Red cell immunization in multiply transfused Malay thalassemic patients.

The development of red blood cell (RBC) isoimmunization with alloantibodies and autoantibodies complicate transfusion therapy in multiply transfused thalassemia patients. Thus, the frequency, causes and prevention of these phenomena were studied among these patients. Clinical and serological data from 58 Malay multiply transfused thalassemic patients who sought treatment at Hospital University Sains Malaysia were collected and analyzed prospectively. Blood samples were subjected to standard blood bank procedures to screen for antibody and subsequent antibodies identification. All patients in our hospital received blood matched for only ABO and Rh (D) antigens. There were 46 (79.3%) patients with Hb E/beta thalassemia, 8 (13.8%) with beta thalassemia major, 3 (5.2%) with Hb H Constant Spring and 1 (1.7%) with Hb H disease. Overall, 8.6% of the patients had alloantibodies and 1.7% had autoantibodies. The alloantibodies identified were anti-E, anti-c, anti-K, anti-Jka, anti-N and anti-S. In conclusion, the transfusion of matched blood is essential for chronically multiply transfused patients in order to avoid alloimmunization. Considering the high frequency of anti E at our hospital, it is advisable to genotype patients and match the red cells for E antigens in multiply transfused thalassemia patients.

Detection of serologic prevalence of anti-CMV antibodies in thalassemia major patients and blood donors

Cytomegalovirus [CMV] infection has been recognized as a complication of blood transfusion. Transfusion-related CMV infection produces dramatic problems in immunocompromised patients including organ transplantation recipients, AIDS patients under immunosuppressive therapy, thalassemia major patients, and premature neonates. Regarding the importance of this infection in multitransfused patients and differences in prevalence of transfusion - related CMV infection in various reports, especially in thalassemia major patients, we decided to detect and compare the prevalence of CMV antibodies in thalassemia patients and blood donors. In this study we detected anti-CMV antibodies [IgGJgM] by Elisa technique. We tested these antibodies in 55 thalassemia major patients [45 non-splenectomized and 10 splenectomized] and 1040 healthy donors. Our results showed that anti-CMV IgG antibody was positive in 89.6% of control group and 100% of thalassamic group, thus indicating of no significant difference in these two groups. Anti-CMV IgM antibody was positive in 0.04% of control group and in 9.1% of thalassemic group showing a significant difference. The prevalence of this antibody was respectively 30% and 4.5% in splenectomized and non-splenectomized groups of patients Absence of significant difference of anti-CMV IgM antibody in patient and control group reflected high frequency of this infection in our population and also the importance of the use of leukocyte free products for high risk blood recipients. Moreover, the significant difference in anti-CMV IgM antibody in splenectomized and non-splenectomized patient groups is related to the role of spleen in clearance of infectious agents and production of IgM antibody in this organ

Clearance of hepatitis TT virus infection among thalassemia children and IVDU.

The novel transfusion transmissible hepatitis virus TTV first isolated by a group from Japan has predominantly been detected in members of groups at high risk for contracting blood borne viruses. Aside from elevated liver enzymes, the symptoms associated with its infection have been reported to range from asymptomatic to hepatic failure. The purpose of the present study was to determine if and to what extent the host's immune response is capable of clearing TTV infection. Hence, we extracted DNA from sera obtained from altogether 201 intravenous drug users (IVDU) and 80 thalassemia children--both groups at high risk of parenteral exposure--and performed PCR using semi-nested primers. Those positive for TTV DNA were once again subjected to PCR after approximately one year in order to determine how many still harbored the virus. Our results showed TTV DNA to be absent in merely 20.6% of the formerly positive IVDU, whereas it was still present in all the thalassemia children who could be tested for the second time. Based on the small sample size and the high-risk environment, these results ought to be interpreted with caution and definitely merit further investigation.

HLA class I antibodies in thalassemic patients.

This study was undertaken to demonstrate the prevalence of HLA class I antibodies among 62 polytransfused patients. The diagnosis included beta-thalassemia major, beta-thalassemia/Hb E disease and severe Hb H disease. Their ages ranged from 1 year to 23 years with the mean age of 10.7 years. The number of packed red cell transfusions ranged from 3 to 235 with the mean of 60 episodes per patient. The standard microlymphocytotoxicity test was performed using 50 panels of lymphocytes which specifically identified the majority of HLA class I antibodies. 31/62 cases (50%) were positive for HLA class I antibodies. The detection of single or multiple antibodies depended upon the number of blood transfusions and the patients' ages. These antibodies were induced by the leukocytes present in the transfused packed red cells. Therefore, leukocyte-reduced packed red cells prepared by either additional inverted centrifrugation or leukocyte filter is suggested for the routine blood bank service.

Prevalence of anti-HCV antibodies in central India.

The study group screened for anti-HCV comprised 789 subjects of hepatitis, renal failure, thalassaemia and healthy voluntary blood donors coming from Central India during July 1992 to November 1995. The prevalence of HCV was low (4.85%) among 103 patients of acute viral hepatitis (AVH) while it was higher (25.64%) among 117 patients of chronic liver disease (CLD) with the highest rate of 31.57 percent in 57 patients of cirrhosis. The anti-HCV positivity among 101 patients with hepatic failure was around 10 percent. High risk groups such as chronic renal failure (CRF) patients mainly on haemodialysis and thalassaemics receiving multiple blood transfusions showed the prevalence of anti-HCV in 41.9 and 25.45 percent respectively. Only 1.78 percent of the 280 voluntary blood donors showed positivity for anti-HCV. Comparison of the data on HCV in the present study with data from other parts of India showed a wide variation in the different centers. The higher prevalence of HCV among CRF patients and thalassaemics indicates the need for screening of the blood units for anti-HCV before transfusion to these high risk patients.

