19022015 Khalid Al Anazi Cytopenias Low WBC counts Neutropenia Lymphocytopenia Monocytopenia Low Hb level Normocytic Anemia Microcytic Anemia Macrocytic Anemia ID: 1035851
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1. ANEMIACollege of Medicine & KKUH 19/02/2015Khalid Al-Anazi
2. Cytopenias** Low WBC counts: - Neutropenia - Lymphocytopenia - Monocytopenia** Low Hb level: - Normocytic Anemia - Microcytic Anemia - Macrocytic Anemia** Low PLT counts: - Primary - Secondary - Immune & non-immune** Pancytopenia
3. Common causes of anemia1- Acute trauma and blood loss2- Chronic infections e.g. hookworm and parasitic infections.3- Chronic diseases e.g. chronic renal failure.4- Nutritional anemia5- Bone marrow failure syndromes: aplastic anemia & myelodysplastic syndrome6- Neoplastic disorders: leukemia, lymphoma & solid tumors7- Endocrine diseases & hormona imbalance8- Immune mediated hemolytic anemia9- DIC & toxin exposure
4. The most common causes of anemia1- Iron deficiency anemia2- Thalassemia3- Sickle cell disease4- Aplastic anemia5- Hemolytic anemia6- Pernicious anemia7- Fanconi anemia
5. Classification of anemias1- Microcytic hypochromic2- Normocytic normochromic3- Macrocytic
6. Investigations of anemia
7. Treatment of anemia * Rx of cause; symptomatic Rx; DIET * Supplements: iron; folate; vit B 12 * IV iron; blood transfusion
8. Classification of hemolytic anemias* Hereditary or acquired* Immune or non-immune* Intravascular or extravascular; intracorpuscular or extracorpuscular* Warm antibody or cold antibody type* Membrane, enzyme or globin chain defect; drug-induced, infection or disease-related
9. Hereditary hemolytic anemias- Sickle cell anemia- Thalassemias- Hereditary spherocytosis- Hereditary elliptosis- G-6-PD deficiency- Pyruvate kinase deficiency
10. Acquired hemolytic anemias1- Immune hemolytic anemias: (a) Autoimmune hemolytic anemia (b) Alloimmune hemolytic anemia (c) Drug-induced hemolytic anemia2- Mechanical hemolytic anemia3- Paroxysmal nocturnal hemoglobinuria4- Infection-related hemolysis5- Drug-induced hemolysis
11. Intracorpuscular defectsExtracorpuscular defectsHereditary- Hemoglobinopathies- Enzymopathies- Membrane defects - Familial HUS Acquired - PNH-Mechanical destruction [microagiopathy] * Drugs * Toxins * Infections * Autoimmune
12. Causes of microangiopathic hemolytic anemia1- HUS2- TTP3- Valve or arterial graft hemolysis4- Mechanical: trauma and burns
13. Drugs that commonly cause hemolysis1- Antimalarials: chloroquine, promaquine2- Antimicrobials: sulfonamides, chloramphenicol, bactrim, nitrofurantoin.3- Miscellaneous: aspirin, dapsone
14. Intravascular defectsExtravascular defects 1- MAHA2- PNH3- Infections4- Snake bites5- Blood transfusion reactions 1- Hemoglobinopathies2- Enzymopathies3- Membrane defects4- Autoimmune hemolytic anemia
15. Warm antibody hemolytic anemiaIgG antibodies bind at 37 o CCold antibody hemolytic anemiaIgM antibodies bind at 4 o C1- Idiopathic: 50%2- CLL3- Lymphoma4- Multiple myeloma5- Ulcerative colitis6- HIV7- SLE, RA8- Solid tumors1- Infections: (a) Mycoplasma (b) EBV2- Neoplasms: (a) CLL (b) Multiple myeloma (c) Walenstrom macroglobulinema (b) Kaposi sarcoma** Elderly individuals** Exacerbation by cold; in winter** Acrocyanosis: blue fingers and toes
