HEMA1LEC LESSON 10 - LEUKEMIA PDF

[TRANS] LESSON 10: LEUKEMIA LEUKEMIA o NOTE: Bone Marrow contain normal stem cells and ETIOLOGY OF LEUKOCYTE NEOPLASM have normal hematopoiesis but for patients with Unknown Origin...

[TRANS] LESSON 10: LEUKEMIA LEUKEMIA o NOTE: Bone Marrow contain normal stem cells and ETIOLOGY OF LEUKOCYTE NEOPLASM have normal hematopoiesis but for patients with Unknown Origin Leukocyte Neoplasm, their bone marrow has a mixture Viral of normal cells and malignant cells (cancerous cells) o Epstein-Barr virus (Burkitt non-Hodgkin lymphoma) ▪ Cancer Cells → normal cells but upon maturation o Human T-cell lymphotropic virus type 1 (HTLV-1) there’s a presence of abnormality. Instead, they o Adult T-cell leukemia/lymphoma will mature normally, they mature into cancerous Bone marrow damage – Radiation exposure, chemicals, cells. and malignancies secondary to cancer treatments o CANCER CELLS VS NORMAL CELLS ▪ When it comes to cell survival, cancerous cell Chromosome defects survives more than normal cells since they tend o Some chromosomal abnormalities are diagnostic for to grab nutrition intended for normal cell leukemic subtypes; ▪ When it comes to structure, cancerous cell is o t(15;17) is diagnostic for acute promyelocytic leukemia. larger than normal cell Genetic factors – Increased incidence in Down syndrome, ▪ When it comes to cell population, cancerous Fanconi, and others cell is more dominant than normal cells. Immune dysfunction – Hereditary and acquired defects in ▪ When it comes to proliferation, cancerous cell the immune system will rapidly proliferate than normal cells and will have a longer lifespan LABORATORY DIAGNOSIS o NOTE: There are normal cells in our body but there is Complete Blood Count (CBC) and Peripheral Blood part in our immune system that kills the cancer cell Smear (PBS) which are the T cells, NK cells. o Leukocytosis (Increase WBC) ▪ Cancer occurs if cancer cells are not killed, and o Neutropenia (decrease neutrophils) they tend to overproliferated o Thrombocytopenia (decrease platelets) Common adverse effects include: Blood Chemistry and Coagulation Tests o Bone marrow suppression, Nausea and vomiting, o LDH (lactate dehydrogenase) and uric acid levels Thrombocytopenia, Neutropenia, Neuropathies, are usually elevated Anorexia, Hepatic, renal, and/or cardiac toxicity, Hair o If DIC is present, laboratory studies show an elevated loss, Stomatitis, Renal toxicity, Diarrhea. prothrombin time, decreased fibrinogen levels, and the ▪ NOTE: Patient intake strong chemicals which can presence of fibrin split products. kill the malignant cells and normal cells which Bone Marrow aspiration and biopsy – provides the leads to bone marrow suppression definitive diagnosis Radiotherapy Cytochemistry – cells are put on a slide and exposed to o NOTE: chemotherapy and radiotherapy are harsh chemical stains (dyes) that react only with certain treatment specially if the type of cancer is aggressive substances found in or on different kinds of cells. and late detected Flow Cytometry and Immunohistochemistry o Radiation is used for all types of leukemia o classifying cells according to proteins on or in the cells. o Used in conjunction with chemotherapy, but it may also o to determine exact type of leukemia be used as CNS prophylaxis to prevent spread of acute Chromosome Testing leukemias to the brain and spinal cord. o normal human cells contain 23 pairs of chromosomes o Cranial irradiation lowers the risk of relapse in acute (bundles of DNA). In some cases of leukemia, a piece leukemias. of chromosome is missing called a deletion. o Used to relieve pain from hepatomegaly and Cytogenetics splenomegaly Fluorescent in situ hybridization (FISH) Hematopoietic Stem cell transplantation Polymerase Chain Reaction (PCR o Bone marrow transplant (BMT) Lumbar Puncture (spinal tap)- CSF fluid o Peripheral blood stem cell transplant (PBSTC) Lymph node biopsy o Umbilical cord blood