Background: In idiopathic autoimmune haemolytic anaemia (AIHA haemolytic antibodies are directed ... more Background: In idiopathic autoimmune haemolytic anaemia (AIHA haemolytic antibodies are directed to every type of red cellsWestern blot studies have shown antibody positivity towards red cell anion channel complex which also includes band 4.2 a protein with similarities to tissue trans glutaminase. Objective: Evaluation of AIHA for anti tissue transglutaminase antibody (Anti tTG). Materials & Methods:Twenty three AIHA patients were tested along with routine hamatogical work up, for a series of auto antibodies and red cell eluates and serum from the patents were tested against solubilised group O red cell ghosts on western blot. Other ancillary investigations were done to rule out complications and secondary causes of haemolysis. Results :11/23 patients(48%) were positive for anti tTG, Four , 3 and 8,7 patients were positive for anti thyroid , anti b2 glycoprotein, lupus anticoagulant and ANA respectively. One patient with anti tTG had biopsy proven celiac disease. Three patient developed DVT and all of them were lupus anticoagulant as well as b2 gp-1 antibody positive.17 had become Coombs test negative on treatment while 21/23 had positive western blot test. Discussion & conclusion:There is strong association of anti tTG antibody with idiopathic AIHA. Aetiological association of this finding needs exploration.
Background: Medical colleges should be the engines of medical research in India however sadly it ... more Background: Medical colleges should be the engines of medical research in India however sadly it is far from that. Materials and methods: Articles published in English literature from 1990's were reviewed along with personal experience of more than 30 years of interacting with various medical institutions of India. Results: Six to ten medical colleges publish more than 60% of research papers in indexed journals out of existing 450 medical colleges in India. There are many reasons why there is very little or poor quality research in medical colleges in India. Poor mentorship, severe patients load, lack of research interest, lack of funding and lack of multicentric co-ordinates research activity, lack of incentive for research, are some of the reasons. Discussion and conclusion: Many of the reasons cited above for good quality research needs are correction. However generous funding should be available as a research fund to the medical colleges both by state and by central government. Both undergraduate and postgraduate curricula needs to be modified to reflect that good medical research is part of good medical practice.
Introduction: Haemoglobinopathies are important causes of inherited disorders with substantial mo... more Introduction: Haemoglobinopathies are important causes of inherited disorders with substantial mortality and morbidity across the world. Therefore, proper utilisation of available screening and diagnostic techniques are important for its diagnosis and management. Areas covered: In this review the authors attempt to: summarise clinical presentations, give a brief account of existing techniques and discuss evolving and advanced A c c e p t e d M a n u s c r i p t techniques for detection and screening of the condition. As prevention of the disease condition is an important community measure to control the disease, techniques involving newborn screening, antenatal diagnosis and point of care tests have been described in addition to more advanced molecular and protein diagnostics. The literature search in this area is covered between 1980-2018 with pubmed as the main source along with authors' own research this area. Expert opinion: Screening and detection of haemoglobinoapathy is best accomplished by a hierarchical approach with the optimum blend of old and newer techniques. Starting with point of care techniques through the commonly used HPLC and high voltage capillary electrophoresis, or modern and high throughput molecular biology and mass spectroscopic techniques can be used depending on specific situations. Every country needs to optimise their techniques depending on the frequency of the problem and available resources.
Background: Malaria caused by Plasmodium vivax and Plasmodium falciparum is common in the Indian ... more Background: Malaria caused by Plasmodium vivax and Plasmodium falciparum is common in the Indian subcontinent. Studies conducted elsewhere have suggested that malarial infection causes intense immunostimulation. We screened patients with malarial infection for autoantibodies and measured the immunoglobulin, circulating immune complex and complement levels to determine the extent of immunological alterations in these patients. Methods: One hundred adults with acute malarial infection confirmed by examination of the peripheral blood smear and 25 age- and sex-matched controls were studied. An autoantibody screen and serum immunoglobulin complement (C3 and C4) and circulating immune complex levels were measured at the time of admission and 4 weeks after they became afebrile. A direct Coomb's test was also done. Results: Anti-ssDNA, anti-dsDNA and rheumatoid factor were positive at the time of admission in 51, 30 and 38 patients respectively. None of the controls were positive for these autoantibodies except for one who was positive for rheumatoid factor. The IgM, IgG and IgA levels were raised in 16, 25 and 36 patients respectively. Circulating immune complex levels were raised in 32 patients and complement C3 and C4 were low in 8 and 31 patients. Follow up studies at 4 weeks in 19 patients showed that the autoantibodies were negative. However, the immunoglobulin, C4 and circulating immune complex levels remained elevated. Six per cent of patients had a positive direct Coomb's test with reticulocytosis at the time of presentation. Conclusion: Acute malarial infection can cause false-positive results for anti-ssDNA, anti-dsDNA and rheumatoid factor and may also cause a rise in the serum immunoglobulin, complement and circulating immune complex levels.
