HAEMATOLOGY MEDICINE & MYELOPROLIFERATIVE DISEASE. Dr Mere Kende MBBS (UPNG), MMED (Path),MAACB, MACTM, MACRRM (Aus) Lecturer-SMHS UPNG
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1 HAEMATOLOGY MEDICINE & MYELOPROLIFERATIVE DISEASE Dr Mere Kende MBBS (UPNG), MMED (Path),MAACB, MACTM, MACRRM (Aus) Lecturer-SMHS UPNG
2 Topics Overview of Hematology in Medicine Myeloproliferative Disease
3 Overview of the Role of Hematology in Systemic Disease Assist diagnosis (anaemia/bleeding ds) Ensure appropriate treatments Follow-up/Monitor Specific Treatments (warfarin/iron/vitamin) Gather Prognostic information (leukaemia) Monitor evolution of complications of therapies (cytotoxic/heparin) Screen evidence of early disease (iron)
4 Tests Common Tests Specific Tests Highly specialised Tests
5 Routine Tests FBE/FBC & differential Red Cell Indices (MCV/MCHC/MCH) Platelet count Blood Film Blood Slides (malaria) ESR
6 Full Blood Exam/Count EDTA tube (purple top) Venous blood Occasionally capillary (finger/heel prick) Blood smears (film & parasites)/differentials count
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9 Age related References
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11 Anaemia Normocytic normochromic Anaemia of chronic disease, blood loss, primary BM failure Megaloblastic/macrocytic: Megaloblastic anemia (B12, folate deficiency) Microcytic hypochromic Iron deficiency, thalassemia
12 PMNs (Polymorphonuclear Neutrophils) (Neutrophils) Normal: 40 76% Increased (neutrophilia) Physiologic (Normal). Severe exercise, pregnancy, Bacterial infections, /tissue damage (DKA) Leukemias
13 Polymorphs Decreased: (neutropenia) Pancytopenia, aplastic anemia, Marrow damage (antitumor drugs), severe overwhelming infections (disseminated infections) Marrow obliteration (myelofibrosis,/malignant infiltrate), Drugs (more than 70, including chloramphenicol,) familial decrease, idiopathic causes (rare)
14 Lymphocytes Normal: 24 44% Increased: Virtually any viral infection (AIDS, whooping cough, EBV) acute and chronic lymphocytic leukemias Decreased: (Normal finding in 22% of population) Stress, burns, trauma, uremia, some viral infections, AIDS, AIDS-related complex bone marrow suppression after chemotherapy, steroids, MS
15 Atypical Lymphocytes >20%: Infectious mononucleosis, CMV infection, infectious hepatitis, toxoplasm <20%: Viral infections (mumps, rubeola, varicella), rickettsial infections, TB
16 Basophils Normal: 0 1% Increased: Chronic myeloid leukemia, after splenectomy, polycythemia, Hodgkin s disease, and, rarely, in recovery from infection and from hypothyroidism Decreased: Acute rheumatic fever, pregnancy, after radiation, steroid therapy, thyrotoxicosis, stress
17 Eosinophils Normal: 1 3% Increased: Allergy, parasites, skin diseases malignancy, drugs, asthma, Addison s disease, collagen vascular diseases (handy mnemonic NAACP: Neoplasm, Allergy, Addison s disease, Collagen vascular diseases, Parasites), pulmonary diseases including Loffler s syndrome Decreased: Steroids, ACTH, after stress (infection, trauma, burns) Cushing s syndrome
18 Monocytes Normal: 3 7% Increased: Bacterial infection (TB, SBE, brucellosis, typhoid, recovery from an acute infection), protozoal infections, infectious mononucleosis, leukemia, Hodgkin s disease, ulcerative colitis, regional enteritis Decreased: Lymphocytic leukemia, aplastic anemia, steroid use
19 Platelets Normal: ,000 μl Platelet counts may be normal in number, but abnormal in function as occurs in aspirin therapy. Abnormalities of platelet function are assessed by bleeding time.
