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Recognize normal/abnormal results and understand their implications Interpret abnormal results, identify possible underlying disease states and perform additional evaluation Identify critical results and take appropriate action Series of tests used to evaluate the composition and concentration of various cellular components of blood › Red Cell Parameters Hemoglobin, RBC, MCV, MCHC, MCH, RDW › White Cell Parameters Differential Count › Platelet Count Automated instruments using anticoagulated whole blood Clots consume platelets and can trap other cells artificially decreasing values Incomplete filling of tubes with blood can cause artifacts by exposing cells to toxic quantities of the tube’s anticoagulants WBC Parameters RBC Parameters Platelet Count Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis › Leukopenia Platelet Disorders › Thrombocytosis › Thrombocytopenia Biconcave disk Clinical significance: transport hemoglobin, measure of the oxygen carrying capacity of blood Regulated by erythropoietin Life span of ~120 days Normal Values are dependent on: › Age Adult Male: 13.516.5 g/L Adult Female: 1215.5 g/L › Gender › Altitude › Tobacco use › Drugs Hematocrit – packed cell volume › Ratio of volume of RBC to volume of blood MCV (mean corpuscular volume) › Normal 80-100 › Microcytic <80 › Macrocytic >100 MCHC (mean corpuscular hemoglobin concentration) › Hemoglobin/RBC › Low = hypochromic MCH (mean corpuscular hemoglobin) › Hemoglobin/Hematocrit RDW (red cell distribution width) › Correlates with the degree of anisocytosis Reticulocyte Count › Young RBC › Normal: 1-2% Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis › Leukopenia Platelet Disorders › Thrombocytosis › Thrombocytopenia Most common hematologic disorder Decrease in the number of circulating red blood cells causing a decrease in oxygen carrying capacity of blood Usually a secondary underlying cause Shortness of Breath Chest Pain Tachycardia Skin/Mucosal Pallor Bleeding Fatigue Blood Loss Anemia Anemia of Decreased RBC Production Anemia with Increased RBC Destruction Microcytic: MCV <80 Normocytic: MCV 80-100 Macrocytic: MCV >100 Microcytic Anemias › Iron Deficiency Anemia › Thalassemia › Sideroblastic Anemia › Chronic Disease Macrocytic Anemias Normocytic Anemias Iron Deficiency Thalassemia Sideroblastic Chronic Disease 1. Dietary Deficiency › Meat deficient diets › Pregnancy 2. Malabsorption › Partial gastrectomy (hypochlorhydria) › Celiac › Chronic diarrhea 3. Chronic Blood Loss › › › › GI Tract - Ulcerative disease, Gastritis, Cancer, Hemorrhods, AV Malformations Menorrhagia Hematuria – Bladder/Kidney Cancers Frequent blood donation/inpatient phlebotomy Diagnosis of Iron deficiency in an adult mandates an evaluation to rule out malignancy Gold Standard: Bone Marrow Biopsy Iron Studies (Fe, Ferritin, TIBC) Iron Iron Saturation Ferritin TIBC Peripheral Smear Low Low Low High Microcytic (low MCV) and Hypochromic (low MCHC) Red Cells Oral Iron Replacement › Ferrous Sulfate 325mg PO TID › Ascorbic Acid can increase absorption › Can cause GI upset/constipation Parenteral Iron › Indicated in cases of intolerance to PO Fe or failure to respond to PO Fe Important to not only treat the iron deficiency, but you must discover and treat the underlying disorder Spectrum of diseases characterized by decreased or lack of production of one or more globulin chains Normal hemoglobin contains four alpha and two beta chains Alpha thalassemias – alpha chain production problem leading to an excess of beta globin chains Beta thalassemias – beta chain production problem leading to excess alpha chains More common in Mediterranean, African and Southeast Asian populations Beta Thalassemia Major – complete lack of production of Beta Globin Chains Beta Thalassemia Minor – loss of one of the two alleles coding for the Betaglobulin gene Complete lack of hemoglobin A production Microcytic (low MCV) hypochromic (low MCHC) red cells Complications: › Bone deformities (EPO stimulated expansion of bone marrow) › Hepatosplenomegaly (extramedullary hemoatopiesis) › Secondary Iron Overload (increased iron absorption and repeated