Indian Journal of Hematology and Blood Transfusion, Dec 1, 2008
Chronic synovitis in severe hemophilia is a painful debilitating condition eventually affecting g... more Chronic synovitis in severe hemophilia is a painful debilitating condition eventually affecting greater than 20% severe hemophilia patients in developing countries. Though this complication is all but eliminated in the countries with advanced hemophilia care and having access to generous factor concentrate replacement, the same can not be said for 80% of the hemophilia patients in the world who live in developing countries. In developing countries chronic synovitis can be treated conservatively with short course of steroid, factor replacement, physiotherapy and splintage. Failing this, chemical or radioactive synoviorthesis give worthwhile remission and relief in 70-80% of the severely affected patients who fail to respond to conservative therapy. We found a short course of Cox-2 (etoricoxib) inhibitor to be an extremely useful adjunct. The role of d-Pencillamine, Thalidomide and inhibitors of matrix metalloproteinases needs to be explored. HLA-B27 was found to be strongly associated with chronic synovitis in hemophilia in one of the studies and this marker in a hemophilia patient may suggest need for more intensive replacement and other therapy in these patients to prevent chronic synovitis.
ABSTRACT Background Hemophilia is a high cost low volume disease. Resource limited nations (RLN) ... more ABSTRACT Background Hemophilia is a high cost low volume disease. Resource limited nations (RLN) usually spend very little on health budget and most of it is spent in dealing with common ailments. Clotting products constitute more than 90% of the total cost of hemophilia care. The manner in which these products can be made accessible for persons with hemophilia (PWH) and how its continuous supply and distribution can be maintained and improved is described in this review. Areas covered Number of PWH in the Resource Limited Nations (RLN); minimum amount of concentrate required to keep a PWH relatively free of bleeds; the different products available for management of PWH; means and ways to minimize and optimize the concentrate usage and purchase on a budget; nonfactor therapy; ways and means to improve the management and allow better quality concentrates in higher quantities for PWH in those countries; adherence as a challenge for RLN country and ways to manage them. The time covered is from 1980s till date. Pubmed was searched mainly for review articles with the key words hemophilia, RLN, concentrate access, alternative therapy. Cross references from these reviews as well as some of the abstracts from international conferences were read. Expert opinion Developing a patient’s society and a bleeding disorder registry are the two most important actions toward ensuring adequate treatment material for PWH in RLN. Government should allocate a budget for hemophilia care depending on the number of PWH diagnosed and future projection of increased numbers of PWH. Population based product requirement may not work initially as only 10–20% of PWH in such a country has been diagnosed hence initial requirement of concentrates should be directed to these patients. Meanwhile efforts should be made to diagnose new cases. Antenatal diagnosis centers should offer antenatal diagnosis and prevent birth of severe hemophilia children. Self sufficiency in plasma based concentrates should be planned and aimed. A national tendering committee can get a good price on the concentrates on global tendering with annual rate contracts (prevents outdating). Avoiding wastage by outdating of the products in large denomination vials will help. Hoarding concentrates in unreasonable amounts should be avoided through good supply chain management. Regular physiotherapy, proper use of optimum amounts of concentrate will reduce per PWH consumption of the factor concentrates. Plasma derived intermediate purity factors, first/second generation recombinant clotting factors are safe and relatively cheaper as well as effective. Also concentrates which are close to their expiry date (>3 < 6 months) are equally effective and cheap. With proper supply chain management such products can be included in the portfolio. Primary prophylaxis with low/ intermediate dose of the concentrates is a cost-effective way to manage the patients and this also reduces inhibitor development. Adherence to therapy is not yet an important issue for RLN countries but will become one in future. With advancement and improvement the country can access alternative non factor concentrates and other newer products.
