Posttransfusion purpura. Report of a case with anti-P1A1 masked by HLA antibodies

A case of posttransfusion purpura is reported in which the laboratory determination of the specificity of the causative antibody was initially confused by the presence in the patient's serum of HLA-directed antibodies. The patient was a multiparous 65-year-old woman with a previous history of blood transfusion. She developed the typical clinical features of posttransfusion purpura 8 days following the transfusion of 6 units of packed red cells. The patient was P1A1 negative, and her serum reacted strongly in a radiolabeled monoclonal antibody assay with both P1A1-positive and -negative platelets. Radioimmunoprecipitation demonstrated that the patient's serum contained antibodies both of anti-P1A1 and anti-HLA specificity. Western blotting of normal platelets incubated with the patient's serum verified that the anti-P1A1 antibody was directed against platelet membrane glycoprotein III.     

Matuhasi-Ogata phenomenon involving anti-ampicillin

A 47-year-old group A, Rh1Rh1 woman treated with intravenous ampicillin for chronic pyelonephritis received two units of blood and also received oral cephalexin. Three months after the transfusions she was noted to have allo-anti-E and anti-c, and a 2+ positive direct antiglobulin test. Anti-E and anti-c could be eluted from her cells, yet neither antigen could be demonstrated on the patient's circulating red blood cells. Also present in the serum and in the eluate was anti- ampicillin antibody. Studies of the patient's red blood cell eluates using ampicillin-treated R1R1 and untreated R2R2 cells demonstrated anti-E complexed with anti-ampicillin in a drug-related example of the Matuhasi-Ogata phenomenon. Artificially created mixtures of anti-E and drug antibody could reproduce the effect in vitro. No effect of cephalexin could be demonstrated. The variability of the Matuhasi-Ogata phenomenon is discussed with regard to the sequence of antibody attachment, and the possible relationship to cephalexin is discussed. Drug antibodies may be involved in the Matuhasi-Ogata phenomenon in cases where another red blood cell antibody cannot be shown to be present.     

A delayed hemolytic transfusion reaction due to anti-Cob

A delayed hemolytic transfusion reaction precipitated by anti-Cob is described in a multiple transfused primigravida woman with sickle-cell disease. Sixteen days after the prophylactic transfusion of the first of 4 units of red cells, she experienced a fall in hemoglobin concentration accompanied by a newly positive antibody screen and direct antiglobulin test. Anti-Cob was identified both in the patient's serum and in an eluate prepared from her red cells.     

Acute hemolytic anemia associated with a chlorpropamide-induced apparent auto-anti-Jka

A patient with acute hemolytic anemia and a positive direct antiglobulin test was found to be Jk(a + b +) with anti-Jka in her serum. For 2 weeks prior to admission, the patient had taken chlorpropamide, a hypoglycemic agent. The drug was discontinued upon the diagnosis of hemolytic anemia, and the hemoglobin concentration gradually increased. When chlorpropamide was added to the patient's serum in vitro, it enhanced the reactivity of the anti-Jka, and 40 days posttransfusion, the serum would only react with Jk(a+) red cells when chlorpropamide was present. These findings suggest that a chlorpropamide-dependent antibody with Jka specificity had formed. We do not know why the antibody induced by chlorpropamide reacted preferentially with Jk(a+) red cells.     

A potent cold autoagglutinin that recognizes type 2H determinant on red cells

An example of an IgM (lambda) cold autoagglutinin against a Type 2H determinant of the ABO blood group system is described. The direct antiglobulin test was positive due to C3d on the patient's red cells. The antibody in the patient's serum was active at 37 degrees C, and the degree of agglutination was almost the same at 37 and 4 degrees C. It agglutinated group O red cells preferentially, but not Bombay (Oh) red cells. The specificity was determined by adsorption with synthetic oligosaccharide immunoadsorbent.     

Erb, an allele to Era, and evidence for a third allele, Er

An antibody against a low-incidence antigen was detected in the serum of a woman whose newborn infant was found to have a positive direct antiglobulin test. The antibody failed to agglutinate 79 examples of red cells having low-incidence antigens and 16 examples of high-incidence antigen-negative red cells. The woman's serum reacted strongly with her husband's red cells in the antiglobulin test and with 5 of 6 Er(a-) cell samples from unrelated donors, suggesting that the antigen has an antithetical relationship to Era. The failure of the serum to react with one Er(a-) cell sample and with cells from the Er(a+) daughter of an Er(a-b+) mother gives evidence for a silent allele, Er. Four Er(b+) bloods were found among 605 random white donors, indicating a gene frequency for Erb of 0.0033.     

