Hematology 2.pdf

Medical Pathology: Hematologic Disorders II CHRIS BORGMAN, OD ASSOCIATE PROFESSOR [email protected] WIL MCGRIFF, OD, MPH ASSOCIATE PROFESSOR [email protected] Lecture Objectives — Understand general principles of CBC test & PT/PTT clotting tests in order to interpret results. — Understand pathophy...

Medical Pathology: Hematologic Disorders II CHRIS BORGMAN, OD ASSOCIATE PROFESSOR [email protected] WIL MCGRIFF, OD, MPH ASSOCIATE PROFESSOR [email protected] Lecture Objectives — Understand general principles of CBC test & PT/PTT clotting tests in order to interpret results. — Understand pathophysiology and clinical findings of coagulopathies discussed. ¡ Thrombocytopenia, hemophilia, von Willebrand’s disease, APLS, Factor V Leiden — Understand pathophysiology, causes, and clinical findings of leukocytes (ie. leukemia), lymphomas, & multiple myeloma disorders. NBEO Outline — Hematopoietic and Lymphoid System ¡ 1. Epidemiology ¡ 2. Symptoms and signs of common blood disorders ÷ a. Non-neoplastic disorders of blood cells ÷ b. Neoplastic disorders of blood cells ÷ c. Non-neoplastic disorders of lymph nodes ÷ d. Neoplastic disorders of lymph nodes ¡ 3. Diagnostic testing and imaging ¡ 4. Pathophysiology and diagnosis Leukocytes aka: WBC’s Lab Test Review: “Complete Blood Count w/ Differential” • See lecture 24 – Hemo 1 — Broad screening test to check general health status — aka: à “CBC with diff” ¡ ¡ ¡ ¡ ¡ ¡ Anemia Infection Inflammation Bleeding disorders Leukemia More… — Uses ¡ Monitor treatment ¡ Diagnose ¡ Check general health status — Test includes: ¡ RBC count Hemoglobin ÷ Hematocrit ÷ Size, volume, shape, etc. ÷ ¡ WBC count Neutrophils ÷ Lymphocytes ÷ Monocytes ÷ Eosinophils ÷ Basophils ÷ ¡ Platelet count ÷ Size, volume, shape, etc. TEST WBC Count RBC Count Platelet Count HIGH LOW “Leukocytosis” “Leukopenia” • • • • • • • • • • *Infection (viral/bacterial) Inflammation Leukemia Myeloproliferative disorders Allergies Intense exercise/stress *Immunosuppression Bone marrow disorders Lymphoma Severe infection (sepsis) “Polycythemia” “Anemia” • • • • • • • • **Polycythemia vera *Chronic hypoxia Dehydration Lung disease Excess EPO production Smoking High altitude living • • • • *Nutritional deficiency --Fe, B12, folate, etc. Acute/chronic bleeding Hemolytic anemia Bone marrow disorder Chronic renal disease “Thrombocytosis” “Thrombocytopenia” • • • • • • • • • • • • **Tissue damage --surgery, trauma, fractures *Infection Cancer Autoimmune Hemolytic anemia Myeloproliferative disease *Immune Drugs (APAP, sulfa) Sepsis Leukemia Lymphoma Chemo/Radiation White Blood Cell HIGH LOW **Neutrophils/PMN’s “Neutrophilia” “Neutropenia” (50-70%) • • • • • Lymphocytes (20-40% of WBCS) (B, T, NK cells) • Monocytes • • • • • • • • *Viral or bacterial infection Leukemia Autoimmune • • • • • *Allergies Parasites Leukemias Drug reactions Active sarcoidosis • • • Leukemias Acute infections Aplastic anemia Leukemia “Eosinopenia” • • • “Basophilia” • **Idiopathic (age related) *Viral Infections --HIV/AIDS, hepatitis, flu Bone marrow damage (ie. Chemo) Corticosteroids Autoimmune “Monocytopenia” “Eosinophilia” Basophils (0.5-3%) (heparin & histamine) **Acute viral infection --VZV, CMV, EBV, HSV *Leukemia Chronic bacterial infection Chronic inflammatory disorder TB, pertussis *Drug-induced Autoimmune Severe infection (sepsis) Immunodeficiency Bone marrow damage “Lymphocytopenia” “Monocytosis” Eosinophils (0-4%) • • • • • “Lymphocytosis” • • • • (2-8%) *Acute bacterial infection