Margot S. Kruskall

Genetic Prediction of Nonresponse to Hepatitis B Vaccine

In previous studies of the antibody response to hepatitis B vaccine in 598 subjects who received a full course of vaccination, we observed a bimodal response, with about 14 percent producing less than approximately 1000 radioimmunoassay (RIA) units. An analysis of the major histocompatibility complex (MHC) HLA and complement types of 20 of the subjects with the lowest responses indicated a greater-than-expected number of homozygotes for the extended or fixed MHC haplotype [HLA-B8, SC01, DR3]. This finding suggested that the lack of a normal response was a recessive MHC-linked trait. In this study, we prospectively vaccinated five homozygotes and nine heterozygotes for this haplotype in the expectation that the homozygotes would produce much lower levels of antibody than the heterozygotes. When the antibody response was assessed two months after the third injection, four of the five homozygotes had produced very low levels (approximately 1000 units or less) of antibody (mean, 467 RIA units; range, less than 8 to 1266), whereas all nine heterozygotes produced more than 2500 RIA units (mean, 15,608; range, 2655 to 28,900) (P less than 0.01). We conclude that the usual response to hepatitis B surface antigen is due to the presence of a dominant immune-response gene in the MHC and that a low response is due to the absence of such a gene and the presence on both chromosomes of MHC haplotypes (such as [HLA-B8, SC01, DR3]) that indicate such a response.

Phlebotomy for diagnostic laboratory tests in adults: pattern of use and effect on transfusion requirements

Although anemia is a frequently observed complication of phlebotomies for laboratory tests in neonates, this problem has received little attention in adult populations. We analyzed the phlebotomy records of 100 hospitalized patients and found that 50 patients who spent all of their hospitalization in general wards had blood samples drawn an average of 1.1 times a day. A mean volume of 12.4 ml a day was drawn, and the total volume drawn during their entire hospitalization was 175.0 ml. In contrast, 50 patients who spent part or all of their hospitalization in an intensive care unit were phlebotomized a mean of 3.4 times a day, for a mean volume of 41.5 ml of blood drawn a day and a total volume of 762.2 ml. Patients in the intensive care unit who had arterial lines had more blood drawn (944.0 ml), more often (4.0 times a day), than patients in the intensive care unit who did not have such lines (300.9 ml; 1.9 times a day). Of 36 patients who received transfusions, 17 (47 percent) had large losses from phlebotomy (greater than 180 ml of red cells) that contributed to their transfusion requirements. We propose the use of sample tubes of the size used in pediatrics, batching of requests for laboratory tests, and review of the cumulative volume of blood removed from individual patients as approaches to reducing blood loss from phlebotomy.

Intravenous immune globulins: an update for clinicians

Immunoglobulins provide the body with an important defense mechanism against infectious agents for the patient with hypogammaglobulinemia. Less well understood is the ability of infused immune globulins to modulate immune-mediated diseases. Many excellent reviews have been written about the scientific and technical aspects of IVIGs. This review uses a different slant, with emphasis on the role of IVIGs in clinical practice and particular attention to the many research and clinical studies published in the past 5 years pertaining to currently available products, indications for use, and reactions, and other complications.

Efficacy of platelet transfusions in immune thrombocytopenia

Records of 11 patients with immune thrombocytopenia (idiopathic and quinidine-induced) were evaluated retrospectively for response to platelet transfusion. Good post-transfusion platelet count increments occurred on one or more occasions in seven of the 11 patients, with 13 of 31 platelet transfusions (42 percent) resulting in immediate post-transfusion increments of 20,000/mm3 or more. Next-day platelet counts remained elevated in association with five of these 13 transfusions. This study demonstrates that, contrary to common opinion, platelet transfusions can raise the platelet count in many patients with immune thrombocytopenia, and therefore may be beneficial in actively bleeding or high-risk patients with this disorder.

Transfusion to blood group A and O patients of group B RBCs that have been enzymatically converted to group O.

BACKGROUND: The transfusion of ABO‐incompatible RBCs is the leading cause of fatal transfusion reactions. Group O RBCs, lacking terminal immunodominant A and B sugars to which humans are immunized, are safe for transfusion to persons of any ABO blood group. With the use of a recombinant α‐galactosidase to remove terminal galactose from group B RBCs, the safety and efficacy of enzyme‐converted group‐B‐to‐group‐O (ECO) RBC components were studied in transfusion‐dependent patients.

Cryoprecipitate. Patterns of use.

The type of coagulation factors and proteins in cryoprecipitate determine the appropriate indications for its use. To determine the pattern of use at a tertiary care medical center, we performed a retrospective audit of cryoprecipitate utilization. A total of 51 patients received 88 pools of cryoprecipitate. In 39 patients, cryoprecipitate was transfused for appropriate indications: hypofibrinogenemia (n = 19), tissue plasminogen activator reversal (n = 1), management of massive transfusion (n = 7), correction of uremic bleeding (n = 2), and for making fibrin sealant (n = 10). Overall, these patients used approximately 80% of the cryoprecipitate transfused. In 12 other patients, cryoprecipitate was transfused inappropriately to attempt reversal of the anticoagulant effects of warfarin therapy (n = 6), to treat impaired surgical hemostasis in the absence of hypofibrinogenemia (n = 4), and to treat hepatic coagulopathy with multiple factor deficiencies (n = 2). The patterns of misuse, involving 24% of all cryoprecipitate orders, suggest a widespread misunderstanding and need for focused education about the coagulation factors and proteins present in cryoprecipitate and appropriate indications for its use.

