Randomized Trial of Diaspirin Cross-linked Hemoglobin Solution as an Alternative to Blood Transfusion after Cardiac Surgery

Background Risks associated with transfusion of allogeneic blood have prompted development of methods to avoid or reduce blood transfusions. New oxygen-carrying compounds such as diaspirin cross-linked hemoglobin (DCLHb) could enable more patients to avoid allogeneic blood transfusion. Methods The efficacy, safety, hemodynamic effects, and plasma persistence of DCLHb were investigated in a randomized, active-control, single-blind, multicenter study in post-cardiac bypass surgery patients. Of 1,956 screened patients, 209 were determined to require a blood transfusion and met the inclusion criteria during the 24-h post-cardiac bypass period. These patients were randomized to receive up to three 250-ml infusions of DCLHb (n = 104) or three units of packed erythrocytes (pRBCs; n = 105). Further transfusions of pRBCs or whole blood were permitted, if indicated. Primary efficacy end points were the avoidance of blood transfusion through hospital discharge or 7 days postsurgery, whichever came first, and a reduction in the number of units of pRBCs transfused during this same time period. Various laboratory, physiologic, and hemodynamic parameters were monitored to define the safety and pharmacologic effect of DCLHb in this patient population. Results During the period from the end of cardiopulmonary bypass surgery through postoperative day 7 or hospital discharge, 20 of 104 (19%) DCLHb recipients did not receive a transfusion of pRBCs compared with 100% of control patients (P < 0.05). The overall number of pRBCs administered during the 7-day postoperative period was not significantly different. Mortality was similar between the DCLHb (6 of 104 patients) and the control (8 of 105 patients) groups. Hypertension, jaundice/hyperbilirubinemia, increased serum glutamic oxalo-acetic transaminase, abnormal urine, and hematuria were reported more frequently in the DCLHb group, and there was one case of renal failure in each group. The hemodynamic effects of DCLHb included a consistent and slightly greater increase in systemic and pulmonary vascular resistance with associated increases in systemic and pulmonary arterial pressures compared with pRBC. Cardiac output values decreased more in the DCLHb group patients after the first administration than the control group patients. At 24 h postinfusion, the plasma hemoglobin level was less than one half the maximal level for any amount of DCLHb infused. Conclusions Administration of DCLHb allowed a significant number (19%) of cardiac surgery patients to avoid exposure to erythrocytes postoperatively.

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Absence of Beneficial Effect of Acute Normovolemic Hemodilution Combined with Aprotinin on Allogeneic Blood Transfusion Requirements in Cardiac Surgery

Anesthesiology ◽

10.1097/00000542-200202000-00009 ◽

2002 ◽

Vol 96 (2) ◽

pp. 276-282 ◽

Cited By ~ 30

Author(s):

Laurent Höhn ◽

Alexandre Schweizer ◽

Marc Licker ◽

Denis R. Morel

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

High Risk ◽

Blood Transfusion ◽

Allogeneic Blood ◽

Surgical Patients ◽

Control Group ◽

Acute Normovolemic Hemodilution ◽

Normovolemic Hemodilution ◽

Normal Cardiac Function

Background The efficacy of acute normovolemic hemodilution (ANH) in decreasing allogeneic blood requirements remains controversial during cardiac surgery. Methods In a prospective, randomized study, 80 adult cardiac surgical patients with normal cardiac function and no high risk of ischemic complications were subjected either to ANH, from a mean hematocrit of 43% to 28%, or to a control group. Aprotinin and intraoperative blood cell salvage were used in both groups. Blood (autologous or allogeneic) was transfused when the hematocrit was less than 17% during cardiopulmonary bypass, less than 25% after cardiopulmonary bypass, or whenever clinically indicated. Results The amount of whole blood collected during ANH ranged from 10 to 40% of the patients' estimated blood volume. Intraoperative and postoperative blood losses were not different between control and ANH patients (total blood loss, control: 1,411 +/- 570 ml, n = 41; ANH: 1,326 +/- 509 ml, n = 36). Allogeneic blood was given in 29% of control patients (median, 2; range, 1-3 units of packed erythrocytes) and in 33% of ANH patients (median, 2; range, 1-5 units of packed erythrocytes; P = 0.219). Preoperative and postoperative platelet count, prothrombin time, and partial thromboplastin time were similar between groups. Perioperative morbidity and mortality were not different in both groups, and similar hematocrit values were observed at hospital discharge (33.7 +/- 3.9% in the control group and 32.6 +/- 3.7% in the ANH group; nonsignificant) Conclusions Hemodilution is not an effective means to lower the risk of allogeneic blood transfusion in elective cardiac surgical patients with normal cardiac function and in the absence of high risk for coronary ischemia, provided standard intraoperative cell saving and high-dose aprotinin are used.

