Immunosuppressive protocols for transplantation and certain hematologic malignancies can prevent the primary immune response to the D blood group antigen.

A review of the published literature on Rh alloimmunization reveals that its incidence varies with the volume of infused D+ red blood cells (RBCs), the probable Rh genotype of the RBCs, and the immune competency of the D- recipient. Among the reports of Rh alloimmunization on different clinical circumstances, we identified five studies in which a combined total of 62 D- recipients of hematopoetic stem cell or solid -organ transplants were transfised with D+ RBCs and none (0%) formed anti-D. The observation that immunosuppressive protocols developed to prevent rejection of tissue and organ transplants also prevented alloimmunization to the D blood group antigen raises the possibility of practical applications in blood transfusion practice.

Nonhemolytic passenger lymphocyte syndrome: donor-derived anti-M in an M+ recipient of a multiorgan transplant.

Passenger lymphocyte syndrome (PLS) is a well-recognized complication that may follow a hematopoietic progenitor cell or solid-organ transplant. Typically, the syndrome presents as acute hemolysis of the recipient's RBCs, which have become serologically incompatible with blood group antibodies formed by passively transfused donor-origin B lymphocytes. Most cases involve anti-A or anti-B. However, there are cases involving non-ABO serologic incompatibility, as well as cases in which the serologic incompatibility was not associated with clinical evidence of hemolysis. This report describes a case of passenger lymphocyte syndrome in an M+ recipient who developed anti-M after receiving a multiorgan transplant from an M- cadaver donor. Although the temporal events and serologic findings were consistent with a diagnosis of PLS, there was no evidence of in vivo hemolysis associated with the identification of a newly formed anti-M. This report includes a literature review of other case reports of PLS associated with non-ABO antibodies in solid-organ and hematopoietic progenitor cell transplant recipients.

Bar code technology improves positive patient identification and transfusion safety.

As a result of human error, an estimated 1 in 12,000 blood transfusions is given to the wrong patient. The cause of nearly all of these errors is failure of hospital personnel to identify positively intended transfusion recipients, their blood samples for cross-matching, or their correct blood components. We describe our experience using a point-of-care bar code transfusion safety system that links patients' bar-coded wristbands, with bar-coded labels on blood sample tubes, blood component bags, and nurses' identification badges. The result was 100 % accuracy of matching patients, their blood samples, and components for transfusions. For verifying information before starting blood transfusions, nurses preferred bar code "double checks" to conventional visual "double checks" by a second nurse. Methods are needed to reinforce nurses' proficiency with technological approaches to transfusion safety, such as software-driven bar code scanning, in situations where transfusions are administered infrequently.

Platelet transfusions: utilization and associated costs in a tertiary care hospital.

We implemented a prospective study to evaluate platelet transfusion utilization, resource use, and costs in a tertiary care hospital over a 6-month period. All hospitalized patients receiving platelet transfusions between July and December 1996 were followed prospectively to determine platelet use and costs. Clinical and financial data were collected, evaluated, and compared to identify trends in resource utilization based on admitting service and platelet-refractory status. One thousand nine hundred forty-four platelet units were transfused to 245 hospitalized patients (50.6% male, mean age 49 years) during the study period. The majority of platelet units transfused were single donor (N = 1,460, 75%) and administered to bone marrow patients and patients with a hematological malignancy/disorder. Median hospitalization costs per admission were $27,750, ranging from a high of $58,729 for admission to the Bone Marrow Transplant service to $13,856 per admission to the Internal Medicine/Other service. Patients were refractory to platelet transfusions during 21.6% of hospitalizations. Hospital stays were longer (35.0 days vs. 14.4 days, P < 0.001) and inpatient hospital costs ($103,956 vs. $37,817, P < 0.001) were more than two and a half times higher for patients refractory to platelet transfusions. Platelet utilization, resource use, and costs vary by admitting service. Refractoriness to platelet transfusion was associated with significantly greater costs and lengths of stay. Monitoring platelet transfusion practices, particularly for patients refractory to platelet transfusions, may be beneficial for limiting costs and improving efficacy.

Management of patients with hematologic malignancies and aplastic anemia who are refractory to platelet transfusions.