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21 Platelets Increased: Sudden exercise, after trauma, bone fracture, after asphyxia, after surgery (especially splenectomy), acute hemorrhage, polycythemia vera, primary thrombocytosis, leukemias, after childbirth, carcinoma, cirrhosis, myeloproliferative disorders, iron deficiency Decreased: DIC, ITP, TTP, congenital disease, marrow suppressants (chemotherapy, alcohol, radiation), burns, snake and insect bites, leukemias, aplastic anemias, hypersplenism, infectious mononucleosis, viral infections, cirrhosis, eclampsia and preeclampsia,, massive transfusionsprosthetic heart valve, more than 30 different drugs (NSAIDs, cimetidine, aspirins, thiazides, others)
22 Platelet count Quantitative (Thrombocytopenia) or Qualitative VWD Glasmans Thromboasthenia
23
24 Hematocrit Normal: Male 40 54%; Female 37 47% Decreased: Anaemias-Megaloblastic (folate or B12 deficiency); iron deficiency; sickle cell; acute or chronic blood loss; hemolysis; anemia due to chronic disease, dilution, alcohol or drugs Increased: Primary polycythemia (polycythemia vera), secondary polycythemia (reduced fluid intake or excess fluid loss, CHD, COAD, CA)
25 ESR Inflammation, Rheumatoid arthritis Infection, bacterial Very high levels >30mm/hr Temporal arteritis Multiple myeloma
26 Blood Film Pancytopenia- Increased- WBC---infection/leukaemia/appendicitis Eosinophilia- parasitosis, allergy Neutrohilia- bacterial infection Lymphocytosis-Viral/EBV, Whooping cough Neutropenia-?need for antibiotics Thrombocytopenia- infection, ITP, drugs, alcohol
27 Blood Film Anaemia-microcytic, normocytic, macrocytic Malaria/parasites Rouleaux Formation (myeloma) Abnormal RBC shapes/sizes Sperocytosis/ovalocytosis Target cell Fragmented red cells Howell Jolley Bodies Sickle cells LE cells Leukaemias-Acute/chronic
28 RBC MORPHOLOGY DIFFERENTIAL DIAGNOSIS Basophilic Stippling: Lead or heavy-metal poisoning, thalassemia, severe anemia Burr Cells (Acanthocytes): Severe liver disease; high levels of bile, fatty acids, or toxins Helmet Cells (Schistocytes): Microangiopathic hemolysis, hemolytic transfusion reaction, transplant rejection, other severe anemias, TTP Howell Jolly Bodies: After splenectomy, some severe hemolytic anemias, pernicious anemia, leukemia, thalassemia
29 Nucleated RBCs: Severe bone marrow stress (hemorrhage, hemolysis, etc), marrow replacement by tumor, extramedullary hematopoiesis Polychromasia (Basophilia): The appearance of a bluish gray red cell on routine Wright s stain suggests reticulocytes. Sickling: Sickle cell disease and trait Spherocytes: Hereditary spherocytosis, immune or microangiopathic hemolysis, severe burns, ABO transfusion reactions Target Cells (Leptocytes): Thalassemia, hemoglobinopathies, obstructive jaundice, any hypochromic anemia, after splenectomy
30 WBC MORPHOLOGY DIFFERENTIAL DIAGNOSIS The following gives conditions associated with certain changes in the normal morphology of WBCs. Auer Rods: AML Döhle s Inclusion Bodies: Severe infection, burns, malignancy, pregnancy Hypersegmentation: Megaloblastic anemias Toxic Granulation: Severe illness (sepsis, burn, high temperature
31 Malaria Parasites
32 Rouleaux Formation
33 Plasma Cells -MM
34 SICKLE CELL
35 MEGALOBLASTIC ANAEMIA
36 Erythroblast/Nucleated Red Cells
37 LE Cells
38 Male/50 AML
39 Female/4 ALL
40 Hypersegmented neutrophils
41 Specific Tests Coagulation studies (Bleeding Time, PT, PTT ) Liver disease Vitamin K deficiency Purpura Hemophilia A/B vwb disease Thromobocytopenia
42
43 Bleeding Time Methods: Duke, Ivy <6 min; Template <10 min (bedside test). A small incision is made, and the wound is wicked with filter paper every 30s until the fluid is clear. In vivo test of hemostasis that tests platelet function, local tissue factors, and clotting factors. Nonsteroidal medications should be stopped 5 7 d before the test because these agents can affect platelet function. Increased: Thrombocytopenia (DIC, TTP, ITP), von Willebrand s disease, defective platelet function (NSAIDs such as aspirin)
44 Partial Thromboplastin Time (Activated)- PTT, APTT Normal: s Evaluates the intrinsic coagulation system. Most commonly used to monitor heparin therapy Increased: Heparin and any defect in the intrinsic coagulation system (includes Factors I, II, V, VIII, IX, X, XI, and XII), prolonged use of a tourniquet before drawing a blood sample, hemophilia A and B
45 Prothrombin Time (PT) Normal: s PT evaluates the extrinsic coagulation system that includes Factors I, II, V, VII, and X. The use of INR instead of the Patient/Control ratio to guide anticoagulant (Coumadin) therapy is becoming standard. INR provides a more universal and standardized result because it measures the control against a WHO standard reference reagent.
46 Therapeutic INR levels are 2 3 for DVT, PE, TIAs, and atrial fibrillation. Recurrent DVT on adequate treatment requires an INR of Mechanical heart valves require an INR of Increased: Drugs (sodium warfarin [Coumadin]), vitamin K deficiency, fat malabsorption, liver disease, prolonged use of a tourniquet before drawing a blood sample, DIC
47 Condition PT PTT Bleeding Time Platelet Count Vitamin K deficiency prolonged prolonged normal normal Warfarin Rx Prolonged Prolonged Normal Normal DIC Prolonged Prolonged Prolonged decrease vwd normal Prolonged Prolonged Normal Liver Disease (early) Prolonged Normal Normal Normal Uremia Normal Normal Prolonged Normal Thromobocytopenia Normal Normal prolonged decreasd Hemophilia A & B Normal prolonged Normal Normal Factor V & X deficiency Prolonged Prolonged Normal Normal Glasmans Thromboasthenia Normal Normal prolonged Normal Bernard Soulier Syndrome Normal Normal prolonged decreasd
48 Coombs Test, Direct (Direct Antiglobulin Test) Normal = negative Uses patient s erythrocytes; tests for the presence of antibody on the patient s cells and used in the screening for autoimmune hemolytic anemia. Positive: Autoimmune hemolytic anemia (leukemia, lymphoma, collagen vascular diseases), hemolytic transfusion reaction, some drug sensitizations (methyldopa, levodopa, cephalosporins, penicillin, quinidine), hemolytic disease of the newborn (erythroblastosis fetalis)
49 Coombs Test, Indirect (Indirect Antiglobulin Test/Autoantibody Test) Normal = negative Uses serum that contains antibody, usually from the patient. Used to check cross-match prior to blood transfusion in the blood bank.