The American Journal of the Medical Sciences, Nov 1, 2017
Background: The objective of this study was to assess the albumin cobalt binding (ACB) test in a ... more Background: The objective of this study was to assess the albumin cobalt binding (ACB) test in a cohort of type 2 diabetes patients. The ACB test is a simple, inexpensive, sensitive and robust test that could have important clinical application in detecting complications of type 2 diabetes mellitus. Materials and Methods: We tested patients with type 2 diabetes without any clinically detectable complications or without any other comorbid conditions for serum ACB levels along with an equal number of age‐ and sex‐matched healthy control subjects. ACB levels were compared after the patients with diabetes were investigated for various complications using standard statistical tests of significance. Results: A total of 100 patients with type 2 diabetes were studied with age‐ and sex‐matched healthy control subjects. Of the 100 patients, 78 had different complications on detailed laboratory testing. The patients with complications had significantly higher ACB test results when compared to the patients with diabetes without complications and to that of the control subjects (0.62 ± 0.04, 0.42 ± 0.07, 0.30 ± 0.05 absorbance units (ABSU)/mL, respectively. P < 0.001). All values in diabetics were significantly higher than that of controls. Conclusions: The serum ACB test is a sensitive indicator of complications developed in type 2 diabetes mellitus. Patients may be followed up with ACB results to detect early complications in this disease.
We studied the prevalence of acquired and genetic thrombophilia in 198 women with recurrent fetal... more We studied the prevalence of acquired and genetic thrombophilia in 198 women with recurrent fetal loss who were having three or more than three abortions. Seventynine women had only early pregnancy losses, that is, first trimester abortions, 30 women had only late pregnancy losses, that is, second and third trimester abortions whereas 89 had both early and late pregnancy losses. The control group included 100 age-matched fertile parous women who did not have any obstetric complications and had at least one normal healthy child. Several genetic and acquired thrombophilia markers were studied. The strongest association was observed with anticardiolipin (odds ratio 22.6, confidence interval 5.7-89, P U 0) followed by lupus anticoagulant, anti-b2 glycoprotein-1, antiannexin. Association of antiphospholipid antibody syndromes was detected with the time of pregnancy loss in anticardiolipin, lupus anticoagulants, which was significantly associated with early pregnancy loss as compared with second and third trimester loss. In case of b2 glycoprotein-1, antiannexin it was less significantly associated with early pregnancy loss as compared with second and third trimester loss. The risk of fetal loss with protein S deficiency was the highest risk observed for any heritable thrombophilia, followed by protein C, factor V Leiden, endothelial protein C receptor, antithrombin III deficiency and b448 fibrinogen polymorphism. Modest risks were also observed with 5,10-methylenetetrahydrofolate reductase, plasminogen activator inhibitor 4G/4G polymorphisms and b448 fibrinogen polymorphism. A combination of two or more than two genetic risk factors were observed in 55 (27.7%), whereas the genetic and acquired risk factors were observed in 107 (54%) of the cases. Thrombophilia is an important contributing factor for both early and late pregnancy losses; approximately two-thirds of our cases of unexplained fetal losses could be explained by acquired or heritable thrombophilia or both, which is in line with other western studies.
Anemia is a common complication in malarial infection, although the consequences are more pronoun... more Anemia is a common complication in malarial infection, although the consequences are more pronounced with Plasmodium falciparum malaria (Ghosh, Indian J Hematol Blood Tranfus 21(53):128-130, 2003). Anemia in this infection is caused by a variety of pathophysiologic mechanisms, and in areas where malaria infection is endemic, co-morbidities like other parasitic infestations, iron, folate and Vitamin B12 deficiency, deficiency of other nutrients, and anemia, which is aggravated by anti-malarial drugs both through immune and non-immune mechanisms, are important considerations. In different endemic areas, βthalassemia, α-thalassemia, Hb S, Hb E, G6PD deficiency, or ovalocytosis in different proportions interact with this infection. Finally, aberrant immune response to repeated or chronic falciparum malarial infection may produce tropical splenomegaly syndrome, a proportion of which show clonal proliferation of B lymphocytes. Cooperation between chronic malarial infection and infection with E-B virus infection in producing Burkitt's lymphoma is well known. In this review, the fascinating and multifaceted pathophysiolgoy of malarial anemia has been discussed.
