Acute hemolytic transfusion reaction secondary to anti-Fy3

A hemolytic transfusion reaction due to anti-Fy3 is reported in an African American patient with no history of sickle cell disease. This 82-year-old African American woman received two units of RBCs for anemia (Hab 7 g/dL) on admission for a left hip fracture. On hospital Day 7, the patient underwent left hip endoprosthesis surgery; she received two units of RBCs on the second postoperative day due to Hb of 6.1 g/dL. Her urine was dark during surgery and postoperatively. Her posttransfusion plasma was red. Her Hb dropped from 8.4 to 6.4 g/dL over 24 hours after the transfusion. Her total bilirubin rose to 4.0 mg/dL, with and LDH value of 1558 U/L and a haptoglobin of 10.9 mg/dL. Both the antibody detection test and the DAT were positive. An anti-Fy3 was identified in the serum and in the eluate. To the best of our knowledge, this is the first case of acute intravascular hemolysis due to anti-Fy3 in a patient without sickle cell disease.     

Large-scale use of red blood cell units containing alloantibodies

Many transfusion services are reluctant to accept red blood cell (RBC) units containing antibodies. We evaluated the impact of accepting routine shipments of our region's inventory of alloantibody- positive RBC units over a 4-month period. All patients' samples received up to 30 days after transfusion of such units were evaluated for the presence of passively acquired antibody, and labor and reagent costs were determined. During the study period, we received 259 alloantibody-containing RBC units, and 253 of these were transfused to 187 patients. Follow-up samples were received on 99 of these 187 patients, and 10 of these patients had detectable passive antibody in posttransfusion antibody screening tests. Two patients had anti-C and -D and eight patients had anti-D. Due to our negotiation of a small discount for antibody-containing units and the use of 20 units based on labeled phenotype rather than antigen typing in our laboratory, we experienced a net savings of $3814 over the 4-month period. This savings was achieved despite some additional costs incurred, including costs of data entry and additional testing on patients' samples. We concluded that large-scale use of RBC units from donors with alloantibodies is safe and likely to have a minimal impact on a busy transfusion service's workload and costs. Furthermore, nationwide use of such units would help alleviate projected blood shortages.     

Recipient factors influencing red blood cell alloimmunization

Red blood cell (RBC) alloantibodies develop in a subset of individuals following exposure to non‐self RBCs through transfusion, pregnancy or other activities; these antibodies can lead to difficulty locating compatible RBCs, acute or delayed haemolytic transfusion reactions, or haemolytic disease of the newborn. Alloimmunization is underestimated due in part to antibody evanescence, the random nature of post‐transfusion antibody screens, fragmented medical care and the lack of widespread antibody registries. Factors that influence who will develop detectable alloantibodies are not well understood. Transfusion burden is one risk factor for alloimmunization, though many highly transfused individuals never form alloantibodies despite exposure to many RBC units (and many non‐self blood group antigens). Individuals with sickle‐cell disease (SCD) and myelodysplastic syndrome (MDS) are more likely to form RBC alloantibodies than most other patient populations. Individuals with rheumatologic and other forms of autoimmunity, though not chronically transfused, are also at higher‐than‐average risk of forming RBC alloantibodies. Inflammation, in a broad sense, is one common thread amongst these diagnoses associated with high prevalence rates of RBC alloimmunization. Reductionist murine models support some types of inflammation (including viral‐like stimuli) around the time of RBC exposure as being associated with an increased likelihood of alloantibody formation. Strategies other than transfusion avoidance or extended antigen matching beyond ABO/Rh would be beneficial to prevent new RBC alloantibody formation, especially in patients at highest risk.     

Fatal hemolytic transfusion reaction due to anti-Ku in a Knull patient

A fatal transfusion reaction due to anti-Ku in a Knull (Ko) patient is reported. The patient was transfused with 34 units of incompatible RBCs during 44 days of hospitalization. Apart from the first transfusion, all subsequent transfusions failed to raise the patient's Hb. No serum antibody was identified until he was transferred to another hospital for dialysis. A compatibility test demonstrated a weak antibody and autocontrol reacting at room temperature by a manual polybrene method. The antibody was considered to be a "cold agglutinin." A blood sample was sent to a reference laboratory where the patient was found to be Knull and the antibody was identified as anti-Ku.     

