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Biomedical subjects

I A Shulman

Publications and source records attributed to I A Shulman.

At least 37 records · Page 2Linked to original sources

The routine use of Rh-negative reagent red cells for the identification of anti-D and the detection of non-D red cell antibodies.

BACKGROUND: Before 1987, fewer than 50 patients per year at the authors' laboratory had a positive antibody detection test due to antepartum Rhesus immunoprophylaxis. However, after 1987, a marked increase was observed in the number of patients who had received Rh immune globulin (RhIG) during pregnancy as part of routine antepartum Rh immunoprophylaxis. In anticipation that an increased use of RhIG during pregnancy would increase the number of patients in whom anti-D was detected by this laboratory, a protocol was developed to abbreviate the process required to identify anti-D. Although this protocol was adopted primarily to address an anticipated increase in antenatal RhIG usage in women, it was also applied to alloimmunized Rh-negative males. STUDY DESIGN AND METHODS: When an Rh-negative patient (male or female) had a reactive screening test for unexpected antibodies and met certain other criteria, the patient's serum was tested with a three-vial set of Rh-negative reagent red cells (Rh-negative screening RBCs), instead of with panels of typed RBCs (panel RBCs), for the identification of anti-D or the detection of non-D antibodies. If the serum under test did not agglutinate or hemolyze Rh-negative screening RBCs, anti-D was identified and no further testing was performed. If the serum agglutinated or hemolyzed Rh-negative screening RBCs, conventional testing with panel RBCs was done to determine the antibody specificity. RESULTS: Rh-negative patients (n = 1174) who had reactive screening tests for unexpected antibodies were tested with Rh-negative screening RBCs; 1079 were found to have anti-D as a single antibody. Seven of these patients subsequently developed a non-D alloantibody, after transfusion or pregnancy, and one patient had anti-C that escaped detection at the time of initial testing with Rh-negative RBCs (a false-negative result). Ninety-two patients had anti-D in combination with a non-D antibody, and three patients had a non-D antibody but not anti-D. Use of the anti-D identification protocol actually reduced the laboratory workload by 176 College of American Pathologists workload units per month, in spite of a marked increase in the number of patients in whom anti-D was detected. No hemolytic transfusion reaction was attributed to the abbreviation of anti-D identification. CONCLUSION: The identification of anti-D may be abbreviated without jeopardizing patient safety. Such a protocol can reduce laboratory workload and might be particularly appealing to health care facilities that perform antibody detection testing on large numbers of Rh-negative pregnant women, especially if antepartum RhIG is administered routinely.

Erythrocytes↗

Is it safe to omit the 37 degrees C reading from pretransfusion red blood cell antibody detection testing?

The routine pretransfusion red blood cell antibody detection test (PADT), performed at the authors' institution, consists of a three-phase, saline-antiglobulin technique (immediate spin, 30-minute incubation at 37 degrees C, IgG indirect antihuman globulin test [IAT]), and each phase is examined for hemolysis and agglutination. To determine if it would be safe to omit reading the 37 degrees C phase of the PADT, a 6-year retrospective review of records (February 1986 to February 1992) was undertaken. Of approximately 280,000 sera tested for unexpected red cell alloantibodies, 1480 (.53%) were reactive at only 37 degrees C. Of 1480 sera, 1313 contained alloantibodies of no or questionable significance (eg, anti-Le(a), anti-Leb, and anti-P1), 71 sera contained antibodies of undetermined specificity, and 10 sera were reactive because of rouleaux. Eighty-six serum samples from 53 different patients contained alloantibodies of potential significance (anti-K, anti-E, etc). These 86 sera represented approximately 2.2% of all reactive sera that contained potentially significant alloantibodies. Although most antibodies (approximately 94%) detected only at 37 degrees C were of no or questionable significance, the other 6% could have increased the risk of missing a potentially significant antibody from approximately 1 in every 4700 sera tested to 1 in every 1875 sera tested, had they not been detected. The authors suggest that the increased risk of an acute or delayed hemolytic transfusion reaction would be too high to justify a procedural change. Based on these data, the authors continue to read the 37 degrees C phase of the PADT for hemolysis and agglutination.

