Impact of platelet transfusion on toxicity and mortality after hematopoietic progenitor cell transplantation.

BACKGROUND: Thrombocytopenia occurs commonly after hematopoietic progenitor cell transplantation (HPCT) and is associated with potential morbidity and mortality. Few studies have examined the impact of platelet (PLT) transfusion on clinical outcomes in HPCT while optimal PLT transfusion strategies after HSCT remain uncertain. STUDY DESIGN AND METHODS: A retrospective single-center cohort study was conducted on 522 patients undergoing HPCT between January 2002 and December 2007. Associations between PLT transfusion events and clinical characteristics with transplant-related outcomes were assessed using univariate and multivariate analysis. RESULTS: Mean number of PLT transfusion events before Day +60 posttransplant was 7.5 (95% confidence interval, 6.7-8.4) with greater number of events after allogeneic compared with autologous HPCT (p < 0.01). Univariate and multivariate analysis confirmed that the number of PLT transfusion events was associated with increased 100-day nonrelapse mortality (p < 0.01), posttransplant length of hospital stay (p < 0.01), need for intensive care unit admission (p < 0.01), and number of organs affected by severe toxicity (p < 0.01). CONCLUSION: HPCT-related toxicity and mortality are associated with increased PLT transfusion events. Alternative strategies to reduce PLT transfusions after HPCT may warrant future study.

Acute extravascular hemolytic transfusion reaction due to anti-Kpa antibody missed by electronic crossmatch.

BACKGROUND: Kpa antigen is a low incidence red blood cell antigen within the Kell system. Anti-Kpa alloantibody may be associated with acute and delayed hemolytic transfusion reactions. CASE STUDY: We report a case of a clinically significant acute extravascular hemolytic transfusion reaction mediated by previously unrecognized (and undetected) anti-Kpa alloantibody. This reaction occurred in a patient who met all criteria for electronic crossmatch, resulting in the transfusion of an incompatible red cell unit. RESULTS: Post-transfusion investigation showed the transfused red cell unit was crossmatch compatible at the immediate spin phase but was 3 + incompatible at the antiglobulin phase. No evidence of intravascular hemolysis was observed upon visual comparison of the pre- and post-transfusion peripheral blood plasma. Further testing showed the presence of anti-Kpa antibody. The clinical course of the patient included acute febrile and systemic reaction. CONCLUSION: Acute extravascular hemolytic transfusion reaction may occur due to undetected anti-Kpa alloantibody. Various strategies for crossmatching are discussed in the context of antibodies to low incidence antigens.

2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema.

BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) and updated this as Hereditary angioedema: a current state-of-the-art review: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema. OBJECTIVE: To update the International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema (circa 2010). METHODS: The Canadian Hereditary Angioedema Network (CHAEN)/Réseau Canadien d'angioédème héréditaire (RCAH) http://www.haecanada.com and cosponsors University of Calgary and the Canadian Society of Allergy and Clinical Immunology (with an unrestricted educational grant from CSL Behring) held our third Conference May 15th to 16th, 2010 in Toronto Canada to update our consensus approach. The Consensus document was reviewed at the meeting and then circulated for review. RESULTS: This manuscript is the 2010 International Consensus Algorithm for the Diagnosis, Therapy and Management of Hereditary Angioedema that resulted from that conference. CONCLUSIONS: Consensus approach is only an interim guide to a complex disorder such as HAE and should be replaced as soon as possible with large phase III and IV clinical trials, meta analyses, and using data base registry validation of approaches including quality of life and cost benefit analyses, followed by large head-to-head clinical trials and then evidence-based guidelines and standards for HAE disease management.

Urgent replacement of a mechanical mitral prosthesis in an anticoagulated patient with Bombay red blood cell phenotype.

PURPOSE: Bombay red blood cell phenotype is an extremely rare blood type for which patients can receive only autologous or Bombay phenotype red blood cells. We report a case of urgent repeat sternotomy for replacement of a mechanical mitral prosthesis in a patient with Bombay phenotype anticoagulated with warfarin, to emphasize the transfusion challenges in such patients. CLINICAL FEATURES: A male of Indian descent presented to hospital with New York Heart Association IV symptoms. His medical history revealed previous mitral valve replacement with a mechanical prosthesis in 2005 and Bombay phenotype blood. Preoperative transthoracic echocardiography demonstrated thrombus obstruction of the mitral prosthesis despite anticoagulation with warfarin. Right ventricular systolic pressure was >100 mmHg with 3+ tricuspid regurgitation. The patient's condition was temporized with diuretics, bronchodilators, and bi-level positive airway pressure ventilation while transfusion medicine and cardiac surgery were consulted for urgent surgery. The patient received vitamin K and prothrombin complex concentrate prior to repeat sternotomy and successful mitral prosthesis replacement. After cardiopulmonary bypass, heparinization was corrected with protamine and followed by a second dose of prothrombin complex concentrate and recombinant activated factor VIIa. Postoperatively, the patient received four units of packed red blood cells, two autologous units and two units of Bombay specific red blood cells. Right ventricular pressures stabilized at 40 mmHg following surgery. The patient recovered following several days of inotropic support with milrinone, diuretics, and bronchodilators. CONCLUSION: Patients with Bombay phenotype red blood cells present as type O, but they are unable to receive red blood cells from any phenotype other than Bombay phenotype. They are able to receive all other blood products, including fresh frozen plasma, cryoprecipitate, platelets, prothrombin complex concentrate, and recombinant activated factor VIIa. Coordination between Canadian Blood Services, transfusion medicine, surgery, and anesthesia is important in managing these patients.

Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis.

BACKGROUND: This case series summarizes our observations of hemolytic reactions after the administration of large amounts of intravenous immune (gamma) globulin (IVIG). STUDY DESIGN AND METHODS: Cases of hemolysis were identified by a decrease in hemoglobin not otherwise explained following IVIG administration. RESULTS: Sixteen cases were identified over a 2 1/2-year period at the Ottawa Hospital of approximately 1000 patients receiving IVIG (1.6%). Characteristics of these patients include a large dose of IVIG, female sex, non-O blood group, and underlying inflammatory state. CONCLUSIONS: Significant hemolysis may occur after the administration of large doses of IVIG. A two-step mechanism of hemolysis is proposed, sensitization by ABO isohemagglutinins followed by phagocytosis by activated macrophages. A simple protocol to facilitate the early detection of such cases is presented.

Hereditary angiodema: a current state-of-the-art review, VII: Canadian Hungarian 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema.

BACKGROUND: We published the Canadian 2003 International Consensus Algorithm for the Diagnosis, Therapy, and Management of Hereditary Angioedema (HAE; C1 inhibitor [C1-INH] deficiency) in 2004. OBJECTIVE: To ensure that this consensus remains current. METHODS: In collaboration with the Canadian Network of Rare Blood Disorder Organizations, we held the second Canadian Consensus discussion with our international colleagues in Toronto, Ontario, on February 3, 2006, and reviewed its content at the Fifth C1 Inhibitor Deficiency Workshop in Budapest on June 2, 2007. Papers were presented by international investigators, and this consensus algorithm approach resulted. RESULTS: This consensus algorithm outlines the approach recommended for the diagnosis, therapy, and management of HAE, which was agreed on by the authors of this report. This document is only a consensus algorithm approach and continues to require validation. As such, participants agreed to make this a living 2007 algorithm, a work in progress, and to review its content at future international HAE meetings. CONCLUSIONS: There is a paucity of double-blind, placebo-controlled trials on the treatment of HAE, making levels of evidence to support the algorithm less than optimal. Controlled trials currently under way will provide further insight into the management of HAE. As with our Canadian 2003 Consensus, this 2007 International Consensus Algorithm for the Diagnosis, Therapy, and Management of HAE was formed through the meeting and agreement of patient care professionals along with patient group representatives and individual patients.

External quality assessment of HLA-B*5701 reporting: an international multicentre survey.

OBJECTIVES: HLA-B*5701 strongly predicts abacavir hypersensitivity (HSR), but implementation of effective routine screening into clinical practice requires testing be practical and accurate. We tested the proficiency of HLA-B*5701 typing among laboratories using sequence-specific primer PCR. DESIGN AND METHODS: DNA panels (1 and 2) were distributed to seven laboratories (A to G) for blinded typing of the HLA-B*5701 allele. Panel 1 (n = 10 samples; n = 7 laboratories) included 3 positives and other closely related B17 subtypes (B*5702, B*5703, B*5704 and B*5801). Panel 2 (n = 96 samples; n = 4 laboratories) included 36 positives among a broad spectrum of other B alleles. Two laboratories (A and B) also submitted 96 routine samples, typed by the same methodology, to the reference centre for additional analysis by sequence-based typing. RESULTS: All laboratories correctly typed panel 1 for HLA-B*5701 carriage. Laboratories A, B and C identified HLA-B*5701 alleles in panel 2 with 100% sensitivity and 100% specificity. Laboratory D reported one false negative, reportedly due to a sampling error. The results obtained for routine samples typed by laboratories A and B and those generated by the reference laboratory using sequencing were fully concordant. CONCLUSIONS: Detection of HLA-B*5701 alleles among laboratories was 100% specific and 99.4% sensitive, indicating that participating HIV testing laboratories were currently offering effective primary screening to identify individuals at high risk of abacavir HSR. Accurate reporting of HLA-B*5701 status is critical for the safe administration of this drug and participation in quality assurance programmes by all sites who report HLA-B*5701 status should be promoted.

Documenting a transfusion: how well is it done?

BACKGROUND: Current practice in transfusion medicine promotes clear documentation of transfusion-related events including the fact that the patient has been informed of the related risks and benefits. STUDY DESIGN AND METHODS: A retrospective review of 1005 patient charts was carried out to determine documentation. RESULTS: Most patients were from general surgery (10.8%) and cardiac surgery (14.1%). In 75 percent of cases the physician had not documented that any discussion had occurred regarding the risks and/or benefits or alternatives. Only 12 percent of charts included information that the patient was subsequently told what blood components were given to them. The discharge summary recorded transfusion information in 32.1 percent of cases whereas the consult note had this information in 26.3 percent. Chart records matched the transfusion medicine records in 60.6 percent of cases. The most common error was in the blood unit identification number. CONCLUSIONS: While accepted in theory, the practice of documenting patient information on transfusion is not well done.

