Immunogenetic studies in various diseases provide potential genetic markers. We have studied the incidence of HLA A, B, C, DR and DQ loci antigen in Rh (D) antigen isoimmunized mothers compared to those nonimmunized isoimmunized Rh negative mothers. Seventy six mothers who were immunized to Rh (D) antigen due to pregnancy (responders) and fifty four mothers who did not develop Rh (D) isoimmunization despite positive pregnancies (nonresponders) were selected for the study. Standard methods of serological HLA typing, ABO and Rh (D) groups, and screening for Rh D antibodies were used. 392 unrelated individuals from the population were compared as controls. In addition 45 unrelated individuals from the same population were typed for HLA DRB and DQB gene using PCR-SSP kits. The genotype frequencies of HLA A2, A3, A28, B13, B17, B35, B52, B60, Cw2, Cw6, DR4, and DQ3 were significantly increased, while the frequencies of the HLA A11, A29, A31, B7, B37, B51, Cw1 and DR9 were decreased in the responder women when compared to the non-responder women. HLA A30 (19) split antigen was not identified in immunized women while HLA A23 (9) split antigen was not identified in non immunized women. HLA A3, B17, Cw2 and DR4 showed a significant relative risk among the immunized responder women. When compared with Rh immunized women (responders) reported from USA, England and Hungary the phenotype frequencies of HLA A11, A24, A28, B5, B17, B40, DR2 and DR5 were increased while HLA A23, B8, B18, and DR6 were decreased in the Indian Rh immunized women. Two locus haplotype frequency analysis observed among the responders women revealed that among the significant haplotypes expressed A2-B5, B7-Cw1, DR2-DQ1 were highly significant haplotypes in positive linkage, while A1-B5, and A1-B7 were in significant negative linkage disequilibrium. The haplotype frequencies were <or= one when these common hapoltypes were compared with control population. Thus in the present study it is evident that the inheritance of HLA A3, B17, Cw2 and DR4 increases the relative risk factor by 2.6 times among Indian Rh isoimmunized women. Further, it is evident that there are significant differences in the observed HLA antigen frequencies and two locus haplotypes in Rh isoimmunized women when compared to women from USA, UK and Hungary due to extreme HLA polymorphism in different populations of the world.

Female↗

PubMed2002

HLA B27 polymorphism in Western India.

We have characterized HLA B27 alleles in a sample population of Maharastra, Western Indians (n = 51), with the aim to investigate the different subtypes present among this population. The study was carried out using polymerase chain reaction with sequence-specific primers (PCR-SSP) and reverse line strip (RLS) techniques. Significant new findings have arisen from this study: B*2704, B*2705, B*2707, B*2708 and B*2714 alleles were found to be present, and two novel B27 alleles, B*2708 and B*2714, were found in this Indian population. In addition, B*2714 was observed in a patient with ankylosing spondylitis. This association has not been previously reported in ethnic groups from India.

Alleles↗

PubMed2002

Low cost autologous peripheral blood stem cell transplantation performed in a municipal hospital for a patient with plasma cell leukaemia.

Autologous peripheral blood stem cell transplantation (PBSCT) is a costly procedure. In India, the cost varies from US$20000 to 25000 and most patients cannot afford it. Using several cost-cutting measures, we were able to treat a patient with plasma cell leukaemia by autologous PBSCT. A 42-year-old-male presented with plasma cell leukaemia. He was treated with VAD therapy, followed by high-dose cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) for mobilization of peripheral blood stem cells. The patient was conditioned with high dose melphalan, followed by autologous PBSCT. The procedure was performed in a municipal hospital in which there was no prior experience with stem cell transplantation. Costs were reduced by: (i) using oral medication whenever possible; (ii) having a relative of the patient prepare his food under medical guidance; (iii) starting G-CSF on day 7 rather than on day 1; (iv) short-term storage of the PBSC in an ordinary refrigerator at 4 degrees C without cryopreservation; (v) infusing a large number of CD34+ cells, which shortened the time to engraftment; (vi) delegating many of the functions of a marrow transplant nurse to a resident physician. The cost of transplantation was thereby reduced to about US$ 6000, with successful engraftment by day +13. The patient remained in remission for 7 months, after which he relapsed and was treated with chemotherapy and electron beam radiation to the skin.

Adult↗

PubMed2002

Development of anti-VWF antibody in a patient with severe haemophilia A following the development of high-grade non-Hodgkin's lymphoma.