Severe malaria infection still kills more than 2.7 million people across the globe every year. Of... more Severe malaria infection still kills more than 2.7 million people across the globe every year. Of the few infections which has shaped human genome over the millennia through the process of natural selection, malaria infection has left its imprints on human genome. Genetic studies on malarial resistance started in the late 1940s with demonstration of protection against malaria in carriers of several haemoglobinopathy genes and further demonstration of increasing prevalence of such genes across the malarious areas of the world. As malaria parasites pass a significant period of its life inside the red cell, many red cell proteins and their genes were studied for polymorphic variants which offers protection against such infection. Total absence of Plasmodium vivax malaria in Western Africa and its linkage with total absence of red cell Duffy antigen is a case in point. Subsequently as a rational extension of the above idea, association of resistance or susceptibility to severe malarial infection were studied with relation to genes of innate immunity, adoptive immunity, cytokine genes, adhesion molecules, coagulation proteins, proteins involved in systemic inflammatory reactions etc. Innumerable studies have shown various kinds of association. However, at present the interest has shifted towards genome wide association studies with malarial infection. Present review stops short of genome wide association and presents a snapshot view of genome association with malaria infection. Key Concepts: The immune system of man has evolved to fight pathogens like malaria parasite. Pathogens have exerted intense selective pressures on the evolution of the immune system of man. Key elements of the adaptive immune system, such as antigen receptors and major histocompatibility complex molecules, show evidence of such selective pressures. Mutation is the key genetic mechanism underlying the co-evolution of the immune system and pathogens. Evolutionary adaptation to malaria involves many more aspects than modification of adoptive and Innate Immune system. Owing to complex life cycle of the parasite and its specific requirements of nutrition and need for protection during its growth, the parasite vulnerability increases due to changes in Nutrient (haemoglobin), Host Enzyme system (Oxidant damage), changes in specialised receptors for entry into cells (Red cells, Hepatocytes) and its ability to adhere to Key cells (Endothelium). Product of metabolism of malaria parasite (Hemozoin) exerts strong immunomodulatory effect. As malaria parasite from different regions of the world exerted selection pressure on different population groups with different genetic endowment (polymorphisms), this resulted in evolution of different key resistant molecules against malaria in different parts of the world. Keywords: falciparum malaria; vivax malaria; red cell; haemoglobin; polymorphisms; HLA antigens; cytokine genes; adhesion molecules; endothelial cells; toll like receptors; haemozoin; immunomodulation
Mediterranean Journal of Hematology and Infectious Diseases, Jun 17, 2017
Background: We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albu... more Background: We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albumin (IMA) assay as a prognostic marker for severe malaria in a medical college setting. Methods: Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy. Results: 100 consecutive patients (50 with vivax and 50 with falciparum malaria) were evaluated. The reference range for ACB assay was established using 50 adult healthy (25 male and 25 female) individuals. 16 out of 50 p. Falciparum-Infected developed complicated malaria. None of the P Vivax patients developed complicated malaria. All malaria infected patients had high ACB levels (P<0.0001). There was a stepwise increase in ACB levels from healthy volunteers to different categories of malaria (P<0.0001) without any overlap. Conclusion: ACB has the potential to be used as a robust simple and inexpensive prognostic marker for organ dysfunction in severe malaria even if an evaluation at multiple sites with a bigger number of patients should be initiated for final recommendation.
Indian Journal of Hematology and Blood Transfusion, Jun 1, 2010
Last quarter of twentieth century and the first 10 years of 21st century has seen phenomenal deve... more Last quarter of twentieth century and the first 10 years of 21st century has seen phenomenal development in haematological pharmacotherapy. Tailor made chemotherapeutic agents, vast array of monoclonal antibodies, epigenetic modifiers, growth factors for red cells white cells and platelets, peptidomimetics as growth factors, newer thrombin inhibitors, safer plasma derived protein molecules, recombinant molecules, newer immunomodulators, enzyme replacement therapy and above all a plethora of targetted molecules targeting innumerable pathways involved in cell division, growth, proliferation and apoptosis has given immense number of clinically usable molecules in the hand of modern haematologists to treat diverse hitherto untreatable haematological disorders effectively. In addition many old molecules are finding newer uses in diverse fields, thalidomide as an antiangiogenic molecule is a prime example of this genre. Present overview has tried to capture this rapidly evolving area in a broad canvas without going into details of indications and contraindications of the use of various drugs.
