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. STUDY DESIGN AND METHODS: Patients (n = 204) with low baseline hematocrits ( < or = 39%), scheduled for orthopedic surgery within 25 to 35 days, were seen every 3 to 4 days for 21 days. At each visit, 450 mL of blood was collected if the hematocrit was > or = 33 percent, and rHuEPO (600 U/kg) or placebo was administered intravenously. RESULTS: One hundred seventy-three patients were evaluable. The number of autologous units collected from the rHuEPO and control groups, respectively, was 4.5 +/− 1.0 and 3.0 +/− 1.1 (p < 0.001), and marrow production of red cells increased by 668 +/− 222 and 353 +/− 155 mL over and above baseline production (p < 0.05). Allogeneic blood transfusion was required by 31 percent of control and 20 percent of rHuEPO patients (p = 0.09). Excluding 8 patients who received > 6 units, 29 percent of control and 14 percent of rHuEPO patients required allogeneic blood (p = 0.015). Logistic regression modeling determined that the risk of allogeneic transfusion was reduced by rHuEPO (p = 0.025). CONCLUSION: The use of rHuEPO stimulates erythropoiesis, permits the storage of more autologous blood, and reduces allogeneic transfusion risk in patients with low hematocrits who are undergoing elective orthopedic surgery. Additional studies are necessary to determine the optimal schedules of rHuEPO administration and autologous blood collection as well as the cost-effectiveness of this strategy.     

Human immunodeficiency virus type 1 activation after blood transfusion

BACKGROUND: Anemia and transfusion are predictors of disease progression in AIDS patients. This study was designed to examine the effects of blood transfusion on human immunodeficiency virus type 1 (HIV-1) expression. STUDY DESIGN AND METHODS: Assays of plasma viral load were performed before and after transfusion in nine HIV-1-infected patients who required blood transfusion for refractory anemia. RESULTS: There was a modest rise in plasma HIV-1 p24 antigen and plasma HIV-1 RNA beginning 1 to 2 weeks after the blood transfusion. The mean change in plasma p24 antigen for all patients was 9.3 +/− 5.1 (mean +/− SE) pg per mL at Week 2 after transfusion and 18 +/− 11.1 pg per mL at Week 4. Plasma HIV-1 RNA levels were unchanged immediately after transfusion and exceeded pretransfusion levels with a mean rise of 84 +/− 40 percent (SE) at Week 1, 70 +/− 27 percent at Week 2, and 67 +/− 38 percent at Week 4 (p equals; 0.006, exact permutation test). There was no increase in spontaneous or interleukin 2-induced lymphocyte proliferation or p24 antigen production by patients' lymphocytes that were examined immediately after blood transfusion. CONCLUSION: The transfusion of blood to persons with advanced HIV-1 infection modestly increases plasma levels of HIV-1. The activation of HIV-1 expression by transfusion may help to explain the accelerated course of HIV-1 disease in recipients of blood transfusion.     

A randomized trial of perioperative hemodilution versus transfusion of preoperatively deposited autologous blood in elective surgery

Hemodilution, one of several methods proposed to decrease homologous blood transfusion in elective surgery, has not been studied in a prospective controlled trial to determine if it is successful. A prospective, randomized controlled study was conducted to determine if hemodilution can serve as an alternative to preoperative autologous blood donation. Fifty patients were randomized to preoperatively deposit 3 units of autologous blood or to undergo hemodilution immediately before elective radical retropubic prostatectomy. All patients were treated under a standard protocol, including surgery performed by a single surgeon. The preoperative deposit groups received a mean of 2.44 +/− 1.0 units of blood; 2 of 25 patients required homologous blood transfusion for blood loss of 2600 mL and 1700 mL. The hemodilution group received a mean of 2.88 +/− 0.4 units of autologous blood: no hemodilution patient received homologous blood. At discharge, the mean hematocrit for the preoperative deposit group was 35.5 +/− 4.9 (0.35 +/− 0.05), and that for the hemodilution group was 31.8 +/− 4.7 (0.32 +/− 0.05) (p less than 0.001). There were no differences in perioperative morbidity in the treatment groups. The best predictor of discharge hematocrit was the initial hematocrit of the patient. It can be concluded that hemodilution can safely replace or at least augment preoperative autologous donations as a means of decreasing homologous blood transfusion in study patients. These results can be applied to any elective surgery procedure in which a 1000-mL blood loss is anticipated. Other advantages of hemodilution, including convenience, lower cost, and better preservation of all components of autologous blood, suggest that this practice deserves wider application.     