stem cell transplant (UCBSTC) Imaging test o X-rays HEMATOPOIETIC MALIGNANCY CLASSIFICATION o Computed tomography (CT) Scan Classified according to cell type: o Magnetic resonance imaging (MRI) Scan o Cell Maturity is used to distinguish between acute and o Ultrasound chronic forms of leukemia o Gallium scan and bone scan o Cell Linage whether as to lymphocytic / myelogenous 2 CLASSIFICATIONS FOR LEUKEMIA: TREATMENT o FAB (French American British Classification) Chemotherapy ▪ Is based on cellular morphology and cytochemical o primarily to prevent replication of malignant cells and to stain results. treat systemic disease, such as leukemia or other ▪ NOTE: Example of cytochemical stain → metastasized cancers. Chemotherapy is used to cure Myeloperoxidase, Sudan black B, Periodic acid and control Schiff, Chloroacetate Esterase A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 1  TRANS: LEUKEMIA ▪ FAB defines acute leukemia as >20% bone GENERAL CHARACTERISTICS marrow blasts. ⚫ Leukemia is a group of malignant disease of o WHO (World Health Organization Classification) hematopoietic tissue, characterized by replacement of ▪ Is based on cellular morphology and cytochemical normal BM elements. stains, but also utilizes information obtained from o Blood cancer. immunologic probes of cell markers, cytogenetics, o Over-proliferation of malignant cells. molecular abnormalities, and clinical syndrome. o BM and circulation have presence of many malignant ▪ NOTE: cell markers such as cluster of cells differentiation which are CD’s specific for WBC ⚫ Leukocytosis, is a normal response to infection, but when ▪ WHO defines acute leukemia as >20% bone leukocytosis becomes chronic or progressively elevates marrow blasts. without obvious cause, then it may indicate malignancy. NOTE: FAB classification is obsolete but mostly used in ⚫ NOTE: (Hindi porket mataas ang WBC, it indicates academic teaching. The classification used today is the leukemia). WHO classification. ⚫ Regardless of the type of leukemia, the abnormal cells WHO classification is anchored on the principle of FAB in the BM depress production of other cells, resulting since it is based on cellular morphology and cytochemical in a number of adverse effects. stain but is more specific because it detects cell markers, o Anemia - especially if the type of leukemia is under clinical syndrome and genetic defects. myelogenous. o Risk of infection occurs if neutrophil count decreases CLASSIFICATION ACCORDING TO CELL MATURITY ◼ Due to BM suppression, there is decreased Acute Leukemia is rapidly progressive disease quantity of mature cells. Therefore, overall characterized by an abnormal expansion of immature function is affected. cells or blasts. o Clotting factors decrease, increasing risk of bleeding o Sudden onset and rapid progression. Blood smear as thrombocytopenia occurs. appearance of blast cells or immature cells o Risk of physiological fracture increases as periosteum Chronic Leukemia is a slowly progressive disorder weakens because of proliferation of cells in the bone characterized by an abnormal expansion of mature cells. marrow. o There is malignancy, but appearance of cells are o Hypertrophy and fibrosis occur in other organs, such mature as the liver, spleen, and lymph glands because of o Over-proliferation of mature cells in bone marrow infiltration of malignant cells and circulation o Increased intracranial pressure, ventricular dilation, o Gradual onset, slow progression. and irritation of the meninges. o Hypermetabolic state deprives cells of nutrients and Table No 1. Comparison of Acute and Chronic Leukemia causes loss of appetite, weight loss, general fatigue, ACUTE CHRONIC and muscle atrophy. Age All ages Adults Clinical Onset Sudden Insidious LYMPHOCYTIC LEUKEMIA Course (untreated) < 6 months 2-6 years ACUTE LYMPHOCYTIC LEUKEMIA (ALL) Leukemic cells Immature Mature Sudden on-set of symptoms and rapid progression of Anemia Mild