An immediate hemolytic reaction induced by repeated administration of oxaliplatin

BACKGROUND: Platinum-based chemotherapy agents have been associated with potentially fatal acute immune-mediated hemolytic anemia. The target antigen, cause of the positive direct antiglobulin test (DAT) and mechanism of hemolysis have been the subject of controversy. CASE REPORT: We report a patient who developed a DAT-positive hemolytic episode after a red cell (RBC) transfusion was delivered during the infusion of her 17th cycle of oxaliplatin. Standard pretransfusion testing was uncomplicated; however, after infusion, the serum was no longer compatible with the transfused units and a strong (4+) panreactive IgG antibody was detected. RESULTS: The patient's serum from 10 days after the episode, only when therapeutic concentrations of oxaliplatin were added, reacted with all RBCs tested using the indirect antiglobulin test (IAT) (3+). The effect was retained with a purified IgG fraction and almost eliminated with IgG-depleted serum. Immunoprecipitation analysis revealed a band with the molecular weight of the Band 3 anion channel only in the presence of the patient's serum and oxaliplatin. CONCLUSION: Our investigations indicated that oxaliplatin interacted with both an IgG antibody and a RBC membrane epitope probably located on the Band 3 anion channel.     

Delayed hemolytic transfusion reaction caused by anti-Jsb in a Js(a+b+) patient

A 39-year-old multiparous woman developed a mixed field positive direct antiglobulin test within 15 days of receiving four units of crossmatch compatible red blood cells. Anti-Jsb was demonstrable in both the serum and the eluate. The case was further complicated by the fact that the patient's pretransfusion red blood cells typed as Js(b+). Serologic studies demonstrated that this was a case of allo-anti-Jsb in a Js(b+) patient which provides evidence of heterogeniety of the Js locus.     

Autoimmune hemolytic anemia associated with IgG auto anti-N

A second case of autoimmune hemolytic anemia mediated by an IgG auto Anti-N is described. The patient's red blood cells were sensitized with both IgG and complement. The serum antibody was not inactivated by 2- mercaptoethanol treatment, and reacted by indirect antiglobulin test at 37 C with monospecific anti-IgG. The IgG antibody eluted from the red blood cells and in the serum showed anti-N specificity. The patient was thought to have systemic lupus erythematosus. Following steroid therapy, the hemolytic anemia resolved with disappearance of the anti-N.     

Positive direct antiglobulin tests at birth without demonstrable maternal antibody

A healthy 38-year-old white woman had two abortions and three live children. Red cells from each of her living children at birth had a strongly positive direct antiglobulin test. Detailed studies on the third child showed that the cells were sensitized by IgG. Maternal serum, tested by a range of techniques against reagent red cells and the husband's cells, showed no unusual antibody. Maternal serum and eluates prepared from red cells of the third child did not react with fresh cells from the older siblings (aged 7 and 10 years). Follow-up on the third child showed that the direct antiglobulin test was positive at 2 months, weakly positive at 4 months, and negative at 8 months. Red cells collected at 8 months of age did not react with the stored eluate prepared from the baby's sensitized red cells at birth. The most likely explanation of these data is that the children inherited a paternal antigen that is only present as a red cell surface-active structure during fetal development.     

Autoimmune hemolytic anemia with anti Jka specificity in a patient taking aldomet

Autoimmune hemolytic anemia (hemoglobin 5.2 g, reticulocyte count 31.0 per cent) developed in a 53-year-old hypertensive woman who was taking Aldomet. Both the patient's serum and the eluate prepared from her red blood cells contained an antibody with anti-Jka specificity. Rapid sustained improvement in the anemia occurred after cessation of Aldomet and a two week course of prednisone therapy. Eight months later, anti- Jka was no longer detectable in the patient's serum and the direct antiglobulin test was nonreactive.     

Two cases of "hrB-like" autoantibodies appearing as alloantibodies

Two cases are described in which autoantibodies mimicked alloantibodies. The direct antiglobulin test (DAT) on the red cells (RBCs) from both patients was negative when routine manual hexadimethrine bromide (Polybrene) and enzyme-linked antiglobulin techniques were used. The RBCs also did not react on direct bromelin and direct Polybrene tests. However, an "hrB-like" antibody was eluted from the RBCs of both patients. The sera from these patients reacted with all e+ hrB+ RBCs but not with e+ hrB-, e-, or their own RBCs. The antibody in the serum of one patient was not adsorbed by R2R2 RBCs. Serologic tests initially suggested (by direct testing and adsorption studies) that the serum antibodies were alloantibodies rather than autoantibodies. RBCs taken from one patient, 8 months after her sample was first referred to our laboratory, reacted with a serum sample from her first admission. An RBC sample taken from the other patient, initially typed e+ and hrB- but 1 month later typed e+ and hrB+ by using the same anti-hrB sera, was used to test the earlier samples.     

