patients with a hemoglobin of greater than 13 g/dL had only an 8% chance of transfusion and if they donated autologous blood, 66% of the blood was wasted. Preoperative anemia was a strong predictor of transfusion risk in patients undergoing unilateral and bilateral total knee replacements and carried a very high allogeneic transfusion exposure risk, even in patients who had donated blood preoperatively. A nomogram was developed using blood volume and predonation hemoglobin to predict transfusion risk and need to predeposit autologous blood in patients undergoing unilateral and bilateral total knee replacements.     

Immune responsiveness in orthopedic surgery patients after transfusion of autologous or allogeneic blood

BACKGROUND: The proposed immunosuppressive effect of blood transfusion is not yet understood, and the clinical relevance is a controversial topic of discussion. STUDY DESIGN AND METHODS: The effect of blood transfusions on the capacity of the host's immunocompetent cells to react to mitogenic stimulation was evaluated. Patients undergoing hip replacement surgery received either allogeneic (n = 13) or autologous (n = 14) buffy coat-depleted red cells or plasma. Patients' blood samples taken before and on Days 1 and 5 after surgery were stimulated in a whole-blood assay. The release of interleukin 2, soluble interleukin 2 receptor, interleukin 6, tumor necrosis factor alpha, interferon alpha 2, and interferon gamma was assessed by enzyme-linked immunosorbent assay. In addition, the white cell counts and frequencies of the lymphocyte subsets CD4+, CD8+, and natural killer cells were analyzed. RESULTS: For both groups, decreased levels of interleukin 2 and interferon-gamma were detected postoperatively, whereas the values for soluble interleukin 2 receptor and tumor necrosis factor alpha showed no significant change. Interferon alpha 2 was decreased on Day 1, but returned to normal by Day 5. Interleukin 6 increased during the time of observation. There were no significant differences between the two groups in cytokine production and lymphocyte-subset analysis that could be attributed to the transfusion of allogeneic blood. CONCLUSION: The transfusion of buffy coat-depleted red cells showed no immediate suppressive effect on the immune function of the host's peripheral blood cells.     

Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery

We have previously documented the safety of 1 unit (50 gram) of human polymerized hemoglobin (Poly SFH-P) in healthy volunteers. This report describes the first patient trial to assess the therapeutic benefit of Poly SFH-P in acute blood loss. Thirty-nine patients received 1 (n = 14), 2 (n = 2), 3 (n = 15), or 6 (n = 8) units of Poly SFH-P instead of red cells as part of their blood replacement after trauma and urgent surgery. There were no safety issues related to the infusion of Poly SFH-P. The plasma hemoglobin concentration ([Hb]) after the infusion of 6 units (300 gram) of Poly SFH-P was 4.8 +/- 0.8 g/dL (mean +/- SD). Although the red cell [Hb] fell to 2.9 +/- 1.2 g/dL, the total [Hb] was maintained at 7.5 +/- 1.2 g/dL. Poly SFH-P maintained total [Hb], despite the marked fall in red cell [Hb] due to blood loss. The utilization of O2 (extraction ratio) was 27 +/- 16% from the red cells and 37 +/- 13% from the Poly SFH-P. Twenty-three patients (59%) avoided allogeneic transfusions during the first 24 hours after blood loss. Poly SFH-P effectively loads and unloads O2 and maintains total hemoglobin in lieu of red cells after acute blood loss, thereby reducing allogeneic transfusions. Poly SFH-P seems to be a clinically useful blood substitute.     