Intraoperative hemodilution and autologous platelet rich plasma collection: two techniques for collecting fresh autologous blood

Intraoperative hemodilution (IH) and autologous platelet rich plasma (APRP) collection are two techniques used to obtain autologous blood in the operating room. They have been used to reduce allogeneic blood exposure in patients undergoing both cardiac and non-cardiac surgery. Both components have the advantage of providing fresh blood not subject to the storage lesion. Whole blood (IH) or platelet rich plasma is removed from the patient as anesthesia is induced and replaced with acellular fluid. The blood is transfused back after bypass or major bleeding has ceased. Although used commonly, the data supporting the use of either technique are controversial. Methodologic problems which have confounded studies evaluating their utility include: poorly defined transfusion criteria, concommitant use of other blood conservation techniques (i.e. cell salvage, pharmacologic agents, hypothermia, controlled hypotension) and changing transfusion practices with greater tolerance of normovolemic anemia. Randomized controlled studies with well defined up to date transfusion criteria are needed to identify patients likely to benefit from these techniques.     

Comparison of a transfusion preparation of newly formed red cells and standard washed red cell transfusions in patients with homozygous beta- thalassemia

BACKGROUND: Previous studies of transfusions of newly formed red cells (neocytes) demonstrated modest extensions of transfusion interval in patients with homozygous beta-thalassemia. STUDY DESIGN AND METHODS: The clinical benefits of a new system of neocyte preparation (Neocel, Cutter Biological, Berkeley, CA), reported to combine ease of preparation with reduction in the transfusion requirements of thalassemia patients, were evaluated. Sixteen thalassemic patients who had undergone splenectomy received eight consecutive, standard, automated, washed red cell transfusions (standard transfusions), followed by eight transfusions with the neocyte preparation (neocyte transfusions). In each arm of the study, mean pretransfusion hemoglobin and mean red cell mass transfused were carefully controlled and were similar. RESULTS: A significant (p < 0.0001) extension of transfusion interval was observed in patients receiving neocyte transfusions (mean +/− SD; 38.7 +/− 34 days; range, 35.0-44.5), over that in those receiving standard transfusions (32.9 +/− 2.5 days; range, 29.6-38.5). The mean prolongation of transfusion interval by neocyte transfusion corresponded to a mean reduction of 25 mL in packed red cells transfused per kg of body weight per patient per year and a mean reduction in transfused iron of 15 percent per year per patient. During neocyte transfusions, blood preparation costs were considerably increased and donor exposure was significantly (p < 0.0005) higher than during the standard transfusion period. CONCLUSION: These data demonstrate that extension of the transfusion interval, and reduction in transfused iron, may be achieved in thalassemic patients by use of the Neocel system. These benefits are achieved, however, with substantial increases in donor exposure and in component preparation costs.     

Acute normovolemic hemodilution is a cost-effective alternative to preoperative autologous blood donation by patients undergoing radical retropubic prostatectomy

BACKGROUND: Preoperative autologous blood donation is accepted as a standard of care for radical prostatectomy. Acute normovolemic hemodilution (ANH) is an alternative method for obtaining autologous blood. The cost and benefits of these two autologous blood-collection techniques are compared. STUDY DESIGN AND METHODS: Thirty consecutive patients scheduled for radical prostatectomy underwent ANH to a target hematocrit level of 28 percent. Blood was transfused in the perioperative period to maintain the hematocrit level > 25 percent. Hematocrit levels, transfusion outcomes and costs, and postoperative outcomes for these patients (hemodilution group) were compared with a matched patient cohort who preoperatively donated 3 units of blood for autologous use in prostatectomy surgery (nonhemodilution group, n = 30). RESULTS: Thirty patients underwent ANH to a hematocrit level of 28.7 +/− 1.7 percent, and 1740 +/− 346 mL (3.5 +/− 0.7 units) of blood were collected. Three (10%) of the patients in each cohort had allogeneic blood exposure. Transfusion costs were 73 percent higher for the nonhemodilution group patients than for the hemodilution group patients ($330 +/− $100 vs. $191 +/− $55, p < 0.001). No differences were found in postoperative outcomes. CONCLUSION: An integrated blood conservation program utilizing hemodilution and a defined transfusion trigger can decrease the requirement for preoperative donation of blood for autologous use in radical prostatectomy. Point-of-care autologous blood procurement is more cost-effective than preadmission donation of autologous blood units.     

