Hemotherapy: from bloodletting magic to transfusion medicine.
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Biomedical subjects
Publications and source records attributed to Paul M Ness.
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BACKGROUND: Multiply transfused patients are at increased risk of developing red cell (RBC) antibodies, as well as antibodies to HLA. Although pretransfusion testing screens for RBC antibodies, no such testing is routinely performed for HLA antibodies. Determining which patients are more likely to make HLA antibodies may be important for patients undergoing elective surgery where platelets (PLTs) may be required. It is hypothesized that patients with RBC alloantibodies may be more likely to have HLA antibodies than previously transfused patients without RBC antibodies. STUDY DESIGN AND METHODS: Blood was collected from 53 adult male surgical patients with RBC alloantibodies and a control group of 69 similar male patients with a history of previous transfusions but no evidence of RBC alloimmunization. The samples were tested for the presence of immunoglobulin G Class I HLA antibodies by enzyme-linked immunosorbent assay. RESULTS: Of the 53 samples from patients with RBC alloantibodies, 12 (22.6%) also had HLA antibodies, whereas only 7 (10.1%) of the 69 patients in the control group had HLA antibodies (p < 0.03). CONCLUSIONS: There is a significant difference between the rates of HLA alloimmunization in male patients with RBC antibodies versus multiply transfused patients without RBC antibodies. Screening for HLA antibodies may be warranted in patients with RBC alloantibodies who might require PLT transfusion support for elective surgery.
BACKGROUND: A murine model would be useful to identify which immune mechanisms could be manipulated to treat or prevent red blood cell (RBC) alloimmunization in patients who become sensitized to multiple or widely expressed antigens. STUDY DESIGN AND METHODS: Transgenic mice (B6CBAF1/J-Tg-Fy(b)) expressing the human Fy(b) antigen of the Duffy (Fy) blood group were donors. Recipient B6CBA-F1 mice received four weekly intravenous (IV) transfusions: either 0.3 mL of washed buffy coat-depleted RBCs or 0.3 mL of RBCs with spleen cells. Titers of immunoglobulin M (IgM) and immunoglobulin G (IgG) were measured in recipient serum samples by flow cytometry with RBCs from donor mice as target cells. Recipient serum samples were also tested against human RBCs of various Fy phenotypes. Additionally, RBC survival studies were performed in alloimmunized mice utilizing biotin-labeled Fy(b) transgenic mouse RBCs. RESULTS: B6CBA-F1 mice receiving washed buffy coat-depleted RBCs first made IgM, followed by IgG alloantibodies to transgenic mouse Fy(b)-positive RBCs. Recipients of Fy(b)-positive RBCs mixed with spleen cells also produced IgM and IgG alloantibodies, but at a slower rate than recipients of washed buffy coat-depleted RBCs. Serum samples showed specificity for Fy3, Fy(b), and Fy6. Decreased survival of transfused RBCs was evident at 24 hours after transfusion. CONCLUSIONS: It is possible to elicit the formation of anti-Fy alloantibodies by IV transfusion in mice that lack Fy antigens. The transfusion of RBCs alone was adequate to stimulate alloantibody production in B6CBA-F1 recipient mice. The survival of transfused Fy(b)-positive RBCs is diminished in sensitized mice. This model will be useful in further studies of RBC alloimmunization.
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The appropriate therapy of autoimmune hemolytic anemia (AIHA) is dependent on the correct diagnosis and classification of this family of hemolytic disorders. Although the majority of cases are warm AIHA, there are several distinct types of cold AIHA and a number of drug-induced etiologies of AIHA, which must be investigated to determine if stopping a drug will induce a remission. In warm AIHA, corticosteroids are standard, followed by consideration of splenectomy in recalcitrant cases. If steroids and splenectomy are insufficient, other forms of immunosuppressive therapy are typically initiated. In cold AIHA, keeping the patient warm in often sufficient, but therapy directed at an underlying lympholiferative disorder may be helpful. Brisk hemolysis, inadequate responses to therapy, and worsening anemia require transfusion therapy. Although the pretransfusion workup is made difficult by the presence of the autoantibody, transfusion services can usually provide blood safe for transfusion by excluding underlying alloantibodies. When transfusion is urgently required and compatible blood cannot be located, incompatible blood may be provided as a life-saving measure. Communication between the transfusion service and the hematologist is critical to assess the risks in these settings. Hemoglobin-based oxygen carriers may provide an important bridging therapy in the future. Requests for "least incompatible" blood do not enhance transfusion safety and often result in unnecessary delays.
