IgG-mediated haemolysis masquerading as cold agglutinin-induced anaemia complicating severe infection with Mycoplasma pneumoniae

Haemolytic anaemia complicating Mycoplasma infection has usually been attributed to IgM cold agglutinins. This report describes a patient with pneumonia due to Mycoplasma pneumoniae in whom severe haemolysis persisted despite declining thermal amplitude and titre of cold agglutinins as the infection resolved. Class-specific antiglobulin (Coombs) testing defined an IgG warm agglutinin coating the patient's erythrocytes that was distinct from the IgM cold agglutinin identified by Sephadex G-200 gel filtration and dithiothreitol inactivation. Monoclonal IgM(γ) and IgK (k) circulating proteins were identified and immuno-electrophoresis of the cold aggulutinin-containing cryoglobulin fraction identified the cold agglutinin as an IgM(γ). In this patient initially presumed to have cold agglutinin induced haemolysis secondary to Mycoplasma infection, an IgG warm agglutinin was identified as the aetiology for the patient's haemolysis, underscoring the clinical relevance of careful evaluation of the mechanism of haemolysis accompanying Mycoplasma pneumonia.     

Severe Haemolytic Anaemia Complicating Infectious Mononucleosis

Summary: Severe haemolytic anaemia complicating infectious mononucleosis. R. K, Woodruff and A. J. McPherson, Aust. N.Z, J. Med., 1976, 6, pp. 569–570.
The case record of a patient suffering from infectious mononucleosis, complicated by severe haemolytic anaemia with overt intravascular haemolysis, is reported. Investigation of such cases usually shows a high titre of cold agglutinins with anti-i specificity. In the case reported, the results of serological investigations were atypical, and suggested that cold agglutinins with anti-l activity (rather than anti-i) were predominant in the aetiology of the haemolysis.     

Apropos of 2 cases of hemolytic anemia in mycoplasma pneumonia

The authors present 2 cases of mycoplasmal pneumonia associated with severe haemolysis. Haemolytic anaemia is a well-known and habitually mild complication of the disease. It is related to a peak of cold agglutinins, which are antibodies that agglutinate red blood cells usually at low temperatures but sometimes at 37 degrees C when they are present in high concentrations. The pathogenesis of cold agglutinins is thought to involve the secretion of peroxides by Mycoplasma pneumoniae with alteration of ed cell antigens which become immunogenic.     

Jaundice and intracardiac tumour

We report the case of a type B lymphoma originating from the mediastinum, characterized principally by massive metastatic invasion of the right cardiac cavities in the form of a projecting mass well visualized at echography responsible of the presenting features of the illness. This lymphoma was, moreover, associated with an auto-immune haemolytic anaemia due to cold agglutinins.     

Practical management of anticoagulation, bleeding and blood product support for cardiac surgery. Part two: transfusion issues

We summarise recent advances in transfusion medicine applicable to cardiac surgery and cardiac transplantation. It is important that clinicians know the risks of blood transfusion in Australia. They should also be aware of the different types of transfusion reaction so that there is early recognition and investigation. Blood conservation strategies including acceptance of normovolaemic anaemia in clinically stable patients are important in reducing the requirement for red cell transfusion. Cytomegalovirus (CMV) seronegative blood products are recommended for heart transplant recipients with no evidence of prior CMV infection. Leucodepletion of units of unknown CMV status reduces the risk of CMV infection and are an acceptable alternative when seronegative units are unavailable. Leucodepletion of cellular blood products has been shown to reduce infection rates postoperatively in a large trial involving cardiac surgical patients. Further studies are needed to confirm this promising finding. Irradiation of blood products eliminates the risk of transfusion-associated graft versus host disease. Routine preoperative screening for cold agglutinins is no longer recommended.     