Tolmetin-induced hemolysis

A case of drug-associated immune hemolysis in a patient taking tolmetin for arthritic pain is described. Serologic tests showed that in the absence of tolmetin, the patient had a negative antibody screening test but a strongly positive direct antiglobulin test. An eluate prepared from the patient's red cells caused agglutination of all cells tested. However, addition of tolmetin revealed a high-titered tolmetin-dependent antibody in the patient's serum; the addition of tolmetin did not affect the results obtained with the eluate. within 3 months after the patient discontinued tolmetin, his hematocrit had increased to 45 percent, and his jaundice and bilirubinuria had disappeared. These results are similar to those described for zomepirac, another of the group of nonsteroidal anti-inflammatory medications.     

A severe transfusion reaction associated with anti-EnaTS in a patient with an abnormal alpha-like red cell sialoglycoprotein

A 71-year-old woman (Ped) received 3 units of red cells (RBCs), compatible by the indirect antiglobulin test but strongly (4+) incompatible by direct agglutination at 37 degrees C. The next day, her plasma hemoglobin was 1252 mg percent and the direct antiglobulin test (DAT) was weakly positive (IgG and C3). Less than 5 percent of the transfused cells could be detected 48 hours posttransfusion. Her clinical condition deteriorated and renal failure developed. The patient died of pulmonary embolism. Her serum contained a strong (4+) IgM agglutinin and a weakly reactive (microscopically positive) IgG antibody, with anti-EnaTS specificity. EnaFS and EnaTS antigens were severely depressed or absent from the patient's RBCs; the ficin-resistant Ena antigen (EnaFR) appeared to be present. Pretransfusion RBC sialic acid level was 53 +/- 2 percent of normal. The patient's RBC membranes were shown to contain sialoglycoproteins beta and delta by sodium dodecyl sulphate polyacrylamide gel electrophoresis with periodic acid Schiff's base staining, with weak staining of components in the regions corresponding to alpha, alpha 2 and alpha delta. The nature of these components was not identified, but their presence suggested that the patient's RBCs expressed a previously undescribed sialoglycoprotein alpha variant.     

Sulindac-induced immune hemolytic anemia

BACKGROUND: Sulindac, a nonsteroidal, anti-inflammatory, indene-derived drug, caused life-threatening immune hemolytic anemia in an individual with back pain. CASE REPORT: A patient was admitted to the hospital with immune hemolytic anemia and kidney and liver failure after several days ingestion of sulindac. The direct antiglobulin test was positive with polyspecific and monospecific anti-IgG but not with anti-C3. The eluate did not react in routine tests but reacted strongly after the addition of sulindac. The serum contained a sulindac-dependent antibody reacting to a titer of 32. The sulindac-dependent antibody was of both IgG and IgM classes and had no apparent blood group specificity. The antibody agglutinated red cells from humans and chimpanzees but not from chickens, rabbits, or sheep, which implied that a specific component on human and chimpanzee red cells was needed for reactivity. The antibody reacted with red cells treated with trypsin, papain, pronase, dithiothreitol, and sialidase. With aggressive medical care, the patient's condition improved. CONCLUSION: These findings appear compatible with the so-called immune complex mechanism for drug-induced immune hemolytic anemia. Physicians are alerted to the severe nature of this syndrome.     

Hemolytic transfusion reaction due to anti-Tca

BACKGROUND: Anti-Tc(a) detects a high-incidence antigen in the Cromer blood group system. Cromer system antibodies have not usually been associated with hemolytic transfusion reactions or hemolytic disease of the newborn. CASE REPORT: Anti-Tc(a) (initially identified in the patient's serum in 1982) was not detected when she was admitted to the hospital with upper gastrointestinal. bleeding. Three units of red cells were administered. The patient was discharged, but was readmitted to the hospital after her hemoglobin fell to 7.1 g per dL. Antibody detection tests remained negative and three additional units were transfused. Over the next 7 days, her hemoglobin steadily fell to 5.5 g per dL. The level of lactate dehydrogenase rose to 1257, the plasma hemoglobin rose to >16 mg per dL, and the haptoglobin decreased to <6 mg per dL. Five days after transfusion, her direct antiglobulin test was weakly reactive with complement-specific antiglobulin reagents. Eluates were nonreactive. Anti-Tc(a) was detected in her serum; no other antibodies were detected. Differential typing failed to detect any circulating Tc(a+) red cells. The antibody was strongly reactive in a monocyte monolayer assay. CONCLUSION: Although Cromer system antibodies have generally not been proven to be clinically significant in transfusion therapy, the destruction of red cells from six units of transfused Tc(a+) red cells in this patient indicates that anti-Tc(a) may have destructive potential in some patients.     