Adult↗

Parasitic infections and their impact on blood donor selection and testing.

There is currently less than a one in a million chance that a blood transfusion within the United States will be complicated by a parasitic infection. However, changes in population demographics and increases in international travel and immigration may all contribute to an increase in the number of parasitemic individuals who present as prospective blood donors. Consequently, a need may arise to develop new policies to prevent transfusion-transmitted parasitic infections. In the present review, the following parasitic infections of concern to the safety of the US blood supply will be discussed: malaria, Chagas' disease, babesiosis, leishmaniasis, toxoplasmosis, and microfilariasis.

Animals↗

Transfusion practice in medical patients.

OBJECTIVE: Blood transfusion raises serious issues of safety and economics. We therefore examined blood usage and its characteristics in medical inpatients, given the relative scarcity of existing data. DESIGN: During a 1-year period, transfusion episodes on two medical services were reviewed by five specialists for justifiability on the basis of generally agreed on guidelines. SETTING: The study was conducted at two institutions, a municipal teaching hospital where house staff deliver care and a community hospital where patients are under the direct care of private physicians. PATIENTS: Four hundred thirty-eight randomly selected transfusion episodes on the medical services of the two institutions were reviewed. MAIN OUTCOME MEASURES: The prevalence of unjustifiable transfusions based only on the information available to the managing physician at the time of transfusion. RESULTS: Eighteen percent of the 438 randomly selected transfusion episodes were viewed as not justifiable by at least four of five reviewers; another 17% were classified as equivocal because two or three reviewers judged them to be not justifiable. The most striking observation was the greater prevalence of nonjustifiable transfusion episodes at the community hospital (26% vs 16% at the teaching institution; P = .0121). Other observations included a tendency for physicians to prescribe transfusions by the numbers (at least 11% of nonjustifiable transfusions) and to overtransfuse. The routineness with which transfusion was viewed by managing physicians was also identifiable by the absence of written transfusion notes in 39% of all episodes reviewed, which incidentally raises questions about the adequacy of the medical chart's documentary functions today. CONCLUSIONS: The rate of nonjustifiable or equivocal transfusion on medical services may be as high as 35%. Reliance on numbers rather than clinical status seems to be a major problem. Education is obviously a critical issue and should also target private practitioners, who seemed to perform less well than physicians in training. Transfusion guidelines that use specific hematocrit values also need to be reexamined.

Blood Transfusion↗

Iron-deficiency anemia: a medically treatable chronic anemia as a model for transfusion overuse.

PURPOSE: Transfusion practice in patients with iron deficiency was reviewed. PATIENTS AND METHODS: During the study period, records of 265 consecutive patients with an unsaturated iron-binding capacity of greater than 53.7 mumol/L were evaluated for possible iron-deficiency anemia. RESULTS: Two hundred sixty-three patients met the study criteria for iron deficiency. Of these patients, 50 received 1 or more units of red blood cells (RBCs). The transfusion therapy of 12 patients could not be justified; physicians used laboratory results rather than the clinical status of the patients to initiate transfusion therapy. As a result, units of RBCs were transfused to raise the hematocrit to an arbitrarily chosen level. Furthermore, iron therapy was not prescribed for 97 of the 263 iron-deficient patients, including 11 of the patients for whom transfusion was justifiable and 2 patients for whom transfusion could not be justified. Based on records reviewed, no work-up was initiated to identify the cause of iron deficiency in 13 patients, including 4 patients who received transfusions. CONCLUSION: These findings suggest that the evaluation and treatment of iron deficiency, including transfusion therapy for that condition, may be problematic. In view of the risks of blood transfusion therapy, improvement in transfusion practices for iron deficiency should be emphasized.

Anemia, Hypochromic↗

The routine use of soluble Lewis antigens in the identification of Lewis system antibodies.