Human cold agglutinins against “Cryptic” erythrocyte antigens

Summary Two examples of human IgM cold agglutinins agglutinated human RBC only after enzyme treatment in vitro. Proteases were optimally effective, neuraminidase was also effective. The cold agglutinins did not coat native RBC but were directed against cryptic RBC determinants. The cold agglutinins belonged to the anti -I/-i complex indicating a new type of I/i determinants. They were strongly accessible to cold agglutinin interaction on native RBC of a patient with congenital dyserythropoietic anaemia. Enzyme treatment of RBC was shown to be not only suited for defining cold agglutinin specificities but also essential for detecting the new type of cold agglutinins, obviously causing autoimmune haemolytic anaemia in vivo.     

Cold Autoagglutinins with Anti-Pr Specificity Associated with Fresh Varicella Infection

Cold agglutinins with the rare anti-Pr specificity were identified in an adult patient with fresh varicella infection. The antibody was of the IgM ? type with subspecificity anti-Pr_3d and caused a haemolytic episode in the patient. In the only previously reported case in which cold agglutinins were associated with varicella infection, the antibody specificity was also anti-Pr.     

Essential monoclonal gammopathy with an IgM paraprotein that is a cryoglobulin with cold agglutinin and EDTA-dependent platelet antibody properties

A patient with apparent anaemia and thrombocytopenia caused by a monoclonal paraprotein is described. The patient's serum contained a monoclonal IgM kappa, a cryoglobulin and a cold agglutinin. The cryoglobulin, similar to the serum paraprotein, was a monoclonal IgM kappa. Serum was studied to determine the relationship of the cryoglobulin with the cold agglutinin. The cryoglobulin and cold agglutinin were found to be the same paraprotein. Moreover, with absorption and elution techniques the reactivity of the autoantibody with both erythrocytes and platelets was demonstrated.
Reports of cryoprecipitable cold agglutinins are rare and therefore this case is exceptional given that the IgM kappa paraprotein was found to be a cold agglutinin which was also reactive with platelets.     

The Correlation of Cold Agglutinin Titrations in Saline and Albumin with Haemolytic Anaemia

Cold agglutinin syndrome (CAS) is usually associated with IgM cold agglutinins with titres exceeding 1000 at 4deg;C and a thermal amplitude of 30-32deg;C. Occasionally patients are encountered who although having clinical and laboratory findings compatible with CAS do not have the characteristic serological findings. Thirty-two patients with a positive direct antiglobulin test due to complement sensitization were studied. Thirty-one of these patients had cold agglutinin titres greater than 64. Twenty-eight had haemolytic anaemia, including one patient with a cold agglutinin titre of only 8 against saline-suspended red cells. 53.6% of sera from patients with haemolytic anaemia reacted at 30deg;C and 7.1% at 37deg;C when albumin was not present, whereas in the presence of albumin all of the sera reacted at 30deg;C and 67.9% reacted at 37deg;C. None of the four patients without haemolytic anaemia reacted at 30deg;C or 37deg;C in the presence of albumin, even though one serum reacted to a titre of 1280 at 4deg;C. Cold agglutinin titres and thermal amplitudes in the presence of bovine albumin were found to correlate better with haemolytic anaemia than reactions without albumin. If bovine albumin is utilized in compatibility testing, multiple cold autoabsorptions may be necessary before alloantibody activity at 37deg;C can be excluded.     

Evidence of parvovirus B19 infection in patients of pre-eclampsia and eclampsia with dyserythropoietic anaemia

Parvovirus B19 (PVB19) infection can induce transient anaemia in patients with increased erythropoiesis. However, the dynamic change within the bone marrow after PVB19 infection is not well understood. Increased erythropoiesis is a physiological phenomenon in puerperital women. Nevertheless, anaemia as a result of PVB19 infection in puerperital women has never been reported. We report one patient with eclampsia and two patients with pre-eclampsia who had transient, severe anaemia during the puerperital period because of PVB19 infection. Viral genomes were detected in the peripheral blood during the anaemic period by polymerase chain reaction and became undetectable after the anaemia was resolved. Viral genomes and protein could also be detected in bone marrow by in situ hybridization and immunohistochemical staining, respectively. Serial aspiration cytology of bone marrow showed severe dysplastic change involving erythroid precursors with a few apoptotic cells at the initial onset of anaemia, markedly increased apoptotic cells that was confirmed by the increased expression of activated caspase 3, around the nadir of anaemia, and a normal marrow picture without features of apoptosis after recovery from anaemia. Our data indicates that PVB19 infection can induce transient, severe dyserythropoietic anaemia in puerperital women with pre-eclampsia/eclampsia and the pathogenetic mechanism may probably involve the induction of apoptosis following PVB19 infection.     