Inflammation Intense exercise/stress Leukemia (CML) Tissue injury 2’ trauma *Not significant Cushing’s / Corticosteroids Sepsis “Basocytopenia” • Not significant Leukemias — Defn: Uncontrolled proliferation of malignant leukocytes ¡ ¡ ¡ Single progenitor cell undergoes malignant transformation Overcrowding of bone marrow Decreased production and function of normal hematopoietic cells ÷ — ie. RBC’s, platelets, other WBC’s Key feature: **Leukocytosis (high) — 2 Types à Acute vs. Chronic ¡ Myeloid cells (ie. RBC, macrophage, granulocytes) ¡ Lymphoid cells (ie. B cells, T cells, NK cells) Leukemias — Signs and symptoms ¡ Anemia ¡ Infection ¡ Weight loss ¡ Bone pain ¡ Elevated uric acid ¡ Liver, spleen, and lymph node enlargement ¡ Bleeding ¡ Skin findings — Petechiae — Purpura — Ecchymosis Acute Leukemias — Undifferentiated or immature cells (“blasts”) — Rapid onset (few weeks) Acute lymphoblastic leukemia (ALL) 1. ¡ ¡ ¡ ¡ ~3,800 cases annually; mean onset 14 years old *Most common childhood leukemia (80%) ~80% survival at 5 years in children / 30-40% in adults Tx: chemotherapy Acute myelogenous leukemia (AML) 2. ¡ ¡ ¡ ~10,600 cases annually *Most common adult leukemia (mean age, 67) Tx: chemotherapy Chronic Leukemias — Mature cells that do not function normally — Slow progression usually 1. Chronic myelogenous leukemia (CML) ¡ ¡ ¡ ¡ ~4,400 cases annually Usually diagnosed in adults 90% survival rate at 5 yrs Standard Tx: medications and/or stem cell transplants ÷ ÷ Chemo Palliative care Chronic lymphocytic leukemia (CLL) 2. ¡ ¡ ¡ ¡ ¡ ¡ ~7,000 cases annually Most diagnosed over age 55 70% asymptomatic at diagnosis 80% survival rate at 5 yrs Lymphadenopathy à rare conversion to NHL (5% cases) Suppression of humoral immunity ÷ ¡ Increased infection with encapsulated bacteria Standard Tx: medications and/or stem cell transplants ÷ ÷ Chemo Palliative care CBC with differential example Anemia & à Leukocytosis Normocytic/Hypochromic & Very Elevated WBC’s à Anemia 2’ Severe Leukemia (likely ALL) Ocular Manifestations of Leukemias — *Eye signs occur in 40% to 70% of cases ¡ Initial presentation may relate to a visual complaint ¡ Ocular infiltrates associated with a poor prognosis — Retinal hemorrhages (57%) ¡ Roth spots (25%) — Extraocular (10%) ¡ Subconjunctival Hemorrhage ¡ Echymosis — Optic Nerve Edema (4%) Ocular Manifestations—Roth Spots — DM* — Leukemia — Anemia — Endocarditis — HIV — Pneumonia — HTN (rare) Coagulopathies Coagulopathies — Defn: disorder characterized by excessive bleeding or clotting… — Coagulopathy causes: ¡ Inherited Platelet abnormality (ie. von Willebrand disease) ÷ Coagulation cascade component abnormality (ie. hemophilia) ÷ ¡ Acquired *Medications (ie. warfarin, ASA, hormonal birth control, etc.) ÷ *Liver disease (clotting factors produced by liver) ÷ ¢ ¢ ¢ Coagulation cascade abnormality Fibrinogen deficiency Platelet number and function Autoimmune (ie. APLS) ÷ Infection (ie. sepsis) ÷ Malignancy (ie. leukemia) ÷ Diet? à Vit. K & warfarin interaction ÷ Typical Lab Tests for Clotting Complete blood count (CBC) w/ differential 1. 