Transfusion safety: realigning efforts with risks

ver the last decade, the efforts of numerous research groups have been directed at decreasing the risk of transmission of viruses through transfusion. Accelerated by the appearance of human immunodeficiency virus (HN) in the blood supply in the early part of the 1980s, these efforts-reducing viral risks through expansion of donor history screening, improvements in infectious disease marker testing, and development of virus inactivation-have led to unqualified successes for the field of transfusion medicine (Fig. 11.’ Quantifiable infectious risks remain; however, the current incidence of transfusion-transmitted infection suggests that the pursuit of additional improvements, while still important, is likely to be more difficult, and questions regarding cost-effectiveness are surfacing2 We believe that some of the energy devoted to avoiding transfusion-transmitted viral diseases should now be focused on additional ways to make transfusions safer. In this commentary, we identify three broad areas of transfusion risk that are in need of substantial and coordinated research attention, each of which has different scientific and practical ramifications. One problem, ABO-related transfusion fatalities, has plagued transfusion practice since its beginning. The incidence and impact of the second problem, bacterial contamination of blood components, have probably been underestimated until recently. Finally, the risks and consequences of the third problem, immune modulation following allogeneic blood transfusion, are significant, not only because of the clinical impact on blood

Preoperative Autologous Blood Donation

THE IMPORTANCE of autologous blood to medical practice has fluctuated considerably over the last century. One hundred years ago, autologous blood transfusion practices offered the only hope for an exsanguinating patient. The principies of compatibility had not been discovered, and transfusions of blood from one individual to another appeared foolhardy; but surgeons could collect blood shed after delivery, strain it through eloth, and return it to the patient. In some cases, this salvaged autologous blood was lifesaving. Autologous blood donation in advance of surgery became a natural extension of this practice in the early part of the 20th century, once it was possible to anticoagulate and store blood in glass containers. The primary purpose of autologous blood was to provide a source of blood, at frrst because homologous blood transfusions were risky, and later to augment marginal homologous supplies. As the safety and availability of blood improved, interest in collecting autologous blood waned. Other advantages of autologous blood, such as the elimination of transfusion-transmitted diseases and immune-mediated reactions, were not seen as sufficiently important to warrant the effort inyolved in autologous donations. Sporadic reports conceming the use of autologous blood continued to appear, ineluding a useful monograph reviewing an assortment of applications for autologous blood collections. 1 Nonetheless, for most programs autologous blood was considered primarily for the patient with multiple alloantibodies, or ąntibodies to high-frequency antigens, for whom homologous donor blood was in limited supply. The identification of the human immunodeficiency virus in the 1980s, and the recognition that it was efficiently spread through blood transfusions, led to a rapid renewal of interest in autologous blood techniques. Between 1982 and 1988, American Association of BloOO Banks (AABB) member surveys found that the number of units of autologous blood collected annually increased each year (from 18,737 in 1982 to 337,773 in 1988 [Fig 1]). New advances, such as the use ofrecombinant human erythropoietin, may catalyze additional growth in autologous collections. Such rapid growth over a very short time period

A comparative study of blood warmer performance.

Massive transfusions of refrigerator-temperature blood may induce hypothermia and life-threatening arrhythmias; for this reason a variety of devices have been developed for rapid blood warming. Blood warmers available in the United States use one of three warming technologies: dry heat, water bath, or countercurrent heat exchange. In the current study we evaluated blood warmers representative of each technology for speed and extent of heat transfer: the Fenwal blood warmer (Fenwal Laboratories; dry heat), the DW-1000 (American Pharmaseal Co.; dry heat), the FloTem IIe (DataChem Inc.; dry heat), the Hemokinetitherm (Dupaco Inc.; water bath), and the H250 and H500 (Level 1 Technologies; countercurrent heat exchange). Only one countercurrent heat instrument (the H500) was able to heat blood > or = 33 degrees C at target flow rates > or = 250 ml/min. Dry heat and water bath blood warmers were unable to warm blood > or = 33 degrees C at target flow rates > or = 100 ml/min. High resistance to flow with the proprietary tubing required for one instrument (the Hemokinetitherm) prevented tests of blood warming at rates > 150 ml/min. We found that instruments that used countercurrent technology warmed blood and saline more effectively than did blood warmers that used either dry heat or water bath technology. Our study also demonstrated the need for close control and standardization of experimental conditions in the evaluation of blood warming devices.

Red cell loss following orthopedic surgery: the case against postoperative blood salvage.

BACKGROUND: Expensive devices have been developed for the collection and transfusion of blood salvaged after hip or knee arthroplasty.