Background: In idiopathic autoimmune haemolytic anaemia (AIHA haemolytic antibodies are directed ... more Background: In idiopathic autoimmune haemolytic anaemia (AIHA haemolytic antibodies are directed to every type of red cellsWestern blot studies have shown antibody positivity towards red cell anion channel complex which also includes band 4.2 a protein with similarities to tissue trans glutaminase. Objective: Evaluation of AIHA for anti tissue transglutaminase antibody (Anti tTG). Materials & Methods:Twenty three AIHA patients were tested along with routine hamatogical work up, for a series of auto antibodies and red cell eluates and serum from the patents were tested against solubilised group O red cell ghosts on western blot. Other ancillary investigations were done to rule out complications and secondary causes of haemolysis. Results :11/23 patients(48%) were positive for anti tTG, Four , 3 and 8,7 patients were positive for anti thyroid , anti b2 glycoprotein, lupus anticoagulant and ANA respectively. One patient with anti tTG had biopsy proven celiac disease. Three patient developed DVT and all of them were lupus anticoagulant as well as b2 gp-1 antibody positive.17 had become Coombs test negative on treatment while 21/23 had positive western blot test. Discussion & conclusion:There is strong association of anti tTG antibody with idiopathic AIHA. Aetiological association of this finding needs exploration.
Background: Medical colleges should be the engines of medical research in India however sadly it ... more Background: Medical colleges should be the engines of medical research in India however sadly it is far from that. Materials and methods: Articles published in English literature from 1990's were reviewed along with personal experience of more than 30 years of interacting with various medical institutions of India. Results: Six to ten medical colleges publish more than 60% of research papers in indexed journals out of existing 450 medical colleges in India. There are many reasons why there is very little or poor quality research in medical colleges in India. Poor mentorship, severe patients load, lack of research interest, lack of funding and lack of multicentric co-ordinates research activity, lack of incentive for research, are some of the reasons. Discussion and conclusion: Many of the reasons cited above for good quality research needs are correction. However generous funding should be available as a research fund to the medical colleges both by state and by central government. Both undergraduate and postgraduate curricula needs to be modified to reflect that good medical research is part of good medical practice.
Introduction: Haemoglobinopathies are important causes of inherited disorders with substantial mo... more Introduction: Haemoglobinopathies are important causes of inherited disorders with substantial mortality and morbidity across the world. Therefore, proper utilisation of available screening and diagnostic techniques are important for its diagnosis and management. Areas covered: In this review the authors attempt to: summarise clinical presentations, give a brief account of existing techniques and discuss evolving and advanced A c c e p t e d M a n u s c r i p t techniques for detection and screening of the condition. As prevention of the disease condition is an important community measure to control the disease, techniques involving newborn screening, antenatal diagnosis and point of care tests have been described in addition to more advanced molecular and protein diagnostics. The literature search in this area is covered between 1980-2018 with pubmed as the main source along with authors' own research this area. Expert opinion: Screening and detection of haemoglobinoapathy is best accomplished by a hierarchical approach with the optimum blend of old and newer techniques. Starting with point of care techniques through the commonly used HPLC and high voltage capillary electrophoresis, or modern and high throughput molecular biology and mass spectroscopic techniques can be used depending on specific situations. Every country needs to optimise their techniques depending on the frequency of the problem and available resources.
Background: Malaria caused by Plasmodium vivax and Plasmodium falciparum is common in the Indian ... more Background: Malaria caused by Plasmodium vivax and Plasmodium falciparum is common in the Indian subcontinent. Studies conducted elsewhere have suggested that malarial infection causes intense immunostimulation. We screened patients with malarial infection for autoantibodies and measured the immunoglobulin, circulating immune complex and complement levels to determine the extent of immunological alterations in these patients. Methods: One hundred adults with acute malarial infection confirmed by examination of the peripheral blood smear and 25 age- and sex-matched controls were studied. An autoantibody screen and serum immunoglobulin complement (C3 and C4) and circulating immune complex levels were measured at the time of admission and 4 weeks after they became afebrile. A direct Coomb's test was also done. Results: Anti-ssDNA, anti-dsDNA and rheumatoid factor were positive at the time of admission in 51, 30 and 38 patients respectively. None of the controls were positive for these autoantibodies except for one who was positive for rheumatoid factor. The IgM, IgG and IgA levels were raised in 16, 25 and 36 patients respectively. Circulating immune complex levels were raised in 32 patients and complement C3 and C4 were low in 8 and 31 patients. Follow up studies at 4 weeks in 19 patients showed that the autoantibodies were negative. However, the immunoglobulin, C4 and circulating immune complex levels remained elevated. Six per cent of patients had a positive direct Coomb's test with reticulocytosis at the time of presentation. Conclusion: Acute malarial infection can cause false-positive results for anti-ssDNA, anti-dsDNA and rheumatoid factor and may also cause a rise in the serum immunoglobulin, complement and circulating immune complex levels.
