Autoimmune haemolytic anaemia treated with multiple transfusions, immunosuppressive therapy, plasma exchange, and desferrioxamine

Severe autoimmune haemolytic anaemia in a five year old boy was unaffected by treatment with prednisone and splenectomy, but subsided after combined immunosuppressive therapy and three plasma exchanges. Over five months, a total of 93 transfusions of concentrated erythrocytes was given (equal to 18.6 grams of iron or 1.1 g/kg BW). This resulted in severe iron overload with cardiac, hepatic, and pancreatic complications, together with growth-retardation. These complications disappeared after treatment with desferrioxamine and vitamin C, but despite a normal growth hormone response to glucagon the concentration of somatomedin in serum remained low. Treatment by plasma exchanges and immunosuppressive agents may therefore be of value in severe haemolytic anaemia refractory to corticosteroids and splenectomy. Iron chelating therapy should be considered if multiple transfusions result in iron overload.     

Autoimmune Haemolytic Anaemia Treated with Multiple Transfusions, Immunosuppressive Therapy, Plasma Exchange, and Desferrioxamine

ABSTRACT. Severe autoimmune haemolytic anaemia in a five year old boy was unaffected by treatment with prednisone and splenectomy, but subsided after combined immunosuppressive therapy and three plasma exchanges. Over five months, a total of 93 transfusions of concentrated erythrocytes was given (equal to 18.6 grams of iron or 1.1 g/kg BW). This resulted in severe iron overload with cardiac, hepatic, and pancreatic complications, together with growth-retardation. These complications disappeared after treatment with desferrioxamine and vitamin C, but despite a normal growth hormone response to glucagon the concentration of somatomedin in serum remained low. Treatment by plasma exchanges and immunosuppressive agents may therefore be of value in severe haemolytic anaemia refractory to corticosteroids and splenectomy. Iron chelating therapy should be considered if multiple transfusions result in iron overload.     

Autoimmune haemolytic anaemia: Recent advances in pathogenesis,diagnosis and treatment

The diagnosis and management of patients with autoimmune haemolytic anaemia demands knowledge of various aspects of both clinical and laboratory medicine. There is an apparent gap of communication between the serologist and the clinical physician due to the high specialization of both. The purpose of this annotation is to close some of these gaps by relating the serological data to the diagnosis, severity of disease, treatment, and prognosis.Abbreviations AIHA autoimmune haemolytic anaemia - DAT direct antiglobulin test     

Renal complications associated with human parvovirus B19 infection in early childhood

A previously healthy two-year-old girl presented with proteinuria and macroscopic haematuria. Laboratory findings included haemolytic anaemia with thrombocytopenia. Interestingly, continuing reticulocytopenia was noted. Therefore an acute parvovirus B19 infection was suspected, which could be confirmed by serological and molecularbiological evidence. This case report underlines renal complications of parvovirus B19 infection in early childhood including haemolytic-uraemic syndrome (HUS)-like episodes, and potential pathogenetic mechanisms are discussed.     

Micro-angiopathic haemolysis, thrombocytopenia and nephrotic syndrome associated with membranous nephropathy in a Vietnamese boy

The unique association of idiopathic diffuse membranous nephropathy and micro-angiopathic haemolytic anaemia and thrombocytopenia is described. A 7 year old Vietnamese boy with a 1-month history of anaemia resistant to oral iron supplements presented with acute onset of nephrotic syndrome. Investigations revealed a micro-angiopathic haemolytic anaemia and thrombocytopenia. There was no associated oliguria or uraemia. Diffuse membranous nephropathy was diagnosed by renal biopsy. Apart from a fourfold rise in enterovirus titres, no underlying cause for the haematological or glomerular abnormalities was found. There was an apparent, partial haematological response to fresh frozen plasma infusions, but not to Vitamin E.     

Acute haemolytic anaemia in typhoid fever

Summary Two G-6-PD deficient children with typhoid fever complicated by acute haemolytic anaemia are reported. One of them had the rare complication of haemoglobinuria. The role of typhoid infection versus chloramphenicol treatment in causing haemolysis in G-6-PD deficiency is discussed. From the Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh.     

Haemolytic uraemic syndrome and thrombotic thrombocytopenic purpura

This review will focus on the classification, symptoms, pathology, pathogenesis and management of haemolytic uraemic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). HUS is characterized by microangiopathic haemolytic anaemia, thrombocytopenia and acute renal failure. Typical cases have been associated with infections caused by Shiga toxin (Stx)-producing bacteria manifested by a diarrhoeal prodrome. Atypical cases have heterogeneous aetiologies not associated with Stx. Certain cases may be hereditary and mutations in complement factor H have been identified in a subset of these patients. TTP is a similar condition characterized by microangiopathic haemolytic anaemia, thrombocytopenia, nephropathy, fever and neurological symptoms associated with mutations in the von Willebrand cleaving protease. The pathological lesion has been termed thrombotic microangiopathy revealing small vessel lesions and platelet thrombosis leading to obstruction of blood flow. Supportive management reduces morbidity and mortality. Patients with atypical HUS and TTP may benefit from specific treatment with plasma infusions or exchange.     