Evaluation of a new whole-blood filter that allows preparation of platelet concentrates by platelet-rich plasma methods

BACKGROUND: A novel WBC-reduction in-line whole-blood (WB) filter that does not retain platelets was evaluated to assess the filtration performance and, after processing WB by the platelet-rich plasma (PRP) method, to analyze the storage quality of filtered platelet concentrate (PC) units. STUDY DESIGN AND METHODS: To analyze the filter retention, blood was collected from random donors into quadruple blood packs with an integral in-line filter (Imuflex WB-SP, Terumo; n = 25) or in standard triple bag systems (n = 30). To assess the in vitro storage characteristics of platelets, 26 WB units were pooled in pairs and redistributed into 13 units that underwent WBC reduction and 13 units that were not WBC reduced. In all cases, WB was separated into RBCs, PCs, and plasma by the PRP method and platelet function was compared. RESULTS: The filtration procedure led to RBC and PC WBC-reduced products that met the AABB and European requirements. The average filtration time was 30 minutes, the filter retained about 45 mL of WB, and there was no further loss of RBCs during the fractionation procedure. In vitro PC storage characteristics of the filtered units were similar to those of the nonfiltered units. CONCLUSION: A 4- and 3-log WBC reduction was observed in RBC and PC units that were produced by the PRP method, with a mean residual WBC content of 0.24 +/- 0.38 x 106 and 0.02 +/- 0.03 x 106 per unit, respectively. The procedure, performed under relatively simple logistics, results in good-quality, standard components that may reduce costs and ease the process of WBC reduction in transfusion services.     

Soluble vascular endothelial growth factor in various blood transfusion components

BACKGROUND: Blood transfusion may reduce survival after curative surgery for solid tumors. This may be related to extracellular content of cancer growth factors present in transfusion components. Vascular endothelial growth factor (VEGF) is a potent stimulator of angiogenesis in solid tumors. The potential content of VEGF in various blood components for transfusion was evaluated. STUDY DESIGN AND METHODS: Soluble VEGF (sVEGF, isotype 165) was determined by an enzyme-linked immunosorbent assay (EIA) in serum and plasma samples and in lysed cells from healthy volunteers. Subsequently, total content of sVEGF was determined in nonfiltered and prestorage white cell-reduced whole blood (WB), buffy coat-depleted saline-adenine-glucose-mannitol (SAGM) blood, platelet-rich plasma (PRP), and buffy coat-derived platelet (BCP) pools obtained from volunteer, healthy blood donors. As a control, total content of platelet-derived soluble plasminogen activator inhibitor type 1 (sPAI-1) was determined by an EIA in the same samples. Finally, the extracellular accumulation of sVEGF was determined in nonfiltered WB and SAGM blood during storage for 35 days and in BCP pools during storage for 7 days. RESULTS: In the healthy volunteers, median total sVEGF content was 97 (range, 20-303) pg per mL in serum and 19 (13-37) pg per mL in plasma (n = 12, p < 0.002) and 445 (280-990) pg per mL in lysed cells. Median total sPAI-1 content was 94 (64-127) ng per mL in serum, 8 (6-11) ng per mL in citrated plasma, and 95 (78-123) ng per mL in lysed cells. In SAGM blood, the median total sVEGF content was 25.3 (3.3-48.4) ng per unit in nonfiltered units and undetectable in white cell-reduced units. Median total sVEGF content was 29.2 (24.8-124.9) ng per unit in nonfiltered PRP and 28.7 (24.5-118.6) ng per unit in white cell-reduced PRP. The sVEGF accumulated significantly in WB, SAGM blood, and BCP pools, depending on the storage time. CONCLUSION: The sVEGF (isotype 165) appears to be present in various blood transfusion components, depending on storage time.     