Indian Journal of Hematology and Blood Transfusion, Dec 1, 2008
Chronic synovitis in severe hemophilia is a painful debilitating condition eventually affecting g... more Chronic synovitis in severe hemophilia is a painful debilitating condition eventually affecting greater than 20% severe hemophilia patients in developing countries. Though this complication is all but eliminated in the countries with advanced hemophilia care and having access to generous factor concentrate replacement, the same can not be said for 80% of the hemophilia patients in the world who live in developing countries. In developing countries chronic synovitis can be treated conservatively with short course of steroid, factor replacement, physiotherapy and splintage. Failing this, chemical or radioactive synoviorthesis give worthwhile remission and relief in 70-80% of the severely affected patients who fail to respond to conservative therapy. We found a short course of Cox-2 (etoricoxib) inhibitor to be an extremely useful adjunct. The role of d-Pencillamine, Thalidomide and inhibitors of matrix metalloproteinases needs to be explored. HLA-B27 was found to be strongly associated with chronic synovitis in hemophilia in one of the studies and this marker in a hemophilia patient may suggest need for more intensive replacement and other therapy in these patients to prevent chronic synovitis.
ABSTRACT Background Hemophilia is a high cost low volume disease. Resource limited nations (RLN) ... more ABSTRACT Background Hemophilia is a high cost low volume disease. Resource limited nations (RLN) usually spend very little on health budget and most of it is spent in dealing with common ailments. Clotting products constitute more than 90% of the total cost of hemophilia care. The manner in which these products can be made accessible for persons with hemophilia (PWH) and how its continuous supply and distribution can be maintained and improved is described in this review. Areas covered Number of PWH in the Resource Limited Nations (RLN); minimum amount of concentrate required to keep a PWH relatively free of bleeds; the different products available for management of PWH; means and ways to minimize and optimize the concentrate usage and purchase on a budget; nonfactor therapy; ways and means to improve the management and allow better quality concentrates in higher quantities for PWH in those countries; adherence as a challenge for RLN country and ways to manage them. The time covered is from 1980s till date. Pubmed was searched mainly for review articles with the key words hemophilia, RLN, concentrate access, alternative therapy. Cross references from these reviews as well as some of the abstracts from international conferences were read. Expert opinion Developing a patient’s society and a bleeding disorder registry are the two most important actions toward ensuring adequate treatment material for PWH in RLN. Government should allocate a budget for hemophilia care depending on the number of PWH diagnosed and future projection of increased numbers of PWH. Population based product requirement may not work initially as only 10–20% of PWH in such a country has been diagnosed hence initial requirement of concentrates should be directed to these patients. Meanwhile efforts should be made to diagnose new cases. Antenatal diagnosis centers should offer antenatal diagnosis and prevent birth of severe hemophilia children. Self sufficiency in plasma based concentrates should be planned and aimed. A national tendering committee can get a good price on the concentrates on global tendering with annual rate contracts (prevents outdating). Avoiding wastage by outdating of the products in large denomination vials will help. Hoarding concentrates in unreasonable amounts should be avoided through good supply chain management. Regular physiotherapy, proper use of optimum amounts of concentrate will reduce per PWH consumption of the factor concentrates. Plasma derived intermediate purity factors, first/second generation recombinant clotting factors are safe and relatively cheaper as well as effective. Also concentrates which are close to their expiry date (>3 < 6 months) are equally effective and cheap. With proper supply chain management such products can be included in the portfolio. Primary prophylaxis with low/ intermediate dose of the concentrates is a cost-effective way to manage the patients and this also reduces inhibitor development. Adherence to therapy is not yet an important issue for RLN countries but will become one in future. With advancement and improvement the country can access alternative non factor concentrates and other newer products.