16. Hemolytic anemiaClinical aspectsLaboratory findings1- Anemic manifestations: * Dizziness * Headache * Fatigue * Palpitations * Pallor * SOB2- Jaundice3- Dark urine4- Splenomegaly5- Gallstones6- Leg ulcers- ↓ Hb- ↑ MCV- ↑ Reticulocyte count- ↑ LDH- ↑ Total & indirect bilirubin- ↓ or absent haptoglobin- Sickling test- HB electrophoresis: Hb S; HbF- Coombs test: direct & indirect- Osmotic fragility test- Blood film: * Sickle cells * Spherocyts* Reticulocytes * Elliptocytes * Target cells * Microcytosis* Pencil cells * Macrocytosis* Hypochromasia
17. Causes of Normocytic Anemia A- Anemia of chronic illness: ** Anemia of chronic renal insufficiency ** Anemia of chronic liver disease; multifactorial ** Anemia of endocrine disease: - Addison's disease - Hypothyroidism B- Hemolytic anemias: ** Sickle cell diseaseC- Bleeding; acute blood lossD- NutritionalE- Early iron deficiency anemiaF- Mixed Anemia [Iron/Folate/Vit B12 deficiency]
18. Blood film of SCA
19. Causes of Microcytic anemia 1- Iron deficiency anemia 2- Thalassemia; α , β 3- Sideroblastic anemia 4- Anemia of chronic illness 5- Anemia of inflammation 6- Lead poisoning
20. Blood Film of Thalassemia
21. Blood Film of IDA
22. Differentiation IDA & Anemia of chronic illness Lab. IndexIron deficiency Chronic Illness Hb↓↓MCV↓↓ or NormalMCH↓NormalMCHC↓NormalIron↓↓Ferritin↓↑TIBC↑↓Sol. Transferrin Receptor Level ↑NormalTransferrin Saturation↓↓RDW↑Normal or ↑Blood FilmMicrocytic; HypochromicPencil & Target cellsNormocytic; NormochromicMicrocytic in severe casesBM Bx↓ or AbsentPresent
23. Causes of Macrocytosis 1- Folate deficiency 2- Vitamin-B12 deficiency 3- Pernicious anemia 4- Alcohol intake 5- Pregnancy 6- Hypothyroidism 7- Liver disease 8- Hemorrhage & hemolysis 9- Myelodysplastic syndrome & aplastic anemia 10- Multiple myeloma and acute leukemia 11- Malabsorption syndrome 12- COPD 13- Copper deficiency 14- Splenectomy 15- Drugs & Toxins: ** Arsenic poisoning ** Bactrim ** Nitrous oxide poisoning ** Metformin ** Anti-retroviral Rx ** Hydroxyurea ** Anti-TB Rx ** Methotrexate
24. Macrocytic anemiaCommon causes:1- Diet: malmnutrition, malabsorption2- Drugs: antifolate drugs, antimicrobials & anticonvulsdants3- Alcohol intake4- Liver disease5- Thyroid disease6- Malignancy: leukemia & myeloma7- BM failure: MDS & aplastic anemia
25. Clinical & laboratory manifestations of macrocytic anemiaClinical aspectsLaboratory findings1- Signs of malnutrition: emaciation2- Manifestations of anemia: * Dizziness * Headache * Fatigue * Palpitations * Pallor * SOB3- Signs of liver disease3- Signs of thyroid disease4- Signs of BM failure:PallorEcchymosesPetechiae - ↓ Hb- ↑ MCV- PLT: normal or ↓- ↑ LDH- Hct, MCH, MCHC- ↓ blood counts; pancytopenia: chronic liver disease, hypersplenism, MDS, aplastic anemia & vitamin B12 deficiency - Renal & hepatic profiles- Coagulation profile- Thyroid function tests- Vitamin B12 & folate levels- Blood film: * Macrocytosis * Hypersegmentation of neutrophils * Rouleaux formation, plasma cells * Dysplastic changes & blast cells - Bone marrow Bx:* Megaloblastic changes* Dysplastic changes* Blasts & plasma cells
26. Blood film of ITP
27. Blood Film of MAHA
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29. Complications of SCDComplication ororgan involvedExamples and detailsInfections1- Pneumonia2- Urinary tract infection3- Pyelonephritis4- Meningitis 5- Acute cholecystitis6- Bacteremia and septicemia Microorganisms involved: Streptococcal pneumonia ; Salmonella species ; neisseria meaningitidis ; Hemophilus influenzae ; Chlamydia pneumonia; Staphylococus aureus ; Myloplasma pneumoniae ; Parvovirus B-19Sickle cell crisesVenoocclusive ; hemolytic ; aplastic ; splenic sequestration crisesBone involvement Dactylitis ; avascular necrosis of bone e.g. femoral