Search

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

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 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.

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.

NA

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

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.