2. Prothrombin Time (PT) ¡ Measures how long it takes blood to clot; extrinsic system ÷ ¡ Normal: 10-15 sec Used to calculate “international normalized ratio” (INR) ÷ Warfarin monitoring 3. Partial Thromboplastin Time (PTT) ¡ Measures how long it takes blood to clot; intrinsic system Normal: 25-35 sec ÷ Heparin monitoring ÷ PT vs PTT: what do they mean together? • The PT & PTT are typically used to “screen” for bleeding disorders Prolonged Normal Short PT Excessive bleeding Normal Excessive clotting PTT Excessive bleeding Normal Excessive clotting Coagulation Cascade Testing: Can We Make This Easier Please? • McGriff discussed this in more depth à Summer semester pathology course – Lecture 3 Said another way…. PT PTT Problem Location Abnormal Normal Extrinsic pathway Normal Abnormal Intrinsic pathway Abnormal Abnormal Final common pathway Normal Normal Grossly normal clotting cascade Bleeding Disorders: “hypo-coagulation” Thrombocytopenia — Clinical finding; not a true diagnosis! — Defn: Lower than normal levels of platelets in the blood ¡ Typically defined as: <100,000 platelets/microliter of blood ¢ Normal: 150,000 to 450,000 platelets/microliter of blood — Usually found incidentally on CBC w/ differential test in optometry… — Many causes: ¡ *Medications/Toxins (ie. NSAIDs, PCN, sulfonamides, *quinine) ¡ Autoimmunity ¡ Pregnancy ¡ Sepsis ¡ Thrombotic Microangiopathies (all 3 involve platelet consumption) ¢ ¢ ¢ ¡ ¡ ¡ Thrombotic Thrombocytopenia Purpura (TTP) Hemolytic Uremic Syndrome (HUS) Disseminated Intravascular Coagulation (DIC) Cancer (ie. Leukemia) Hypersplenism Many more… — Workup: find underlying cause (can be very challenging); refer to PCP Lab Test Review: “Complete Blood Count w/ Differential” • See lecture 24 – Hemo 1 — Broad screening test to check general health status — aka: à “CBC with diff” ¡ ¡ ¡ ¡ ¡ ¡ Anemia Infection Inflammation Bleeding disorders Leukemia More… — Uses ¡ Monitor treatment ¡ Diagnose ¡ Check general health status — Test includes: ¡ RBC count Hemoglobin ÷ Hematocrit ÷ Size, volume, shape, etc. ÷ ¡ WBC count Neutrophils ÷ Lymphocytes ÷ Monocytes ÷ Eosinophils ÷ Basophils ÷ ¡ Platelet count ÷ Size, volume, shape, etc. TEST WBC Count RBC Count Platelet Count HIGH LOW “Leukocytosis” “Leukopenia” • • • • • • • • • • *Infection (viral/bacterial) Inflammation Leukemia Myeloproliferative disorders Allergies Intense exercise/stress *Immunosuppression Bone marrow disorders Lymphoma Severe infection (sepsis) “Polycythemia” “Anemia” • • • • • • • • **Polycythemia vera *Chronic hypoxia Dehydration Lung disease Excess EPO production Smoking High altitude living • • • • *Nutritional deficiency --Fe, B12, folate, etc. Acute/chronic bleeding Hemolytic anemia Bone marrow disorder Chronic renal disease “Thrombocytosis” “Thrombocytopenia” • • • • • • • • • • • • **Tissue damage --surgery, trauma, fractures *Infection Cancer Autoimmune Hemolytic anemia Myeloproliferative disease **Drugs (NSAIDs, quinine) *Immune Sepsis Leukemia Lymphoma Chemo/Radiation Thrombocytopenia — Signs and Symptoms ¡ ¡ ¡ ¡ ¡ ¡ ¡ Profuse bleeding during surgery or after dental work Spontaneous bleeding from gums or nose Easy or excessive bruising Prolonged bleeding from cuts Petechiae Blood in urine or stools Unusually heavy menstrual flows — Secondary consumptive causes ¡ ¡ DIC TTP-HUS — Dx: blood draw à CBC c diff, PT/PTT — Treatment à find underlying cause ¡ ¡ ¡ Transfusion Immunosuppression Splenectomy Hemophilia — Inherited inability to form blood clots ¡ *Intrinsic problem à abnormal PTT — Typically X-linked à M>>F ¡ Range of severity can vary — 3 types: ¡ *Hemophilia A: Factor VIII ÷ ¡ Hemophilia B: Factor IX ÷ ¡ ~1 in 5000 births ~1 in 20k births Hemophilia C: Factor XI ÷ Very rare — Tx with replacement therapy via infusions — Ocular manifestations ¡ Increased risk of hemorrhage formation in any ocular tissues Von Willebrand Disease — *Intrinsic problem à abnormal PTT — Three