A 9-year-old-boy with severe haemophilia A (factor VIII < 1%) developed colicky abdominal pain with swelling in the left iliac fossa for 4 weeks. His LDH level was 1423 IU/l (normal range < 220 IU/l) and his uric acid, 6.8 mg/dl. A computerised tomography (CT) scan of the abdomen demonstrated a tumour of the terminal ileum and mild hepatosplenomegaly. Pre-operative screening for factor VIII inhibitor was negative. Post-operatively, the patient needed high doses of factor VIII to maintain haemostasis. The tumour was found to be a high-grade lymphoma of Burkitt's type. He recovered from his operation and chemotherapy was commenced. Investigations demonstrated an anti-von Willebrand factor (VWF) antibody. He subsequently relapsed and died of progressive disease. Development of anti-VWF antibody in lymphoma is well known, but development of this antibody in a haemophilia A patient developing lymphoma has not been reported. The present case shows that antibody to VWF should be considered as a possible reason for an increased factor VIII requirement in such patients.

Burkitt Lymphoma↗

PubMed2002

Carrier detection and prenatal diagnosis in haemophilia in India: realities and challenges.

Organizing services for haemophilia in developing countries with few resources is a formidable task. There is wide variation in haemophilia care and management between developing and developed countries. The management of a genetic disorder such as haemophilia becomes difficult in developing countries where scanty resources are allocated mainly to nutrition and infectious diseases as a first priority. In a country such as India, with one billion people and with a wide diversity in cultural, educational and financial conditions, educating people about such diseases is difficult and will take a long time to have an effect on attitudes. Meanwhile, attempts are being made at several centres in India to develop carrier detection and prenatal diagnosis for this disease. Counselling a carrier for detection of her carrier status remains problematic in India because marriages are still largely arranged by the parents of prospective brides and bridegrooms. Hence, the very idea of communicating the carrier status to the bridegrooms' families may lead to cancellation of the marriages, and concealing the carrier status is associated with guilt both for the bride's parents as well as the bride. Prenatal diagnosis and carrier detection in India therefore must be discussed in this context.

Clinical Competence↗

PubMed2002

Genomic interaction in haemophilia: uncharted territory.

Explore the source record for details and available documents.

Blood Coagulation Factors↗

PubMed2002

First-time development of FVIII inhibitor in haemophilia patients during the postoperative period.

Development of inhibitor to FVIII in haemophilia patients is well-known and is not uncommon. However, their development for the first time during the postoperative period has hardly been reported. In a developing country such as India, where resources are limited, development of such an eventuality may prove disastrous. However, as many of our patients are sparingly treated, therefore, even if they test negative for the inhibitor preoperatively, they may get the requisite FVIII antigenic stimulation during the preoperative and immediate postoperative period, leading to the development of inhibitors during this critical time of wound healing. We describe here six patients who developed such an inhibitor, from a group of 35 patients with haemophilia A who underwent various surgical procedures (19%). We stress that such an eventuality may not remain rare in developing countries as more patients of severe haemophilia undergo surgery and are therefore challenged for the first time in their life with large amounts of FVIII concentrate during their preoperative period.

Adolescent↗

PubMed2002

Danazol therapy in factor X deficiency: more questions than answers.

Explore the source record for details and available documents.

Adult↗

PubMed2002

Common human leucocyte antigen haplotypes in Indians--its implications in finding unrelated compatible bone marrow donors.

All over the world there have been efforts to make unrelated stem cell registries to cater for patients who do not have a compatible family donor and are in need of allogenic stem cell transplantation. Donors of Indian origin are poorly represented all these registries. Approximately 10 million Indians live outside India, and a substantial number of them live in the developed West. Hence when some of these patients of Indian origin need unrelated stem cell donor, they search the available National Marrow Donor Program (NMDP) registry database and invariably do not get a human leucocyte antigen (HLA) matched donor. They come to India, where a haphazard search for the donor ensues and it invariably ends in failure. Hence, we have compiled the data of our laboratory and other published reports in population HLA studies from India and abroad to show several common haplotypes from these studies. It is hoped that this will give the busy clinician an idea whether a search for prospective unrelated stem cell donor for an Indian patient is likely to succeed or not.

Bone Marrow Transplantation↗

PubMed2002

Frequency distribution of antigens in the human platelet antigen-1 system in the western Indian population.