to severe Mild disease. Life expectancy is 5.0 X less severe 10% homogeneous, small, hyper-clumped lymphocytes and FAB CLASSIFICATION OF ALL smudge cells HAIRY CELL LEUKEMIA (HCL) Found in adults over 50 years old. more common in males (7:1) B cell malignancy (CD19, CD20 positive). Massive splenomegaly; extensive bone marrow 1. FAB L1 involvement results in dry tap Most common childhood on bone marrow aspiration leukemia (2-10 y/o) Laboratory: Pancytopenia; cytoplasm of lymphocytes Small Lymphoblasts; shows hair-like projections; hairy cells are tartrate- resistant homogenous appearance acid phosphatase (TRAP) stain positive. Best prognosis Most T cell ALLs are FAB L1 PROLYMPHOCYTIC LEUKEMIA (PLL) Appearance of immature Found in adults; more lymphocytes in the circulation. common in males. Marked splenomegaly 2. FAB L2 Laboratory: Characterized Most common in adults by lymphocytosis (>100 X Large Lymphoblasts; 109/L) with many heterogenous appearance prolymphocytes Appearance of abnormal Anemia and thrombocytopenia lymphocytes in the circulation OTHER LYMPHOID MALIGNANCIES PLASMA CELL LYMPHOMA 3. FAB L3 NEOPLASMS Multiple Myeloma Hodgkin Lymphoma Most common in adults (classical) Leukemic phase of Burkitt's Waldenstrom Non-Hodgkin Lymphoma Lymphoma Macroglobulinemia Seen in both adults and children Mycosis fungoides Lymphoblasts are large and uniform with prominent nucleoli; cytoplasm stains deeply PLASMA CELL NEOPLASMS basophilic and may show vacuoles Plasma cell neoplasms are diseases in which causes Poor prognosis abnormal growth of plasma cells in the bone marrow. The abnormal plasma cells can also form tumors in the CYTOLOGIC L1 L2 L3 bone or soft tissue. FEATURES o Plasmacytoma Cell Size Predominantly Large, Large, o Multiple myeloma small heterogenous homogenous Nuclear Homogenous Heterogenous Finely stippled Chromatin and MULTIPLE MYELOMA homogenous Nuclear Shape Regular, Irregular, clefting Regular (round is a cancer formed by malignant plasma cells. occasional and indentation to oval) o abnormal proliferation of plasma cells in the bone clefting common marrow. Nucleoli Absent One or more, often large One or more prominent Monoclonal gammopathy causes B cell production of Cytoplasm Scanty Variable, often Moderately excessive IgG (most common) or IgA, with decreased moderately abundant, production of other globulins. abundant strongly Excessive IgG or IgA production by myeloma cells causes basophilic Cytoplasmic Variable Variable Prominent increased blood viscosity. vacuolation Found in adults over 60 years old; incidence higher in males. A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 3  TRANS: LEUKEMIA Identified on serum protein electrophoresis by an "M" spike HL are more likely to arise in the upper portion of the body in the gamma-globulin region. (neck, underarms or chest) Bence Jones Protein (free light chains-kappa or lambda) NHL can arise in lymph nodes throughout the body but can found in the urine; toxic to tubular epithelial cells; cause also arise in normal organs kidney damage. 4 STAGES OF NON-HODGKIN LYMPHOMA Laboratory: bone marrow plasma cell >30%; marked o STAGE 1: Cells are found in ONLY ONE LYMPH rouleaux; increased ESR, blue background on blood smear; NODE OR ONLY ONE PART OF TISSUE OR ORGAN plasma cells and lymphocytes on blood smear. o STAGE 2: The lymphoma cells are found in at least TWO LYMPH NODE AREAS on the same side of the Discussion: Plasma cells produce antibodies in the form of body or only above or below the diaphragm. immunoglobulins. These cells arise from B lymphocytes upon o STAGE 3: Lymphoma is IN LYMPH NODES ABOVE antigenic stimulation, maturing into plasma cells capable of AND BELOW THE DIAPHRAGM. secreting large quantities of antibodies. There are several o STAGE 4: in addition to lymph cell spread, lymphoma classes of immunoglobulins, including IgG, IgA, IgM, IgE, and cells are found IN SEVERAL PARTS OF ONE OR IgD. In multiple