Autoimmune Haemolytic Anaemia with the Unusual Combination of both IgM and IgG Autoantibodies

Abstract. Two patients with autoimmune haemolytic anaemia of no obvious aetiology are presented. Both cases had IgM autoantibodies which were cold agglutinins with anti-I specificity and were complement binding. Both cases also had IgG autoantibodies which were incomplete, of wide thermal range and also had anti-I specificity, but were not complement binding. The red cells of both patients were coated with C4d/C3d and IgG.     

Development of Mixed-Type Autoimmune Hemolytic Anemia and Evans’ Syndrome following Chicken Pox Infection in a Case of Low-Titer Cold Agglutinin Disease

We describe a patient with low-titer cold agglutinin disease (CAD) who developed mixed-type autoimmune hemolytic anemia (AIHA) and idiopathic thrombocytopenia following chicken pox infection. At least 1 year before admission to hospital, the patient had mild hemolytic anemia associated with low-titer cold agglutinins. A severe hemolytic crisis and thrombocytopenia (Evans' syndrome) occurred several days after infection with chicken pox, and the patient was referred to our hospital. Serological findings revealed the presence of both cold agglutinins and warm-reactive autoantibodies against erythrocytes, and the diagnosis was mixed-type AIHA. Following steroid therapy, the hemoglobin (Hb) level and platelet count improved. The patient was closely followed over a 10-year period with recurrent documented hemolysis after viral or bacterial infections. Warm-reactive autoantibodies have not been detected in the last 2 years, and only the immunoglobulin M anti-I cold agglutinins with a low titer and wide thermal amplitude have remained unchanged. Therefore, the patient has received at least 10 mg prednisolone daily to maintain a Hb level of 10 g/dL. To the best of our knowledge, no adult case of low-titer CAD that has evolved into mixed-type AIHA and Evans' syndrome after chicken pox infection has been previously reported in the literature.     

The Ultrastructure of Bone Marrow Histiocytes in Megaloblastic Anaemia and the Anaemia of Infection

S ummary . An electron-microscopic study was made of the iron in the histiocytes in niegaloblastic anaemia and in the anaemia of infection. The particulate iron seen by Prussian Blue staining in the histiocytes in megaloblastic anaemia was demonstrated by electron microscopy to be bound in the vesicles, while the diffuse iron staining in the anaemia of infection was related to the free dispersion of iron-containing particles in the cytoplasm of the histiocytes. The phagocytosis of erythroblasts at various stages of maturity occurred in cases of niegaloblastic anaemia and resulted in a picture showing every stage of degradation. Phagocytosis of erythroblasts by histiocytes was not seen in the marrows of patients with the anaemia of infection nor did it occur in niegaloblastic anaemia in remission.     

Reappraisal of the Role of Anti-i in Haemolytic Anaemia in Infectious Mononucleosis