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Investigation of the Use of Drained Blood Reinfusion after Total Knee Arthroplasty: A Prospective Randomised Controlled Study

Journal of Orthopaedic Surgery ◽

10.1177/230949900501300203 ◽

2005 ◽

Vol 13 (2) ◽

pp. 120-124 ◽

Cited By ~ 23

Author(s):

SC Cheng ◽

TSL Hung ◽

PYT Tse

Keyword(s):

Total Knee Arthroplasty ◽

Blood Transfusion ◽

Blood Loss ◽

Haemoglobin Level ◽

Knee Arthroplasty ◽

Allogeneic Blood Transfusion ◽

Allogeneic Blood ◽

Control Group ◽

Total Knee ◽

Postoperative Haemoglobin

Purpose. To compare the use of a blood salvage and reinfusion system with standard allogeneic blood transfusion after total knee arthroplasty—a procedure associated with significant postoperative blood loss. Methods. Between June 2002 and May 2004, 60 patients undergoing total knee arthroplasty were randomly allocated into a reinfusion group (n=26) or a control group (n=34). Patients in the reinfusion group had their blood reinfused from drains within 6 hours of surgery. Both groups received allogeneic blood transfusions according to specified transfusion criteria if the haemoglobin level fell below 90 g/l, or in the presence of severe anaemic symptoms. Haemoglobin levels and drain output were recorded daily for 3 consecutive days after surgery. Results. There was no significant difference between the 2 groups in demographic data, drain output, total blood loss, and mean postoperative haemoglobin levels. Significantly more allogeneic blood was required by the control group than by the reinfusion group (p=0.022). Conclusion. Postoperative reinfusion of drained blood reduced the need for blood transfusion after total knee arthroplasty, while having an effect on postoperative haemoglobin level equivalent to standard allogeneic blood transfusion.

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Autologous Blood Donation in Cardiac Surgery: Reduction of Allogeneic Blood Transfusion and Cost-Effectiveness

Journal of Cardiothoracic and Vascular Anesthesia ◽

10.1053/j.jvca.2005.04.017 ◽

2005 ◽

Vol 19 (5) ◽

pp. 589-596 ◽

Cited By ~ 37

Author(s):

Wulf Dietrich ◽

Klaus Thuermel ◽

Sophie Heyde ◽

Raimund Busley ◽

Karin Berger

Keyword(s):

Cardiac Surgery ◽

Cost Effectiveness ◽

Blood Transfusion ◽

Blood Donation ◽

Autologous Blood ◽

Allogeneic Blood Transfusion ◽

Allogeneic Blood ◽

Autologous Blood Donation

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HIT Antibody Seropositivity and Thromboembolic Events After Cardiac Surgery

Blood ◽

10.1182/blood.v118.21.1159.1159 ◽

2011 ◽

Vol 118 (21) ◽

pp. 1159-1159

Author(s):

Thomas L. Ortel ◽

Ian Welsby ◽

David F Kong ◽

John A. Heit ◽

Elizabeth Krakow ◽

...

Keyword(s):