50 Hb Electrophoresis (thalassaemia/sickle Cell) G6PD Assays (G6PD deficiency) vwf assays (von Willebrand Disease) BM Biopsy/aspirate- (aplastic anaemia/myeloma/tb granuloma) Iron studies/ferritin Assay/sTR B12/folate Assay/MMA
51 Reticulocyte
52 Hemolysis/Reti culocytosis Extrinsic Intrinsic Microangi pathic Antibody Mediated Infective Membrane Disorder Enzyme Disorder Hb Disorder
53 Hemoglobin (plasma/urine) Bilirubin (urine/plasma) Urobilinogen Haptoglobulin/AST/LDH D-dimer (PE/DVT)
54 Disseminated Intravascular Coagulation hypofibrinogenemia, Elevated fibrin degradation products (d-dimer) Thrombocytopenia Prolonged PT. D-dimer is the most sensitive,
55 Elevated Liver enzymes PTT may or may not be prolonged. ~ 25% of cases, a microangiopathic hemolytic anemia (fragmented red ) Antithrombin III levels may be markedly depleted. plasminogen and 2 -antiplasmin may be low.
56 Highly Specialised Assays DNA studies (sickle cell; hemochromatosis) Karyotyping Philadelphia Chromosomes (9,22)
57 Myeloproliferative Diseases Essential to diagnosis Acquired clonal abnormalities of the hematopoietic stem cell Stem cell gives origin ----qualitative and quantitative changes are seen in all these cell lines. CML- specific characteristic chromosomal changes are seen. Morphological abnormalities to 2 or more cells lines
58
59 Can evolve from one for to another All Disorders can Progress to AML
60 CLASSIFICATIONS Myeloproliferative syndromes Polycythemia vera Myelofibrosis Essential thrombocytosis Chronic myeloid leukemia Myelodysplastic syndromes Acute myeloid leukemia
61 Cause Idiopathic/Unknown Cytotoxic Chemotherapy
62 Clinical Features of MPD Generalised Fatique Anemia Increased risk of Infections Increased thrombotic episodes Organomegaly Hyperviscosity Syndrome
63 Polycythemia Vera Essentials of Diagnosis Increased red blood cell mass (>60%). Splenomegaly (75%). Normal arterial oxygen saturation. Usually elevated white blood count ( /ul) and platelet count ( /ul).
64 Other Features Hyperviscocity/incraesed thrombosis Iron deficiency Hypercellular marrow High vitamin B12 (increased transcobalamin III) Hyperuricemia
65 Causes
66 Treatment Weekly phlebotomy (aim PCV<45%) Myelosuppressive therapy (hydroxyurea) Allopurinol (hyperuricemia)
67 Essential Thrombocytosis Essentials of Diagnosis Elevated platelet count in absence of other causes >2million/mcl (reactive usu<1million/mcl) Normal red blood cell mass. Absence of Philadelphia chromosome.
68 Other Features Median Age: 50 60; W>M Thrombosis (abdomen) Burning sensation of tips of finger Splenomegaly (25%) BM increased megakaryocytes WBC<30,000/mcl
69 Treatment Hydroxyurea Aspirin (thrombosis)
70 Myelofibrosis Essentials of Diagnosis Striking splenomegaly. Teardrop poikilocytosis on peripheral smear. Leukoerythroblastic blood picture; giant abnormal platelets. Hypercellular bone marrow with reticulin or collagen fibrosis.
71 Blood Film- Tear drops red cells
72 Bone Marrow -Fibrosis
73 Chronic Myelogenous Leukemia Essentials of Diagnosis Strikingly elevated white blood count. Markedly left-shifted myeloid series but with a low percentage of promyelocytes and blasts. Presence of Philadelphia chromosome or bcr/abl gene
74 CML- Increased WBC
75 Bone Marrow-Increased M: E ratio
76 CML Bone Marrow Hypercellular, increased myeloid/megakaryocyte/no fat
77 General Clinical Features of MPD Anaemia Increased thrombosis tendencies Splenomegaly/hepatomegaly Bone Pain Night sweats/increased risk of infections Hyperviscosity syndrome
78
79 References Current Medical Diagnosis and Treatment 2008 LG. Gomella, SA. Haist; Clinicians Pocket Reference 11 th Edition 2007 Harrison s Text of Medicine 17 th Edition
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