Patients with hematologic malignancies or aplastic anemia may have reduced responses to platelet transfusions after multiple transfusions of standard red blood cells or platelet components. This situation, conventionally described as 'refractoriness' to platelet transfusions, may result from immune or non-immune causes. Non-immune causes include fever, infections, hypersplenism, disseminated intravascular coagulation, antibiotics, or veno-occlusive disease. Immune causes include platelet-reactive alloantibodies, which are typically antibodies to human leukocyte antigens (HLA) or, less commonly, antibodies to human platelet antigens (HPA). Transfused HLA-matched platelets often have satisfactory posttransfusion survivals, but few transfusion services have the donor and logistical resources to sustain a prolonged course of platelet transfusions requiring four-antigen matches. The availability of commercially marketed kits for crossmatching samples of potential donors' platelets with a recipient's serum has facilitated donor-recipient matching. Also, platelet crossmatching may be used to select a suitable unit of from several candidates platelets that have been identified to be partial HLA matches. The high likelihood of decreased efficacy of platelet transfusions in HLA-alloimmunized recipients makes avoidance of exposure to HLA-bearing leukocytes a priority. This goal is facilitated by lowering transfusion 'triggers' for cellular blood components, particularly for prophylactic platelet transfusions, by reducing the leukocyte content of components by leukocyte-reduction filters and, possibly by ultraviolet-B irradiation of leukocyte-containing products.

Immunoprophylaxis using intravenous Rh immune globulin should be standard practice when selected D-negative patients are transfused with D-positive random donor platelets.

A 67-year-old female developed excessive bleeding and thrombocytopenia following cardiovascular surgery. Her blood type was group A, D-. The only platelet products available in the transfusion service were random donor platelet concentrates from D+ donors. She was transfused with a pool of 6 D+ random donor platelet concentrates. Anti-D undetected in her pretransfusion serum by solid-phase antibody screen was present 11 days later. Retrospectively, the patient provided a history of having two pregnancies more than 40 years ago, prior to the availability of immunoprophylaxis by Rh immune globulin (RhIG). Although studies have shown that as many as 19 percent of D- people may develop anti-D following transfusion of platelets from D+ donors, there is no specific standard requiring immunoprophylaxis with RhIG to prevent Rh alloimmunization after transfusion of random donor platelet concentrates from D+ donors. In contrast, vigorous efforts are routine for preventing Rh alloimmunization in D- patients requiring red cell transfusions or D- females during pregnancy or after delivery of D+ newborns. The absence of a comparable practice standard for platelet transfusions is based, in part, on concern that intramuscular injections of conventional RhIG may cause local hemorrhage in thrombocytopenic persons. The recent availability of a Food and Drug Administration-approved preparation of intravenous RhIG makes Rh immunoprophylaxis in thrombocytopenic patients safe and practical. We recommend that intravenous RhIG be considered if it is necessary to transfuse random donor platelet concentrates from D+ donors to D- recipients. As a minimal standard, intravenous RhIG should be administered to all D- females of childbearing age who are recipients of pools of random donor platelet concentrates from D+ donors.

Carboplatin-induced immune hemolytic anemia.

BACKGROUND: A case of acute hemolysis following therapy with carboplatin, an anticancer chemotherapeutic agent, was investigated. Hemolytic anemia has been associated with cisplatin, a related drug, but not with carboplatin. CASE REPORT: An 8-year-old boy was treated for an astrocytoma by monthly intravenous injections of carboplatin. Lower back pain was noted after 26 monthly injections, and overt intravascular hemolysis occurred after the 27th injection. The direct antiglobulin test was 4+ with anti-IgG and 1+ with anti-C3d. RESULTS: Blood samples obtained on Days 28 and 56 after the last injection were tested for carboplatin-dependent antibody. The direct antiglobulin test was 1+ with anti-IgG; the eluate was 1+ with and without carboplatin. The serum indirect antiglobulin test was negative in the absence of carboplatin, 3+ to 4+ in the presence of carboplatin, and 1+ with carboplatin-coated cells. Day 56 serum antibody titer was 64 (agglutination at 37 degrees C), 512 (indirect antiglobulin test) in the presence of carboplatin, and 8 (indirect antiglobulin test) with carboplatin-coated cells. CONCLUSION: The findings indicate a carboplatin-induced antibody reacting in vitro by a complex mechanism combining elements of "immune complex," drug adsorption, and autoantibody mechanisms. Drug-dependent hemolysis is a previously unreported but potentially serious complication of carboplatin therapy.