The American Journal of the Medical Sciences, Nov 1, 2017
Background: The objective of this study was to assess the albumin cobalt binding (ACB) test in a ... more Background: The objective of this study was to assess the albumin cobalt binding (ACB) test in a cohort of type 2 diabetes patients. The ACB test is a simple, inexpensive, sensitive and robust test that could have important clinical application in detecting complications of type 2 diabetes mellitus. Materials and Methods: We tested patients with type 2 diabetes without any clinically detectable complications or without any other comorbid conditions for serum ACB levels along with an equal number of age‐ and sex‐matched healthy control subjects. ACB levels were compared after the patients with diabetes were investigated for various complications using standard statistical tests of significance. Results: A total of 100 patients with type 2 diabetes were studied with age‐ and sex‐matched healthy control subjects. Of the 100 patients, 78 had different complications on detailed laboratory testing. The patients with complications had significantly higher ACB test results when compared to the patients with diabetes without complications and to that of the control subjects (0.62 ± 0.04, 0.42 ± 0.07, 0.30 ± 0.05 absorbance units (ABSU)/mL, respectively. P < 0.001). All values in diabetics were significantly higher than that of controls. Conclusions: The serum ACB test is a sensitive indicator of complications developed in type 2 diabetes mellitus. Patients may be followed up with ACB results to detect early complications in this disease.
We studied the prevalence of acquired and genetic thrombophilia in 198 women with recurrent fetal... more We studied the prevalence of acquired and genetic thrombophilia in 198 women with recurrent fetal loss who were having three or more than three abortions. Seventynine women had only early pregnancy losses, that is, first trimester abortions, 30 women had only late pregnancy losses, that is, second and third trimester abortions whereas 89 had both early and late pregnancy losses. The control group included 100 age-matched fertile parous women who did not have any obstetric complications and had at least one normal healthy child. Several genetic and acquired thrombophilia markers were studied. The strongest association was observed with anticardiolipin (odds ratio 22.6, confidence interval 5.7-89, P U 0) followed by lupus anticoagulant, anti-b2 glycoprotein-1, antiannexin. Association of antiphospholipid antibody syndromes was detected with the time of pregnancy loss in anticardiolipin, lupus anticoagulants, which was significantly associated with early pregnancy loss as compared with second and third trimester loss. In case of b2 glycoprotein-1, antiannexin it was less significantly associated with early pregnancy loss as compared with second and third trimester loss. The risk of fetal loss with protein S deficiency was the highest risk observed for any heritable thrombophilia, followed by protein C, factor V Leiden, endothelial protein C receptor, antithrombin III deficiency and b448 fibrinogen polymorphism. Modest risks were also observed with 5,10-methylenetetrahydrofolate reductase, plasminogen activator inhibitor 4G/4G polymorphisms and b448 fibrinogen polymorphism. A combination of two or more than two genetic risk factors were observed in 55 (27.7%), whereas the genetic and acquired risk factors were observed in 107 (54%) of the cases. Thrombophilia is an important contributing factor for both early and late pregnancy losses; approximately two-thirds of our cases of unexplained fetal losses could be explained by acquired or heritable thrombophilia or both, which is in line with other western studies.
Anemia is a common complication in malarial infection, although the consequences are more pronoun... more Anemia is a common complication in malarial infection, although the consequences are more pronounced with Plasmodium falciparum malaria (Ghosh, Indian J Hematol Blood Tranfus 21(53):128-130, 2003). Anemia in this infection is caused by a variety of pathophysiologic mechanisms, and in areas where malaria infection is endemic, co-morbidities like other parasitic infestations, iron, folate and Vitamin B12 deficiency, deficiency of other nutrients, and anemia, which is aggravated by anti-malarial drugs both through immune and non-immune mechanisms, are important considerations. In different endemic areas, βthalassemia, α-thalassemia, Hb S, Hb E, G6PD deficiency, or ovalocytosis in different proportions interact with this infection. Finally, aberrant immune response to repeated or chronic falciparum malarial infection may produce tropical splenomegaly syndrome, a proportion of which show clonal proliferation of B lymphocytes. Cooperation between chronic malarial infection and infection with E-B virus infection in producing Burkitt's lymphoma is well known. In this review, the fascinating and multifaceted pathophysiolgoy of malarial anemia has been discussed.