OBJECTIVES: To describe a case of a ceftriaxone-induced hemolytic anemia and hepatitis leading to multiple organ failure and death in an adolescent with hemoglobin SC disease and to review the previous cases of this rare and potentially fatal disorder in children. DESIGN: Case report and literature review. SETTING: Intensive care unit. PATIENT: Adolescent with hemoglobin SC. INTERVENTIONS: Emergency treatment. MEASUREMENTS AND MAIN RESULTS: After 4 days of ceftriaxone therapy, the adolescent experienced an acute hemolytic reaction (hemoglobin decreased to 5 g/dL with hemoglobinuria) and severe hepatitis (all enzymes increasing dramatically including aminoaspartate transferase >20,000 IU/L). Renal failure and ultimately multiple organ failure ensued, and the patient died on hospital day 19. Direct antiglobulin tests on red cells obtained from the patient on hospital day 2 showed microscopic agglutination with polyspecific and anticomplement (C3) antiglobulin reagents. Plasma samples showed macroscopic agglutination reactions when incubated in the presence of ceftriaxone, many days after cessation of ceftriaxone, indicating the continued presence of ceftriaxone-dependent antibodies. CONCLUSIONS: Drug reactions leading to hemolysis are relatively uncommon, and a total of ten cases of ceftriaxone-induced hemolytic anemia have been reported in children. The present case describes an adolescent who ultimately died on hospital day 19 from multiple organ failure, although the presentation of this case seems atypical in several respects. Children with clinical syndromes that place them at risk for hemolysis and children who frequently require broad spectrum antibiotics present unique diagnostic challenges, and the possibility that hemolytic syndromes may be due to ceftriaxone must be considered.
BACKGROUND: Transmission of human herpesvirus-8 (HHV-8) by blood transfusion in the United States appears plausible but has not been demonstrated. The objective of this study was to evaluate evidence of HHV-8 transmission via blood transfusion. STUDY DESIGN AND METHODS: Serum specimens were collected before and 6 months after surgery from 406 patients who enrolled in the Frequency of Agents Communicable by Transfusion study (FACTS) in Baltimore, Maryland, from 1986 to 1990. The change in HHV-8 serostatus was measured by a lytic-antigen immunofluorescence assay. RESULTS: Of the 284 patients who were initially HHV-8-seronegative and who received transfusions, 2 seroconverted, 1 with a postsurgery antibody titer of 1:160 and the other with a titer of 1:1280. These patients received 12 and 13 units of blood, respectively. None of the HHV-8-seronegative patients who did not receive transfusions seroconverted. If seroconversion was caused by transfused blood, the transmission risk per transfused component was 0.082 percent. CONCLUSIONS: This is the first report suggesting transmission of HHV-8 via blood components in the United States. Because linked donor specimens were not available, other routes of transmission cannot be excluded; however, the evidence is consistent with infection being caused by transfusion. Future studies should include contemporary US populations with linked donor specimens and populations at higher risk for HHV-8 infection.
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BACKGROUND: Febrile nonhemolytic transfusion reactions (FNHTR) is a relatively common complication associated with allogeneic transfusion. Because WBCs have been implicated in the mechanism of FNHTRs, it has been proposed that the transfusion of leukoreduced RBCs should be associated with a decreased incidence of FNHTRs. These reactions are generally not life threatening, but they are expensive in their management, evaluation, and associated blood-product wastage. Over the past several years, the proportion of leukoreduced RBCs has increased at Johns Hopkins Hospital in an effort to move toward complete leuko-reduction. A retrospective analysis is reported here of FNHTRs in RBC recipients as the inventory increased in percentage of leukoreduced RBC units. STUDY DESIGN AND METHODS: Between July 1994 and December 2001, all transfusion reactions (TRs) associated with the transfusion of allogeneic RBCs were retrospectively analyzed. Both computerized data and individual TR reports were reviewed. Patients who had both allergic and febrile features were included as part of both categories. TRs were reported as a percentage of total units transfused. Two time periods were selected for direct comparison. July to December 1994 represents the time period before the initiation of an increase in leuko-reduction. July to December 2001 represents a time period when almost complete leukoreduction (99.5%) had been achieved. The TR data were compared between these two time periods, comparing a time before leuko-reduction to a time period after leukoreduction had been achieved. The trends in TRs over the entire 7.5-year period of July 1994 to December 2001 were also assessed. RESULTS: In the initial period before the initiative to move toward leukoreduction, 96 percent of our RBC inventory was non-leukoreduced. In the study period after leukoreduction, 99.5 percent of our RBC inventory was leukoreduced. When comparing these two time periods, the incidence of FNHTRs decreased from 0.37 percent to 0.19 percent (p = 0.0008). The trend over the entire 7.5-year study period confirms the decrease in FNHTRs as the percentage of leukoreduced RBCs increased. The incidence of allergic TRs has remained unchanged over this time period. CONCLUSIONS: As our institution has increased its inventory of leukoreduced RBCs to approximately 100 percent, selective leukoreduced protocols have been discontinued. The incidence of FNHTRs has decreased significantly and the rate of allergic reactions has essentially remained unchanged. Leukoreduction is effective in decreasing FNHTRs associated with the transfusion of allogeneic RBCs.