transfusions) Asymptomatic condition Microcytosis and a normal RDW If anemia is present, usually mild Hemoglobin electrophoresis › Beta Thalassemia and Severe Alpha Thalassemia Mild alpha thalassemia detection › Alpha:Beta Ratio › Molecular testing › Neither test is widely available Depends on the severity of the genetic defect and the clinical sequelae Minor Thalassemias › Often asymptomatic and require no therapy Major Thalassemias › Chronic transfusions › Iron chelation › Splenectomy Avoid Routine Iron Supplementation Characterized by ineffective erythropoiesis and presence of ringed sideroblasts in the bone marrow “Ringed” – accumulation of iron in the mitochondria that surround the periphery of the nucleus Hereditary Ideopathic Drug-Associated › Alcohol, INH, Chloramphenicol Lead Poisoning › Basophilic Stippling No cure for hereditary condition Prevent iron overload/chelation Drug induced › Often resolves when offending agent discontinued Isoniazid associated – can be overcome with high dose pyridoxine supplementation › Can reverse anemia and allow for continuation of drug Microcytic Anemias Macrocytic Anemias › Vitamin B12 Deficiency › Folate Deficiency › Drug Induced Normocytic Anemias MCV >100 Can be categorized based on features seen on peripheral smear Megaloblastic – oval macrocytes; hypersegmented polymorphonuclear lymphocytes (PMN) › >5 lobes Non-Megaloblastic Megaloblastlc Vitamin B12 Deficiency Folic Acid Deficiency Drug induced Non-Megaloblastic Liver Disease Hypothyroidism Alcohol Induced Reticulocytosis (hemolysis) Etiologies: › › › › Pernicious Anemia Gastrectomy/Gastric Bypass Ileal disorders Inadequate intake Additional Symptoms: › › › › › Diarrhea/abdominal pain Numbness/paresthesia Glossitis Motor weakness/spasticity Decreased proprioception Vitamin B12 level Serum Methylmalonic Acid and Homocystine levels Anti-intrinsic Factor or Anti-parietal Cell Antibodies Endoscopic evaluation Surgical History Vitamin B12 1mg IM or SC › Daily x7 days, then › Weekly for 4 weeks, then › Monthly thereafter Hematologic abnormalities take about 2 moths to resolve Neurologic abnormalities can take up to 18 months to resolve; however, may be permanent Inadequate intake Decreased absorption › Celiac, bacterial overgrowth, drugs (dilantin) Increased requirement › Hemolytic Anemia, Pregnancy, Hemodialysis Iatrogenic – Folic Acid Antagonists › Methotrexate, Trimethoprim Appears similar to Vitamin B12 deficiency; however, no neurologic symptoms Folic Acid 1mg PO daily Hematologic abnormalities should resolve in about 2 months Important to rule out concurrent Vitamin B12 deficiency › Folic Acid may improve the hematologic parameters in Vitamin B12 deficiency but wont correct any underlying neurologic symptoms Purine Analogs (azathioprine) Pyrimidine Analogs (5-FU, ARA-C) Hydroxyurea Anticonvulsants (dilantin, phenobarbital) Treatment: › Stop offending agent › Tolerate mild anemia if therapeutic benefit of drug is justified Microcytic Anemias Macrocytic Anemias Normocytic Anemias › Hemolytic Anemias G6PD Deficiency Spherocytosis Microangiopathic Hemolytic Anemia (DIC/TTP/HUS) › Malignancy/Bone Marrow Infiltration › Myelodysplastic Syndrome › Anemia of Chronic Kidney Disease Elevated Reticulocyte Count › Hemolytic Anemia › Acute Bleeding Decreased Reticulocyte Count › Malignancy/Marrow infiltration Leukemia/lymphoma, Myeloma, Granulomatous Disease › Stem Cell Disorders Myelofibrosis, Aplastic Anemia/Pure RCB Aplasia, Myelodysplasia › Medical Conditions Chronic Kidney Disease, Anemia of Chronic Disease Anemias with increased RBC destruction Jaundice, splenomegaly, brown/red urine Laboratory abnormalities: › Increased LDH › Decreased Haptoglobin › Increased unconjugated bilirubin › Increased reticulocyte count › Positive Direct Coombs Test Disordered Hemoglobin Synthesis › Sickle Cell RBC Membrane Disorders › Spherocytosis › Elliptocytosis RBC Enzyme Disorders › G6PD Deficiency › Pyruvate Kinase Deficiency › Hexokinase Deficiency X-linked disorder that leads to hemolysis in the presence of an oxidative stress Hemoglobin loses its ability to maintain a reduced state and precipitates within the RBC and cells lyse