Pooling blood donor samples to reduce the cost of HIV-1 antibody testing.

Accurate, low cost testing of donated blood is a goal of the global effort to reduce the spread of the human immunodeficiency virus (HIV-1). We describe a modified enzyme immunoassay (EIA) method for detecting HIV-1 antibody (anti-HIV-1) in 15-sample pools. In this preliminary study, the modified EIA was as sensitive for detecting weakly seropositive samples, and as specific for testing HIV-1 Western blot-negative or Western blot-indeterminate results, as testing individual samples by the standard EIA. A simulation of field operations was conducted using pools of blood donor samples collected in the United States and in Shanghai, People's Republic of China. Implementation of the modified EIA method and testing 15-sample pools for anti-HIV-1 is a reliable strategy for reducing the cost of large scale testing of donated blood for anti-HIV-1 in areas of low seroprevalence.

IgA anaphylactic transfusion reactions.

IgA anaphylactic transfusion reactions are rare events, estimated to occur in 1 in 20,000 to 47,000 transfusions. The signs and symptoms of these reactions do not differentiate them from other causes of anaphylaxis. The diagnosis of an anaphylactic transfusion reaction is established by showing an IgA-antibody in the patient's serum. Most laboratories that test for IgA antibodies rely on the PHA method, which uses red blood cells that are coated with serologically defined IgA multiple myeloma proteins. We tested sera referred from Red Cross regional blood centers and hospitals from patients with suspected IgA anaphylactic reactions and found an IgA antibody in 76.3% of IgA-deficient patients. However, only 17.5% of all samples referred contained an IgA antibody, indicating that most persons with suspected IgA anaphylactic reactions had experienced acute generalized reactions that were from causes other than anti-IgA transfusion. Using PHIA to measure serum concentrations of IgA and PHA to detect IgA antibodies, we found the frequency of IgA deficiency (< 0.05 mg/dL) and class-specific anti-IgA in random blood donors to be approximately 1 in 1,200. Titers of anti-IgA did not distinguish these seemingly healthy blood donors from patients with a history of an anaphylactic transfusion reaction. Because the frequency of 1 in 1,200 greatly exceeds the observed frequency of anaphylactic reactions in transfused persons, we conclude that using PHA for anti-IgA does not reliably predict risk for an anaphylactic transfusion reaction. Additional research is needed to define a more specific marker to identify those persons who are truly at risk for these serious, but rare, complications of blood transfusion.

Human T-lymphotropic virus type II in Panamanian Guaymi Indians.

BACKGROUND: Currently, human T-lymphotropic virus type II (HTLV-II) is the most prevalent human retrovirus, detected in persons presenting to donate blood in the United States. Only scant information is available with which to counsel HTLV-II-seropositive deferred donors or other persons about the ways in which they may spread HTLV-II to others. STUDY DESIGN AND METHODS: To increase understanding of the modes of transmission of HTLV-II, a seroepidemiologic study was conducted among Panamanian Guaymi Indians, a recently identified focus of endemic HTLV-II infection. Subjects were tested for serologic evidence of infection by HTLV-II, HTLV type I, hepatitis B virus, and nine other infectious agents by enzyme immunoassays and specific confirmatory tests. RESULTS: Nine (8.3%) of 109 persons tested HTLV-II-seropositive. HTLV-II seropositivity was more likely in persons with serologic evidence of prior hepatitis B virus infection. Sexual contact with HTLV-II-seropositive partners, but neither parenteral exposure nor breast-feeding, was identified as a risk factor for HTLV-II. CONCLUSION: In Guaymi Indians, HTLV-II appears to be spread primarily through sexual transmission.

Immune-mediated hemolysis in a postoperative patient Case report: anti-U and differential diagnosis.

