Entity

Time filter

Source Type


Shetty S.,National Institute of Immunohaematology ICMR
Blood Cells, Molecules, and Diseases | Year: 2014

FVIII inhibitor development in haemophilia A (HA) patients, especially those with severe manifestations is a serious adverse effect in patients with haemophilia A, and the clinical management of these patients is very difficult as most don't respond to conventional treatment. Many genetic and non-genetic risk factors have been proposed however, these are diverse in different population groups, highlighting the importance of determining specific risk factors for each population. F8 mutations and especially inversions, which are the most common causative mutation in severe HA, have been significantly associated with inhibitor development earlier, however there is no conclusive data so far with regard to Indian haemophiliacs. This study provides novel evidence that intron 22 inversions in the F8 gene are indeed significantly associated with FVIII inhibitor development in Indian haemophiliacs. Further studies with other risk factors would enable better insights into the immune response towards FVIII in these patients, and possibly help to characterize patients at a higher risk for inhibitor development. © 2014 Elsevier Inc. Source


Patil R.,National Institute of Immunohaematology ICMR
Blood Coagulation and Fibrinolysis | Year: 2016

Dysfibrinogenemia is a very challenging disorder, and there are no firm guidelines on treatment for pregnant patients with dysfibrinogenemia. A 37-year-old patient with a history of six unexplained recurrent miscarriages was referred for thrombophilia testing. Elevated procoagulant microparticles were found, for which during her seventh pregnancy anticoagulant therapy was initiated. However, she again miscarried and bled excessively. She was then diagnosed with dysfibrinogenemia. DNA sequence analysis revealed a novel homozygous insertion–deletion in exon 7 in FGB. Dysfibrinogenemia is very difficult to diagnose and even after diagnosis, the treatment varies with the patientʼs symptoms. In this case, anticoagulant therapy failed. With her history of recurrent miscarriages, it is clear that pregnancy without any treatment is not an option. Few reports suggest a combination of intravenous fibrinogen infusions along with anticoagulants in which successful pregnancy outcome was achieved. The present case thus stresses on the need for some treatment guidelines in such cases. Copyright © 2016 YEAR Wolters Kluwer Health, Inc. All rights reserved. Source


Deshpande R.,National Institute of Immunohaematology ICMR
Blood Coagulation and Fibrinolysis | Year: 2016

Congenital combined deficiency of coagulation factors VII and X are mainly attributed to large deletions involving both the genes in chromosome 13 or occasionally due to the coincidental occurrence of independently occurring mutations. We report the molecular basis of congenital combined deficiency of factors VII and X in a 6-year-old female child. Direct DNA sequencing of both factor VII (F7) and factor X (F10) genes showed a novel homozygous missense mutation p.Cys90Tyr (c.307G>A) in exon 4 of F10. No mutations were detected in F7; however, the patient was homozygous for three polymorphic alleles known to be associated with reduced factor VII levels. The present case illustrates the synergistic effect of multiple polymorphisms resulting in phenotypic factor VII deficiency in the absence of a pathogenic mutation. Copyright © 2016 YEAR Wolters Kluwer Health, Inc. All rights reserved. Source


Shetty S.,National Institute of Immunohaematology ICMR | Ghosh K.,National Institute of Immunohaematology ICMR
Haemophilia | Year: 2015

Summary: The major therapy for haemophilia is plasma derived or recombinant clotting factors which are evolving steadily to increase potency, stability and half-life. Research in the area of haemophilia therapeutics, however, is not restricted only to modifications in the recombinant products, but alternate therapeutic strategies are being developed which are in different phases of experimental and clinical trials. This chapter reviews the diverse molecular innovations which are being developed for alternate therapeutic approaches in haemophilia. The data is mainly extracted from the literature and the Conference abstracts. Some of the novel therapeutic approaches include inhibition of anticoagulant pathway factors (activated protein C, antithrombin, tissue factor pathway inhibitor) by monoclonal antibodies, peptide inhibitors, DNA or RNA aptamers, use of variant coagulation factors (factor Xa, factor Va) which are more resistant to inactivation or enzymatically more active and antibody-mediated therapy including a humanized anti-factor IXa/X bispecific antibody mimicking factor VIII. Other approaches include nonsense mutation suppression, induction of prothrombotic microparticles by P-selectin-immunoglobulin chimeras, suppression of fibrinolytic potential either by antifibrinolytics or by the use of mutant molecules of fibrinolytic inhibitors. Few products are proposed as 'stand alone' treatment for haemophilia, while a few can be used as adjuvant therapies to recombinant factors with an aim to reduce the amount of factor intake. All efforts are underway to produce an alternate, novel drug for haemophilia which will have an increased half-life, subcutaneously injectable, non-immunogenic and effective both in the presence and absence of inhibitors. © 2014 John Wiley & Sons Ltd. Source


Shetty S.,National Institute of Immunohaematology ICMR | Ghosh K.,National Institute of Immunohaematology ICMR
Journal of Thrombosis and Haemostasis | Year: 2012

See also Tagliaferri A, Franchini M. Cancers in patients with hemophilia: a retrospective study from the Italian Association of Hemophilia Centers: a reply to a rebuttal. This issue, pp 1201-2. Tagliaferri A, Di Perna C, Santoro C, Schinco P, Santoro R, Rossetti G, Coppola A, Morfini M, Franchini M, on behalf of the Italian Association of Hemophilia Centers. Cancers in patients with hemophilia: a retrospective study from the Italian Association of Hemophilia Centers. J Thromb Haemost 2012; 10: 90-9. © 2012 International Society on Thrombosis and Haemostasis. Source

Discover hidden collaborations