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Biomedical subjects

I A Shulman

Publications and source records attributed to I A Shulman.

At least 19 recordsLinked to original sources

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

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

When should antibody screening tests be done for recently transfused patients?

The American Association of Blood Banks (AABB) requires that blood samples used for pretransfusion testing of recently transfused (or pregnant) patients must be obtained within 3 days of scheduled transfusions. This requirement, which became effective in July 1988, amended Standard G2.000 of the AABB, which previously required that pretransfusion testing must be done on blood samples obtained within 2 days of scheduled transfusions. The present study was designed to estimate the risk associated with adopting the amended version of Standard G2.000. Sixty patients who developed significant unexpected alloantibodies after transfusion were studied retrospectively. Thirteen of the 60 patients were found to have newly detectable antibodies within 83 hours of a sample reported to be negative for the new antibody. Had the amended version of Standard G2.000 been in effect, the detection of some of these antibodies might have been delayed up to 24 hours. It was estimated that the implementation of the new AABB requirement at the authors' institution could potentially place about 1 in 3000 transfused patients at risk for an acute or delayed hemolytic transfusion reaction.

Blood Group Incompatibility

The impact of screening a heterogeneous donor population for alanine aminotransferase and hepatitis B core antibody. Experience at a large southern California hospital.

To reduce the transmission of non-A, non-B (NANB) hepatitis, the American Association of Blood Banks (AABB) has recommended that donors be screened for elevated levels of alanine aminotransferase (ALT) and for the presence of antibody to hepatitis B core antigen (anti-HBc). In this survey of 5,336 donors, the authors report the impact of using both of these surrogate tests on a heterogeneous donor population that was composed of white, black, Hispanic, and Asian donors. Hispanic and male donors had relatively high ALT levels, and black and Asian donors had a higher prevalence of anti-HBc than their respective counterparts. The overall impact of using both surrogate tests resulted in a discard rate of 12.1% with a disproportionately high percentage of Hispanic and male donors excluded because of ALT testing and black and Asian donors because of anti-HBc testing. It appears that surrogate testing has a much greater impact on blood collection facilities that rely considerably on Hispanic, Asian, black, or male donors than those that largely draw white or female donors.

Black or African American

The risk of bacterial growth in units of blood that have warmed to more than 10 degrees C.

Most transfusion services discard unopened units of blood that have been returned to the blood bank more than 30 minutes after the issuance or have attained a temperature of more than 10 degrees C. The objective of this study was to learn the prevalence of bacterial growth, if any, in the units of blood that were exposed twice, for six hours each time, to room temperature during their refrigerated storage. All of the 396 units cultured were negative except one red cell unit that grew a Bacillus species, probably B. subtilis. Further studies suggested that the growth of B. subtilis was due to laboratory contamination. The authors concluded that more work is needed to study the bacterial growth and the effect on red cell enzymes in the units of blood that are exposed to room temperature for varying periods or are returned to the blood bank after 30 minutes of issuance. If no adverse effect is noted, the policy of not reissuing such units may need revision so that more units could be salvaged.

Bacteria

Can storage of thawed cryoprecipitate be extended to more than six hours?

Fresh-frozen plasma (FFP) and cryoprecipitate both contain Factors I and VIII, however thawed FFP may be stored at 1-6 degrees C for 24 hours, but thawed cryoprecipitate may only be stored at 1-6 degrees C for six hours when used for Factor VIII content. To determine whether it would be safe and effective to extend the storage period of thawed cryoprecipitate from 6 to 24 hours, Factor VIII (and fibrinogen) levels were measured in 25 units of cryoprecipitates immediately on thawing and at 6 hours and 24 hours thereafter. The Factor VIII activity level decreased to 86% of the original activity level within 6 hours, but the drop between 6 and 24 hours was relatively small. Eighty percent of the original activity was still present at 24 hours after thawing. The fibrinogen level decreased to 87% of the original level within 6 hours but remained stable between 6 and 24 hours. Additional testing showed that fibrinogen levels remained stable between 6 and 74 hours. These data suggested that the storage of thawed cryoprecipitate might be extended to 24 hours when this blood product is used for Factor VIII content and to 74 hours when it is used for fibrinogen content. Furthermore, the lack of prohibition on the use of cryoprecipitate that has been thawed for more than six hours and stored at 4 degrees C for its fibrinogen content seems reasonable.