Approximately 3 percent of the blood samples tested at the authors' laboratory have contained unexpected red cell (RBC) antibodies, of which about one-third have been anti-Le(a) or anti-Le(b). Although these antibodies are usually clinically insignificant, considerable workload was expended in their identification. In hopes of reducing this workload, an alternative approach for identifying these antibodies was implemented. If a patient had no history of unexpected antibodies, with the exception of Lewis system antibodies, and if the results of serum antibody detection testing were typical for the presence of anti-Le(a) and/or anti-Le(b), the serum was treated with commercially standardized soluble human Le(a) and Le(b) blood group substances, and the Lewis phenotype of the patient's red cells was determined. If the treated serum demonstrated specific antibody neutralization and the red cell phenotype was Le(a-b-), the results were interpreted as positive for anti-Le(a) or anti-Le(b), and no further antibody identification workup was performed. If the patient was Le(a+b-) or Le(a-b+), or if the treated serum failed to demonstrate specific antibody neutralization, the serum was tested against panels of reagent RBCs that were licensed for the identification of unexpected antibodies. During the study period (8-1-89 to 6-16-90), 498 of 46,965 patients' samples met the criteria for testing for specific antibody neutralization. Of these 498 blood samples, 452 showed specific neutralization of antibody activity by Lewis substance and were Le(a-b-). Only 1 of these samples was discovered to contain an additional non-Lewis antibody (anti-Bg).(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗

Use of a questionnaire to identify potential blood donors at risk for infection with Trypanosoma cruzi.

Trypanosoma cruzi is the protozoan parasite that causes American trypanosomiasis (Chagas' disease). Chagas' disease is endemic in Latin America. The infection is usually seen in poor people who live in rural areas in substandard housing, where they are bitten by infected reduviid bugs. Transmission also can occur by blood transfusion. Infected individuals who immigrate to the United States might donate blood if they are asymptomatic and unaware of their infection. This study evaluated the usefulness of a questionnaire for identifying T. cruzi-infected individuals among prospective blood donors who met all American Association of Blood Banks, Food and Drug Administration, and State of California criteria for donor eligibility. Seventy-two of 3492 otherwise eligible donors were disqualified because of their answers on the questionnaire. Forty-five of these 72 agreed to be tested serologically, and 2 were positive for T. cruzi antibodies. One of six autologous blood donors tested also was positive for T. cruzi antibodies. We conclude that the questionnaire selected a subgroup of Latin Americans at high risk for T. cruzi infection. The deferral of these high-risk individuals clearly reduced the risk of transmission of T. cruzi by transfusion, without intolerably decreasing the supply of donated blood.

Blood Donors↗

The effect of methyldopa and procainamide on suppressor cell activity in relation to red cell autoantibody production.

Kirtland et al (1980) suggested that methyldopa caused the production of red cell (RBC) autoantibodies by causing a persistent increase in lymphocyte cyclic AMP, which inhibited suppressor T cell function, leading to unregulated autoantibody production in some patients. They showed that significantly higher lymphocyte cyclic AMP concentrations were generated by lymphocytes from healthy donors after adding methyldopa, and by lymphocytes from patients who were receiving methyldopa compared to lymphocytes from healthy donors without methyldopa present. They also showed that methyldopa affected suppressor cell activity. We measured the effect of methyldopa and procainamide on suppressor cell activity, using a similar approach to Kirtland et al (1980). Suppressor cell activity was measured by measuring the amount of IgG, produced in vitro, by B cells following mitogen stimulation preceded by a 24 h incubation period. We found no significant increase in the amount of IgG generated by normal donor lymphocytes, when methyldopa or procainamide was present during the preincubation period. This is in contrast to the findings of Kirtland et al (1980). We also measured the amount of IgG generated in vitro by mitogen-stimulated lymphocytes from patients (with and without positive direct antiglobulin tests) taking methyldopa and compared this to the amount of IgG generated by lymphocytes from normal donors and patients (with and without positive direct antiglobulin tests). The results were similar for each group. This does not agree with the findings of Kirtland et al (1980) who found that lymphocytes from patients taking methyldopa produced more IgG in vitro than lymphocytes from normal donors. Our results do not support the hypothesis that methyldopa and procainamide induce autoantibodies by affecting suppressor cell function.