head (osteonecrosis) ; osteomyelitisRenal involvement Hyposthenuria; glomerulopathy; end-stage renal disease; microalbuminuria; renal insufficiency; contrast and analgesic nephropathiesPulmonary involvementPulmonary emboli ; restrictive lung disease; acute chest syndrome ; pulmonary hypertension; lung infectionsCardiac complicationsCardiomyopathy; myocardial infarction; heart failureNeurological sequelaeIschemic stroke; silent cerebral infarctions; convulsionsChronic hemolysisAnemia (may be severe); cholelithiasis; priapism; risk of aplasia; hyperbilirubinemia; leg ulcers; pulmonary hypertensionMiscellaneousComplications Delayed growth; delayed sexual maturation; proliferative retinopathy; iron overload and hemochromatosis; organ dysfunction and failure; drug toxicity; narcotic dependence and abuse; priapism; hyposplenism, splenic dysfunction and auto-splenectomy.
30. General Measures1- Analgesia for pain2- Oral and intravenous hydration3- Folic acid supplements4- Penicillin prophylaxis5- Antimicrobials for infectious complications6- Blood transfusion7- Exchange blood transfusion8- Oxygen supplementation9- Mechanical ventilation in respiratory distress10- Joint replacement therapy for a vascular necrosis e.g. hip joint11- Chelation therapy for iron overload
31. Specific and targeted therapies1- Drugs that increase HbF production hydroxyurea; vorinostat; valproic acid; panobinostat; sodium dimethylbutyrate; decitabine and azacytidine; pomalidomide2- Anti-oxidant therapies: glutamine; N-acetylycystine; alpha-lipoic acid; omega - 3 fatty acids3- Gardos channel inhibitors4- Vascular tone targetting: IV magnesium5- Anti - sicking agents e.g. Aes-1036- Blockade of adhesive pathways: intravenous immunoglobulin; anti-selectins; propranolol; tinzaparin7- Anticoagulants for vascular thrombosis8- Anti-platelet agents: prasugrel9- Anti- inflammatory agents: regadenoson10- Statins; for vascular protection11- Phytomedicines; including plant mixtures12- Investigational therapies e.g. nitrous oxide
32. Potentially curative therapies 1- Gene replacement therapy 2- Various forms of stem cell therapies
33. Preventive measures1- Avoidance of dehydration, extremes of temperature, physical exhaustion, high altitude without oxygen supplementation, certain medications such as meperidine and G-CSF 2- Health education 3- Screening programs 4- Family and genetic counselling
34. Complications of blood transfusionEarly complicationsLate complications1- Hemolytic reactions: Immune & delayed2- Non-hemolytic febrile reactions3- Allergic reactions to proteins: anaphylactic reactions in IgA defy4- TRALI; transfusion-related acute lung injury5- Secondary reactions to bacterial contamination6- Circulatory overload: pulmonary edema7- Air embolism8- Thrombophlebitis9- Hyperkalemia10- Hypothermia11- Clotting abnormalities: with massive transfusions12- Citrate toxicity1- Transmission of infections:* Viral infections: - Hep A negligible - Hep B 1:100,000 - Hep C ˂ 1: 1,000,000 - HIV 1&2 ˂ 1: 4,000,000 - CMV - JC virus* Bacterial infections: - Salmonella - Treponema pallidum - Staph. aureus & epidermidis - Brucella - Yersinia enteroclitica - Bacillus2- GVHD: donor T- cells3- Iron overload with repeated transfusions4- Immune sensitization: rhesus D antigen
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36. How to minimize transfusion complication
37. Blood Film of AML
38. Blood Film of MDS
39. BM Bx of Aplastic Anemia
40. BM Bx of Myelofibrosis
41. Malarial Blood Film [Plasmodium falciparum]
42. THANK YOU