We present the differential diagnosis for a Coombs-positive immune hemolysis having onset during hospitalization and, in particular, during the postoperative period. The stimulus for this article was a delayed hemolytic transfusion reaction (DHTR) due to anti-U following open-heart surgery. The initial clinical and serologic findings led us to consider other causes of immune hemolysis which are reviewed in this article. To our knowledge, this is the fourth case of a DHTR due to anti-U to be reported in the medical literature.

An analysis of 9,918 consecutive perioperative autotransfusions.

The efficacy of perioperative autotransfusion (PAT) can be evaluated by the reduction in homologous transfusion accompanying its use. An alternative approach is to evaluate the amount of blood salvaged and retransfused. An analysis of 9,918 consecutive PAT procedures in various surgical specialties revealed that the average return of autologous blood salvaged was equivalent to 2.61 units of erythrocytes ("packed cells"). Cardiac operation had the greatest average number of units recovered (4.65), while orthopedic operation had the least (1.05). This method of analysis demonstrates that significant quantities of blood can be salvaged during PAT procedures.

Human T-cell lymphotropic virus type I and II in transfusion medicine.

As a consequence of migrating populations, IV drug use and, to a lesser extent, blood transfusions, endemic HTLV-I and HTLV-II infections have spread to nonendemic geographic regions. Although the risk that a person infected with HTLV-I will develop significant disease--even over a lifetime--is estimated to be relatively low, our awareness of the serious diseases associated with other retroviruses requires a cautious approach to blood transfusion. Reports from Japan and the United States indicate that programs testing donated blood and excluding units with HTLV-I antibodies have been highly successful in interrupting the spread of HTLV-I by transfusions. One unanticipated outcome of testing large numbers of people in the United States for HTLV-I antibodies has been recognition of the relatively high prevalence of HTLV-II infection, particularly among IV drug users. The long-term effects of HTLV-II infection are also unknown. Until the natural history and clinical consequences of HTLV-II infection are clearly understood, it is only prudent that blood donated by persons identified to be HTLV-II carriers also be excluded.

Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors--an assessment of the efficacy of testing in donor screening. The HIV-Antigen Study Group.

BACKGROUND: We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. METHODS: More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. RESULTS: Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three of the antigen-positive donors had other markers of infectious disease that would have resulted in the exclusion of their blood; two had risk factors for HIV-1 that should have led to self-exclusion. Of 220 blood units with repeatedly reactive p24 antigen whose presence could not be confirmed by neutralization (0.04 percent of the donations studied), none were positive for HIV-1 antibody, HIV-1 by polymerase chain reaction (120 units tested), or virus culture (76 units tested)--attesting to the specificity of confirmatory neutralization. CONCLUSIONS: The finding that no donation studied was positive for p24 antigen and negative for HIV-1 antibody suggests that screening donors for p24 antigen with tests of the current level of sensitivity would not add substantially to the safety of the U.S. blood supply.

Retroviral infections transmitted by blood transfusion.

Modifications in donor screening and the introduction of laboratory testing of donated blood for anti-HIV-1 and anti-HTLV-I have resulted in a significant reduction in the risks of retroviral infections from blood transfusion. Presently, the American Red Cross detects an average of eight carriers of human immunodeficiency virus, type 1 (HIV-1) per 100,000 otherwise acceptable blood donors (0.008 percent), compared with an average of 35 per 100,000 (0.035 percent) when testing for HIV-1 antibodies began in 1985. Surveillance studies in the United States indicate a small likelihood that HIV-2 carriers will pass current screening procedures and be accepted as blood donors. Even if an HIV-2-infected person were to be accepted as a blood donor, there is a 42-92 percent likelihood that this person's blood would be detected as infective for HIV-2 and excluded because of serological cross-reactions that occur in the EIA for HIV-1 antibodies. During 1989, which was the first year that donated blood was routinely tested for antibodies to human T-lymphotropic virus, type I (HTLV-I) in the United States, approximately nine in 100,000 donors (0.009 percent) were confirmed positive for antibodies to HTLV-I, and their donated blood was excluded. Subsequent testing has revealed that a significant number of these persons whose sera was reactive by the HTLV-I EIA were, in fact, infected by HTLV-II. Epidemiological studies of human retroviral infections (HIV-1, HIV-2, HTLV-I, and HTLV-II) continue to provide important data and direction for improving criteria for qualifying blood donors.