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Oxygen-carrying hemoglobin (Hb) solutions are under intense investigation as an alternative to allogeneic red cell transfusion during surgery, with or without acute normovolemic hemodilution. We present a case in which an investigational Hb solution was used as an adjunct to acute normovolemic hemodilution, and as a replacement for surgical blood loss in a patient undergoing complex aortic reconstruction with a large blood loss.
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PURPOSE OF REVIEW: Transfusion, in the setting of autoimmune hemolytic anemia, can be a complicated and potentially dangerous proposition. RECENT FINDINGS: The selection and delivery of an appropriate red blood cell unit must focus on several areas: (1) the laboratory detection of the autoantibody, (2) the detection of clinically significant red blood cell alloantibodies potentially masked by the autoantibodies, and (3) the selection and delivery of appropriate, although potentially incompatible, units. In addition, alternatives to red blood cell transfusion, specifically red blood cell substitutes, may also play an important role in the clinical treatment of these patients in the future. SUMMARY: In this article, we will review the most recent developments in the transfusion management of patients with autoimmune hemolytic anemia, specifically focusing on published articles between the period of May 2002 to April 2003.
While transfusion-transmissible diseases, including AIDS and viral hepatitis, continue to spread especially in developing countries, the issue of safeguarding the world's blood supply is of paramount importance. China houses more than 20% of the earth's population, and thus its blood supply has the potential to affect the global community. In recent years, Chinese blood centres have tried to improve the nation's blood safety. Although substantial progress has already been made, many daunting difficulties remain. Traditional cultural barriers need to be overcome to successfully mobilise volunteer blood donors. Gaps in information and technology still need to be closed. Insufficiency of economic resources also restrict the blood bank industry. Other developing countries face many of the same challenges as China.
BACKGROUND: Human polymerized hemoglobin (PolyHeme, Northfield Laboratories, Evanston, IL) is a universally compatible, immediately available, disease-free, oxygen-carrying resuscitative fluid being developed as a red cell substitute for use in urgent blood loss. PolyHeme should be particularly useful when red cells may be temporarily unavailable. This article assesses survival at life-threatening RBC hemoglobin concentration ([Hb]) in massively bleeding patients who do not receive red cells. STUDY DESIGN: There were 171 patients who received rapid infusion of 1 to 20 units (1,000 g, 10 L) of PolyHeme in lieu of red cells as initial oxygen-carrying replacement in trauma and urgent surgery. The protocol simulated the unavailability of red cells, and the progressive fall in RBC [Hb] in bleeding patients was quantified. Thirty-day mortality was compared with a historical control group of 300 surgical patients who refused red cells on religious grounds. RESULTS: A total of 171 patients received rapid infusion of 1 to 2 units (n = 45), 3 to 4 units (n = 45), 5 to 9 units (n = 47), or 10 to 20 units (n = 34) of PolyHeme. Forty patients had a nadir RBC [Hb] < or = 3 g/dL (mean, 1.5 +/- 0.7 g/dL). But total [Hb] was adequately maintained (mean, 6.8 +/- 1.2 g/dL) because of plasma [Hb] added by PolyHeme. The 30-day mortality was 25.0% (10/40 patients) compared with 64.5% (20/31 patients) in historical control patients at these RBC [Hb] levels. CONCLUSIONS: PolyHeme increases survival at life-threatening RBC [Hb] by maintaining total [Hb] in the absence of red cell transfusion. PolyHeme should be useful in the early treatment of urgent blood loss and resolve the dilemma of unavailability of red cells.
BACKGROUND: FV inhibitors are a largely preventable iatrogenic coagulopathy in which the frequency is increasing in clinical practice. STUDY DESIGN AND METHODS: Three cases associated with our institution are reported. A systematic review of the MEDLINE database was performed, and reference lists were reviewed to identify relevant publications. RESULTS: One hundred twenty-six cases of FV inhibitors have been reported in the world's literature. Eighty-seven have been reported in the last decade, of which two thirds are due to exposure to bovine thrombin. Bovine thrombin-associated FV antibodies develop in 40 to 66 percent of cardiac surgery patients and in 20 percent of neurosurgery patients. Thirty-three percent of reported patients developed bleeding complications. Inhibitors persisted on average 2.3 months. Standard coagulation assays do not reliably predict clinical manifestations. Multimodality therapy, including immunosuppression, is useful for treatment of symptomatic patients. CONCLUSIONS: FV inhibitors are a common complication of bovine thrombin exposure that can have devastating clinical consequences. Transfusion medicine specialists and hematologists can play a critical role in reducing the incidence of FV inhibitors by educating the medical community about safer alternative fibrin sealants.