Transfusions of least-incompatible blood with intravenous immunoglobulin plus steroids cover in two patients with rare antibody.

BACKGROUND: The therapeutic value of the use of intravenous immunoglobulin (IVIG) to correct anemia and thrombocytopenia as a result of immunologic causes (hemolytic disease of the fetus and newborn and fetal or neonatal alloimmune thrombocytopenia) have been well established. Few published papers exist regarding the use of IVIG in adult settings. We report two patients with clinically significant antibodies against high-incidence antigens, who were successfully transfused with incompatible red blood cells (RBCs), in conjunction with IVIG plus steroids and IVIG. CASE REPORTS: Case 1 was a 25-year-old patient (Hb SC) who was admitted with low hemoglobin (Hb) and low reticulocyte count. A diagnosis of parvovirus-induced RBC hypoplasia was made. The patient's sample contained anti-E, anti-N, and anti-U. The Hb decreased to 37 g/dL and urgent transfusion was provided with E-, N-, "least-incompatible" RBC units covered by IVIG and hydrocortisone. Case 2 was a 54-year-old patient who was admitted after a road traffic accident. Nonspecific weak antibody was detected. She received 6 units of least-incompatible RBCs. She was transferred to another hospital and received 2 least-incompatible units. Hb level decreased further and an additional unit was transfused. Samples were referred to the reference laboratory and strong anti-Jra detected. As there was clinical and laboratory evidence of hemolysis and Jr(a-) units were not available, IVIG was prescribed and least-incompatible units were transfused. RESULTS: There were no hemolytic transfusion reactions, hemolysis ceased, and anemia improved in both cases. CONCLUSION: Prophylaxis with IVIG plus steroids and IVIG should be considered as a therapeutic option when transfusion of incompatible units is necessary.

SMIM1 underlies the Vel blood group and influences red blood cell traits.

The blood group Vel was discovered 60 years ago, but the underlying gene is unknown. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel. To identify the responsible gene, we sequenced the exomes of five individuals negative for the Vel antigen and found that four were homozygous and one was heterozygous for a low-frequency 17-nucleotide frameshift deletion in the gene encoding the 78-amino-acid transmembrane protein SMIM1. A follow-up study showing that 59 of 64 Vel-negative individuals were homozygous for the same deletion and expression of the Vel antigen on SMIM1-transfected cells confirm SMIM1 as the gene underlying the Vel blood group. An expression quantitative trait locus (eQTL), the common SNP rs1175550 contributes to variable expression of the Vel antigen (P = 0.003) and influences the mean hemoglobin concentration of red blood cells (RBCs; P = 8.6 × 10(-15)). In vivo, zebrafish with smim1 knockdown showed a mild reduction in the number of RBCs, identifying SMIM1 as a new regulator of RBC formation. Our findings are of immediate relevance, as the homozygous presence of the deletion allows the unequivocal identification of Vel-negative blood donors.

An unusual case of an acute hemolytic transfusion reaction caused by an autoanti-I.

In general, naturally occurring cold autoagglutinins react optimally at low temperatures. We describe a young child who experienced an acute hemolytic transfusion reaction by an unusual autoanti-I. The IgM autoanti-I was detected at 4°C (titer 256) and also reacted at 30°C. This case highlights the potential hazard of transfusing units of blood immediately upon removal from the blood refrigerator, especially into neonates and children of small stature.

High anti-A titres may not preclude ABO-incompatible renal transplantation: an autoantibody could be the culprit.

ABO-incompatible live donor renal transplantation is a growing field. To avoid hyperacute rejection, pre-operative ABO antibody titres should be < 8. There are a number of therapeutic measures used to reduce these titres if they are high. This case report describes a patient initially found to have an extremely high anti-A IgG titre (512). The high titre results were concomitant with a positive atypical antibody screen, which showed no specificity on identification. A strategy to assess true titre levels and remove sub-clinical autoantibodies was devised, leading to successful transplantation.

Mixed-type autoimmune haemolytic anaemia: unusual cases and a case associated with splenic T-cell angioimmunoblastic non-Hodgkin's lymphoma.

The diagnosis of mixed-type autoimmune haemolytic anaemia (AIHA) is based on demonstrating the presence of "warm" IgG auto-antibody and "low titre" ( < 64 at 4 degrees C), "high thermal amplitude" (reacting at or >30 degrees C) "cold" IgM auto-antibody. Mixed-type AIHA is uncommon. Red cell agglutination on the peripheral blood film is a common finding in mixed-type AIHA and can lead, initially, to a mis-diagnosis of cold haemmagglutinin disease (CHAD). Mixed-type AIHA is rare and can be idiopathic or secondary, often associated with systemic lupus erythematosus (SLE) and lymphoma. In general, patients with mixed-type AIHA show a dramatic response to steroid therapy and frequently require few or no transfusions. We report two unusual cases of mixed-type AIHA. Case one was unusual as the patient developed AIHA while on steroid medication. Case two, we believe, is the first reported case of splenic T cell angioimmunoblastic non-Hodgkins lymphoma (NHL) associated with mixed-type AIHA. The patient failed to respond to steroids, intravenous immunoglobulin, chemotherapy and treatment with rituximab. The patient received 33 units of red cells over a 9-week period. She finally underwent splenectomy with resolution of haemolysis. DAT tested with monospecific reagents, and thorough serological investigations is required to reach the diagnosis of mixed-type AIHA. Awareness of this condition is important as management may be different from either treating warm AIHA or CHAD.

Use of intravenous immunoglobulin and intravenous methylprednisolone in hyperhaemolysis syndrome in sickle cell disease.

Hyperhaemolysis syndrome (HS), a syndrome in which there is destruction of both donor and recipient red cells after transfusion, is well recognised in patients with sickle cell disease and beta-thalassaemia. It has also been reported in a patient with myelofibrosis. In acute forms of HS, evidence of red cell antibody-mediated haemolysis is lacking, and it has been proposed that the transfused and the patient's own red blood cells were destroyed by hyperactive macrophages. Continuation of transfusion may be lethal as this can further exacerbate haemolysis. We report two cases of HS successfully treated with IVIg and IV methylprednisolone. The cessation of haemolysis following administration of IVIg and IV methylprednisolone supports the view that hyperactive macrophages contribute to the RBC destruction. IVIg and methylprednisolone appear to have a synergistic effect on suppressing the activity of macrophages.