myeloma, there is an abnormal proliferation of MORE ORGANS OR TISSUES plasma cells. This overproduction of plasma cells often leads to STAGE A: No symptoms (patient has no weight loss, fever an excess of immunoglobulins, particularly IgG (most common) or night sweats) or IgA. The elevated levels of these immunoglobulins can STAGE B: Presence of any of the following symptoms: increase blood viscosity. Weight loss (10% or more in the last six months) fever (greater than 101.5 F) night sweats, severe itching. WALDENSTROM MACROGLOBULINEMIA Monoclonal gammopathy causes B cell production of MYCOSIS FUNGOIDES excessive IgM (macroglobulin) and decreased Most Common types of cutaneous T cell lymphoma that production of the other immunoglobulins. affects the skin Found in adults over 60 years old. A sign of mycosis fungoides is a red rash on the skin Lymphadenopathy and hepatosplenomegaly; no bone wherein Sezary Syndrome, cancerous T cell are found tumors. 4 PHASES OF MYCOSIS FUNGOIDES: Identified on serum protein electrophoresis by an "M" spike o 1. PREMYCOTIC PHASE – A scaly, red rash in areas in the gamma globulin region. of the body that usually are not exposed to the sun. Laboratory: marked rouleaux, increased ESR, blue o 2. PATCH PHASE – Thin, reddened, eczema-like background to blood smear; plasmacytoid lymphocytes, rash. plasma cells and lymphocytes on blood smear. o 3. PLAQUE PHASE – Small raised bumps (papules) or hardened lesions on the skin which may be LYMPHOMA reddened. A. Proliferation of malignant cells in solid lymphatic tissue. o 4. TUMOR PHASE – Tumors form on the skin, may B. Initially localized; may spread to bone marrow and blood. develop ulcers and the skin may get infected. C. Clinical symptom: Lymphadenopathy D. Diagnosis: Tissue biopsy, CD surface markers, SEZARY SYNDROME cytogenetics, DNA analysis/PCR Variant of Mycosis Fungoides Skin all over the body is reddened, itchy, peeling and HODGKIN’S LYMPHOMA painful. There may also be patches, plaques or tumors on is a primary malignant tumor of the the skin lymph nodes, rarely affecting the It is not known if the Sezary Syndrome is an advanced form extranodal lymphoid tissue. of Mycosis Fungoides or a separate disease. 2 TYPES: LABORATORY: A. Classic Hodgkin Lymphoma (cHL) o CBC, PBS, Skin biopsy, Immunophenotyping, t- accounts for about 95% of all cases of cell receptor (TCR) gene rearrangement test, Flow Hodgkin lymphomas in developed cytometry (Tumor markers) are CD2, CD3 and countries. CD4 Positive. Hallmark: Reed-Sternberg cells - cancer cells in cHL. MYELOCYTIC / MYELOGENOUS LEUKEMIA o It has owl’s eye appearance ACUTE LEUKEMIA Is of sudden onset and rapid progression unless treated B. Nodular Lymphocyte Predominant Hodgkin Lymphoma and is characterized by the presence of blast cells in (NLPHL) peripheral blood and bone marrow. Accounts for about 5% of cases Classified as L1, L2, L3 NLPHL usually starts in lymph nodes in the neck or under the arm. It can occur in people of any age and is more CHRONIC LEUKEMIA common in men than in women. This type of HL is treated differently from the classic types Is of gradual onset and slow progression and is POPCORN CELL – Large cancer cells in NLPHL which are characterized by the presence of more mature cells in the variants of Reed Sternberg Cells. peripheral blood and bone marrow. Appearance of smudge cells in peripheral blood smear. NON-HODGKIN LYMPHOMA ACUTE MYELOGENOUS LEUKEMIA (AML) If the Reed Sternberg cells is not present Or Acute Myeloproliferative Disorders The first sign of the disease is often the appearance of There is an unregulated proliferation of the Myeloid Cell. enlarged lymph nodes A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 4  TRANS: LEUKEMIA Classified using morphology, cytochemical stains, CD markers, and cytogenetics. Platelets and Erythrocytes can be affected. o Note: Difference of Lymphocytic Leukemia in Myelogenous Leukemia, Myeloid Cells are affected