Effectiveness of very low doses of subcutaneous recombinant human erythropoietin in facilitating autologous blood donation before orthopedic surgery

BACKGROUND: Clinical and pharmacokinetic data suggest that very low doses of subcutaneous recombinant human erythropoietin (rHuEPO) may be effective in a preoperative autologous blood deposit program. STUDY DESIGN AND METHODS: Fifty-two patients, scheduled for orthopedic surgery, were enrolled in a double-blind and placebo-controlled study. Patients were randomly assigned to the placebo group or to receive 30, 60, or 100 IU per kg of rHuEPO subcutaneously twice a week for 2 weeks before surgery. The dose of rHuEPO that was effective in facilitating the collection of 4 units of blood in the 2 weeks before surgery and that prevented a sharp decrease in hematocrit was determined. RESULTS: Only in patients receiving 100 IU per kg of rHuEPO did the outcome measurements differ significantly from those in the placebo group. With a higher (p < 0.01) cumulative increase in red cell volume during the study period (297 +/− 127 vs. 121 +/− 44 mL), 64 percent of those receiving 100 IU per kg of rHuEPO were able to donate 4 units of blood for autologous use, as compared with 23 percent of the placebo group (p < 0.05). Allogeneic transfusion was avoided, and the preoperative hematocrit and reticulocyte count were significantly higher in the patients receiving 100 IU per kg of rHuEPO (p < 0.05 and p < 0.01, respectively). CONCLUSION: Subcutaneously administered rHuEPO at a dose of 100 IU per kg twice a week for 2 weeks is effective in facilitating the collection of blood for autologous use and may improve the cost- benefit ratio of blood conservation interventions. Doses < or = 60 IU per kg are ineffective in facilitating such collections in this surgical setting.     

Subcutaneous administration of recombinant human erythropoietin before cardiac surgery: a double-blind, multicenter trial in Japan

BACKGROUND: Dose and injection times have not previously been determined for subcutaneously administered recombinant human erythropoietin that would allow sufficient deposition of blood for autologous use in cardiac surgery. STUDY DESIGN AND METHODS: A double- blind, multicenter trial of placebo (Group 1) and recombinant human erythropoietin at 12,000 IU (Group 2) and at 24,000 IU (Group 3) was performed on 114 patients at 26 institutions to determine the dosage that would permit an 800-g preoperative deposit of blood for autologous use. The test drug was administered subcutaneously on Days 21, 14, and 7 prior to operation, and oral iron preparations at 200 mg per day were given for 21 days. There were 28 patients in Group 1, 28 in Group 2, and 30 in Group 3, with 28 excluded for a violation of the protocol. RESULTS: Blood was safely drawn 14 and 7 days before operation from 22 patients in Group 1 (78.6%), from 26 in Group 2 (92.9%), and from all patients in Group 3 (p = 0.018). The hemoglobin level on the day before operation decreased by 1.1 +/− 1.1 g per dL (11 +/− 11 g/L) in Group 1 and by 0.9 +/− 0.9 g per dL (9 +/− 9 g/L) in Group 2 and rose by 0.1 +/− 0.8 g per dL (1 +/− 8 g/L) in Group 3, compared to initial levels. Allogeneic blood transfusion could be avoided in 62, 89, and 90 percent of Group 1, 2, and 3 patients, respectively (p = 0.013). CONCLUSION: The present study shows that subcutaneously administered recombinant human erythropoietin at a dose of 24,000 IU per week for 3 weeks is effective and sufficient to allow the safe deposition of 800 g of blood for autologous use in cardiac surgery.     

Removal of ABO-incompatible red cells from lymphocytapheresis and granulocytapheresis components before transfusion

BACKGROUND: The collection of allogeneic lymphocytapheresis and granulocytapheresis components containing significant volumes of ABO- incompatible red cells is sometimes necessary. STUDY DESIGN AND METHODS: Twenty-nine ABO-incompatible lymphocytapheresis components collected for transfusion to three patients and 11 ABO-incompatible granulocytapheresis components collected for transfusion to five patients were depleted of red cells by gravity sedimentation aided by the addition of hetastarch solution. The efficacy of red cell depletion and white cell retention and the complications of transfusion were analyzed. RESULTS: Lymphocytapheresis components contained 82 +/− 13 percent of the original white cells and 5 +/− 3 mL of red cells after depletion; however, for those components containing < 70 mL of red cells before depletion (n = 12), white cell recovery was 92 +/− 5 percent. After depletion, granulocytapheresis components contained 96 +/− 3 percent of the original white cells and 6 +/− 2 mL of red cells. No clinical or laboratory evidence of hemolysis was observed after the transfusion of any leukapheresis component. CONCLUSION: Red cells can be effectively removed from leukacytapheresis components by a simple gravity sedimentation technique with added hetastarch. This allows safe transfusion of ABO-incompatible components.     

