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Monoclonal antibodies Ab (MoAb) are increasingly becoming part of therapeutic armamentarium for haematologists and haemato-oncologists. This review brings together commonly used antibodies in one place for brevity and novel understanding.Pubmed and Scopus databases were explored focusing on MoAb in clinical haematological practice. Emphasis was given to current review articles. The data base was searched from 1997 till present. 24 different antibodies, most of which are in use were discussed. Antibodies are used for diverse conditions i.e. malignant and benign haematological conditions, treatment at various phases of stem cell transplantation. These antibodies were used both alone or in combination with various chemotherapy, targeted small molecules or as immunoconjugates. Some of the side effect profiles of these antibodies were common and some were unique. Unusual infections or organ dysfunctions were noted. Improved function of antibodies by protein engineering is also advancing rapidly. Dosage, frequency and route of administration depended on the convenience and condition for which the antibody is used.MoAbs are increasingly used in haematology practice either alone or in combination with other types of therapy for improved out come in various haematological conditions.Monoclonal antibodies are antibodies produced on an industrial scale in vitro. These are proteins that are directed against many macromolecules in our body which have a pathogenic role in causing different diseases. By producing these antibodies in a large amount on an industrial scale and modifying them for better action by molecular engineering, a large portfolio of therapeutic antibodies has been produced. A large number of monoclonal antibodies are used in hematological practice. Some familiarity with them and their usage are required for all hematologists even if it is outside their own day-to-day practice and expertise. Moreover, how modern biotechnology and antibody engineering technology are changing the facet of this therapy is also worthy of understanding. The present review encapsulates this area of advancing application and research.

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

Objectives: Monoclonal antibodies (MAs) are increasingly becoming part of therapeutic armamentarium for hematologists and hemato-oncologists. There is paucity of review on majority of these antibodies in one place. The objective of this review is an attempt to fill the gap in paucity of review on majority of these monoclonal antibodies (MAs) in one place. Material and Methods: ‘Pubmed’ and ‘Scopus’ database was explored focusing on monoclonal antibodies (MAs) in clinical hematological practice. Emphasis was given to the more recently published review articles on different monoclonal antibodies (MAs). Results: In the present review, a total of 23 different monoclonal antibodies (MAs) were discussed; some are very frequently used and some rarely. Monoclonal antibodies (MAs) are used for treatment of diverse hematological conditions, i.e. malignant and benign disorders and at various phases of stem cell transplantation. These antibodies were used either alone or in combination with various chemotherapeutic agents, targeted small molecules or as immunoconjugates. Some of the side effect profiles of these antibodies were common and some were unique to the particular monoclonal antibody (MA). Unusual infections or organ dysfunctions were noted. Improved function of antibodies by protein engineering is also advancing rapidly. Dosage, frequency and route of administration depended on the convenience and condition for which the antibody is used. Conclusion: Monoclonal antibodies (MAs) are going to stay for hematological practice. Some amount of familiarity with their usage, advantages, disadvantages and side effects are essential in clinical practice.

D- Dimer levels from peripheral blood are increasingly used to assess various pathological conditions. Initially, an area for hematologists, now this analyte is evaluated more extensively from many specialties of medicine. Covid-19 infection has not only added a new dimension to D-Dimer level assessment in this disease but has also shed newer lights to the underlying pathophysiological mechanisms for its elevation in this disease.Innate variability in measuring D- Dimer levels, Impact of various techniques in measuring D- Dimer, nonavailability of uniform controls and standards, molecular heterogeneity of the product, how it is produced. Reasons for raised D- Dimer in covid-19 infection. D- Dimer in other pathological states. Articles with relevant key words from 1990 searched in PubMed were utilized for review.: D-Dimer has important application in diagnosis, prognosis, management, and understanding various conditions. Its level can rise with increased coagulability of blood, sepsis, cytokine storm, snake bite, etc. Renal function, age influences its reference ranges. Units of measurement, its expression varies in different reports needing international standardization. In Covid-19 infection its levels correlate with stage of the disease, pathology, and complications.

Introduction: Hemoglobinopathies are important causes of inherited disorders with substantial mortality and morbidity across the world. Therefore, proper utilization of available screening and diag...