that is why platelets and erythrocytes are also affected. In AML, there is a FAB Classification from M0 to M7. A. FAB M0 – MINIMALLY DIFFERENTIATED Nucleus occupies most of the cell Image 4. FAB M3 Nuclear membrane and chromatin are fine 2-3 nucleoli are seen E. FAB M4 (ACUTE MYELOMONOCYTIC LEUKEMIA) The cytoplasm stains blue forms a rim around the nucleus >20% marrow myeloblast with >20% cells of monocytic and does not contain any inclusions. origin Myeloid Markers: CD13, CD33, CD34 NAEGELI’S type of Leukemia Proliferation of unipotential stem cell CFU-GM that gives rise to monocytes and granulocytes. M4Eo → subclass of FAB M4 that presents with Eosinophilia. Image 1. FAB M0 B. FAB M1 (AML WITHOUT MATURATION) Image 5 & 6. FAB M4 (Left) FAB M4Eo (Right) Shows 20% or more marrow myeloblasts May have Auer Rods F. FAB M5 (ACUTE MONOCYTIC LEUKEMIA) >30% marrow monoblasts Also known as Schilling’s Leukemia Has two variants: o M5a → seen in children with 80% monoblasts in the bone marrow. ▪ Myeloid Markers: del(11), t(9;11) Image 2. FAB M1 ▪ >80% monoblasts ▪ 20% marrow myeloblasts May have Auer Rods Chromosome abnormality: t(8;21) Image 7. FAB M5 G. FAB M6 (ACUTE ERYTHROLEUKEMIA) Also known as DI GUGLIELMO SYNDROME 20% marrow myeloblasts and >50% dysplastic marrow Image 3. FAB M2 normoblasts Normoblasts are PAS positive, CD34, & CD71 positive D. FAB M3 (ACUTE PROMYELOCYTIC LEUKEMIA Myeloblasts are SBB, MPO positive, C13, CD15, & CD33 positive >20% marrow promyelocytes Myeloid Markers: Abnormalities CH5 AND CH7 With bundles of Auer Rods called Faggot Cells DIC associated Chromosome Abnormality: t(15;17) Image 8. FAB M6 A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 5  TRANS: LEUKEMIA H. FAB M7 (ACUTE MEGAKARYOCYTIC LEUKEMIA) Characterize by a proliferation of megakaryoblasts in the bone marrow; blasts may have cytoplasmic blebs. Difficult to diagnosis with cytochemical stains. Myeloid Markers: CCD41, CD42, CD61 Image 9. FAB M7 SUMMARY OF FAB CLASSIFICATION NAME OR MORPHOLOGY MPO SBB SPECIFIC NONSPECIFIC PAS DISORDER (Myeloperoxidase) (Sudan ESTERASE ESTERASE (Periodic Black B) Acid Schiff) M0 Acute myeloblastic >20% blasts – – – – – leukemia: mimally No granules differentiated M1 Acute myeloblastic >20% blasts + + – – – leukemia with no Few granules maturation +/- Auer rods M2 Acute myeloblastic >20% blasts ++ ++ + – – leukemia with 20% blasts Present Present Present – – promyelocytic Promyelocytes leukemia Prominent granules ++ Auer rods Faggot cells M4 Acute >20% blasts ± ± ± ++ – myelomonocytic >20% monoblasts leukemia + Auer rods M4eo Acute >20% blasts ± ± ± ++ – myelomonocytic >20% monocytes leukemia with >5% abn eos eosinophilia + Auer rods M5 Acute monoblastic >20% blasts ± ± – ++ ++ leukemia with or >80%monocytes without maturation and promonocytes with/without differentiation M6 Acute >80% erythroid – – + +++ + erythroleukemia >30% proerythroblast + Auer rods M7 Acute >30% + – + +++ + megakaryocytic >50% leukemia Megakaryoblasts Cytoplasmic budding SUMMARY OF FAB CLASSIFICATION Watch the recording for better understanding of the table and Note from the Discussion: the differences of FAB classification o MPO stands for Myeloperoxidase; SBB stands for Sudan Black B; PAS stands for Periodic Acid Schiff. MYELOPROLIFERATIVE DISORDERS These are the cytochemical tests together with Specific Clonal hematopoietic disorders caused by genetic and Nonspecific Esterase. mutations in the HSC. o 1st Column → FAB Classification; 2nd Column → Defect in receptor tyrosine kinase responsible for cell Corresponding Names (disorder) of the Classification; division. 