Leads to Heinz Body formation and hemolysis Bite cells Precipitants of hemolysis: Infection – E. coli, salmonella, S. pneumoniae, vital hepatitis Drug Induced › Antimalarials (primaquine and chloroquine) › Antibiotics (sulfonamides, nitrofurantoin) Fava Beans Napthalene Diagnosis made by measuring G6PD activity level › Should be checked 3-4 weeks after hemolytic episode for accurate results › Measuring during hemolytic episode will give false negative results certain subtypes Treatment is supportive › Transfusions/Folic Acid supplementation › Avoiding precipitants of hemolysis Autosomal Dominant, mostly commonly in people of Northern European decent Defect in a membrane cytoskeletal protein leading to spherocyte formation Physical Examination: splenomegaly secondary to extravascular hemolysis Peripheral blood smear: Spherocytes Diagnosis: Osmotic fragility test Treatment: splenectomy (corrects anemia, not underlying defect) and supportive transfusions Small, dark, dense, hyperchromic red blood cells lacking central pallor Increased MCHC Immune Related › Transfuision Reactions › Cold Agglutinin › Warm Auto Antibody Non-immune related › Microangiopathic Hemolytic Anemia › Infection › PNH › Prosthetic Heart Valves Potential Causes › TTP/HUS › DIC › Malignant Hypertension › Metastatic Malignancy Malfunction of coagulation/secondary hemostasis Usually secondary (Infection, trauma, immunemediated reactions, obstetric complications) Inappropriate systemic thrombosis of small/mid-sized vessles Depleted clotting factors leading to potential for lifethreatening hemorrhage Labs: in addition to anemia › › › › Thrombocytopenia Abnormal coagulation tests Elevated fibrin split products Decreased fibrinogen Peripheral Smear: Schistocytes Treatment aimed at underlying disorder › Patients are usually gravely ill Microangiopathic hemolytic anemia and thrombocytopenia Neurologic changes, Fever, Renal Dysfunction (Predominates in HUS) Involves microvascular damage and platelet destruction/aggregation; high shear stress and endothelial damage Typically sporadic; HUS can be associated with verotoxin and E. coli O157:H7 (typically in children) Classis Pentad of Findings › Thrombocytopenia (typically <40,000) › Microangiopathic Hemolytic Anemia Elevated LDH, Decreased Haptoglobin, elevated reticulocyte count, peripheral smear schistocytes › Neurologic Changes › Renal Dysfunction Elevated Creatinine, Decreased Urine output › Fever Bleeding › Coagulation studies typically normal Abdominal Pain/Nausea/Vomiting/Diarrhea Additional Potential Etiologies: › Drug exposure: Quinine, Mitomycin C, Bleomycin, Cisplatin, Cyclosporine, Plavix › HIV infection › Systemic Lupus Erythematosis › Metastatic Adenocarcinoma Treatment: Urgent Plasmapheresis Metastatic Cancer to the Bone Marrow Leukemias/Lymphomas/Myelomas Peripheral smear: Nucleated RBC, teardrop cells, immature WBC Bone marrow biopsy core usually needed for diagnosis; often a “dry tap” Heterogeneous group of clonal hematopoietic stem cell disorders with the presence of dysplastic changes in one or more cell line Associated with inappropriate apoptosis and excessive bone marrow proliferation Peripheral cytopenias and dysplastic changes in the bone marrow Mean age of diagnosis: 68 Slight male predominance Environmental Links: › Smoking, benzene, organic chemicals, herbicides, pesticides, fertilizers, petroleum and diesel derivatives Prior Chemotherapy or Radiation › Melphalan, chlorambucil, cyclophosphamide Refractory cytopenias Anemia and fatigue › Macrocytic or normocytic Infections, bleeding Symptoms depend on cytopenias present and their severity CBC: Macrocytic anemia (other cytopenias) Low reticulocyte count Peripheral Smear: macrocytic red cells, hypogranular granulocytes with pseudoPelger-Huët anomaly, giant platelets Bone Marrow Biopsy Type of MDS Peripheral Blood Blasts OR Bone Marrow Blasts Refractory Anemia (RA) ≤1% <5% Refractory Anemia with Ringed Sideroblasts (RARS) ≤1% <5% Refractory Anemia with Excess Blasts (RAEB) <5% 5-20% (1:5-9%; 2:9-19%) Refractory Anemia with Excess Blasts in Transformation (RAEB-T) ≥5% 21-30% Chronic Myelomonocytoc Leukemia (CMML) <5% ≤20% with >1000 