BACKGROUND: Neonatal alloimmune thrombocytopenic purpura (NAITP) occurring because of fetomaternal incompatibility in the human platelet antigen-1 (HPA-1) system is increasingly being detected worldwide. Several studies have reported the frequency and distribution of HPA-1 alleles in different countries and ethnic populations. A paucity of data regarding the frequency of the antigens in the HPA-1 system in the Indian population prompted an undertaking of this study. The molecular method of genotyping the platelet antigens is preferred to serology. It will enable future prenatal diagnosis in mothers suspected to have NAITP so that they can be managed better. STUDY DESIGN AND METHODS: Five hundred six unrelated subjects were screened for the alleles in the HPA-1 system, of which 185 were healthy males and 321 were females. DNA was extracted from the peripheral blood WBCs of these subjects, followed by PCR amplification and agarose gel electrophoresis of the PCR-amplified products. RESULTS: Four hundred two out of 506 subjects (79.44%) were found to be homozygous for HPA-1a. Ninety-nine subjects (19.57%) were heterozygous HPA-1a/HPA-1b, and five subjects out of 506 (0.99%) were homozygous for HPA-1b. CONCLUSION: Homozygosity for HPA-1b exists in the Indian population at a frequency of 0.99 percent, whereas homozygosity for HPA-1a is present in approximately 79 percent of the population. Hence, 0.98 x 0.79 of the females (0.77%) in the reproductive age group are likely to be pregnant with an HPA-1a-positive fetus, leading to a setting in which NAITP might develop. The development of NAITP also depends on the HLA type of the mother; nevertheless, the number of pregnancies in which the fetus is at risk for NAITP in India is quite significant.

Adolescent↗

PubMed2002

Seronegative spondarthritis and human leucocyte antigen association.

The human leucocyte antigen (HLA) B27 has been associated with seronegative spondarthritis universally, but the associations varies (19-94%) in different Indian population groups. It is possible that this variation is due to patient selection bias. Here, we use strict clinical, radiological and serological criteria to select 79 patients with seronegative spondarthritis (SSA) and compare them with 110 healthy, normal individuals from the same ethnic background. The standard National Institute of Health (NIH) microlymphocytotoxicity assay is used to evaluate HLA B27 status in both groups. Significant association between HLA B27 and AS disease was found (odds ratio [OR]: 72.22; P<0.0001; confidence interval [CI]=1.5-3.8) when compared to the control group. Furthermore, HLA B5 was decreased when compared to the control group (OR: 0.39; P<0.01). Those in the 20-40 age group were more vulnerable, with a male preponderance (7:1) over females. These findings confirm the strong association of the HLA B27 allele with various types of spondarthritis and suggest that allele detection would help in the diagnosis of AS where clinical presentation is unclear and in identifying family members at risk.

Adult↗

PubMed2002

Genetic disorders in haematological practice in India.

Haemoglobinopathies represent a significant national health burden in India. The distribution of specific disorders varies geographically and by community. Heterozygote frequencies of beta-thalassaemia range from 1 to 15%, resulting in an estimated 20 million carriers. HbS is mainly present in tribal and non-caste communities, with carrier prevalences of up to 40%. By comparison, alpha-thalassaemia carriers are found in both the caste and tribal communities, and can reach a frequency of >90% in the latter case. Community control of haemoglobinopathies relies mainly on out-reach education programmes and genetic counselling, with antenatal diagnosis offered in specific major centres. Only partial data are available on the prevalence of haemophilia, but it has been estimated that there are some 50,000 affected individuals nationwide, with an additional 1,500 new cases born each year. RFLP-based techniques have been established to detect mutations in the factor VIII and IX genes, enabling the limited introduction of carrier detection and antenatal diagnosis.

Journal Article↗

PubMed2002

Spectrum of inherited bleeding disorders from Western India.

OBJECTIVE: The study was undertaken to assess the magnitude and diversity of different bleeding disorders in Western India. MATERIALS AND METHODS: 768 cases referred to our Institute for evaluation of an underlying bleeding diathesis were investigated appropriately to detect the cause of the abnormal hemostatic function. RESULTS: 630 patients were diagnosed to have hereditary bleeding diathesis. Amongst these, 598 patients had a coagulation disorder while only 32 patients had a platelet function abnormality. Amongst the coagulation disorders, hemophilia A (70.5%) was the most common disorder followed by hemophilia B (14%) and VWD (10.8%). Glanzman's thrombasthenia (84.3%) was the most common platelet function disorder followed by Bernard-Soulier syndrome (12.5%). Some rare disorders have also been diagnosed. CONCLUSION: In spite of their apparent rarity, India has a substantial number of cases of inherited bleeding disorders. A large number of these patients is referred to many tertiary care institutions. It is therefore desirable that district hospitals must develop their laboratories to detect most of these disorders so that the patients need not travel long distances to get an appropriate diagnosis and proper management. All 1st degree female relatives of severe and moderate hemophilia must get factor assays done because some of them may be vulnerable to post-procedural or post-traumatic bleeding.

Blood Coagulation Disorders, Inherited↗