The presurgical management with erythrocytapheresis of a patient with a high-oxygen-affinity, unstable Hb variant (Hb Bryn Mawr)

BACKGROUND: Hemoglobin (Hb) Bryn Mawr is an unstable Hb variant resulting in congenital hemolytic anemia. This variant Hb also has an increased affinity for oxygen. The perioperative transfusion management of this disorder is described, and the first genomic analysis of this Hb variant is given. CASE REPORT: An 11-year-old boy, heterozygous for Hb Bryn Mawr, was referred for cholecystectomy. Sequence analysis of genomic DNA confirmed that the patients was heterozygous for a T-->C transition in the codon for amino acid 85, causing a substitution of serine for phenylalanine in the beta-globin chain. On the basis of whole-blood O2 dissociation studies, projected tissue O2 delivery would have been suboptimal during general anesthesia; therefore, a partial red cell exchange transfusion was performed to lower variant Hb and prevent tissue hypoxia during surgery. The red cell mass to be exchanged (50%) was determined from the calculated increase in O2 delivery capacity required to maintain an O2 extraction of 4 to 5 mL of O2 per dL of whole blood. The p50 of whole blood from the patients immediately after the exchange transfusion was 16.0 torr. At the time of surgery, the p50 was normal (25.9 torr). The patient's whole blood 2,3 DPG levels were 4.70 mmol per mL of red cells (before transfusion) (normal range = 4.8 +/- 0.3 mmol/mL red cells), 4.07 mmol per mL of red cells (immediately after transfusion), and 4.55 mmol per mL of red cells (48 hours after transfusion). CONCLUSION: This patient with Hb Bryn Mawr was prepared for surgery with a partial exchange transfusion to prevent tissue hypoxia during anesthesia. Decreased 2,3 DPG levels immediately after transfusion resulted in increased O2 affinity of whole blood; however, 48 hours after exchange transfusion, a normal p50 (due to both removal of variant Hb and regeneration of 2,3, DPG) was observed. Partial exchange transfusion is useful in the preoperative management of patients with Hb variants characterized by increased O2 affinity.     

Methods for reduction of homologous blood transfusions in operative medicine

For ethical and socio-economical reasons (cost-explosion in transfusion-medicine, patient's individual destiny), development and consistent application of allogeneic transfusion sparing techniques in surgery is a challenge to anesthesiologists, surgeons and blood-bankers. The combination of different techniques, i.e. autologous predonation, hemodilution, choice of anesthetic regimen, deliberate hypotension, application of antifibrinolytic agents and autotransfusion of intraoperatively saved blood allow for avoidance of allogeneic blood transfusion even in patients presenting important intraoperative hemorrhage. The present article summarizes (1) risks associated with transfusion of allogeneic blood, (2) actually applied pre- and intraoperative techniques to reduce transfusion of allogeneic blood and (3) new concepts (administration of erythropoietin, hyperoxic ventilation and administration of artificial oxygen carries) to further increase the efficacy of autologous predonation and preoperative normovolemic hemodilution.     

Effect of recombinant human erythropoietin on transfusion risk in coronary bypass patients

BACKGROUND: Patients having a cardiac operation frequently require allogeneic blood transfusions despite surgical blood-conservation techniques. Recombinant human erythropoietin (Epoetin alfa) may augment this conservation by stimulating erythropoiesis. The safety and efficacy of perioperative use of Epoetin alfa to reduce the need of allogeneic transfusion was studied. METHODS: A multicenter double-blind, placebo-controlled, parallel-group study involved 182 patients having coronary artery bypass grafting and randomized to receive Epoetin alfa (300 or 150 IU/kg) or placebo subcutaneously for 5 days before, on the day of, and for 2 days after operation. RESULTS: Perioperative Epoetin alfa resulted in greater increases in baseline to preoperative hemoglobin levels and hematocrit (300 IU/kg) and in presurgery to postsurgical day 1 reticulocyte counts versus placebo (p < or = 0.05). However, there was no significant difference in transfusion requirements. Incidences of adverse events were similar in all study groups. CONCLUSIONS: Lower incidences of allogeneic blood exposure were observed in both Epoetin alfa-treated groups; however, the differences between all treatment groups were not significant. This was probably due to the relatively short 5-day preoperative course of Epoetin alfa therapy. There were no significant differences between the three groups relative to safety. Epoetin alfa was well tolerated in this population.     