Blood Preservation

Immune hemolytic anemia associated with biclonal cold autoagglutinins.

A 65-year-old man with bladder outlet obstruction due to prostatic hypertrophy was incidentally discovered to have cold-antibody autoimmune hemolytic anemia (cold-aggluthinin syndrome; CAS) due to autoanti-I (titer 1,024 at 4 degrees C and 64 at 30 degrees C), and a biclonal gammopathy. Immunofixation electrophoresis of serum and a red blood cell eluate revealed the patient's autoantibody to be biclonal IgM kappa and IgA kappa. No underlying cause could be determined to explain the development of either the biclonal gammopathy or the CAS. To our knowledge, this is the first reported case of CAS associated with a biclonal gammopathy and biclonal cold autoagglutinins of the IgM kappa, IgA kappa type.

Aged

Autoanti-Ge associated with severe autoimmune hemolytic anemia.

Severe autoimmune hemolytic anemia due to anti-Ge is described. The patient's red cells had a positive direct antiglobulin test, and they typed as Ge+ using saline reactive reagents. Anti-Ge was eluted from her RBCs, and her serum had an IgG and IgM anti-Ge2,3.

Adult

The risk of an overt hemolytic transfusion reaction following the use of an immediate spin crossmatch.

The major crossmatch must include an anti-human globulin test, unless the transfusion recipient has no apparent significant unexpected antibodies, in which case the use of only an immediate spin crossmatch method is considered acceptable. However, a minority of laboratories utilize only an immediate spin crossmatch as their routine major crossmatch, possibly because contemporary antibody screening tests occasionally miss detecting some unexpected antibodies, and these missed antibodies are more often detected by the anti-human globulin crossmatch than by the immediate spin crossmatch. In the present study, 20 hospitals were surveyed to determine how often an acute hemolytic transfusion reaction would occur when only an immediate spin crossmatch was used as the major crossmatch method. During the study period, 1.3 million immediate spin crossmatches were performed, and five patients experienced acute overt hemolytic transfusion reactions that were believed to be caused by antibodies that were missed by both the antibody screening test and immediate spin crossmatch (one hemolytic event per 250,000 immediate spin crossmatches). The implicated antibodies were anti-Jka, anti-Wra, anti-C, anti-c, and anti-Kpa. These survey data demonstrate that the routine crossmatching of blood using an immediate spin crossmatch may rarely result in an acute hemolytic transfusion reaction if the antibody screening cells used during pretransfusion compatibility testing fail to detect some clinically significant red blood cell antibodies.

Blood Group Incompatibility

Compatibility of ADSOL-stored red cells with intravenous solutions.

Five percent dextrose in water (D5W) and lactated Ringer's (RL) are two intravenous solutions that are incompatible with citrate phosphate dextrose (CPD) anticoagulated RBCs. Hemolysis, agglutination, and clotting can occur when RBCs are mixed with, infused together with, or transfused in the same line following administration of these fluids. Although minimal plasma remains in units of RBCs containing adenine-saline-dextrose solution (ADSOL; Fenwal Laboratories, Deerfield, IL), clots are seen immediately after contact is made with RL. Clumping and hemolysis are seen when ADSOL-stored RBCs or saline-washed RBCs are mixed with D5W. This study reinforces the unsafe practice of mixing RBCs with certain intravenous solutions.

Adenine

The sensitivity and specificity of the immediate-spin crossmatch.

The immediate-spin (IS) crossmatch is used to detect ABO incompatibility between donor red cells (RBCs) and the serum of the intended recipient. However, this test may be positive in the absence of ABO incompatibility (false positive) or it may be negative when ABO incompatibility exists (false negative). During a 25-month study, the rates of both false-positive and false-negative IS crossmatch results were evaluated, and the sensitivity and specificity of the IS crossmatch were determined. During the study period, 53,656 IS crossmatches were performed for patients without significant RBC antibodies. Fifty-five patients had positive IS crossmatches, and no false-negative reactions were found. In tests of 55 patients with positive IS crossmatches, 77 false-positive and 5 true-positive reactions were noted. The causes of the false-positive reactions were rouleaux (36 patients), cold-reactive antibodies (8 patients), a combination of rouleaux and cold-reactive antibodies (2 patients), fibrin clot (1 patient), and undetermined (3 patients). The sensitivity and specificity of the IS crossmatch were 100 and 99.86 percent, respectively. Laboratory personnel should be aware that the IS crossmatch may have false-positive or false-negative results, and they should develop written protocols to distinguish quickly between true-positive and false-positive reactions.