Effect of an assessment of fibrin-based rotational thromboelastometry on blood transfusion and clinical outcomes in cardiovascular surgery: A cohort study

The clinical importance of viscoelastic testing in patient blood management when performing cardiovascular surgery is increasing. We aimed to examine the effect of a blood transfusion protocol including an assessment of fibrin-based rotational thromboelastometry on transfusion volume, mortality, and bleeding complications in patients undergoing cardiac or thoracic aortic surgery. We retrospectively studied a cohort of 376 consecutive patients who underwent cardiopulmonary bypass before (control group: 150 cardiac and 35 thoracic aortic surgeries) and after (assessment group: 154 cardiac and 37 thoracic aortic surgeries) introducing the fibrin polymerization assessment with thromboelastometry in the blood transfusion protocol. The transfusion volume and clinical outcomes were compared between the control and assessment groups, and the standardized (mean) difference (S[M]D) was calculated as an indicator of statistical effect size. Compared with the control group, the assessment group had a lower total blood transfusion volume (mL) in cardiac (2720 ± 1282 vs. 2034 ± 1330, p < 0.0001, [SMD] = 0.68) and thoracic aortic surgeries (5236 ± 2732 vs. 3714 ± 1768, p < 0.0001, SMD = 0.67). The 1-year mortality rates were 1.9 % and 2.7 % in cardiac and thoracic aortic surgeries, respectively. Significant differences were not observed in the 1-year mortality (3.2 % vs. 1.0 %, p = 0.16, relative risk [RR] = 0.32 with 95 % confidence intervals [CI] = 0.06–1.57, SD = 0.15), re-exploration for bleeding (4.8 % vs. 2.6 %, p = 0.28, RR = 0.53 with 95 % CI = 0.18–1.57, SD = 0.12), and major bleeding (17.3 % vs. 13.0 %, p = 0.31, RR = 0.75 with 95 % CI = 0.46–1.22, SD = 0.12) rates between the control and assessment groups. The assessment of fibrin polymerization with thromboelastometry using the blood transfusion protocol reduced the blood transfusion volume in cardiovascular surgery.     

Storage of interim platelet units for 18 to 24 hours before pooling: in vitro study

BACKGROUND: The Atreus 3C system (CaridianBCT) automatically produces three components from whole blood (WB), a red blood cell (RBC) unit, a plasma unit, and an interim platelet (PLT) unit (IPU) that can be pooled with other IPUs to form a PLT dose for transfusion. The Atreus 3C system also includes a PLT yield indicator (PYI), which is an advanced algorithm that provides an index that is shown to correlate well with the amount of PLTs that finally end up in the IPU bag. The aim of our in vitro study was to compare the effects of holding WB overnight versus processing WB fresh (2‐8 hr), both with 18‐ to 24‐hour storage of the IPUs before pooling into a transfusable PLT dose. STUDY DESIGN AND METHODS: WB was processed either fresh (within 8 hr after collection, Atreus F) or after overnight storage (14‐24 hr, Atreus S) without agitation at 22 ± 2°C. After a subsequent resting time of 18 to 24 hours on a flat‐bed shaker, five IPUs were selected for pooling with 200 mL of PAS II for in vitro quality assessments during a 7‐day storage period (n = 10 in each arm). IPUs were selected for pooling using the PYI of the Atreus 3C system. RESULTS: During storage, the glucose concentration was lower (p < 0.05) and the lactate concentration was higher (p < 0.05) in Atreus S pools, but no differences in the glucose consumption rate were noted. Adenosine triphosphate levels and hypotonic shock response reactivity were higher in Atreus S (p < 0.05). No significant differences in PLT counts, contents, mean PLT volume, lactate dehydrogenase, pO₂, pCO₂, extent of shape change, and CD62P between groups were detected. pH was maintained higher than 6.8 (Day 7). With exception of 2 units in the Atreus S arm, swirling remained at greater than 2 in all units at all times. CONCLUSION: Our results suggest that PLTs prepared from fresh or overnight‐stored WB and pooled after 18 to 24 hours meet necessary in vitro criteria without any relevant differences between both groups. Using the PYI, comparable yields can be obtained between WB processed within 2 to 8 hours and WB stored overnight.     

