Warm IgM Anti-IT Causing Autoimmune Haemolytic Anaemia

Abstract. A patient with autoimmune haemolytic anaemia due to an autoagglutinin of anti-I^T specificity is reported. The antibody was of the IgM class and bound complement; unexpectedly, it reacted optimally at 37°C. A prozone was noted when testing serial dilutions of the patient's serum against appropriate red cells in saline, but was not found when testing an eluate prepared from the patient's red cells. Investigations suggested that the prozone was due to a blocking antibody of high molecular weight, which appeared to be specific for I and I^T.     

Autoantibodies of U Blood Group Specificity in Autoimmune Haemolytic Anaemia

Autoantibody specificity in acquired haemolytic anaemia of the warm antibody type has been thought to be directed against Rh antigens or the precursors from which they arise. In many cases Rh_null red cells fail to react with these antibodies, providing apparent support for the assumption that they have Rh specificity. Rh_null red cells are also non-reactive with anti-U sera, and in addition have abnormal S and s antigens. We have studied 50 cases of warm antibody autoimmune haemolytic anaemia looking particularly for possible U, S or s blood group specificity of the causative antibodies. In the majority of cases the antibodies were found to be directed against antigens of the Rh complex, but in three cases multi-specific autoantibodies were shown to have complex specificity involving the Rh and U blood groups.     

Autoimmune Haemolytic Anaemia in Children

S ummary . Forty-four children with autoimmune haemolytic anaemia (AIHA) are described: 31 had acute, subacute or chronic disease with warm autoantibodies and 13 had acute or chronic anaemia with cold autoantibodies. The commonest forms were the acute and subacute types with warm autoantibodies and these were more frequent in young children, while chronic AIHA occurred mainly among children at puberty. In about 16% the anaemia was accompanied by a chronic disorder but in over 50% the anaemia was preceded by an acute infection or immunization. The former gave rise mainly to chronic anaemia, but the latter was associated with the acute and subacute forms. In general the prognosis was good and death was never caused by anaemia per se. The prognosis was worse in patients with clinical features of thrombocytopenia and bleeding and with the immunological findings of free autoantibodies in the serum and a positive direct antiglobulin test. In acute and subacute forms, treatment with corticosteroids and sometimes with blood transfusions was effective. In chronic forms of the disease it was often necessary to give additional immunosuppressive drugs or/and to perform a splenectomy.     

Activated T-Cells in Autoimmune Haemolytic Anaemia

In 12 of 14 patients with clinically active autoimmune haemolytic anaemia high levels (9-78%) of homologous and autologous rosetting cells were found in the peripheral blood. In 10 of these patients, who were observed over a period of 2 years, the levels bore a direct relationship to the activity of the disease. The cells so identified were T-lymphocytes. The role of cells, identified by this method in AIHA, is discussed.     

Familial Autoimmune Haemolytic Anaemia Associated with Rheumatoid Arthritis and Pernicious Anaemia

S ummary . A family was studied in which one son, a daughter and a paternal aunt showed clinical and laboratory evidence of autoimmune haemolytic disease. The father has long-standing rheumatoid arthritis, another son has proven pernicious anaemia while one daughter, though clinically well, exhibits mild serological abnormality. Other clinically normal members of this family were also investigated. Anti-parietal cell antibodies were demonstrated in one case of autoimmune haemolytic disease in addition to being noted in the serum of the member with pernicious anaemia. The direct antiglobulin reaction was strongly positive in those affected by haemolytic disease, but in addition a weak positive reaction was demonstrated in the case of pernicious anaemia where eluate studies indicated the possibility of an antibody similar in nature to the one present in the haemolytic cases, rather than a non-specific reaction. The pattern of cold auto-antibodies, warm auto- and iso-antibodies and other abnormal serology found in the blood of different members of this family would appear to suggest a common hereditary basis for the diseases present.     