ABO Blood-Group System

A review of donor alanine aminotransferase testing. Implications for the blood donor and practitioner.

To reduce the incidence of post-transfusion non-A, non-B hepatitis, the American Association of Blood Banks has required that serum alanine aminotransferase activity be used to screen blood donors. Consequently, approximately 2% to 3% of all blood donations will be discarded owing to an elevated alanine aminotransferase level. In addition, approximately 0.7% of blood donors will be notified of an abnormal alanine aminotransferase result. While some of these donors may have viral hepatitis, factors such as the donor's age, gender, body weight, ethnic background, alcohol intake, diet, and exercise must also be considered when interpreting an elevated alanine aminotransferase level. Donors with significant or persistently elevated alanine aminotransferase levels should have their conditions evaluated so that treatable diseases can be recognized and/or treated.

Alanine Transaminase

Adverse reactions to blood transfusion.

The transfusion of whole blood and blood components is usually a temporarily effective means of correcting red cell, white cell, platelet, and coagulation factor deficits. Unfortunately, blood and blood components are occasionally unavoidably unsafe, which results in a spectrum of adverse reactions following transfusion. These reactions may be immunologically or nonimmunologically mediated, and may vary in severity from mild to fatal. Physicians should weigh the potential risks versus the potential benefits of each blood transfusion. Only when the benefits clearly outweigh the risks should a blood transfusion be administered. Transfusionists must carefully monitor each blood transfusion for signs and symptoms of transfusion reactions in order to minimize their adverse effects.

Humans

Blood transfusion in medically treatable chronic anemia. Pernicious anemia as a model for transfusion overuse.

Transfusion practice in patients with treatable, readily recognizable, chronic anemia was reviewed because such patients only infrequently need to be transfused. Pernicious anemia with hemoglobin concentration below 100 g/L was chosen as the model for this assessment. Sixty-two (51%) of 122 patients received blood transfusion, although most patients had chronic, low-grade symptoms despite their low hemoglobin levels and could have been satisfactorily managed without transfusion. Only 34 of the 122 had findings suggesting an urgent need to raise the blood cell count, but their transfusion rate (44%) was no different from that in patients without such findings. These observations in pernicious anemia indicate that transfusion of patients with medically reversible anemia is a common problem. They further suggest that current transfusion usage overemphasizes laboratory results (ie, hemoglobin levels) at the expense of clinical assessment of severity of symptoms. Improvement of current practice is needed, particularly in view of valid concerns about the serious side effects of transfusion, shortages of available blood resources, and health care costs.

Adolescent

Safety in transfusion practice. Is it safe to eliminate the major crossmatch for selected patients?

If a patient has no clinically significant unexpected antibodies, a major crossmatch is not required prior to blood transfusion so long as a test method that demonstrates ABO incompatibility is done. In this study, the safety of using a noncrossmatch method for detecting ABO incompatibility was compared with the use of an immediate spin crossmatch (ISCX). This noncrossmatch method consisted of the duplicate ABO testing of blood recipients, the repeated ABO testing of donor blood, and a clerical check to assure that only ABO matched or compatible blood was selected for transfusion. During the one-year study, 7124 patient samples were tested in duplicate for ABO, 26,942 U of red blood cells received from blood collection facilities were retested for ABO, and 23,962 U of blood selected for transfusion based on the noncrossmatch method were tested by an ISCX. ABO test results were concordant for 7115 of 7124 patient samples and discordant for nine. Seven of the nine discordant patient test results were resolved prior to transfusion, and two were inadvertently overlooked. ABO test results were concordant for 26,922 of 26,942 donor units and discordant for 20. Seventeen of the 20 discordant donor test results were resolved prior to transfusion and three were inadvertently overlooked. Two ABO incompatibilities were missed by the noncrossmatch method but were detected by the ISCX. Unless clerical errors can be totally eliminated, it may be safer to retain the ISCX.

ABO Blood-Group System