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Blood dyscrasias
- 1. DRUG-INDUCED BLOOD DYSCRASIAS DR. CH.PAVANI
- 4. INTRODUCTION… Dyscrasias – “Morbid general state resulting from the presence of abnormal material in the blood. Applied to disease affecting blood cells or platelets”
- 5. INTRODUCTION… Toxic doses/sometimes even in therapeutic doses leads to various blood dyscrasias • Impaired production of blood cells Aplastic anaemia • Increased destruction of blood cells Hemolytic anaemia • Derangement of blood cell functions Methaemoglobinemia
- 6. DRUG INDUCED ANEMIAS Folic acid inhibitors: • DHF reductase inhibitors or folic acid antagonists: • Associated with impaired absorption or utilization of folic acid Those which cause vitamin B 12 malabsorption
- 7. DRUG INDUCED ANEMIAS • NSAIDS and Anticoagulants - “Iron deficiency anemia”. • Pyridoxine responsive anemia – caused by Isoniazid- Hypochromic microcytic anemia. • Probably due to inability of iron to get incorporated in hemoglobin
- 9. APLASTIC ANEMIA Most severe form Fortunately Rare After 2 weeks to 6 months after stopping drug in most cases Pancytopen ia and hypocellula r bone marrow >50% mortality and recovery, if happens, occur after many months of illness
- 10. APLASTIC ANEMIA Drugs causing are Phenylbutazone, Oxyphenbutazone, Indomethacin, Antineoplasticdrugs Chloramphenicol Other drugs Gold salts, Benzene, DDT, antithyroid drugs, sulphonamides sulphonylureas
- 11. ATG & ALG cause anaphylaxis, serum sickness or temporary exacerbation of cytopenia. Main therapeutic choice Allogenic bonemarrow transplantation Immuno suppression with (ATG), (ALG) or cyclosporine Apart from Supportive & nursing therapy, blood transfusions,. Drugs in cancer chemotherapy extension of their pharmacological action
- 13. • Immunosuppression effective in 70-80% of patients. • GCSF, erythropoietin and large doses of androgen may help some patients • Glucocorticoids such as prednisolone 20-40mg/day, may control hemorrhage
- 14. HEMOLYTIC REACTIONS • Occur with drugs which oxidize hemoglobin • Glutathione in reduced form protects RBC from oxidizing agents. Glucose 6 phosphate de hydrogenase maintains Glutathione in reduced form. • Drug damaged RBC show precipitated denatured Hemo globin - Heinz bodies
- 15. G6PD DEFICIENCY RBC deficient in G6PD, reduced glutathione (GSH), or glutathione reductase are more susceptible. It is hereditary deficiency, more in Negros, rare in whites, also noted in Indians
- 16. DRUGS CAUSING HEMOLYSIS IN G6PD DEFICIENCY • Antibacterial agents: Sulphonamides,Furozolidone,Nitrofurantoin, Chloramphenicol,Fluoroquinolones • Anti leprosy drugs (sulphones): Diaminodiphenyl sulphone, Sulphoxone • Antimalarials : Primaquine, Quinine • Miscellaneous :Salicylates,Naphthalene,Methylene blue
- 17. G6PD DEFICIENCY Drugs can cause hemolysis by immune mechanism mediated by circulating antibodies Eg: Methyldopa , Quinine, Quinidine Patients with abnormal hemoglobins may develop hemolysis if they are given sulfonamides or 8 - amino quinoline drugs
- 18. G6PD DEFICIENCY Treatment is symptomatic Glucocorticoids such as hydrocortisone may produce beneficial effects in blood dyscrasias caused by immune mechanisms
- 19. METHEMOGLOBINEMIA Oxygen carriage by Hb depends on Fe in ferrous form Sulfonamides, Bismuthsubnitrate, ammonium nitrate and nitrites oxidise Hb Iron to ferric state Infants below 6 months are more susceptible probably due to low RBC NADH which normally reduces methemoglobin to hemoglobin
- 20. METHEMOGLOBINEMIA NADH ALSO GENETICALLY DEFICIENT IN CERTAIN SUBJECTS TREATMENT IS STOPPING THE DRUG ADMINISTERING 50 ML OF 1% METHYLENE BLUE IV WHICH IS AN EFFECTIVE ANTIDOTE.