Evaluation of platelet transfusion triggers in a tertiary-care hospital.

BACKGROUND: Our 1100-bed referral hospital uses approximately 12,000 units of random-donor platelets (PLTs) and 1,900 units of single-donor apheresis PLTs per year with a mean of 23 percent outdating. An analysis of patterns of utilization has been undertaken to evaluate practice. STUDY DESIGN AND METHODS: Over a 9-month period, data were collected on a total of 1682 transfusion episodes in 464 patients. When the pretransfusion count was greater than 10 x 10(9) per L an attempt was made to identify the specific indications for PLT transfusions such as bleeding. RESULTS: The majority (78%) of PLTs were transfused when the counts were above 10 x 10(9) per L. The mean pretransfusion counts for different services were: bone marrow transplant (BMT) 17.4 x 10(9) per L, hematology-oncology 14.6 x 10(9) per L, the Heart Institute 3 x 10(9) per L, and other services 36 x 10(9) per L. The percentage of transfusions given to patients with a count greater than 10 x 10(9) per L varied by service with 79 percent in BMT, 60 percent in hematology and oncology, 98 percent at the Heart Institute, and 81 percent in other services. Routine monitoring of counts shows a mean increment of 10.2 x 10(9) per L per transfusion. One hour posttransfusion counts, 24-hour posttransfustion counts, and documentation of clinical justification for transfusions was often not available. CONCLUSIONS: The data show that most patients who receive PLTs have pretransfusion counts of more than 10 x 10(9) per L and more than one-third have pretransfusion counts of greater than 20 x 10(9) per L. The medical literature supports prophylactic PLT transfusion based solely on the count when the PLT number is 10 x 10(9) per L or less. Above this level additional justification is needed although there are different points of view concerning the appropriate triggers. Our data suggest that there is a need for clear hospital transfusion guidelines and ongoing monitoring of PLT use.

The effect of patient-controlled analgesia on coadministered red blood cells.

BACKGROUND: Patient-controlled analgesia (PCA) provides effective pain control. The possibility of administrating opioids in the same line as red blood cells (RBCs) for patients with poor venous access has been entertained. The literature on this approach is not extensive, but generally cautionary. STUDY DESIGN AND METHODS: Standard concentrations of morphine, hydromorphone (Dilaudid), and meperidine (Demerol) were used to determine the effect on RBCs. Three in vitro approaches were used: 1) continuous low-dose opioid infusion with a single bolus, 2) continuous infusion with multiple boluses, and 3) assessment of RBCs with different concentrations of opioids in test tubes. Samples were assayed for hemoglobin (Hb), mean corpuscular volume (MCV), plasma Hb, potassium, and lactate dehydrogenase, and a peripheral blood smear was made. RESULTS: Addition of each drug as a single or multiple bolus(-es) with continuous infusion showed the same effects as normal saline. In vitro exposure of Demerol at a 1:2 ratio (drug:blood) increased the MCV (110 fL), at 1:1 the MCV was 120 fL, and there was 4.5 percent hemolysis. At 2:1, hemolysis increased to 9.2 percent. Both morphine and Dilaudid had similar effects as normal saline. CONCLUSION: Morphine, Dilaudid, and Demerol, given as a bolus in the intravenous line, have the same effects as those seen with saline. When mixed directly with the blood for more than 1 hour, however, Demerol caused increasing RBC swelling and at high, nontherapeutic concentrations, caused hemolysis. Our study suggests that analgesia delivered via PCA may be safely coadministered with RBCs. Further clinical study is warranted.

Seven-day storage of random donor PLT concentrates.

BACKGROUND: PLT concentrates are licensed for use up to a maximum of 5 days of storage. Increasing storage to 7 days would improve the logistics of supply and have the potential to reduce wastage. STUDY DESIGN AND METHODS: PLTs were prepared from CP2D blood with standard procedures (n = 16) and then WBC-reduced. Sampling was carried out at 3, 5, and 7 days for PLT count, pH, aggregation to ADP and collagen, hypotonic shock response, Kunicki morphology score, thromboelastogram response, pO2, and pCO2, and PLT activation (CD62) was carried out by flow cytometry. Additionally, PLTs stored for 7 days were transfused into thrombocytopenic patients, and the CCI was calculated. RESULTS: Some of the in vitro tests such as the aggregation response to single stimuli showed decreased values with time. The hypotonic shock was well maintained for 7 days (77%-68%); the Kunicki morphology score showed progressive shape change (300 to 164). The CCI of 7-day PLTs averaged 16,000 (n = 9). CONCLUSIONS: The data indicate acceptable in vitro PLT function at 7 days. Transfusion of the 7-day-old CP2D PLTs resulted in an appropriate posttransfusion increment in thrombocytopenic patients. Random donor PLTs collected into CP2D can be successfully stored for 7 days before use.