Analysis of the routine use of polyethylene glycol (PEG) as an enhancement medium

This study compared the performance of polyethylene glycol (PEG) and low-ionic saline solutions (LISS) as enhancement media for routine use in a large transfusion service. A PEG additive solution (PEG plus LISS) was compared to a LISS additive (LISS plus polymers) and to an albumin-indirect antiglobulin test (A-IAT). Fifty serum samples containing clinically significant alloantibodies and fifty samples without alloantibodies were tested. Following an acute hemolytic transfusion reaction (HTR) involving an anti-K that was not detected with LISS but was retrospectively found to be reactive with PEG, an additional 151 samples received for antibody screening were prospectively evaluated in parallel using PEG and LISS. PEG detected all clinically significant antibodies in the 50 previously tested samples, with mean reactivity scores greater than LISS or A-IAT. In the prospective study, PEG detected 35 clinically significant antibodies and 10 clinically insignificant antibodies, while LISS detected only 15 clinically significant antibodies and 33 clinically insignificant antibodies. PEG appears to increase detection of significant antibodies while decreasing detection of insignificant antibodies. PEG was therefore substituted for LISS as an enhancement medium and has been in routine use for 12 months, with no reported acute or anamnestic HTRs in 6,353 transfusions.     

Case report: atypical presentation of anti-Rg(a)

The Rodgers (Rg(a)) antigen is a plasma protein that binds to the red blood cell (RBC) membrane. About 2 to 3% of the transfusion-recipient white population lacks the antigen and can produce anti-Rg(a) antibody. We report the case of a 70-yr-old man who presented with a medical history of hairy cell leukemia and profound pancytopenia that required RBC and platelet (PLT) transfusions. The patient had received 2 units of RBCs and 4 PLT concentrate pools. He was typed as O Rh(D) positive, with positive reactions in all 3-screen cells using the polyethylene glycol (PEG) indirect antiglobulin test/IAT (anti-IgG). Three antibody identification panels were performed, which all proved to be negative. A direct antiglobulin test and an auto-control were run, which were also negative. Since further investigations were needed, the patient's blood sample was sent to a reference laboratory where anti-Rg(a) was identified. Since the percentage of antigen-positive cells in the red cell panel was low, crossmatch compatible units of RBCs were transfused with no discernible immediate or delayed transfusion reaction. This report should alert hospital transfusion service personnel to recognize that, although the panel cells are usually reliable for antibody identification purposes, they may not have the antigens that are present on the screening cells.     

Acute hemolytic transfusion reaction caused by anti-Coa

Coa is a high-frequency blood group antigen in the Colton blood group system expressed on red blood cells (RBCs) of approximately 99.8 percent of random persons. Anti-Coa has been reported to cause delayed hemolytic transfusion reactions, hemolytic disease of the newborn, and accelerated clearance of RBCs in vivo. Acute hemolytic transfusion reactions (AHTRs) have not previously been reported. A 58-year-old man was hospitalized for vascular surgery. Initial blood bank evaluation revealed anti-Fya. The patient received six units of RBCs during his initial hospitalization and developed anti-E. A subsequent sample was sent to the reference laboratory when all units of RBCs appeared incompatible. Additional studies, including alloadsorptions, revealed the presence of anti-E, anti-Fya, and an apparent warm autoantibody. One unit of least-incompatible RBCs was transfused during surgery. The patient had an increase in temperature. Hemoglobinuria and a decrease in hematocrit were also noted. Due to the clinical impression of an AHTR, the pre- and postreaction samples were reevaluated in the reference laboratory and demonstrated the presence of anti-Coa in both. Based on clinical and laboratory evaluation this patient appears to have had an AHTR due to anti-Coa. This is the first known reported case of an AHTR caused by anti-Coa.     

Hemolytic transfusion reactions due to anti-e+f detectable only by nonstandard serologic techniques

A patient was transfused with a total of 14 units of red blood cells (RBCs) over 33 days (January 14 to February 15) at two hospitals. Febrile transfusion reactions were noted on three occasions, and hemoglobinuria was seen twice. Alloantibodies were not detected in a sample dated February 14, following a transfusion reaction, and this sample was referred to the North London Blond Transfusion Centre. Further samples were also obtained from before and after all transfusions at both hospitals. The patient's RBCs typed as A, D+, probable Rh phenotype (cDE/cDE). The direct antiglobulin test was negative, and serum samples following the second transfusion were red/brown in color. Serologic investigations were inconclusive on all samples taken until February 13 (after the fourth transfusion). At this time, a weak anti-e reacting by manual polybrene technique and an anti-e+f reacting by two-stage papain technique were detected. The serum also contained potent HLA antibodies. The patient subsequently received leukocyte-depleted group A, cDE/cDE RBCs with out any untoward effect. This case demonstrates the importance of a complete transfusion history and emphasizes that alloantibodies detectable only by nonstandard techniques can be clinically significant.     