L'infection extrapulmonaire à Mycoplasma pneumoniae

Pneumonia is the main site of infection with Mycoplasma pneumoniae in paediatric age. Nevertheless it can also give rise to other manifestations, with or without respiratory involvement. In the present review are described some unusual clinical features of M. pneumoniae in children. Encephalitis and meningoencephalitis is the most frequent neurological manifestation, but cases of meningitis, myelitis, and polyradiculitis, have been reported. Cardiac involvement is potentially severe, including pericarditis and myocarditis. Cold agglutinin haemolytic anaemia is the most frequent haematologic manifestation. Skin, renal, gastro-intestinal, osteoarticular, and other manifestations have also been reported in the literature. The pathogeny of these extrapulmonary infections is not fully elucidated and the treatment remains partly controversial. Extrapulmonary complications can occur as a result of direct invasion and/or autoimmune response.     

Haemolytic uraemic syndrome.

The haemolytic uraemic syndrome is an acute illness characterised by the occurrence of renal injury, haemolytic anaemia with red cell fragmentation and thrombocytopenia. Haemorrhagic diathesis, arterial hypertension and neurological manifestations often complicate the acute phase of the disease. In this article, we shall discuss in more detail the aspects of this phase. Data obtained in 72 patients treated at the Wilhelmina Children's Hospital in Utrecht, from 1964 to 1977, are used to illustrate the characteristics of the disease.     

Haemolytic anaemia in association withEscherichia coli 0157 infection in two sisters

Two sisters, 2 and 5 years of age, suffered from acute haemolytic anaemia occurring after gastroenteritis withEscherichia coli 0157. One patient developed clinical signs of severe and acute intravascular haemolytis and sepsis. She received transfusion and antibiotic therapy. The second patient presented with mild to moderate haemolytic symptoms only. None of them developed renal impairment. In serum of both children, elevated titres of short-lived agglutinins were demonstrated in the indirect haemagglutination assay consisting of sheep erythrocytes coated with lipopolysaccharide fromE. coli 0157. By immunoblot analysis IgM antibodies against the 0157 lipopolysaccharide were demonstrated in the acute phase sera but not in follow up sera taken 2 months after disease. On erythrocyte membranes, adsorption of microbial antigens was detected by use of a pool-immunoglobulin fluorescence test. The immunological status of both patients was normal. Complete recovery from haemolytic disease was observed without further therapy. Microbial antigens attached to the cell surface were assumed to be the pathophysiological cause ofE. coli 0157 associated haemolytic anaemia in two siblings.     

Haemolytic anaemia associated with acquired toxoplasmosis

A 2 year old girl presented with fever, malaise, a maculopapular rash and lymphadenopathy followed by the onset of haemolytic anaemia and massive splenomegaly. Serology was consistent with acquired toxoplasmosis. A 6 week course of pyrimethamine resulted in a rise in the haemoglobin and reduction of the splenomegaly. During the subsequent 10 years, pyrimethamine treatment of three similar acute episodes resulted in similar clinical responses. There was no spontaneous improvement in the haemolytic anaemia or splenomegaly when pyrimethamine was initially withheld for 6, 1, and 1.5 months respectively during three of these episodes. Investigations did not reveal an immunodeficiency state. This case suggests the possibility of a previously unreported causal association between acquired toxoplasmosis and haemolytic anaemia in a child.     

Autoimmune haemolytic anaemia in a newborn infant

The case is reported of an infant with autoimmune haemolytic anaemia of perinatal onset. Combined treatment with steroids and cyclosporin was necessary to improve haemolysis and reduce the high transfusion requirements. Treatment was discontinued at 13 months of age. The child was healthy at the follow up at 24 and 36 months of age.     

Micro-angiopathic haemolysis, thrombocytopenia and nephrotic syndrome associated with membranous nephropathy in a Vietnamese boy

Abstract The unique association of idiopathic diffuse membranous nephropathy and micro-angiopathic haemolyi anaemia and thrombocytopenia is described. A 7 year old Vietnamese boy with a 1-month history of anaemia resistant to oral iron supplements presented with acute onset of nephrotic syndrome. Investigations revealed a micro-angiopath haemolytic anaemia and thrombocytopenia. There was no associated oliguria or uraemia. Diffuse membranous nephropathy was diagnosed by renal biopsy. Apart from a fourfold rise in enterovirus titres, no underlying cause for the haematological or glomerular abnormalities was found. There was an apparent, partial haematological response to fresh frozen plasma infusions, but not to Vitamin E.     

Haemolytic anaemia associated with acquired toxoplasmosis

Abstract A 2 year old girl presented with fever, malaise, a maculopapular rash and lymphadenopathy followed by the onset of haemolytic anaemia and massive splenomegaly. Serology was consistent with acquired toxoplasmosis. A 6 week course of pyrimethamine resulted in a rise in the haemoglobin and reduction of the splenomegaly. During the subsequent 10 years, pyrimethamine treatment of three similar acute episodes resulted in similar clinical responses. There was no spontaneous improvement in the haemolytic anaemia or splenomegaly when pyrimethamine was initially withheld for 6,1, and 1.5 months respectively during three of these episodes. Investigations did not reveal an immunodeficiency state. This case suggests the possibility of a previously unreported causal association between acquired toxoplasmosis and haemolytic anaemia in a child.     