Monocytes/microL Usually supportive Dependent on degree/severity of findings Erythropoietin support Transfusion support Chemotherapy Bone Marrow Transplantation Due to Erythropoietin Deficiency Generally anemia begins when the creatinine clearance in <45 mL/min and worsens with increasing renal failure Treat underlying CKD and cause Can support with subcutaneous erythropoietin with adjustment in dose based on response Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis › Leukopenia Platelet Disorders › Thrombocytosis › Thrombocytopenia Laboratory finding of increased RBC number and subsequently hemoglobin and hematocrit Can be primary (Polycythemia Vera) or secondary Initial evaluation: determine underlying cause and minimize potential complications Hypertension Thrombosis Pruritus Erythromelalgia Joint Pain Headache Weakness Visual disturbance Weakness Palpable splenomegaly Gout/Kidney stones (increased cellular turnover) Suspected when hematocrit elevated Can also have associated elevation in platelets or white blood cells Erythropoietin level › Low in Polycythemia Vera › High in Secondary Polycythemia Oxygen saturation › Low levels can suggest secondary causes JAK-2 Mutation Status › JAK2 V617F mutation is identified in >90% PV Complete evaluation for secondary causes Hypoxemia leading to EPO overproduction › Lung disease, high altitude, smoking, right-to-left heart shunts, sleep apnea, obesity hypoventilation EPO overproduction › Tumors – renal, hepatoma, fibroids, pheochromocytoma Androgen Therapy Relative Erythrocytosis (decreased plasma volume) › Diuretics, blood doping Most common myeloproliferative disease Major Criteria Hemoglobin >18.5/16.5g/dL Presence of JAK2 mutation Minor Criteria Bone Marrow Biopsy: Hypercellularity for Age with prominent erythroid proliferation Low EPO level Endogenous erythroid colony formation in vitro Diagnosis requires either Both Major and 1 Minor or 1st Major and 2 Minor Criteria Goal: reduce blood volume to normal and prevent complications (thrombosis) Phlebotomy to a goal Hematocrit of <45% for men; <42% for women Aspirin Therapy If refractory to Phlebotomy: hydroxyurea Can progress to myelofibrosis and/or acute leukemia Immune system cells involved in protecting the body from infectious disease and foreign invaders Derived from a mulitpotent stem cell in bone marrow (hematopoietic stem cell) Several types of leukocytes with different primary functions When evaluating abnormalities in WBC number must also consider which subtype of WBC is involved Neutrophil – mature WBC of the Granulocyte series; part of the innate immune system Lymphocyte – facilitate humoral and cellular immunity against foreign proteins and pathogens. Monocyte – Large phagocytic WBC; serves as part of the innate immune system Eosinophil – WBC implicated in inflammatory/allergic response Basophil – WBC that is active in the inflammatory response Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis Neutrophilia Lymphocytosis Monocytosis Eosinophilia › Leukopenia Platelet Disorders › Thrombocytosis › Thrombocytopenia Primary › Myeloproliferative Disorders (CML, PV, ET) › Chronic Idiopathic Neutrophilia › Down’s Syndrome Secondary › Infection › Stress (physical or emotional) › Drugs – steroids, lithium, G-CSF › Non-hematologic malignancy › Asplenia Uncontrolled proliferation of mature and maturing granulocytes Associated with the fusion of two genes: › BCR on chromosome 9 › ABL1 on chromosome 22 Reciprocal translocation creates the fusion protein BCR-ABL Up to 50% can be asymptomatic Malaise/Fatigue Weight Loss Night sweats Splenomegaly/Andominal discomfort Leukostasis – Headache, neurologic deficits (usually with WBC>300,000) High leukocyte count Hypercellular marrow Basophilia PCR/Chromosome analysis for BCR-ABL Peripheral smear: Left shifted WBC (myeloblasts, myelocytes, metamyelocytes and band forms) and Basophilia Phase Symptoms/Signs Chronic Gradual rise in WBC, splenomegaly, hyperleukocytosis <15%/20% blasts PB/BM <20% Basophils Accelerated Escape of blood counts from treatment control Myelofibrosis >15-30%/>20-50% blasts PB/BM >20% basophils Blastic Weight loss, B symptoms, bone pain, increased