3rd Column → distinct characteristics. WHO Classification: o Increased amount / Highly positive amount of Auer o Chronic Myelogenous Leukemia Rods is called Faggot Cells. These are seen in the o Polycythemia Vera FAB M3 or Acute promyelocytic leukemia, because in o Essential Thrombocytopenia promyelocytic stage, primary granules are high (stage o Primary Myelofibrosis where they are first seen). o Similarities: All are greater than 20 Blast Cells o Differences: (1) Percentage of Blast Cells, (2) Appearance of other blast cells, (3) Cytochemical Testing. A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 6  TRANS: LEUKEMIA CHRONIC MYELOGENOUS LEUKEMIA Excess of number or over proliferation of “mature” granulocytes Occurs at all ages but is seen predominantly in middle aged. Numerically increased, but functionally impaired granulocytes. WBC count = >300 x 109/L Chromosomal abnormality (Philadelphia chromosome) Proliferation of mature granulocytes Found mainly in adults 45 years of age and older; often diagnosed secondary to other conditions. Blood findings include mild anemia, and WBC markedly increased, may have a few circulating blasts. Can mimic a NLR (Leukemoid Reaction) o NBT Dye Test or Nitro Blue Tetrazolium Test – to differentiate Leukemoid Reaction and Chronic Myelogenous Leukemia ▪ Leukemoid Reaction LAP score – decreased ▪ Chronic Myelogenous Leukemia LAP score - increased Philadelphia chromosome t(9;22) o T (translocation) of chromosome 9 and 22. o It affects BCR-ABL gene Figure: FISH of Chronic Myelogenous Leukemia POLYCTHEMIA VERA Increased blood volume and viscosity (hyperviscosity syndrome). It affects the Common Myeloid Progenitor (CMP), hence it affects the production of cell. Figure: Chronic Myelogenous Leukemia PBS Figure: PBS of Polycythemia Vera Figure: Polycythemia Vera Figure: Philadelphia chromosome Table: Relative VS. Absolute RELATIVE ABSOLUTE DIAGNOSIS OF CHRONIC MYELOGENOUS Pseudopolycythemia True polycythemia LEUKEMIA Apparent rise of RBC level Chronic condition that in the blood results from abnormal WBC Count = >300 x 109/L (Leukocytosis) bone marrow stem cells (+) FISH (Fluorescence In Situ Hybridization) Due to Burns, Dehydration, It can be Primary or Bone Marrow Aspirate – to assess bone marrow cell Stress Secondary environment Gaisbock Syndrome A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 7  TRANS: LEUKEMIA Table: Primary VS Secondary SUMMARY OF MYELOGENOUS LEUKEMIA PRIMARY SECONDARY (MYELOID) A neoplastic clonal Cause by either natural or It can be Acute Myelogenous Leukemia (AML) or myeloproliferative disorder artificial increases in the Chronic Myelogenous Leukemia (CML) that characterized by production of Acute Myelogenous Leukemia (AML) increase in RBCs, WBCs erythropoietin (EPO), o It is classified under FAB (M0 – M7) and platelets hence an increased o Learn the percentage and cytochemical testing. production of erythrocytes Chronic Myelogenous Leukemia (CML) Consistent mutation in JAK2 Variable: Erythropoietin o Philadelphia Chromosome t(9;22) Gene (increase or decrease) ▪ T (translocation) of chromosome 9 and 22. ▪ It affects BCR-ABL gene DIAGNOSTIC CRITERIA Myeloproliferative Disorders Major Criteria: o Chronic Myelogenous Leukemia o Elevated Hemoglobin o Polycythemia vera o Identification of JAK2 kinase o Essential Thrombocytopenia Minor Criteria: o Decreased Erythropoietin (EPO) o Increased LAP score o Splenomegaly o Arterial oxygen saturation of 92% or greater o Platelets = >400 x 109/L o Leukocytes = >12 x 109/L ESSENTIAL THROMBOCYTOPENIA Proliferation of megakaryocytes causing marked increase in circulating platelets. WHO Criteria: >450 x 109/L REFERENCES Notes from the discussion by Prof. Charmaine P. Peralta, RMT, MSMT National University powerpoint presentation: Prof. Figure: PBS of Essential Thrombocytopenia Charmaine P. Peralta, RMT, MSMT Figure: Essential Thrombocytopenia SIGNS AND SYMPTOMS OF ESSENTIAL THROMBOCYTOPENIA Thromboses o Platelets plugs formation o Head: Headache, Dizziness, Weakness o Hands and Feet: Numbness, Burning Bleeding o Nosebleed o Bruises Splenomegaly A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 8  TRANS: LEUKEMIA A. BAGOOD, S.A. BURGOS, K.D. JUDAL, R.A. LUZADAS, A.J. MANGILIT, S.M. REAMBONANZA, S.C. TUMAGAY, N.T. VELASCO | BSMT 9