S ummary . Current literature implies that haemolytic anaemia in infectious mononucleosis is regularly caused by the temporary production of high thermal amplitude cold agglutinins of anti-i specificity. More recently, Capra et al (1969) suggested interaction between IgG anti-i and anti-IgG antibodies as the cause of haemolytic anaemia in infectious mononucleosis. A detailed serologic evaluation of three patients during moderate to severe haemolytic anaemia in infectious mononucleosis revealed high thermal amplitude anti-i in only one. This patient's direct antiglobulin test (DAT) was negative using anti-IgG but was 3 + using anti-C₃ and -C₄. The serum antibody titre against cord or adult Oi cells was 512 at 4°C and 4 at 31°C. The anti-i was inhibited by mercaptoethanol, and anti-IgG was not found in the patient's serum. Patient 2 had a negative DAT and patient 3 had a 2 + DAT using anti-C₃ and anti-C₄. Anti-i was present only in low titre at 4°C and was unreactive at 20°C. It was inhibited by mercaptoethanol. These patients' sera contained anti-IgG antibodies. In none of our patients were warm autoantibodies detected. This data demonstrates that haemolytic anaemia in infectious mononucleosis is not necessarily associated with high thermal amplitude anti-i. Further, since the anti-i antibodies in patients 2 and 3 were of low titre, were inhibited by mercaptoethanol, and did not react at physiologic temperatures, the mechanism of haemolysis in these patients does not seem related to the interaction of anti-IgG and IgG anti-i antibodies. Further work is necessary to clarify the mechanism of haemolytic anaemia in infectious mononucleosis.     

Malaria in pregnancy: adverse effects on haemoglobin levels and birthweight in primigravidae and multigravidae

BACKGROUND: In areas of endemic transmission, malaria in pregnancy is associated with severe maternal anaemia and low birthweight babies. The prevalence of infection is highest in primigravidae (PG), and hence control efforts are usually geared towards this high risk group. Using a sensitive measure of placental infection, we investigated the relationship between active-acute, active-chronic and past placental infection with maternal anaemia and low birthweight in women of all gravidities. METHODS: Between January 1996 and July 1997, 912 women delivering in Kilifi District Hospital, Kenya, were recruited. Haemoglobin and peripheral malaria slides were taken prior to delivery, placental biopsies and smears were taken at the time of delivery and birthweight and maternal height and weight were measured soon after birth. Information was obtained on socio-economic and educational status. The association between placental malaria, severe anaemia and low birthweight was investigated for women of different gravidities. FINDINGS: By placental histology, the prevalence of active or past malaria in all gravidities was high, ranging from 64% in PG to 30% in gravidities 5 and above. In gravidities 1-4, active malaria infection was associated with severe maternal anaemia, adjusted OR 2.21 (95% CI 1.36, 3.61). There was a significant interaction between chronic or past malaria and severe anaemia in their effects on birthweight, whereby the risk of low birthweight was very high in women with both chronic or past placental malaria and severe anaemia: OR 4.53 (1.19, 17.2) in PG; 13.5 (4.57, 40) in gravidities 2-4. INTERPRETATION: In this area of moderate malaria transmission, women of all parities have substantially increased risk of low birthweight and severe anaemia as a result of malaria infection in pregnancy. The risk of low birthweight is likely to be particularly high in areas with a high prevalence of severe anaemia.     

Clinical and immunologic features of transient cold agglutinin hemolytic anemia

Atypical pneumonitis, often induced by infection with Mycoplasma pneumoniae, is frequently associated with elevated cold agglutinin titers but only rarely with significant hemolytic anemia. An example and documentation of the clinical and immunologic course of such transient cold agglutinin hemolytic anemia is presented, and the immunochemical characteristics of cold agglutinins in this syndrome are assessed in regard to their biologic implications and diagnostic significance. Transient cold agglutinins, such as observed in this case, commonly appear to be of a restricted polyclonal character and as first demonstrated in this case may possess structural determinants usually considered unique for monoclonal cold agglutinins. Although the immunopathogenetic mechanisms and certain clinical manifestations of the various forms of cold agglutinin hemolytic anemia appear similar, the immunogenic basis of cold agglutinin production and the molecular structure of transient cold agglutinins are quite distinctive and provide reasonably reliable guidelines for the differential diagnosis of the cold agglutinin syndromes and for consideration of appropriate clinical management.     