Autoantibodies in thalassaemia major: relationship with oral iron chelator L1.

Ninety patients with thalassaemia major were investigated for the occurrence of antinuclear antibodies (ANA), and those with ANA were tested for antibodies to histones (AHA). ANA were detected in 7 of 27 thalassemics on oral iron chelator L1, and in 2 of 63 thalassaemics not on L1 (p < 0.01). AHA were seen in 4 of 7 thalassemics receiving L1 with positive ANA, and in none of the 2 not receiving L1 (p < 0.03). Joint pains were seen in patients receiving L1, but in none of the patients not receiving L1. There was no correlation between hepatitis B or HIV positivity and presence of ANA or joint pains. While some amount of background ANA-positivity was found in patients with thalassaemia major, it was significantly more in patients receiving L1. Laboratory evidence of drug-induced lupus-like reaction was seen only in patients who received L1. In view of serious concerns about the safety of L1 and wide variations in the incidence and severity of adverse reactions reported by different sources, an urgent regulatory audit of all trial centres is essential.

Anti-nuclear antibody positivity in multi-transfused thalassemia major.

The frequency of anti-nuclear antibodies (ANA) was evaluated in multi-transfused patients of thalassemia major. Twelve out of 83 patients (14.5%) had positive ANA at titres of 1:80 or above. The results were compared with age and sex matched healthy controls who showed positive results in only 1 of 52 cases (1.9%; p less than 0.05). Antibody against double stranded DNA was absent. ANA positivity was found to correlate with higher age (p less than 0.01), more amount of blood transfused (p less than 0.01), splenectomy status (p less than 0.01), higher levels of serum ferritin (p less than 0.01) and presence of hepatitis B surface antigen (p less than 0.01) and antihepatitis C antibody (p less than 0.01).

Frequency of hepatitis B, C and D and human immunodeficiency virus infections in multi-transfused thalassemics.

Of forty multi-transfused thalassemia patients (26 males, 14 females; mean age 8.1 +/- 5.3 years, range 1-35) with no clinical or biochemical evidence of liver disease, HBsAg, anti-hepatitis C virus and anti-human immunodeficiency virus antibodies were present in 18 (45%), 7 (17.5%) and 1 (2.5%) cases respectively. Three of the 18 (16.7%) HBsAg positive patients were anti-delta antibody positive. Our results indicate that more than 50% of multi-transfused thalassemia patients show serological evidence of one or more of hepatitis B, C and D and human immunodeficiency virus infection.

Serological responses to hepatitis B virus infection in multi-transfused thalassemic children.

One hundred children with beta-thalassemia major were studied prospectively. A one time analysis of serum samples was carried out for a battery of hepatitis B viral markers viz., HBsAg, anti-HBs and anti-HBc. Seven mutually different serological patterns were observed. The commonest profile seen in 49 patients was a combined seropositivity for anti-HBc and anti-HBs indicating past HBV infection with persisting immunity. Definite evidence of active HBV infection (seropositivity for HBsAg and/or HBeAg) was demonstrated in 10 cases, six of these were HBsAg positive. Anti-HBc positivity alone was detected in 17 patients. The remaining 24 children were seropositive for anti-HBs alone suggesting a possible passive transmission of anti-HBs through blood transfusion.

Estudios inmunológicos en talasemia mayor / Immunologic studies in thalassemia major

Los pacientes con talasemia mayor (TM) presentan defectos inmunes secundarios la estimulación antigénica y sobrecarga de hierro que resultan de su contínuo tratamiento con alteraciones cuantitativas en las subpoblaciones linfocitarias sanguíneas, como defectos funcionales en la citotoxicidad natural (NE), en la diferenciación B, en la inmunorregulación por células T, y en la actividad efectora de los fagocitos. Los pacientes con TM de hasta 10 años de edad tienen una distribución linfocitaria similar a la de controles normales y lo mismo ocurre con la función de sus fagocitos. Los pacientes de más de 10 años presentan una linfocitosis, con aumento de linfocitos B y en los pacientes esplenectomizados, también de los linfocitos T-CD8 positivos. El defecto en los fagocitos consiste en una disminución en la generación de metabolitos tóxicos del O2 durante el estallido respiratorio, con menor capacidad candidicida, pero con capacidad fagocitica normal. Este defecto es proporcional a la edad y a la concentración de ferritina sérica o sea que a mayor edad y/o sobrecarga de hierro, mayor defecto en los fagocitos. Las disfunciones B, T y NK eran independientes de la edad de los pacientes, observándose incluso en pacientes de menos de años, aunque se las atribuye a las transfusiones de sangre. Algunos defectos se pueden encontrar incluso en los portadores de TM, específicamente en la función B y NK, lo que sugiere un componente genético. La TM constituye un modelo humano que se pese a su...