Cardiac Surgery ◽

Bypass Surgery ◽

Primary Outcome ◽

Thromboembolic Events ◽

Hemorrhagic Events ◽

Cardiac Bypass ◽

Antibody Elisa ◽

Postoperative Setting ◽

The Relationship

Abstract Abstract 1159 Background. Heparin induced thrombocytopenia (HIT) is an immune disorder where platelets are activated by antibodies to a complex of platelet factor 4 antigen and heparin (PF4/H), leading to thrombocytopenia (HIT) and, potentially, thrombosis (HITT). Documentation of anti-PF4/H antibodies in addition to the appropriate clinical findings is essential for making a diagnosis of HIT. In the post-cardiac bypass surgery setting, however, the frequency of elevated anti-PF4/H antibodies is high, whereas the frequency of clinical HIT or HITT is relatively uncommon. Several studies have shown that the presence of anti-PF4/H antibodies may be associated with an increased frequency of adverse outcomes, even in the absence of clinical HIT. The primary objective of this study was to determine the relationship between a positive PF4/H antibody in the postoperative setting with adverse thromboembolic events occurring up to 3 months after cardiac surgery. Methods. Patients undergoing cardiac surgery who were not going to be treated with chronic anticoagulation postoperatively were eligible for this multi-center prospective cohort study. Data were collected daily during hospitalization, and then at 30 and 90 days after surgery using a structured interview format with a standardized questionnaire that included all thrombotic as well as hemorrhagic events, platelet counts, and utilization of antithrombotics in the postoperative setting. The primary outcome variable was a composite endpoint comprising arterial and venous thrombotic events and other miscellaneous events compatible with HIT, as well as death attributable to an event compatible with HIT. Citrated plasma was collected at baseline, pre-discharge (∼4–5 days after surgery), and the 30 day follow-up visit, processed, and stored at −80°C for testing. Laboratory analyses included an anti-PF4/H antibody ELISA (GTI, Waukesha, WI) on all samples, a high-heparin confirmatory test on samples with an OD reading >0.40, and a serotonin release assay (SRA) on all postoperative samples with an OD reading >0.40. A sample size of 800 patients was estimated in order to detect a 3% difference in thromboembolic events assuming a 2 to 10-fold increase risk attributable to seropositivity. Chi-squared testing was used to test the relationship between the primary outcome and postoperative anti-PF4/H levels. Results. Informed consent was obtained from 1030 eligible patients between August 2006 and May 2009, and laboratory and follow-up data were analyzable for 1016 patients. Thirty-day antibody data were available for 888 patients, and fully complete laboratory and 90-day follow-up data were available for 815 patients. The average age was 62 ± 12 years, and 73% of participants were male. A total of 769 patients underwent coronary artery bypass grafting and 237 underwent valve repair or replacement. During the entire study period, there were 17 (1.7%) deaths, 46 thromboembolic events in 44 patients (4.3%), and 25 hemorrhagic events in 24 patients (2.4%). Using an OD cutoff of 0.40 for the ELISA, 339 patients (33.4%) were positive for anti-PF4/H antibodies at the time of discharge, and 630 patients (62%) were positive by day 30. There was no correlation between seropositivity for anti-PF4/H antibodies at the day of discharge or at day 30 and the primary outcome (p=0.47 and 0.73, respectively). Incorporating the high-heparin confirmatory step did not improve the relationship between positive antibody results and the primary outcome. Using a higher cut-off value for the anti-PF4/H antibody ELISA of 1.0 decreased the number of patients with positive results (96 patients at the time of discharge [9.4%] and 221 patients at the 30-day follow-up visit [21.8%]), but this did not improve the relationship between antibody positivity at the day of discharge or day 30 and the primary clinical endpoint, since most patients with the primary endpoint had an ELISA OD below 1.0 (75th percentile of 0.90; 90th percentile of 1.22). Similarly, using the SRA did not identify a relationship between assay results and outcome. Conclusions. The presence of anti-PF4/H antibodies in the postoperative setting following cardiac bypass surgery is not associated with an increased risk for thromboembolic complications. Positive anti-PF4/H results in this clinical setting should be interpreted with caution and only in the context of clinical suspicion for HIT. Disclosures: Ortel: Instrumentation Laboratory: Consultancy; Eisai: Research Funding; GSK: Research Funding. Welsby:CSL Behring: Speaker; CSL Behring: Membership on an entity's Board of Directors or advisory committees; NovoNordisk: Principal Investigator. Heit:Daiichi Sankyo: Honoraria; Ortho-McNeil Janssen: Honoraria; Covidien: Honoraria.

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Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention

Blood ◽

10.1182/blood-2008-10-167643 ◽

2009 ◽

Vol 113 (15) ◽

pp. 3406-3417 ◽

Cited By ~ 360

Author(s):

Eleftherios C. Vamvakas ◽

Morris A. Blajchman

Keyword(s):

Cardiac Surgery ◽

Blood Transfusion ◽

Allogeneic Blood Transfusion ◽

Allogeneic Blood ◽

Randomized Controlled ◽

The Us ◽

Low Levels ◽

Pathogen Reduction ◽

Transfusion Guidelines ◽

Related Mortality

Abstract As the risks of allogeneic blood transfusion (ABT)–transmitted viruses were reduced to exceedingly low levels in the US, transfusion-related acute lung injury (TRALI), hemolytic transfusion reactions (HTRs), and transfusion-associated sepsis (TAS) emerged as the leading causes of ABT-related deaths. Since 2004, preventive measures for TRALI and TAS have been implemented, but their implementation remains incomplete. Infectious causes of ABT-related deaths currently account for less than 15% of all transfusion-related mortality, but the possibility remains that a new transfusion-transmitted agent causing a fatal infectious disease may emerge in the future. Aside from these established complications of ABT, randomized controlled trials comparing recipients of non–white blood cell (WBC)–reduced versus WBC-reduced blood components in cardiac surgery have documented increased mortality in association with the use of non-WBC–reduced ABT. ABT-related mortality can thus be further reduced by universally applying the policies of avoiding prospective donors alloimmunized to WBC antigens from donating plasma products, adopting strategies to prevent HTRs, WBC-reducing components transfused to patients undergoing cardiac surgery, reducing exposure to allogeneic donors through conservative transfusion guidelines and avoidance of product pooling, and implementing pathogen-reduction technologies to address the residual risk of TAS as well as the potential risk of the next transfusion-transmitted agent to emerge in the foreseeable future.

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