Plasmodium infection,anaemia and mosquito net use among school children across different settings in Kenya

Objective To investigate risk factors, including reported net use, for Plasmodium infection and anaemia among school children and to explore variations in effects across different malaria ecologies occurring in Kenya. Methods This study analysed data for 49 975 school children in 480 schools surveyed during a national school malaria survey, 2008–2010. Mixed effects logistic regression was used to investigate factors associated with Plasmodium infection and anaemia within different malaria transmission zones. Results Insecticide‐treated net (ITN) use was associated with reduction in the odds of Plasmodium infection in coastal and western highlands epidemic zones and among boys in the lakeside high transmission zone. Other risk factors for Plasmodium infection and for anaemia also varied by zone. Plasmodium infection was negatively associated with increasing socio‐economic status in all transmission settings, except in the semi‐arid north‐east zone. Plasmodium infection was a risk factor for anaemia in lakeside high transmission, western highlands epidemic and central low‐risk zones, whereas ITN use was only associated with lower levels of anaemia in coastal and central zones and among boys in the lakeside high transmission zone. Conclusions The risk factors for Plasmodium infection and anaemia, including the protective associations with ITN use, vary according to malaria transmission settings in Kenya, and future efforts to control malaria and anaemia should take into account such heterogeneities among school children.     

Link between Helicobacter pylori infection and iron-deficiency anaemia in patients with coeliac disease.

BACKGROUND: Iron-deficiency anaemia is a frequent finding in coeliac disease. Recent investigations have identified Helicobacter pylori infection as a factor responsible for iron deficiency. We investigated the potential relationship between H. pylori and iron-deficiency anaemia in patients with coeliac disease. METHODS: We conducted a prospective observational cohort study on coeliac patients evaluated for iron-deficiency anaemia. An upper gastrointestinal endoscopy was performed and biopsy specimens of duodenal and gastric mucosa were taken for histological examination and assessment of Helicobacter pylori status. RESULTS: The initial database was 386 subjects. Of these, 24 were excluded because of concomitant potential causes of iron deficiency. Of the 362 enrolled patients, H. pylori was detected in 77 (21%) subjects; of these 55 (71%) had iron-deficiency anaemia. Among the 285 H. pylori-negative subjects, 81 (28%) showed anaemia (P < 0.001). We did not find significant differences in gastric histological aspects between patients with or without iron deficiency anaemia. CONCLUSIONS: This study shows a significant association between H. pylori infection and iron-deficiency anaemia in patients with coeliac disease. The discovery of iron-deficiency anaemia in coeliac subjects may constitute another indication for the diagnosis and treatment of this worldwide infection.     

Haemolytic anaemia in previously healthy adult patients with CMV infections: report of two cases and an evaluation of subclinical haemolysis in CMV mononucleosis

Whereas haemolytic anaemia is commonly encountered in infants and young children with cytomegalovirus (CMV) infections, it is an infrequent complication of CMV-induced infections in previously healthy adults. The data from 2 such patients are presented. One patient's Hb fell to a level of 36 g/l, and she required prednisone and blood transfusions. Her direct antihuman globulin test (DAT) was positive (IgG), and her red blood cell survival (51Cr) revealed a T 1/2 of 5 d. Both saline-agglutinating and low-molecular-weight cold agglutinins (CA) (4 degrees C) that reacted against both cord and adult cells were identified. In the second case, a moderate haemolytic anaemia (lowest Hb 87 g/l) was accompanied by negative DAT and CA studies. 20 other patients with CMV-mononucleosis were evaluated for evidence of subclinical haemolysis. Reticulocyte counts greater than 3.0% were noted in 9 of these patients. Haptoglobin values were below 0.5 g/l in 13 patients, and a positive DAT was recorded in 3/10 cases. This study documents haemolysis in many non-immunosuppressed adult patients with CMV infections. The mechanism responsible remains obscure.     

An IgG kappa-monotypic anti-Pr 1h associated with fresh varicella infection

The first cold agglutinin occurring in an adult patient with fresh varicella infection is described. The antibody caused a hemolytic crisis. It had anti-Pr 1h specificity. It belonged to the rare cold agglutinins of the IgG class and was a kappa-monotypic (monoclonal) antibody.