blasts Marrow Failure : thrombocytopenia and anemia >30%/>50% blasts PB/BM Drugs targeting BCR-ABL tyrosine kinase Can provide long term disease control Supplanted previous standard therapies such as bone marrow transplant Imatinib mesylate (Gleevec) was the initial targeted therapy developed for this indication Several additional second and third generation TKI drugs are available and can be used in firs or subsequent lines of therapy Reactive › Viral infections: EBV, CMV, VZV, influenza › Other infections: pertussis, toxo. › Stress: trauma, smoking › Autoimmune: LGL, RA Malignant › ALL › CLL › Follicular Lymphoma › Marginal Zone Lymphoma › Hairy cell › Other Lymphomas Evaluation: Blood Lymphocyte Morphology Peripheral Blood Flow Cytometry Neoplasm of small mature lymphocytes Can involve peripheral blood, bone marrow, organs or lymph nodes (SLL) Most common leukemia in United States Diagnosed by the demonstration of an absolute lymphocytosis and a clonal population of lymphocytes expressing CD5, CD19, CD20 and CD23 along with low levels of surface immunoglobulins Lymphocytosis on screening blood test Asymptomatic lymphadenopathy Abdominal fullness Fatigue/decreased exercise tolerance Other constitutional symptoms Most patients with early CLL are asymptomatic and have a relatively good long term prognosis Historically several trials of early chemotherapy did not demonstrate survival benefit Deferral of treatment/Watch and Wait is the standard of care for early stage disease with monitoring every 3-6 months Treatment is reserved for symptomatic or rapidly progressive disease Usually <10% of total WBC Relatively non-specific finding Asplenia Inflammation (sarcoid, IBD) Autoimmune Disorders Steroids Infections (VZV, TB, malaria) Malignancy (Hodgkins, CMML) Numerous allergic, infectious and neoplastic disorders Allergic – Atopic, Medications (NSIDS, ASA, allopurinol, PCN, cephalosporins) Infectious – parasitic, fungal Specific organ disease – eosinophilic esophagitis, asthma, skin disease, renal/vascular disease Hematologic Neoplasm – Hypereosinophilic syndrome, tumor associated, mastocytosis Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis › Leukopenia – Neutropenia: ANC <1500 Lymphopenia: ALC <1000 Platelet Disorders › Thrombocytosis › Thrombocytopenia Widely variable implications; life-threatening to benign Benign (familial) Neutropenia › African, W Indian, Sephardic Jews, Yemenites, Arab Jordans Acquired Neutropenia › › › › Post infectious (bacterial, viral, paracytic) Drug-induced – within 3 months Autoimmune/Collagen Vascular Disorders Immune Mediated Hospitalized Patient › Drugs, Toxins, Sepsis, Virus › Bone marrow failure (rarely isolated neutropenia) Infections: TB, HIV, hepatitis, malaria Congenital Immune Deficiencies Immunosuppressive therapy: Rituxan, steroids Chemotherapy/Radiation Autoimmune disorders Lymphoma Sarcoid Alcohol Abuse Malnutrition Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis › Leukopenia Platelet Disorders › Thrombocytosis › Thrombocytopenia Laboratory finding of elevated platelets >450,000/microL Can be primary (essential thrombocytosis) or secondary Is the thrombocytosis reactive or a result of bone marrow overproduction? Is there any immediate risk to the patient? Asymptomatic Laboratory Finding Vasomotor symptoms: Visual disturbance, Lightheadedness, Headaches, Palpitations, Atypical Chest Pain, Erythromlealgia, Paresthesias Thrombosis (15% at presentation) Major Hemorrhage (5-10% of patients over disease course) Splenomegaly (less than 50%) Iron Deficiency Severe Trauma/Burns Post-Splenectomy or CABG Metastatic Malignancy Acute Pancreatitis Chronic Infections (TB) Rheumatologic Disorders/Vasculitis IBD/Celiac Disease Careful patient history to exclude reactive causes of thrombocytosis Iron Studies, CRP/ESR, Peripheral Smear JAK-2 Mutation (present in 55-60% of essential thrombocytosis cases) Bone Marrow Biopsy (increased Megakaryocytes) One of the myeloproliferative disorders WHO Criteria for Diagnosis of ET Sustained Platelet Count >450,000 Bone Marrow showing proliferation of Megakaryocytes Does not meet the criteria for the diagnosis of another MPD JAK2 mutation