Elucidation of Alloantibodies in Autoimmune Haemolytic Anaemia

Forty-one patients with autoimmune haemolytic anaemia (AIHA), who had free antibody in their sera, were investigated for the presence of alloimmune erythrocyte antibodies using the ZZAP autoabsorption technique. Patients were subdivided into three risk categories: (I) no prior pregnancy or transfusion; (II) history of pregnancy and/or one to five transfusions; and (III) greater than 5 transfusions. A total of 13 (32%) of the 41 patients exhibited significant alloantibodies. Of 11 category-I patients 2 (18%) had significant alloantibodies. Eight (31%) of the 26 category-II patients had significant alloantibodies and 3 (75%) of the 4 category-III patients had significant alloantibodies after absorption. The majority showed Rh specificity: anti-E(8), -C(3), -Cw(1). Anti-K was found in 6 samples and 1 had anti-Fya. Alloantibodies had not been suspected prior to autoabsorption in 10 (77%) of the 13 patients with alloantibodies. These findings underline the importance of performing autoabsorption in AIHA when free autoantibody is present in the serum. Additionally, Rh phenotyping performed on ZZAP-treated cells showed complete agreement with that ascertained using pure IgM Rh typing sera and untreated cells.     

Autoimmune Haemolytic Anaemia due to Anti-Phospholipid Antibodies

The clinical course and laboratory findings of a patient with autoimmune haemolytic anaemia due to anti-phospholipid antibodies and secondary to a systemic lupus erythematosus-like syndrome are described. IgG and IgM with anti-phospholipid activity coexisted in both sera and acid eluates prepared from the patient's red cells, as demonstrated by ELISA using a panel of anionic and neutral phospholipids. The anti-erythrocyte binding activity of eluted autoantibodies, determined by a radioactive antiglobulin technique, was totally inhibited by absorption with phospholipid micelles. The patient's serum also contained an IgM warm haemolysin detectable with enzyme-treated cells only, as well as anti-C, -E and -S alloantibodies.     

Autoimmune Haemolytic Anaemia in New Zealand Black Mice

Mice of the NZB strain spontaneously develop autoimmune haemolytic anaemia and reticulum cell neoplasms, and they harbour murine leukaemia virus. This triad of autoimmunity, malignancy, and virus infection is explored in experiments designed to show how the autoimmune haemolytic disease and/or the virus are transmitted to NZB hybrids derived naturally, by ovum transplantation, and from allophenic parents. Possible cellular mechanisms for the autoimmune process are reviewed, and evidence for a genetic, hormonal, or viral aetiology of autoimmune haemolytic anaemia is discussed.     

125I-Transferrin Turnover in Rabbits with Haemolytic Anaemia

The metabolism of purified ¹²⁵I-labelled homologous transferrin in rabbits with haemolytic anaemia was compared to that in control rabbits and no significant differences were found. During 3 weeks of haemolysis plasma transferrin concentrations did not change appreciably. The fractional turnover rate was 43% of the intravascular pool per day. The intravascular pool was 45% of the total exchangeable transferrin.     

An Association of Pregnancy and Autoimmune Haemolytic Anaemia

14 cases of pregnancy-associated autoimmune haemolytic anaemia were analyzed. 4 cases were diagnosed during pregnancy; 10 cases became pregnant during the remission period of the disease. 6 cases were secondary to systemic lupus erythematosus. In the first group, the anaemia developed in the third trimester whereas in the second group the Hb fell slightly in the first trimester and rapidly between the third and fourth month of gestation. Only 1 case could withstand the hazard of pregnancy uneventfully; 4 needed corticosteroid and delivered normal infants; 2 developed toxaemia of pregnancy; in 5, either therapeutic or spontaneous abortion was noted and 1 death occurred due to renal complication. Abortion was induced in 1 case due to socio-economic indications.     

Successful Treatment of Refractory Autoimmune Haemolytic Anaemia by Plasmapheresis

A 16-year-old female was admitted because of rapidly progressive fatigue, severe anaemia and icterus. The S-bilirubin was 190 μmol/l, COHb 7.3% and high amounts of free Hb in plasma were present. The Coombs' direct test was strongly positive with anti-IgG but negative with anti-IgM and anti-C3. Conventional therapy with very high doses of hydrocortisone i.v., cyclophosphamide, azathioprine, and transfusions of washed packed red cells proved ineffective. During 5 consecutive days she also received i.v. infusions of gammaglobulin (25 g each day). Nevertheless, her condition deteriorated and 3 plasma exchanges were carried out with impressive clinical and laboratory effects. After the 3rd plasma exchange, the patient did not require further transfusions of packed red cells. Therapy with corticosteroids could be rapidly reduced and she was discharged after 5 weeks with a normal blood picture. Since then she has remained in excellent health.     