Primary intracerebral small lymphocytic non-Hodgkin''s lymphoma with plasmacytoid differentiation, associated with prominent extracellular proteinaceous deposits

Surgical treatment is increasingly used for patients with medically re fractory seizures. Valproate (VPA) is an effective, widely used anticonvulsant in this patient population, but believed by some researchers to increase surgical bleeding because of quantitative thrombocytopenia and functional defects in platelet aggregation. Because we have observed no clinical evidence that perioperative administration of VPA increases blood loss or complications related to postoperative bleeding in patients undergoing temporal lobectomy at our institution, we sought to test this hypothesis. We made a retrospective review of the medical records of all patients who underwent epilepsy surgery at the University of California, San Francisco Medical Center, from September 1986 through January 1993. Patients who had a temporal lobectomy and whose medical records documented preoperative platelet counts and pre- and postoperative hematocrit and hemoglobin values were included. We excluded patients who had cranial surgery before temporal lobectomy and those with intracranial neoplasms or vascular malformations. Patients were divided into two groups: those who received VPA in the immediate preoperative period and those who had not received VPA recently. We compared the estimated surgical blood loss and the estimated change in red blood cell (RBC) volume between groups by unpaired t tests. The charts of 87 consecutive patients qualified for inclusion in the study. Patients in the VPA group had relative (but not absolute) thrombocytopenia preoperatively (235 +/- 64 vs. 277 +/- 69 k in the No-VPA group). There were no differences in the estimated blood loss, RBC volume, or in the incidence of postoperative transfusion. VPA apparently does not increase complications of hemostasis during therapeutic surgical resections for epilepsy. Therefore, we do not recommend routinely discontinuing VPA before craniotomy.     

Recombinant human erythropoietin as adjuvant treatment for autologous blood donation in elective surgery with large blood needs (> or = 5 units): a randomized study

BACKGROUND: Autologous blood transfusion presents no infectious or immunologic side effects. The aim of this randomized study was to determine the impact of recombinant human erythropoietin (rHuEPO) on the donation of 5 units of autologous blood by nonanemic patients who were candidates for elective surgery with transfusion requirements of > or = 5 units. STUDY DESIGN AND METHODS: Starting on Day -35, 420 mL of blood was taken weekly. All patients received 200 mg of iron saccharose complex intravenously at each visit and six subcutaneous injections of rHuEPO (141 U/kg) or placebo between Days -21 and -7. RESULTS: Of 50 patients, 45 completed the study (placebo, 21; rHuEPO, 24). Total red cell production was higher in the rHuEPO group (p = 0.001). Donation of 5 units was possible for 67 percent (placebo group) and 79 percent (rHuEPO group) of patients (p = 0.5). The mean number of blood units donated was 4.6 (placebo group) and 4.7 (rHuEPO group). More patients in the placebo group received allogeneic blood (9/21 [43%] vs. 6/23 [26%]), although the difference did not reach significance (p = 0.34). CONCLUSION: In nonanemic patients donating 5 units of blood, rHuEPO associated with intravenous iron increased total red cell production. However, no difference was found between the rHuEPO and placebo groups with regard to the number of units of autologous blood donated of the number of patients receiving allogeneic blood transfusion.     

Laparoscopic pull-through procedure for Hirschsprung''s disease

BACKGROUND: We investigated the suitability of two commercially available in-vitro bleeding tests (IVBT), the PFA-100 and the Hepcon HMS, to predict blood loss following operations with extracorporeal circulation (ECC) and compared them with conventional coagulation studies. METHODS: In 40 patients subjected to elective open heart surgery with ECC a blood sample was taken before and after ECC to measure platelet count, prothrombin time, aPTT, D-dimers, fibrinogen, and PFA-100 and Hepcon HMS data. The postoperative blood loss was recorded hourly until removal of drains. RESULTS: A significant correlation was found between total blood loss (250-1750 ml) and the preoperative PFA-100 (r = 0.41, p = 0.022), the preoperative platelet count (r = -0.42, p = 0.007), the preoperative D-dimer concentration in the plasma (r = 0.41, p = 0.01), and duration of ECC (r = 0.35, p = 0.044). There was no significant correlation between blood loss and the Hepcon HMS system. CONCLUSIONS: Although a significant correlation was found between blood loss and the PFA-100 IVBT, the practical value of these tests in the clinical situation is limited due to a great variability in individual results.     