Efficacy of preoperative donation of blood for autologous use in radical prostatectomy

To determine the amount of blood lost, the number of transfusions, and the effectiveness of preoperative autologous blood donation in radical prostatectomy, 163 patients' records from 1987 to 1991 were reviewed at four university hospitals and three community hospitals. Calculated red cell volume lost was 1003 +/− 535 mL (mean +/− SD), which corresponds to 44 +/− 18 percent (mean +/− SD) of total red cell volume. Preoperative donation of blood for autologous use reduced the rate of transfusion of allogeneic blood from 66 to 20 percent (p < 0.001). Of the patients who donated 1 to 2 units, 32 percent received allogeneic blood; 14 percent of those who donated 3 units received allogeneic blood. Donation of 4 units reduced the allogeneic transfusion rate to 11 percent. However, as the number of units donated increased (1-3 units), the units not transfused also increased (0-21%). Ninety-one (56%) of 163 patients donated fewer than 3 units. Autologous blood donation is effective in minimizing the transfusion of allogeneic blood to radical prostatectomy patients, but many patients do not donate enough blood (< 3 units). The donation of 3 units of blood for autologous use is recommended for patients who undergo radical prostatectomy.     

Levels of tissue inhibitor of metalloproteinases-1 in blood transfusion components

Blood transfusion during surgery for solid tumors may reduce patient survival because of various bioactive substances present in blood preparations. The antiproteolytic protein tissue inhibitor of metalloproteinases-1 (TIMP-1) present in large quantities in platelets has been shown to stimulate cell growth and to inhibit apoptosis and may therefore be considered to influence tumor progression. We measured TIMP-1 levels in blood transfusion preparations, especially in plateletcontaining preparations, before and after leucofiltration and at different timepoints during storage. The mean TIMP-1 levels in whole blood (WB) and plateletrich plasma (PRP) were slightly reduced by leucofiltration; WB: 41.6 mug/L versus 34.9 mug/L, PRP: 139.8 mug/L versus 127.2 mug/L. However, with prestorage leucofiltration, TIMP-1 levels in buffy-coat-derived platelet (BCP) pools were significantly reduced from 134.2 mug/L to 102.2 mug/L (p=0.0013). In saline-adenineglucose-mannitol (SAG-M) blood preparations in which the platelet content is reduced by more than 99%, TIMP-1 could not be detected. Extracellular TIMP-1 accumulated significantly in non-filtered WB and in aferesis platelet concentrates (APC), but TIMP-1 was at no time detectable in SAG-M blood during storage. In conclusion, TIMP-1 is present in various platelet-containing blood preparations, but not in platelet-free preparations such as SAG-M, indicating that most of the TIMP-1 measured in blood preparations originates from platelets. Furthermore, TIMP-1 levels increased during storage in preparations containing platelets, which suggests a continuous disintegration of platelets. These data imply that information on preoperative blood transfusions should be taken into account when evaluating plasma TIMP-1 levels in patients.     

Use of recombinant human erythropoietin to assist autologous blood donation by anemic rheumatoid arthritis patients undergoing major orthopedic surgery