Intraepithelial eosinophils in esophagitis

Red blood cell alloantibody production was studied in 90 neonates who received a mean of 14.1 transfusions (range 2-35) from an average of 8.9 donors during the first three months after birth. Standard antibody detection procedures were done with the use of a selected red blood cell panel. No unexpected alloantibodies were detected. These findings suggest, at a 99% confidence level, that neonates do not make red blood cell alloantibodies in response to transfusion, indicating that repeated compatibility testing is probably unnecessary. Thus, following initial antibody screening and compatibility tests, further compatibility testing can be eliminated.     

Unappreciated risk factors for transplant patients: HLA antibodies in blood components

One of the more aggressive approaches in renal transplantation is the use of plasmapheresis (PP) and intravenous immunoglobulin to eliminate donor-directed human leukocyte antigen (HLA) alloantibodies. A potential complication of a PP protocol is iatrogenic hypocoagulability resulting from the removal of coagulation factors. To prevent bleeding, hypocoagulable patients may require transfusions with fresh frozen plasma (FFP) and/or cryoprecipitate (Cryo). Although HLA alloantibodies in these components have been linked to complications, such as transfusion-related acute lung injury (TRALI), whether they cause complications following transfusion into allograft recipients is unknown. The incidence of complications would be dependent, in part, upon the frequency of HLA alloantibodies in the various blood components. In this study, segments from 77 units of FFP, 66 units of Cryo, 106 units of packed red blood cells (RBCs), and 59 units of apheresis platelets (Plts) were tested for antibodies to HLA class I and class II antigens using FlowPRA, an HLA antigen-specific flow cytometric assay. On average, 22% of blood components tested contained HLA alloantibodies, tenfold greater than previously reported. This unappreciated frequency of HLA alloantibodies in blood components may pose a risk to transplant patients requiring transfusions by promoting allograft dysfunction or loss.     

Transfusion of multiple units of Js(b+) red blood cells in the presence of anti-Jsb in a patient with sickle beta-thalassemia disease and a review of the literature

Jsb is a high-frequency antigen. Anti-Jsb is a rare alloantibody, and its clinical significance is poorly documented. We report a case in which a 12-year-old boy of Nigerian descent with sickle beta- thalassemia presented with multiple alloantibodies, including a panagglutinin and acute chest syndrome, necessitating the emergent transfusion of five units of phenotype-similar, crossmatchincompatible RBCs, four of which were given during an exchange transfusion. The patient was later found to have anti-Jsb. In addition to routine serologic methods to study the patient's RBCs and plasma, a monocyte monolayer assay (MMA) was performed on the patient's samples obtained 2 and 9 days after transfusion of the Js(b+) RBCs to determine the potential clinical significance of the anti-Jsb. Various laboratory parameters including quantitative hemoglobin fraction analyses were used to monitor for increased RBC destruction. The MMA reactivity of the patient's anti-Jsb increased from 2.3 percent on day 2 after transfusion to strongly positive at 88 percent and 66.5 percent (with and without the addition of fresh serum) 1 week later. MMA reactivity of greater than 5 percent is associated with increased RBC destruction. There was no clinical or laboratory evidence of increased hemolysis above baseline. However, decreased RBC survival was suggested by the relatively brisk decrease of the HbA1 fraction after the transfusions. The current case and others reported in the literature suggest that anti-Jsb may have limited potential for causing overt hemolysis. However, in patients with underlying hematologic disease, even mildly increased RBC destruction may pose problems clinically,and thus transfusion of Js(b+) RBCs should be avoided. In emergent situations, the potential of adverse effects of transfusing incompatible units should be balanced against the risk of withholding transfusion. Family members, especially siblings, should be considered as potential designated donors for patients with antibodies directed against high-frequency antigens. Available reports on anti-Jsb in the literature are also reviewed.     

A case of severe hemolytic disease of newborn due to alloimmunization in primigravida

Red blood cell (RBC) alloimmunization which is the production of antibodies in response to foreign red cell antigen(s) may occur through exposure to cells or tissues from a genetically different member of same species via transfusion, transplantation or pregnancy. It may cause hemolytic disease of fetus and newborn (HDFN). Usually the incidence of HDFN due to irregular erythrocyte antibody is rare in primigravida. Here we report a primigravida pregnant woman who developed multiple alloantibodies and the neonate developed severe HDFN. A 36-year-old primigravida pregnant woman who had no history of significant medical issues except surgery done for severe endometriosis 1 year back and she had no history of previous blood transfusion presented to us for delivery. The antibody screening came out to be positive with a reaction in cell I and cell II of the antibody screening panel. Further, a mixture of anti D + anti C + anti E alloantibodies were identified using 16 cells panel, select cells and red cell phenotyping. The neonate developed severe HDFN which was managed with phototherapy, exchange transfusion and IvIg. There was no exposure history for sensitization except bleeding in early 2nd trimester. There was a significant discrepancy among mother, father and neonate Rh phenotype which was resolved with clinical history of Invitro fertilization (IVF) with sperm donation. This index case illustrates the need of antibody screening in primigravida antenatal women specially for Rh D negative high risk cases. It also shows importance of Rh Kell typing in sperm donors for future transfusion support of the child.     