Effects of the intensity and timing of asbestos exposure on lung cancer risk at two mining areas in Quebec

BACKGROUND: Bone marrow transplantation (BMT) has been limited in the past by the availability of matched donors for patients. Over the past decade, the use of umbilical cord blood (UCB) as a source of hematopoietic stem cells has revolutionized the field of BMT, providing a source of hematopoietic stem cells for an increasing number of patients in need of a transplant. RESULTS: Umbilical cord blood transplantation (UCBT) appears to result in sustained engraftment of donor hematopoiesis similar to results achieved with marrow and peripheral blood hematopoietic stem cells. Early results indicate that UCBT is associated with a lower incidence and less severity of graft-versus-host disease than other sources of stem cells, potentially decreasing the morbidity and mortality of BMT. As the potential of UCBT has been realized, cord blood storage facilities have been established to provide UCB. The rapid emergence of UCBT has transformed a waste product of birth into a life-saving resource. Its use, however; has raised numerous ethical and medical concerns unique to this alternative source of stem cells. CONCLUSIONS: Umbilical cord blood transplantation represents a major advance in providing another stem cell source to patients in need of allogeneic hematopoietic stem cell transplantation. As with all new technologies, UCBT will have to be carefully studied over the next several years to determine its safety, efficacy, and precise indications in comparison with other sources of hematopoietic stem cells. The ethics of UCBT must properly respect the rights and needs of both donors and recipients.     

Avidity of IgG antibodies distinguishes primary from non-primary cytomegalovirus infection in pregnant women

OBJECTIVE: To define the epidemiology, risk factors, and unadjusted cost of hemorrhages related to cardiothoracic operations. STUDY DESIGN: We conducted two case-control studies to evaluate the risk of hemorrhage following cardiothoracic operations. The definition of hemorrhage required one of the following: reoperation for bleeding, postoperative loss of greater than 800 mL of blood over 4 hours, or surgeon-diagnosed excessive intraoperative bleeding. SETTING: The cardiothoracic surgery service of a university hospital. RESULTS: Of 511 patients undergoing cardiothoracic operations, 93 (18%) met the definition of hemorrhage. In the first case-control study, 3 (14%) of 21 cases and 0 of 42 controls died (odds ratio [OR], 15.0; 95% confidence interval [CI95], 1.18-191.55). Compared with controls, cases received significantly more packed red blood cells intraoperatively (OR, 1.18/100 mL; CI95, 1.01-1.38), and significantly more platelets (OR, 3.26/100 mL; CI95, 1.47-7.26) and fresh frozen plasma (OR, 1.73/100 mL; CI95, 1.05-.84) in the intensive-care unit. Cases were more likely than controls to receive protamine postoperatively (OR, 3.74; CI95, 1.27-11.02). Previous sternotomy, preoperative aspirin or heparin, and preoperative laboratory values did not predict bleeding. The median unadjusted hospital cost was $3,458 higher for patients who suffered hemorrhage than for controls. To decrease costs, hetastarch (acquisition cost $45/500 mL) was substituted for albumin (acquisition cost $76/100 mL) in the pump priming solution (estimated possible cost savings, $7,000-$53,000/year). Because hemorrhage rates increased subsequently, we conducted a second case-control study that identified patient age (P=.02) and use of greater than 5 mL/kg of hetastarch (OR, 1.82) as risk factors for hemorrhage. The cost of treating hemorrhages exceeded all estimates of possible cost savings ($7,000-$53,000 per year). CONCLUSIONS: Our definition of hemorrhage identified patients who required increased volumes of blood products and who had an increased crude mortality rate and a higher unadjusted cost of hospitalization. Patient age and hetastarch use were risk factors for hemorrhage. Efforts to save money by substituting less expensive products inadvertently may increase costs by increasing the probability of perioperative adverse events.