BACKGROUND: In rheumatoid arthritis (RA) patients undergoing orthopedic surgery, anemia is the major factor in the use of allogeneic blood. STUDY DESIGN AND METHODS: To determine whether recombinant human erythropoietin (rHuEPO) could allow preoperative autologous blood procurement and reduce allogeneic blood exposure, 11 RA patients who were unable preoperatively to deposit blood for autologous use because of their anemia (baseline hematocrit < 34% [0.34]) and who were scheduled for primary total hip replacement or total knee replacement were treated intravenously with 300 U per kg of rHuEPO in combination with intravenous iron saccharate (100 mg), given twice weekly for 3 weeks. The transfusion treatment was compared with that in 12 control patients with comparable baseline hematologic values who underwent the same operation. RESULTS: Control patients could not preoperatively deposit any blood for autologous use, while all but one of the rHuEPO- treated patients deposited 2 or more units (mean, 2.6 +/− 0.6; range, 2- 4) (p < 0.001). The control group received more allogeneic units (2.6 +/− 1.6 vs. 0.8 +/− 0.8) (p = 0.009). Moreover, 50 percent of the rHuEPO-treated patients, as compared with 8 percent of controls, completely avoided allogeneic transfusion. CONCLUSION: Recombinant human erythropoietin is safe and effective in stimulating erythropoiesis, allowing preoperative donation of blood for autologous use, and reducing exposure to allogeneic blood for RA patients who are unable preoperatively to deposit blood because of anemia.     

Levels of tissue inhibitor of metalloproteinases-1 in blood transfusion components

Blood transfusion during surgery for solid tumors may reduce patient survival because of various bioactive substances present in blood preparations. The anti-proteolytic protein tissue inhibitor of metalloproteinases-1 (TIMP-1) present in large quantities in platelets has been shown to stimulate cell growth and to inhibit apoptosis and may therefore be considered to influence tumor progression. We measured TIMP-1 levels in blood transfusion preparations. especially in platelet-containing preparations, before and after leucofiltration and at different time-points during storage. The mean TIMP-1 levels in whole blood (WB) and platelet-rich plasma (PRP) were slightly reduced by leucofiltration; WB: 41.6 microg/L versus 34.9 microg/L. PRP: 139.8 microg/L versus 127.2 microg/L. However, with prestorage leucofiltration. TIMP-1 levels in buffy-coat-derived platelet (BCP) pools were significantly reduced from 134.2 microg/L to 102.2 microg/L (p=0.0013). In saline-adenine-glucose-mannitol (SAG-M) blood preparations in which the platelet content is reduced by more than 99%,. TIMP-1 could not be detected. Extracellular TIMP-1 accumulated significantly in non-filtered WB and in aferesis platelet concentrates (APC), but TIMP-1 was at no time detectable in SAG-M blood during storage. In conclusion. TIMP-1 is present in various platelet-containing blood preparations, but not in platelet-free preparations such as SAG-M, indicating that most of the TIMP-1 measured in blood preparations originates from platelets. Furthermore, TIMP-1 levels increased during storage in preparations containing platelets. which suggests a continuous disintegration of platelets. These data imply that information on preoperative blood transfusions should be taken into account when evaluating plasma TIMP-1 levels in patients.     

Mannose-binding lectin is involved in multiple organ dysfunction syndrome after cardiac surgery: effects of blood transfusions

BACKGROUND: Serum levels of mannose-binding lectin (MBL), a recognition molecule of the lectin pathway of complement, are highly variable, based on genetic variation. After cardiac surgery, extracorporeal circulation and ischemia-reperfusion injury initiate a systemic inflammatory response, which can evolve to multiple organ dysfunction syndrome (MODS). Preoperative transfusions of allogeneic white blood cells (WBCs) contribute to infectious and inflammatory complications. This study investigates the role of MBL in relation to blood transfusions and complications after cardiac surgery. STUDY DESIGN AND METHODS: In cardiac surgery patients who participated in a randomized trial comparing leukoreduced with buffy coat-depleted red blood cell (RBC) transfusions, circulating MBL was measured pre- and postoperatively by enzyme-linked immunosorbent assay (ELISA). Data were related to the incidence of complications and to the transfusions the patients received. RESULTS: Patients with high preoperative serum MBL levels (>400 ng/mL) show a significant (52 +/- 12%) decrease of serum MBL postoperatively, whereas patients with low serum MBL levels (< or =400 ng/mL) show a significant increase of serum MBL levels after surgery (140 +/- 106%), which was further enhanced by fresh-frozen plasma (FFP) transfusions. MBL levels were not associated with infections, sepsis, or death. Patients with MBL deficiency (MBL < or = 80 ng/mL) were protected against development of MODS (p = 0.016), whereas FFP transfusion abolished this protection (p = 0.048). CONCLUSION: Cardiac surgery is associated with MBL consumption, independent of the transfusion of allogeneic WBCs. Patients with MBL deficiency develop no MODS, unless they have been transfused with FFP, which is associated with MBL reconstitution. Therefore, sustained MBL deficiency may be a favorable status for patients undergoing cardiac surgery.     