Haemolytic Transfusion Reaction Caused by Anti-Lea

A severe hemolytic transfusion reaction due to the presence of a potent anti-Le^a in the patient's serum is described. The antibody was markedly hemolytic in vitro, especially against enzyme treated red cells. With carefully supervised therapy and restriction of fluids the patient recovered without any apparent kidney damage. The results of red cell and saliva studies on the patient's family are given.

Résumé

Les auteur décrivent une réaction transfusionnelle grave due à la présence d'un anti-Le^a puissant dans le sérum d'une patiente. Cet anticorps était très fortement hémolytique in vitro et plus spécialement à l'égard d'érythrocytes traités par des enzymes protéolytiques.
Grâce à une étroite surveillance du traitement et à la diète hydrique, la patiente a pu se remettre sans lésions rénales apparentes irréversibles. Les auteurs présentent les résultats des examens pratiqués sur la salive et les érythrocytes des membres de la fade de la patiente.

Zusammenfassung

Eine schwere hämolytische Transfusionsreaktion, bedingt durch die Anwesenheit eines kräftigen Anti-Le^a-Antikörpers im Patientenserum, wird beschrieben. Der Antikörper wirkte in vitro als Hämolysin; die Lyse enzymbehandelter Erythrozyten war besonders ausgepragt. Unter sorgfältiger Therapie mit Flüssigkeitsbeschränkung genas der Patient ohne erkennbaren Nierenschaden. Die Ergebnisse der serologischen Erythrozyten- und Speichelanalyse der Familie des Patienten werden mitgeteilt.     

Specificity of Acquired Haemolytic Anaemia Autoantibodies and their Scrological Characteristics

S ummary . An inbred group of beagle dogs deficient in factor VII has been used to provide a reagent for the assay of factor VII in human plasma. Dilutions of human plasma were tested in a one-stage system with beagle dog plasma, brain extract and calcium chloride. It was found that, if the concentration of factor V in the beagle dog plasma was reduced and a dilute human brain extract used, log clotting time was directly related to log concentration of factor VII. Assays using beagle dog plasma and human plasma deficient in factor VII gave comparable values. A range of factor-VII activity is reported for normal human plasma samples.     

Characterisation of Autoantibodies to Erythrocytes in Autoimmune Haemolytic Anaemia by Chloroquine

Chloroquine splits autoantibodies from erythrocytes of patients with autoimmune haemolytic anaemia in vitro. After the removal of chloroquine from the samples the autoantibodies can be identified in the eluates. With one exception the autoantibodies of patients with idiopathic autoimmune haemolytic anaemia (AIHA) and severe haemolysis were completely split from the cells, whereas the autoantibodies of patients with symptomatic AIHA and moderate anaemia, of patients with diseases unrelated to haemolysis, and of healthy persons, were not completely split from the erythrocytes. In general, autoantibodies, which are associated with severe haemolysis, were more easily split from the red cells by chloroquine. The eluted IgG incomplete warm autoantibodies were only in part specific to Rh antigens. The Rh specificity does not correlate with the absence of presence of increased haemolysis. The inhibition of the autoantibodies and the splitting or 'loosening' of the antigen-antibody linkage with the immunocomplex by chloroquine could be responsible of a longer survival of autoantibody-coated red cells in patients with AIHA.     

Immediate Haemolytic Transfusion Reaction Due to Anti-Inb

An immediate haemolytic transfusion reaction was investigated in a patient with intestinal cancer. The causative antibody was directed against a high-frequency antigen Inb that was presumably produced as a result of pregnancies. This is the first case of a severe transfusion reaction due to this alloantibody.     

Megaloblastic Anaemia of Infancy and Vitamin B12

The haematological status of 30 infants with a syndrome characterized by satisfactory growth, abnormal pigmentation, developmental retardation, hypotonia of muscles, hepatosplenomegaly, with or without tremors, has been studied. Anaemia of a moderate degree was seen in all. All but four had megaloblastic erythropoiesis. Serum vitamin B₁₂ levels were below 100 pg./ml. By increasing the infants' intake of vitamin B_12>, by raising the concentration of the vitamin in maternal milk, megaloblastic erythropoiesis could be corrected to normoblastic erythropoiesis. The other clinical manifestations of the syndrome also responded to the administration of vitamin B₁₂ to varying degrees.