Background: Multiple myeloma (MM) is cancer of the plasma cell characterized by interpatient heterogeneity, in most of the cases it is incurable. It is the second most common hematological malignancy. Overall survival of patients has significantly increased recently. Lot of research is going on for prognostic factors, which can predict disease and response to therapy. During the past decades, biomarkers: M protein and β2 microglobulin have shaped the knowledge about MM. This study was undertaken to evaluate the role of prognostic factors in newly diagnosed and few follow up patients of MM before, during and after the treatment in Indian population.Methods: We analyzed 177 samples (90 MM patients and 87 healthy control) for creatinine, calcium, phosphorus, LDH, total protein, albumin, globulin, β2M, Immunoglobulines (Igs), IgG, IgA, IgM, Kappa light chain and Lambda light chains, serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE).Results: The result of our study are significant at p

Medical colleges should be the engines of medical research in India however sadly it is far from that.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.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.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.

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: Long term health implications in women who develop hypertensive disorders of pregnancy (HDP) include an increased risk of developing cardiovascular diseases (CVD) later in life. So based on this the present study was undertaken to investigate parameters of metabolic syndrome in normal pregnant and preeclamptic women. Methods: Serum HDL cholesterol, serum triglycerides, fasting blood sugar levels and blood pressure (systolic and diastolic) were estimated in 100 normal pregnant women (controls) and 100 pregnant women with preeclampsia (cases) and comparison between cases and age matched controls of age group 18-35 years done using ‘z’ test. Study was carried out between 2011 to 2015. All statistical analyses were performed using GRAPH PAD PRISM version 5.00 software and Microsoft Office Excel 2007 software. Results: Serum triglyceride (TG), fasting blood sugar levels and blood pressure (systolic and diastolic) were significantly elevated (p < 0.0001) while high density lipoprotein (HDL) was significantly decreased (p < 0.0001) in preeclamptic group than in control group. Conclusions: Serum triglyceride (TG), fasting blood sugar levels and blood pressure (systolic and diastolic) were significantly elevated (p < 0.0001) while high density lipoprotein (HDL) was significantly decreased (p < 0.0001) in preeclamptic group than in control group.

There are significant challenges in managing haemophilia patients in developing countries. These challenges are (i) Lack of proper health care infrastructure and human resources suitable for haemophilia care (ii) Competing health care priorities of the government. (iii) Lack of penetrance of medical insurance in the population. (iv) Lesser visibility of the haemophilia patients in health care system (v) Low awareness across the medical profession, population and the policy makers about the condition (vi) Non availability of factor concentrates (vii) Inadequate utilization of knowledge for reducing factor concentrate use. (viii) Inadequate pain relief (ix) Challenges due to inhibitor developing (x) Viral hepatitis & (xi) Lack of research publications relevant to the country are some of the challenges faced by PWH for their management in developing country. The solutions are not easy but development of a strong patient organization with linkages with World Federation of Haemophilia is an important initial step. Following that internal and international twinning, use of internal sources, strong advocacy programme targeting government, doctors, opinion makers will solve many of the challenges in the time to come.

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 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.

Background: The second most common solid tumor in children is Neuroblastoma (NB). In about 90% of cases of NB, elevated levels of catecholamines or its metabolites are found in the urine or blood which includes Vanillylmandelic Acid (VMA) and Homovanillic Acid (HVA). Ferritin, Neuron-Specific Enolase (NSE) and Lactate Dehydrogenase (LDH) are commonly assessed in children suspected to have NB, and the levels of these markers are commonly used for differential diagnosis. Multiple clinical and imaging tests are needed for accurate patient assessment. Iodine 123(123I) Metaiodobenzylguanidine (MIBG) is the first-line functional imaging agent used in neuroblastoma imaging. To evaluate the utility of these marker present study was undertaken with 91 NB patients and 40 normal healthy control.Methods: The study comprised of blood samples and 24 hour’s urine sample from 40 normal healthy subjects and 91 untreated patients with histologically proven Stage III and IV NB cases referred to our institute. Method used for NSE was Enzyme Immunoassay (Elisa), serum Ferritin was MIA, LDH-photometry and VMA by Column Chromatography.Results: Amongst the parameters studied VMA showed highest sensitivity (91%), specificity (94.4%) positive predictive value (97.8%) and 85% negative predictive value at the cut off levels of 7mg/ ml of creatinine as compared to other studied parameters.Conclusions: This study suggests that the detection of VMA in combination with routine histological examination, MIBG scan, serum NSE and LDH may improve the diagnosis of Neuroblastoma.