Effect of clopidogrel on bleeding after coronary artery bypass surgery.

OBJECTIVE: Platelet dysfunction is a common cause of bleeding after coronary artery bypass graft surgery. This study explores the effects of clopidogrel on bleeding complications after coronary artery bypass graft surgery. DESIGN: Prospective observational study of patients undergoing coronary artery bypass graft. SETTING: Tertiary care center. PATIENTS: A total of 247 patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: None. MEASUREMENTS: Primary end point was need for reexploration secondary to bleeding. Secondary end points included need for transfusion of blood products and chest tube output. MAIN RESULTS: Eight (3.3%) of 247 patients required reexploration secondary to bleeding. Clopidogrel recipients had higher incidence of reexploration for bleeding (9.8 vs. 1.6, p =.01) with an odds ratio of 6.9 (95% confidence interval, 1.6-30). Clopidogrel also increased the percentage of patients receiving packed red blood cell transfusion (72.6 vs. 51.6%, p =.007), the number of packed red blood cell units (3 vs. 1.6, p =0.0004), and the number of cryoprecipitate units (2.4 vs. 1.2, p =.04) transfused after coronary artery bypass graft surgery. Among clopidogrel recipients, a trend for increased transfusion of platelet units (4.3 vs. 1.7, p =.05) and fresh frozen plasma units (1.1 vs. 0.6, p =.08) also was found. CONCLUSIONS: Preoperative use of clopidogrel in combination with aspirin is associated with increased need for surgical reexploration as well as risk of packed red blood cell and cryoprecipitate transfusions after coronary artery bypass graft surgery.     

Influence of early re-infusion of autologous shed mediastinal blood on clinical outcome after cardiac surgery.

Various strategies have been proposed to decrease allogeneic blood transfusion requirements after cardiac surgery. The aim of the study was to evaluate the efficacy of collected and re-infused autologous shed mediastinal blood on a patient's postoperative course. Ninety patients who underwent heart surgery with cardiopulmonary bypass (CPB) were studied. The patients were divided into two groups: Group 1 (n=41) received the centrifuged autologous shed mediastinal blood collected from the cardiotomy reservoir 4 hours after surgery; in Group 2 (n=49) all shed mediastinal blood was discarded (control group). Haemoglobin (Hb), haematocrit (Hct), C-reactive protein values, and leucocyte count were compared before surgery, at 4 h and 20 h after surgery, and on the fifth postoperative day. We have measured serum procalcitonin (PCT) concentration at 4 h and 20 h after CPB. We assessed drained blood loss within 20 postoperative hours. Leucocyte count, Hb, Hct values, C-reactive protein, and procalcitonin concentration did not differ between the groups before and at 4 h after surgery. Hb, Hct level, and leucocyte count were similar at 20 hours and on the fifth day after surgery. At 20 hours after surgery, an increase of serum PCT concentration (>0.5-2 ng/mL) was more frequent in Group 2 (58.3% vs. 33.3%; p = 0.03). On the fifth postoperative day, C-reactive protein concentration was lower in Group 1 (71.74 +/- 15.23; p <0.01) compared to Group 2 (93.53 +/- 20.3). Postoperative blood loss did not differ between the groups. Requirement for allogeneic blood transfusion was significantly lower in Group 1 (14.6% vs. 38.8%; p < 0.02). Patients in Group 1 developed less infective complications compared with Group 2 (2.4% and 16.3%, respectively; p < 0.05). The length of postoperative in-hospital stay was shorter in Group 1 compared with Group 2 (9.32 +/- 2.55 and 16.45 +/- 6.5, respectively; p < 0.05). We conclude that postoperative re-infusion of autologous red blood cells processed from shed mediastinal blood did not increase bleeding tendency and systemic inflammatory response and was effective in reducing the requirement for allogeneic transfusion, the rate of infective complications and the length of postoperative in-hospital stay.