Anti-D auto-immunization in a patient with weak D type 4.0

We report the case of a 56-year-old patient with blood group O+C?c+E?e+K?, followed for a myelodysplasic syndrome and treated by regular pheno-identical and compatible (RBCs) transfusion since December 2007. In June 2009, a positive crossmatch was found with 2 RBCs O+C?c+E?e+K?. A positive anti-body screening with a positive autocontrol was detected and anti-D was unidentified in the patient's serum. The DAT was positive (IgG) and elution identified an anti-D. The following assumptions were then made: it could be a partial D phenotype with anti-D alloantibodies or RH: 1 phenotype with an anti-D auto-antibodies. Molecular analysis by multiplex PCR and sequencing have depisted a weak D type 4.0 phenotype. In October 2009, over three months of RH:?1 RBC transfusion, the antibody screening and DAT (IgG) remained positive, and an eluate made from the patient's erythrocytes contained an anti-D. All these funding confirmed the autoimmune nature of the anti-D. This case report illustrates the importance of a well-conducted and immunohematological laboratories test in order to distinguish between auto- or allo-immune of anti-D in a RH: 1 poly-transfused patients. This distinction is of great importance for transfusion support.     

Indicators of clinically significant red cell antibodies produced by sensitized lymphocytes in liver transplant patients

It has been documented that transplanted livers can carry sensitized lymphocytes that subsequently produce red cell antibodies. We evaluated immunohematological variables in liver donors and recipients for indicators that might be predictive of serological red blood cell (RBC) destruction mediated by the passenger lymphocytes. Organ donor sera with antibody scores greater than ( > ) 60 correlated with a positive direct antiglobulin test (DAT) and need for increased RBC transfusion in liver transplant recipients. We therefore propose an antibody screen on all potential liver donors and titration of unexpected alloantibodies; titration of ABO antibodies of liver donors who demonstrate minor ABO-incompatibilities with their recipients; and, when needed, transfusion of group O RBCs to recipients of livers from donors with minor ABO-incompatibility who have antibody scores >60.     

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.     

Case report: immune anti-D stimulated by transfusion of fresh frozen plasma

FFP has occasionally been reported to generate an immune response to RBC antigens (e.g., anti-D and anti-Fya). The Council of Europe requires that each unit of FFP have less than 6 x 10(9)/L RBCs. However, there is considerable variation internationally in the method of production and the level and assessment of RBC contamination of FFP. This study reports the case of a 63-year-old group B, D- man who received multiple transfusions of D- blood products over a 4-month period. Seven months later the patient's antibody screen remained negative and he was transfused with seven units of D- RBCs and six units of FFP, four of which were D+. Two months later anti-D, -E, and -K were detected in his plasma. Although the anti-E and anti-K could have resulted from transfusion of antigen-positive RBCs, the anti-D could have resulted only from transfusion of the D+ FFP. The D status of FFP is currently not considered when selecting products for transfusion even though the D antigen is highly immunogenic and the level of RBC contamination of FFP is not always known. This case highlights that transfusion of FFP is a stimulus for RBC antibodies and that when a patient has had a recent transfusion of FFP, consideration should be given to obtaining a sample for pretransfusion testing within 3 days before a scheduled RBC transfusion. In addition, the D status of FFP should be considered before administering FFP to premenopausal D- women.     

Utilization patterns of frozen autologous red blood cells. Experience in a referral center and a community hospital

The risks of homologous blood transfusion have motivated some blood centers and private industry to consider providing long-term storage of frozen, autologous red blood cells as a service. The usefulness of this practice is unknown. We performed a retrospective analysis of frozen autologous red blood cell use in two hospitals. Records were available for 21- and 9-year intervals, respectively. A total of 104 autologous units were cryopreserved for 41 patients. Fifteen (37%) of 41 patients received one or more of their stored units of red blood cells. Twenty-two patients had autologous units frozen in anticipation of elective surgery; 11 (50%) of these 22 patients received some or all of their stored units. Sixteen patients had autologous units stored because of potential transfusion problems related to rare blood types or to the presence of multiple blood cell alloantibodies, and another 3 patients had units frozen simply at their personal request. Only 4 (21%) of these latter 19 patients who donated without a specific planned use eventually received their frozen autologous red blood cells. Long-term autologous frozen red blood cell storage can improve medical management of some patients with anticipated surgical procedures or unusual requirements for transfusion. However, our study suggests that most autologous units frozen without specific planned use will not be transfused.     