Haemolytic anaemia and renal failure associated with antibodies to trimethoprim and sulfamethoxazole

Aim: The aim of this study was to support a clinical diagnosis of drug‐induced immune haemolytic anaemia (DIIHA). Background: DIIHA is rare and has only been described twice with the antibiotic combination of trimethoprim (TMP) and sulfamethoxazole (SMX). Methods/Materials: Serologic tests for drug antibodies were performed using methods previously published by our laboratory. Results: A 44‐year‐old woman experienced body aches, chills, chest pressure, nausea and a rash while receiving TMP–SMX; a week later her haemoglobin was low and she was in renal failure. At the hospital, the direct antiglobulin test (DAT) was positive (C3 only) and the serum reacted with all red blood cells (RBCs) by the gel method only (TMP–SMX is present in the RBC diluent used for the gel method). At the Red Cross immunohaematology laboratory, the patient's serum was reactive in the presence of TMP–SMX (haemolysis and positive antiglobulin test), pure TMP (positive antiglobulin test using anti‐IgG only) and pure SMX (haemolysis and positive antiglobulin test using both anti‐IgG and anti‐C3). The patient was treated with transfusions and haemodialysis and was discharged after a week in stable condition. Conclusion: We describe a patient who appeared to have haemolytic anaemia and renal failure associated with antibodies to both TMP and SMX.     

An auto-anti-M causing hemolysis in vitro

A 64-year-old white man, who had never received a transfusion, was found to have anti-M in his serum. The antibody agglutinated all M+ red cells in room-temperature tests. When the ionic strength of the test milieu was reduced by use of an additive solution and the tests were incubated at 37 degrees C, the antibody hemolyzed M + N- but not M+N+ red cells. All M+ red cells reacted in indirect antiglobulin tests using polyspecific antiglobulin reagents when such tests followed an initial incubation at room temperature. When red cells and the patient's serum were warmed to 37 degrees C before being mixed, no antibody activity was demonstrable. The antibody was adsorbed to exhaustion onto M+N- and M+N+ red cells (including the patient's own), and its activity was destroyed by dithiothreitol. There was no evidence of in vivo red cell destruction by the autoantibody. No previously reported example of anti-M has been shown to activate complement in conventional in vitro tests. This example was extraordinary in that it caused sufficient complement activation to present as an in vitro hemolysin.     

Coombs' negative immune hemolytic anemia with anti-E occurring in the red blood cell eluate of an E-negative patient

A previously untransfused 20-year-old man presented with a seven day history of malaise, fatigue, jaundice, dark urine and splenomegaly. Hemolytic anemia was indicated by a hemoglobin of 8.7 mg/dl, reticulocyte count 8 per cent, Lactic dehydrogenase 389 iu/L, bilirubin 4.3 mg/dl (direct 0.1 mg/dl), and undetectable haptoglobins. Tests for nonimmunologic mediated hemolytic anemia were negative. The direct antiglobulin test (DAT) was repeatedly negative with polyspecific, anti-IgG, -IgA, -IgM and anti-C3 antisera. The patient's serum contained a weak anti-I, anti-E strongly reactive by indirect antiglobulin test (IAT) and an antibody reactive against all cells tested. The latter antibody reacted weakly by the IAT but strongly against enzyme-treated cells (Titer 160). Eluates from the patient's red blood cells only reacted with E+ red blood cells. The patient typed E negative. He was treated for warm autoimmune hemolytic anemia (AIHA) with high doses of prednisone. By the twelfth day his response allowed the medication to be tapered and by one month from the onset of treatment laboratory studies had returned to normal. The DAT remained negative, however, following recovery, anti-E could not be eluted from the red blood cells. Anti-E remained in his serum and the titer of the enzyme reactive antibody had decreased to 16. It is suggested that the anti-“E-like” antibody may represent auto anti-Hr preferentially reacting with E+ red blood cells. A unique feature in the case is the presence of a specific antibody eluted from cells that appear to lack that antigen in a DAT-negative patient with AIHA.     

A "normal" individual with a positive direct antiglobulin test: case complicated by pregnancy and unusual autoantibody specificity

A "normal" individual with a positive, direct antiglobulin test is described. In common with many other "normal" persons in whom a similar finding has been made, there was no evidence of an increased rate of in vivo red blood cell destruction in this patient. The patient successfully completed a pregnancy during the time that detailed serologic studies on her autoantibodies were being performed. Although the maternal autoantibodies were demonstrable in both an eluate made from the red blood cells of her newborn infant, and in the cord serum, there was no reason to believe that the antibodies caused red blood cell destruction in the infant. The case was of further interest because of the specificities of some of the autoantibodies. Although the mother and child were both C-negative, eluates from their red blood cells contained what ostensibly appeared to be anti-C. Studies that showed that the antibody could be totally adsorbed with C-negative, as well as C-positive red blood cells, proved that this was another example of an autoantibody mimicking an alloantibody. Although this autoantibody appeared initially to have anti-C specificity it was eventually shown to be more closely related to anti-Hr or anti-Rh34, than to anti-C.