Hemophilia A & B are congenital bleeding disorders affecting 1:10-20,000 population and 1:20 to 40,000 population respectively. Hemophilia represents the prototype of high cost low volume disease. Eighty persons of world hemophilia population lives in financially poor developing countries, where

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, beta-thalassemia, alpha-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.

Antineutrophil cytoplasmic antibody (ANCA) is often used in the laboratory to confirm paucicellular vasculitis like Wegener's granulomatosis, Churg Strauss syndrome or polyarteritis nodosa in the presence of suggestive clinical features. In tropical countries, tuberculosis, leprosy and, occasionally, malaria can produce clinical features similar to a vasculitic illness and all the three infections are known to be associated with auto antibodies. We tested 318 patients suffering from malaria, tuberculosis or leprosy for ANCA positivity. ANCA positivity was found in 19%, 32% and 30% of malaria, tuberculosis and leprosy patients (Pradhan V, Badakere S, Shankarkumar V, Iyer Y, Ghosh K, Karnad D, Indian J Malariol, 39:51-59, 2002; Pradhan V, Badakere S, Ghosh K, Pawar A, Indian J Med Sci, 58:283-288, 2004a; Pradhan V, Badakere S, Shankarkumar V, Lepr Rev, 75:50-56, 2004b), respectively, raising the possibility that ANCA positivity with clinical features suggestive of vasculitis in tropical countries may even be related to the background noise of this seropositivity caused by one of these three infections rather than confirming the diagnosis of paucicellular vasculitis. Hence, one should be careful about the background noise of ANCA positivity caused by these infections while diagnosing a vasculitic illness.

Hereditary haemorrhagic telangiectasia (HHT): Negotiating between the Scylla of bleeding and Charybdis of thrombosis

Three apparently immunocompetent patients died in the intensive care unit at Loni Hospital, Ahmednagar, Maharashtra, India, between 2001 and 2006 due to multiorgan failure and Strongyloides stercoralis septicaemia following a short course of corticosteroid (prednisolone) therapy of 6-17 days for peripheral blood eosinophilia associated with urticaria and angioneurotic oedema, bronchospasm, and generalised aches and pains, respectively. None of the patients had any obvious lymphoproliferative disorder, solid tumour or HIV 1+2 infection as an underlying immunosuppressive condition. These three patients highlight the extreme caution that must be exercised in administering a moderate dose of oral corticosteroid even for a short period of time as well as the high degree of suspicion that needs to be maintained if there is clinical deterioration following corticosteroid therapy.

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

Hemostasis research in India has a long history considering the fact that it is one of the youngest specialities in the world. If we take creation of prothrombin time (PT) test as one of the beginning of modern hemostsis research, then the specialty is no older than 60 years. School of Tropical Medicine Kolkata, Banaras Hindu University, All India Institute of Medical Sciences at Delhi, Christian Medical College at Vellore, Post Graduate Institute of Medical Education and Research at Chandigarh, and KEM Hospital at Mumbai contributed substantially in defining various bleeding disorders in our country. Unfortunately, some of these institutes are no longer as active in the field as they used to be. Currently, the Institute of Immunohaematology at Mumbai, Chrstian medical College at Vellore, and All India Institute of Medical Sciences at Delhi are actively engaged in hemostsis research in India. Developing prenatal diagnostic technologies, mutation detection of various hemostatic disorders, developing low-cost management technologies for hemophilia, and other bleeding disorders are becoming important present day research activity in the area of hemostasis in addition to age old areas of prevalence and unusual case description studies. Entry of many new corporate hospitals, development of structured postgraduate training program in hematology, and easy availability of instruments and reagents are likely to foster further growth in this area of medical research in India in future.

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.

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.