Complete hematopoietic recovery after continuous iron chelation therapy in a patient with severe aplastic anemia with secondary hemochromatosis

A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. He had received continuous transfusions because an HLA-matched marrow donor was unavailable. Following a continuous, approximately 5-yr transfusion, he was noted to develop hemochromatosis. He had a dilated cardiomyopathy and required diuretics and digitalis, multiple endocrine and liver dysfunction, generalized bleeding, and skin pigmentation. A total volume of red blood cell transfusion before deferoxamine therapy was about 96,000 mL. He received a regular iron chelation therapy (continuous intravenous infusion of deferoxamine, 50 mg/kg/day for 5 days q 3-4 weeks) for approximately seven years after the onset of multiple organ failures. His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. He has not received any transfusions for the last four years. This finding suggests that a continuous deferoxamine infusion may play a role in the immune regulation in addition to iron chelation effect.     

Mechanisms responsible for delayed and immediate hemolytic transfusion reactions in a patient with anti-E + Jk(b)+ Di(b) and anti-HLA alloantibodies

Immediate hemolytic transfusion reactions (IHTR) occurred in the course of delayed hemolytic transfusion reactions (DHTR). An 84-year-old man had received a blood transfusion 20 years ago. Progressive anemia developed, because of continuous bleeding from a bladder tumor. He was transfused with concentrated red blood cells (CRC) which were Rh-E antigen negative, because he had anti-E antibodies (day 0). He received CRC on day 3, and underwent resection of bladder tumor on day 6. Although crossmatch-compatible CRCs were prepared for the operation, those were not required and were kept in a refrigerator in the ward. On day 9, when a CRC kept in the ward was transfused, he suddenly had a IHTR. In order to analyze a mechanism of IHTR, the anti-Jk(b) and anti-Di(b) antibodies, anti-HLA antibodies and the concentrations of inflammatory cytokines were measured in serum samples. The anti-Jk(b) and anti-Di(b) antibodies increased prior to IHTR experienced on day 9. The concentrations of IL-6 and IL-1beta increased from day 2, while the concentration of IL-8 increased from day 7. The anti-HLA class I antibody could be detected 2 days before IHTR. Thus, the anti-Jk(b) and anti-Di(b) antibodies induced the production of inflammatory cytokines and symptoms of DHTR and IHTR. The anti-HLA class I antibody could be produced in spite of using the filer for removing leukocytes, and may take part in the induction of IHTR. Further, blood products should be transfused soon after completing a crossmatch test in patients with anti-RBC alloantibodies.     

Red-cell alloimmunization profile in multi transfused patients: Findings and insights of a blood transfusion service

ObjectivesBlood transfusion is a key intervention for decreasing morbidity and mortality in many cases and, besides its importance, potentially fatal consequences of incompatible transfusion are a great risk to patients. This study evaluated the incidence and specificity of erythrocyte alloantibodies in multi-transfused patients enrolled at an important Regional Blood Center.Materials/methodsThis was a single-center retrospective cohort study that eveluated patients enrolled at a Regional Blood Center in a period of four years. A total of 29,128 patient samples were screened, out of which 79 (0.27%) were multiple-transfused patients with alloantibodies identified.ResultsThe most common alloantibody found was anti-E (22.55%) followed by anti-D (14.71%), anti-C (5.88%), anti-c (5.88%), anti-e (1.96%) and anti-C^w (0.98%). We also identified combinations of alloantibodies (25.32%), 5.88% of which showed an IgG autoantibody isolated or combined with alloantibodies. The most frequent reason for the need of blood transfusion included cases of surgery, emergency and urgency (36.71%).ConclusionsA low rate of development of alloantibodies in multi-transfused patients was found, which could be a consequence of the implementation of red blood cell phenotyping for patients who may receive frequent transfusions, as in the case of some hematological neoplasms and hemoglobinopathies. However, the most common alloantibodies identified were against the Rh and/or Kell systems, with high clinical significance since both can cause delayed hemolytic transfusion reactions. Thus, the implementation of reliable antibody screening tests and the transfusion of phenotyped units for selected patients in all transfusion services represent important measures to increase transfusion safety.