- 21. NEUTROPENIA • Specific depression of leucocytes, particularly granulocytes, • Drugs known to cause it do so relatively frequently (1:1000- 1:100) • Amidopyrine and Dipyrone cause it by immune mechanism • Patient’s serum with specific antibodies lyses granulocytes in the presence of the drug • With drugs like Phenothiazines and AntiThyroid compounds, exact mechanism is unknown
- 22. DRUGS CAUSING NEUTROPENIA AND AGRANULOCYTOSIS • Tranquilizers: Chlorpromazine and related drugs, Meprobamate • Analgesics :Amidopyrine , Phenylbutazone , Oxyphenbutazone, Indomethacin • Antibacterial : Chloramphenicol, Sulfonamides, Streptomycin, Cotrimoxazole • Antithyroid drugs:Propylthiouracil, Methimazole, Potassium perchlorate
- 23. NEUTROPENIA Periodic blood counts may not predict neutropenia Patients taking such drugs should be warned about unexplained fever or sore throat with ulceration, should report immediately
- 24. NEUTROPENIA Mortality >20%, mainly due to infection, which needs prompt treatment Blood transfusion may be necessary Treatment is with human GCSF
- 25. THROMBOCYTOPENIA • Less frequent, in most cases due to immune mechanism. • Quinidine is most commonly involved • All drugs causing aplastic anemia also cause thrombocytopenia
- 26. DEMONSTRATION fresh normal blood with patient’s serum clot retraction is prevented.
- 27. DRUGS CAUSING THROMBOCYTOPENIA • Anti arrhythmics– quinidine, procainamide • Antibacterials:Sulfonamides,Penicillin,Rifampicin • Antiepileptics: Phenytoin, Carbamazepine, Valproic acid • Diuretics:Thiazides,Furosemide,Acetazolamide • H1receptorantagonists:Cimetidine, Ranitidine` • Miscellaneous:Alpha methyl dopa, Goldcompounds, Danazol, Heparin, Quinine
Editor's Notes
- Methotrexate,Pyrimethamine,Trimterene,Trimethoprim, Diamidine compounds.-dhf Phenytoin,Primidone,Barbiturates,Cycloserine,Alcohol, probably oral contraceptive agents-imp absorptn PAS, Colchicine, Neomycin, Alcohol-vit b12
- deficiency of all three cellular components of the blood (red cells, white cells, and platelets).-pancytopenia Hypercellular cond is seen in myelodysplastic syndrome.
- Autologous bone marrow transplant. The term auto means self. Stem cells are removed from you before you receive high-dose chemotherapy or radiation treatment. The stem cells are stored in a freezer. After high-dose chemotherapy or radiation treatments, your stems cells are put back in your body to make normal blood cells. This is called a rescue transplant. Allogeneic bone marrow transplant. The term allo means other. Stem cells are removed from another person, called a donor. Most times, the donor's genes must at least partly match your genes. Special tests are done to see if a donor is a good match for you. A brother or sister is most likely to be a good match. Sometimes parents, children, and other relatives are good matches. Donors who are not related to you, yet still match, may be found through national bone marrow registries. Umbilical cord blood transplant. This is a type of allogeneic transplant. Stem cells are removed from a newborn baby's umbilical cord right after birth. The stem cells are frozen and stored until they are needed for a transplant. Umbilical cord blood cells are very immature so there is less of a need for perfect matching. Due to the smaller number of stem cells, blood counts take much longer to recover.
- recommended for those whom marrow transplantation is not available.
- Hemolytic reaction in normal people can occur if concentration of drug is high
- erythrocyte enzyme nicotinamide adenine dinucleotide hydrogen-NADH