Autoantibodies↗

Alanine aminotransferase levels in Hispanics.

To prevent posttransfusion viral hepatitis, screening of potential blood donors includes the measurement of serum alanine aminotransferase (ALT) levels. The current use of single system-wide ALT cutoffs to determine acceptability of a blood unit or donor may not be appropriate, since male and Hispanic blood donors have much higher rejection rates than other donors, based solely on ALT level. Serum ALT measurements from the Hispanic Health and Nutrition Examination Survey were used to confirm these ALT elevations within general population samples of Mexican Americans, Cubans, and Puerto Ricans. Until specific tests are available to detect all hepatitis viral infections, testing blood donors for ALT levels will likely continue. Health personnel should be cautious in their interpretation of "elevated" ALT levels in these Hispanic populations.

Adult↗

Effect of blood transfusion on serum iron and transferrin saturation.

The effect of transfusion of packed red blood cells on serum iron level, total iron-binding capacity, and transferrin saturation was studied. Samples of blood from 37 hemodynamically stable patients were obtained for analysis at various intervals following the transfusion of packed red blood cells. In 10 patients with possible iron deficiency, a significant rise in serum iron level and transferrin saturation occurred during the 24 hours following transfusion, which persisted at a marginally significant level up to 36 hours. In the remaining 27 patients, a significant rise was also noted in serum iron level and transferrin saturation results, but the rise did not persist beyond the 24 hours after transfusion. No change in total iron-binding capacity was noted in either group. These data show that the diagnosis of iron deficiency (based on a transferrin saturation of < 0.16) might be missed if iron studies are performed on patients within 24 hours following packed red blood cell transfusion. Therefore, if serum iron studies are obtained for patients suspected of having iron deficiency anemia, these studies are best done on blood samples obtained before blood transfusion.

Blood Transfusion↗

Safety in transfusion practices. Red cell compatibility testing issues.

Pretransfusion compatibility testing, if performed properly, helps to maximize the effectiveness of transfusion therapy and to minimize the risk of hemolytic transfusion reactions. Each laboratory should select the procedures and protocols that are best suited to meet their patient care and institutional needs. Quality assessment monitoring of the elements of compatibility testing helps to ensure a high level of safety for patients receiving transfusion therapy.

Antibodies↗

Inhibition of immunoglobulin production by parathyroid hormone. Implications in chronic renal failure.

Available data indicate that B cell proliferation is inhibited in chronic renal failure and this is due to excess blood levels of PTH. This defect may also affect immunoglobulin production. We examined production of IgG, IgM and IgA by B cells stimulated with Staphylococcus aureus Cowan I (SAC) or with pokeweed mitogen (PWM) after eight days of culture and evaluated the effect of PTH on this process in 34 hemodialysis patients and 44 normal subjects. IgG, IgM and IgA production by B cells from patients was lower (P less than 0.01) than by B cells from normal subjects. Both 1-34 and 1-84 PTH inhibited (P less than 0.01) immunoglobulin production by B cells from normal subjects and dialysis patients. However, this inhibitory effect was evident in dialysis patients only with the higher dose of PTH. The inhibition of immunoglobulin production by PTH occurred only when the hormone was added at the initiation of the B cell culture. Inactivation of PTH abolished its inhibitory effect on immunoglobulin production. Agents that stimulate cAMP production (forskolin, cholera toxin) and the cAMP analogue, 8-bromoadenosine 3',5' cyclic monophosphate inhibited immunoglobulin production by B cells from both normal and dialysis patients, and the degree of inhibition was not different between the two groups. The calcium inophore A23187 also inhibited IgG, IgA and IgM production by B cells from normal subjects and dialysis patients; there was no significant difference in the degree of inhibition between the two groups. The resting levels of cytosolic calcium in B cells of dialysis patients was significantly (P less than 0.01) higher than that of B cells from normal subjects. The data show that: (1) immunoglobulin production is impaired in dialysis patients; (2) B cells of dialysis patients have elevated resting levels of cytosolic calcium; (3) PTH inhibits IgG, IgA and IgM production and this effect is at least partly mediated by PTH-induced cAMP production and alterations in cytosolic calcium into B cells; (4) this inhibitory effect is mediated by events that affect initial stages of B cell proliferation and maturation; (5) the requirement for high dose of PTH for its inhibitory effect on B cells from dialysis patients is probably due to desensitization and/or down-regulation of PTH receptors on B cells. The results are consistent with the proposition that impaired immunoglobulin production by B cells from dialysis patients is at least partly due to the state of secondary hyperparathyroidism in these patients.