Severe malaria infection still kills more than 2.7 million people across the globe every year. Of... more Severe malaria infection still kills more than 2.7 million people across the globe every year. Of the few infections which has shaped human genome over the millennia through the process of natural selection, malaria infection has left its imprints on human genome. Genetic studies on malarial resistance started in the late 1940s with demonstration of protection against malaria in carriers of several haemoglobinopathy genes and further demonstration of increasing prevalence of such genes across the malarious areas of the world. As malaria parasites pass a significant period of its life inside the red cell, many red cell proteins and their genes were studied for polymorphic variants which offers protection against such infection. Total absence of Plasmodium vivax malaria in Western Africa and its linkage with total absence of red cell Duffy antigen is a case in point. Subsequently as a rational extension of the above idea, association of resistance or susceptibility to severe malarial infection were studied with relation to genes of innate immunity, adoptive immunity, cytokine genes, adhesion molecules, coagulation proteins, proteins involved in systemic inflammatory reactions etc. Innumerable studies have shown various kinds of association. However, at present the interest has shifted towards genome wide association studies with malarial infection. Present review stops short of genome wide association and presents a snapshot view of genome association with malaria infection. Key Concepts: The immune system of man has evolved to fight pathogens like malaria parasite. Pathogens have exerted intense selective pressures on the evolution of the immune system of man. Key elements of the adaptive immune system, such as antigen receptors and major histocompatibility complex molecules, show evidence of such selective pressures. Mutation is the key genetic mechanism underlying the co-evolution of the immune system and pathogens. Evolutionary adaptation to malaria involves many more aspects than modification of adoptive and Innate Immune system. Owing to complex life cycle of the parasite and its specific requirements of nutrition and need for protection during its growth, the parasite vulnerability increases due to changes in Nutrient (haemoglobin), Host Enzyme system (Oxidant damage), changes in specialised receptors for entry into cells (Red cells, Hepatocytes) and its ability to adhere to Key cells (Endothelium). Product of metabolism of malaria parasite (Hemozoin) exerts strong immunomodulatory effect. As malaria parasite from different regions of the world exerted selection pressure on different population groups with different genetic endowment (polymorphisms), this resulted in evolution of different key resistant molecules against malaria in different parts of the world. Keywords: falciparum malaria; vivax malaria; red cell; haemoglobin; polymorphisms; HLA antigens; cytokine genes; adhesion molecules; endothelial cells; toll like receptors; haemozoin; immunomodulation
Mediterranean Journal of Hematology and Infectious Diseases, Jun 17, 2017
Background: We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albu... more Background: We evaluated albumin cobalt binding (ACB) assay also known as Ischaemia Modified Albumin (IMA) assay as a prognostic marker for severe malaria in a medical college setting. Methods: Consecutive adult patients admitted with both vivax and falciparum malaria were evaluated with ACB assay at the time of admission. Detailed work up and individual patient directed management were instituted in addition to immediate artemisin based antimalarial therapy. Results: 100 consecutive patients (50 with vivax and 50 with falciparum malaria) were evaluated. The reference range for ACB assay was established using 50 adult healthy (25 male and 25 female) individuals. 16 out of 50 p. Falciparum-Infected developed complicated malaria. None of the P Vivax patients developed complicated malaria. All malaria infected patients had high ACB levels (P<0.0001). There was a stepwise increase in ACB levels from healthy volunteers to different categories of malaria (P<0.0001) without any overlap. Conclusion: ACB has the potential to be used as a robust simple and inexpensive prognostic marker for organ dysfunction in severe malaria even if an evaluation at multiple sites with a bigger number of patients should be initiated for final recommendation.
Indian Journal of Hematology and Blood Transfusion, Jun 1, 2010
Last quarter of twentieth century and the first 10 years of 21st century has seen phenomenal deve... more Last quarter of twentieth century and the first 10 years of 21st century has seen phenomenal development in haematological pharmacotherapy. Tailor made chemotherapeutic agents, vast array of monoclonal antibodies, epigenetic modifiers, growth factors for red cells white cells and platelets, peptidomimetics as growth factors, newer thrombin inhibitors, safer plasma derived protein molecules, recombinant molecules, newer immunomodulators, enzyme replacement therapy and above all a plethora of targetted molecules targeting innumerable pathways involved in cell division, growth, proliferation and apoptosis has given immense number of clinically usable molecules in the hand of modern haematologists to treat diverse hitherto untreatable haematological disorders effectively. In addition many old molecules are finding newer uses in diverse fields, thalidomide as an antiangiogenic molecule is a prime example of this genre. Present overview has tried to capture this rapidly evolving area in a broad canvas without going into details of indications and contraindications of the use of various drugs.
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