Autologous peripheral blood stem cell transplantation and anti-B-cell directed immunotherapy for refractory auto-immune haemolytic anaemia

 We report the clinical course of a 6.5-year-old boy with refractory auto-immune haemolytic anaemia. Due to failure of conventional immunosuppressive therapy, an autologous peripheral blood stem cell transplantation was performed. The conditioning regimen consisted of cyclophosphamide and anti-thymocyte globulin. The patient was reinfused with 2.6 × 10⁶ CD34 positive selected, B- and T-cell-depleted peripheral blood stem cells per kg body weight. He showed a partial response with a reduced demand for red blood cell transfusions. However, due to persistence of the haemolytic process he was started on rituximab therapy on day +40 post-transplant. Following two doses of rituximab, the patient improved rapidly and developed a sustained complete response. After 10 months, haemolysis recurred and responded again to rituximab therapy without the necessity for red blood cell transfusions. 15 months after initial antibody treatment, however, the patient developed a second relapse which was now refractory to rituximab therapy although CD20+ B-lymphocytes were cleared from the peripheral blood. Conclusion Our case report suggests that rituximab and autologous peripheral blood stem cell transplantation are important though not curative elements in the treatment of patients with severe auto-immune haemolytic anaemia who are refractory to conventional immunosuppressive therapy. Received: 11 January 2001 and in revised form: 17 March 2001 / Accepted: 27 March 2001     

Simultaneous occurrence of the haemolytic uraemic syndrome and acute post-infectious glomerulonephritis

We report on two children, a 12-year-old boy and a 6-year-old girl, with simultaneous occurrence of clinical and laboratory features consistent with both diarrhoea-negative haemolytic uraemic syndrome (D-HUS) and acute post-infectious glomerulonephritis (APGN). Both presented with acute renal insufficiency, hypertension and oedema. Laboratory evaluation revealed micro-angiopathic anaemia with burr cells, thrombocytopenia, elevated lactic dehydrogenase and low complement C3. Urinalysis showed marked proteinuria and haematuria. Renal biopsy was characteristic of APGN, but not of HUS. The outcome was good in both children. Conclusion The simultaneous occurrence of diarrhoea-negative haemolytic uraemic syndrome and acute post-infectious glomerulonephritis is rare. The outcome is generally good as is expected in the latter condition in contrast to the former. Received: 10 August 2000 / Accepted: 20 September 2000     

New drugs for childhood anemia

New drugs, recently available for treatment of different forms of anaemia, have somehow changed the therapeutic scenario in paediatric haematology. The aim of this review is to focus on the newest molecules discussing indications, clinical usefulness and related problems. Erythropoietin, the specific growth factor of red cell precursors, is now an established option for anaemia of chronic renal failure, prematurity, bone marrow transplantation and chemotherapy. Anti-CD20 monoclonal antibody, a novel cytotoxic molecule for mature B lymphocytes, has proven to be effective in the treatment of refractory autoimmune cytopenias. Haemoglobin analogues are currently under investigation, in order to obtain a synthetic oxygen-carrier that can substitute blood transfusions. Finally drugs that are able to increase the production of haemoglobin F have been used in thalassemias and haemoglobinopathies. For patients with sickle cell disease, hydroxyurea is no longer an experimental tool; it has given rise to several trials, where it has proven to be effective in terms of both clinical and haematological improvement.     

Autoimmune haemolytic anaemia in an asymptomatic carrier of hepatitis B virus.

A patient with ''warm type'' autoimmune haemolytic anaemia (AIHA) was also an asymptomatic carrier of hepatitis B virus (HBV). Although the direct antiglobulin test became negative after the anaemia had recovered spontaneously, antigenaemia of HBV persisted and the serum transaminase level remained normal or borderline. AIHA has not previously been described in association with the asymptomatic carrier state of HBV.     

Liver transplant for giant cell hepatitis with autoimmune haemolytic anaemia

Giant cell hepatitis (CGH) with autoimmune haemolytic anaemia (AHA) is a distinct entity with an aggressive course. Immunosuppression may help early disease. A case is reported of a child with GCH and AHA with early disease recurrence after liver transplantation for end stage liver disease.     

Role of haematological,pulmonary and renal complications in the long-term prognosis of patients with lysinuric protein intolerance

Three patients with lysinuric protein intolerance are reported. The first patient displayed severe haemolytic anaemia, bone marrow erythroblastophagocytosis, renal tubular disease and interstitial lung disease. Despite treatment with citrulline and low-protein diet, this child died at the age of 18 months. The second patient is now 24 years old and has chronic interstitial lung disease and focal renal glomerulosclerosis. The third patient, now 5 years old, has severe chronic interstitial lung disease. A 6-month treatment with prednisone was ineffective in the second and third patients.