8-Bromo Cyclic Adenosine Monophosphate↗

Transmission of parasitic and bacterial infections through blood transfusion within the U.S.

The American public has become aware that viral infections can be transmitted by blood transfusions; however, less attention has been paid to nonviral agents that are similarly transmitted. Although donors are tested routinely for serologic evidence of Treponema pallidum infection (syphilis), there are no other bacterial infections for which donors are routinely tested, and no testing is done routinely to detect parasitic infections. Although current preventive strategies appear effective in preventing the transmission of nonviral agents by transfusion, changing population demographics, increased travel and immigration, and increased occurrence of certain asymptomatic bacterial infections in blood donors may require new policies to maintain the safety of the U.S. blood supply. This review focuses on the parasitic and bacterial infections that might pose a risk to transfusion recipients in the U.S.

Babesiosis↗

The sensitivity of antibody detection testing using pooled versus unpooled reagent red cells.

Because the sensitivity of antibody detection testing may be reduced when pooled reagent red blood cells (RBCs) are used, the American Association of Blood Banks (AABB) prohibits the use of pooled reagent RBCs when performing pretransfusion antibody detection testing. This restriction imposed upon the use of pooled reagent RBCs is based, at least in part, on the belief that pooled reagent RBCs are less likely to detect clinically significant antibodies than are sets of unpooled reagent RBCs. Little data, however, have been published to support this contention. In the present study, the data show a decreased sensitivity for antibody detection when pooled reagent RBCs are used. This reduced sensitivity could result in failure to detect some clinically significant RBC alloantibodies, which might result in the occurrence of overt hemolytic transfusion reactions, especially if an indirect antiglobulin test is not performed at the time blood is crossmatched.

Journal Article↗

Storage of thawed cryoprecipitated AHF is better at room temperature than at 1 degree C to 6 degrees C for factor VIII content.

Before November 1989, both the American Association of Blood Banks and the Food and Drug Administration required that thawed cryoprecipitated antihemophilic factor (AHF) should be used immediately or be stored at room temperature and administered within 6 hours. However, in November 1989, the American Association of Blood Banks changed the requirement for storage of thawed cryoprecipitated AHF from room temperature to 1 degree C to 6 degrees C, while the Food and Drug Administration still required thawed cryoprecipitated AHF to be stored at room temperature. The present study was designed to measure and compare the factor VIII activity in 10 bags of thawed cryoprecipitated AHF that were split into aliquots and stored at room temperature and at 1 degree C to 6 degrees C. At 6 and 24 hours after thawing, the mean factor VIII activities (% of normal) of the room temperature-stored cryoprecipitated AHF were 741% and 680% vs 650% and 608% for the 1 degree C- to 6 degrees C-stored cryoprecipitated AHF (P less than .05 at 6 hours and P = .11 at 24 hours). The storage of thawed cryoprecipitated AHF at 1 degree C to 6 degrees C also resulted in precipitation of both factor VIII and fibrinogen. These data show that it is better to store thawed cryoprecipitated AHF at room temperature vs 1 degree C to 6 degrees C for factor VIII activity. These data also suggest that adequate levels of factor VIII are maintained in thawed cryoprecipitated AHF that has been stored at room temperature for up to 24 hours.

Chemical Precipitation↗