Intraoperative autotransfusion in cardiac operations. Effect on intraoperative and postoperative transfusion requirements.

The Southern Arizona Regional Red Cross Blood Program, in cooperation with two cardiac surgery groups, examined the effect of intraoperative autotransfusion on red cell, plasma, and platelet usage during and after cardiac operations. The study evaluated whether intraoperative autotransfusion influenced intraoperative or postoperative blood usage and whether regular use was more effective than selective use. The study demonstrated that intraoperative autotransfusion reduces intraoperative and postoperative blood use and that regular use of intraoperative autotransfusion is more effective than selective use.

Seroprevalence and epidemiological correlates of HTLV-I infection in U.S. blood donors.

Screening for human T-lymphotropic virus type I (HTLV-I) antibodies was performed on sera from 39,898 blood donors at eight blood centers in geographically distinct areas of the United States. Ten donors (0.025 percent) showed evidence of HTLV-I seropositivity by enzyme immunoassays; this was confirmed by protein immunoblot and radioimmunoprecipitation. Seroprevalence rates ranged from 0 to 0.10 percent at the locations sampled, with HTLV-I antibodies found predominantly in donors from the southeastern and southwestern United States. Matched case-control interviews and laboratory studies were performed on five seropositive women and two seropositive men who participated in an identity-linked collection of sera from a subset of 33,893 donors at six of the eight blood centers. Four of the women and both men are black; one woman is Caucasian. Four of the seven seropositive individuals admitted to prior intravenous drug abuse or sexual contact with an intravenous drug user. Sexual contact with native inhabitants of an HTLV-I endemic area was the only identified risk factor for one male. The distribution of HTLV-I antibodies in this U.S. blood donor sample corroborates the previously reported epidemiology of this agent and suggests that additional donor screening measures, including the testing of donated blood for HTLV-I markers, may be necessary to prevent the spread of HTLV-I to transfusion recipients.

Detection of antibodies to human T-lymphotropic virus type 1 (HTLV-1).

Sera from 39,898 blood donors were tested for HTLV-1 antibodies using two enzyme immunoassays (EIA). Sera testing initially reactive (IR) were retested in duplicate by both EIAs. Sera testing repeatedly reactive (RR) were further tested by two Western blots (WB) and by two radioimmunoprecipitation assays (RIPA). There were 176 (0.44%) EIA IR and 68 (0.17%) RR results. On WBs, 10 of the 68 EIA RR sera demonstrated reactivity to HTLV-1 gag gene-encoded core protein p24, with or without reactivity to other core proteins (p19, p28, p53/55). These ten sera were the only ones demonstrating reactivity on RIPAs to other HTLV-1 gene products - env gene-encoded glycoproteins gp46, gp61/68, or tat gene-encoded HTLV-1 transcriptional activator p40x. These ten sera were interpreted as positive for HTLV-1 antibodies. Of the remaining 58 EIA RR sera, 21 were negative by WBs and RIPAs, 37 sera demonstrated reactivity to various combinations of p19, p28, and p53/55, but not to p24 on WBs. These 37 sera were interpreted as "indeterminate", because they were negative by RIPAs. We conclude that: 1) EIA testing and WB/RIPA verification identified 10 (0.025%) HTLV-1 infected individuals among 39,898 low-risk blood donors; 2) anti-p24 may be a more sensitive and specific indicator of HTLV-1 infection than antibodies to p19, p28, or p53/55; and 3) presently, both WB and RIPA are needed to verify HTLV-1 EIA reactivity.

Hepatitis B core antibody (anti-HBc) in blood donors in the United States: implications for surrogate testing programs.

In order to evaluate the operational implications of excluding donated blood with antibody to hepatitis B core antigen (anti-HBc), the American Red Cross tested 107,473 voluntary blood donations for anti-HBc in 72 test sites during a 1-week period. The system-wide prevalence of anti-HBc was 2.60 percent, with a range of 0.55 to 6.38 percent, depending on geographic region. For the American Red Cross, which collects approximately one-half of the blood supply in the United States, excluding donated blood with anti-HBc would result in a loss of approximately 159,500 units during the first year.