As compared to haemophilia, although the clinical features and the management strategies for rare coagulation factor deficiencies are discussed, little is known about them. This study was undertaken to assess the distribution, clinical presentation and treatment of patients with rare coagulation factor deficiency disorders in a cross-sectional population of India. Blood samples and other clinical details from patients suspected of rare coagulation factor deficiencies were collected by the Haemophilia Treatment Centers across India and were diagnosed at National Institute of Immunohaematology, Mumbai. A total of 321 cases of rare clotting factor deficiencies were diagnosed, of which 88% were severe, 10% moderate and 2% mild. Commonest deficiency encountered was factor XIII (FXIII) (30%) followed by FX (15.6%), FVII (15%), fibrinogen (12.1%), FXI (9%), combined V and VIII deficiency (5.6%) and congenital multiple vitamin K-dependent coagulation factor deficiency (MCFD, 2.1%). Major representation of these deficiencies was from Southern and Western India (82%). Mucocutaneous bleeding was the commonest clinical presentation (59%); intracranial (IC) haemorrhage was seen in 18% of the patients; menorrhagia was an important clinical pointer in women in the reproductive age group (78%); 8% of the severe cases had no history of bleeding and 73% of the FXIII deficiency cases had umbilical stump bleeding. The major therapeutic products used was fresh frozen plasma (64%), cryoprecipitate (15%), whole blood (15%), antifibrinolytics (5%) and recombinant FVIIa (1%). A distinct pattern in the distribution of rare clotting factor deficiencies was observed which was based on multiple factors that include ethnicity and the available diagnostic facilities in different regions of this vast country.

A serious complication of replacement therapy in patients with bleeding disorders is the development of 'inhibitors', particularly FVIII inhibitors in haemophilia A patients. This leads to an increase in the management cost, morbidity and mortality, especially post-operatively. The mechanism of FVIII inhibitor development is quite complex and it is difficult to predict inhibitor development, but a prompt and accurate diagnosis is critical as early therapy can save lives. The aim of this study was to screen patients with bleeding disorders in India for inhibitors, and to analyse and compare the prevalence of inhibitors in different regions in India. Patient details were recorded and blood samples were collected in sodium citrate vacutainers from 1,505 patients with bleeding disorders, in different cities in India. Coagulation and inhibitor screening assays were performed, followed by the Bethesda assay in inhibitor positive samples to quantify the FVIII inhibitor titre. Out of the 1,505 samples analysed, 1,285 were Haemophilia A patients, out of which 78 (6.07 %) were positive for 'FVIII Inhibitors'. The highest incidence of FVIII Inhibitors was seen in South India (13.04 %). The highest incidence of 20.99 % was observed in Chennai, followed by Hyderabad (13.33 %), Jammu (9.90 %) and Guwahati (8.51 %), respectively, with respect to the samples analysed. The other regions showed an inhibitor incidence <8 %. The incidence of inhibitors in haemophilia A patients is different in different regions of India; this may be due to the intensity of treatment, type of product or the genetic characteristics of these patients.

Background: Recent studies in experimental mice have shown that mild deficiency of methylenetetrahydrofolate reductase (MTHFR) enzyme confers protection against malaria, thus providing an important basis for the hypothesis that MTHFR polymorphism, i.e. C677T, might have been subjected to selection pressure against malaria. The present study was undertaken in a malaria endemic region in North East India to assess whether a similar selection advantage exists for other genes in folate metabolism pathway.Methods: A total of 401 subjects including 131 symptomatic malaria, 97 asymptomatic malaria and 173 normal healthy controls were analysed for nine polymorphisms (single-nucleotide polymorphisms [SNPs] in eight genes and insertion/deletion in one gene): MTHFR C677T, methionine synthase reductase (MTRR) A66G, glutamate carboxypeptidase II (GCPII) C1561T, cystathionine beta-synthase (CBS) 844ins68, reduced folate carrier-1 (RFC-1) G80A, serine hydroxymethyltransferase (SHMT) C1420T, methionine synthase (MTR) A2756G, MTHFR G1793A (D 919G), glycine N-methyltransferase (GNMT) 1289 by PCR-RFLP technique. Differences in frequencies of genotype distribution of each polymorphic marker between these groups were evaluated.Results: MTRR A2756G, SHMT C1420T, GCPII C1561T, MTRR A2756G and GNMT C1289T and RFC1 G80A polymorphisms showed significantly different prevalence between different groups analyzed. No significant differences were seen in the distribution of other polymorphisms. Conclusions:The study gives a clue for the possible selection of specific polymorphisms in the genes involved in the folate metabolism pathway by malaria parasite.

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