positive or, if JAK2 negative, an unrevealing evaluation for secondary causes of thrombocytosis Decision to treat is based on risk stratification Low Risk Age <60 No CV Risk Factors PLT <1,500,000 No prior thrombosis Consider ASA Intermediate Risk Not High or Low Risk Consider ASA High Risk Age >60 Prior thrombosis Consider ASA and Cytoreductive therapy Patients >60 years, Aspirin should not be used if platelets >1,500,000 because of increased risk of bleeding Low and Intermediate Risk patients should be observed and cytoreductive therapy initiated when platelets are >1,500,000 Myelosuppressive Agents – Hydroxyurea (usually the first agent of choice) Maturation Modulators – Anagrelide Antiplatelet Agents Plateletpheresis – in extreme, acute situations Goal of cytoreductive treatment should be a sustained platelet count <400,000 Red Cell Disorders › Anemia › Polycythemia White Cell Disorders › Leukocytosis › Leukopenia Platelet Disorders › Thrombocytosis › Thrombocytopenia Platelet count less than the lower level of normal (130-150,000/microL) Surgical Bleeding (solely due to low platelets) starts with <50,000/microL Spontaneous Bleeding <10-20,000/microL Decreased Platelet Production › › › › Infection: HIV, hepatitis C, parvovirus Chemotherapy/Radiation Alcohol Congenital/Acquired Bone Marrow Failure Increased Platelet Destruction › Drugs: heparin, Valproic Acid, quinine, Bactrim, Digoxin, Amiodarone, H2-blockers › Autoimmune Platelet Destruction: ITP, TTP/HUS › DIC Pseudothrombocytopenia › Platelet Clumping Inadequately anti-coagulated or incompletely mixed samples can form a clot that traps platelets Exposure of blood to the anti-coagulant EDTA may induce platelet clumping; platelet clumps are counted as leukocytes instead of platelets › 0.1% of people have EDTA dependent agglutinins If observed platelet count should be repeated using heparin (green top tube) or sodium citrate (blue top tube) as the anticoagulant If citrate is used as the anticoagulant the platelet count should be adjusted based on a correction factor to account for dilution Acquired thrombocytopenia caused by autoimmune destruction of platelets Typical presentations: › Markedly reduced platelet counts and mucocutaneous bleeding › Asymptomatically with mildly decreased platelets found incidentally Generally idiopathic but can be associated with disorders of immune dysregulation or lymphoproliferation No single test is diagnostic of ITP; primarily a diagnosis of exclusion New onset isolated thrombocytopenia with no other readily identifiable cause Requires careful review of patient’s medications, peripheral smear review and screen for viral causes Initial Management: Corticosteroids › 60-75% initial response rate Additional Treatments: › IVIG 1gm/kg x2 days › Anti-D 75 mcg/kg/day (Rh+, non-anemic patients only) › Rituxan 375mg/m2 IV weekly x4 doses › TPO Agonists Romiplostim (N-plate) Eltrombopag (Promacta) Aplasia Acute leukemia, myelodysplasia, myeloma Infiltration with lymphoma, solid tumours, tuberculosis Megaloblastic anemia Paroxysmal nocturnal hemoglobinuria Myelofibrosis Group of disorders characterized by uncontrolled proliferation of myeloid or lymphoid progenitor cells that gradually replace normal hematopoiesis in the bone marrow › Acute Myeloid Leukemia (AML) › Acute Lymphoblastic Leukemia (ALL) Several subtypes exist based upon the specific cell type which has become malignant Usually present with bone marrow failure and pancytopenia Tissue infiltration by leukemic blasts Fatigue, dyspnea, fever, infection, bleeding, bone pain Anemia, thrombocytopenia, neutropenia, DIC, hyperuricemia, elevated LDH Elevated peripheral blood WBC with increased blast population Therapy is individualized based on patient factors (age, co-morbidities) and disease factors (sub-type, molecular mutations, cytogenetics) High dose chemotherapy Bone Marrow Transplant Palliative chemotherapy Primary palliative care Lichtman, M. et.al. Williams Hematology, seventh edition. McGraw-Hill Medical. 2006 Rodgers, G. and Young, N. The Bethesda Handbook of Clinical Hematology, second edition. Lippincott, Williams and Wilkins. 2010. Images from UptoDateOnLine as sited.