types: (Type 1 à 75-85%) ¡ *Most common inherited bleeding disorder ¡ M=F ¡ 1 in 100 to 1 in 1,000 people affected — Effects ¡ Bleeding tendencyàseverity varies — Pathogenesis ¡ Von Willebrand factor deficiency ÷ ¡ ¡ protein required for platelet adhesion Can be combined with Factor VIII deficiency Low platelet aggregation à poor thrombus formation — Most are asymptomatic à monitor only Clotting Disorders: “hyper-coagulation” Antiphospholipid Syndrome — Incidence: 1 in 100k ¡ 70% Female — Intrinsic clotting problem ¡ *Abnormal PTT more common — Autoimmune disorder ¡ Primary ¡ Secondary SLE (40-50%) ÷ Sjogrens (42%) ÷ RA (33%) ÷ Giant cell arteritis (20%) ÷ — MOA: **Hypercoagulability — Etiology: ¡ *Idiopathic ¡ Rare familial form — Complications ¡ DVT ¡ Pulmonary embolism ¡ Stroke (20% CVAs <50 yo) ¡ TIA ¡ Recurrent spontaneous abortion (10-15%) — Dx ¡ Lab Tests: Anti-cardiolipin antibodies ÷ Anti-beta2 glycoprotein antibodies ÷ Lupus anticoagulant ÷ — Treatment ¡ Anticoagulation APLS à Increased Thrombosis Risk! • *Elevated risk for thrombotic events • MOA: increased clotting risk à hypercoagulability See Lecture 4 – Fluid & Hemodynamics lecture Factor V Leiden Mutation — *Final common pathway problem à abnormal PT & PTT — *Most common form of inherited thrombophilia ¡ (+)mutation in ~3-8% US pop. — Complications: ¡ ¡ ¡ ¡ — European descent ; M=F ¡ White > Hispanic > AA > Asian — Increased risk of clotting ¡ factor V cannot be inactivated by activated protein C like normal — Only ~10% of those with mutation actually get clots Deep vein thromboses Pulmonary embolus Increased embolus risk Pregnancy loss increases ÷ 2-5x increased risk — Tx: ¡ ¡ ¡ ¡ Anticoagulation D/c birth control? Stop smoking Avoid immobility Miscellaneous: Multiple Myeloma Multiple Myeloma — Most common primary bone cancer ¡ Occurs most frequently in elderly adults > young adults ¡ Males>Females — Malignant proliferation of plasma cells in bone marrow ¡ B-cell lineage à Plasma cells ÷ ¡ Immature hypergammaglobulinemia ÷ ¡ Nodular masses in bone marrow à plasmacytomas Increased infection due to abnormal immunoglobulin production Monoclonal gammopathy à paraproteinemia ÷ Increased risk of clots/ischemia MM à Increased Thrombosis Risk! • *Elevated risk for thrombotic events • MOA: paraproteinemiaà hyperviscosity! See Lecture 4 – Fluid & Hemodynamics lecture Multiple Myeloma Multiple Myeloma — Symptoms ¡ ¡ *Hypercalcemia *Renal failure ÷ ¡ ¡ *Anemia *Bone pain/lesions ÷ ¡ (~50% of patients) Fractures possible Recurrent infections } “CRAB” — Diagnosis ¡ ¡ ¡ “Punched out” bone lesions Bence-Jones proteins in urine *Monoclonal proteins in plasma ÷ ÷ Aka: “M-proteins” Test: serum protein electrophoresis — Treatment ¡ ¡ ¡ ¡ Monitor Immunosuppression High-dose chemo Bone marrow transplantation QUICK REVIEW/OVERVIEW Quick Summary: Bleeding vs. Clotting Disorders Increased Bleeding Risk Increased Clotting Risk Thrombocytopenia Antiphospholipid Syndrome Hemophilia Factor V Leiden Mutation Von Willebrand’s Disease Sickle Cell Disease Spectrum Leukemia Multiple Myeloma Lymphadenopathy Lymphadenopathy — Defn: swollen lymph nodes ¡ Head/neck (55% cases) — Causes: ¡ **Immunologic or inflammatory conditions (40+%) ÷ ¡ ¡ *Viral/bacterial infection *Benign enlargement (30%) Neoplastic disease (1%) Lymphoma (HL & NHL) ÷ Leukemia ÷ ¡ Endocrine disorders — Enlarged spleen indicates lymphoproliferative disease Hodgkin’s Lymphoma — ~8000 cases annually; 84% survival rate — Painless neoplastic tumors of the lymph nodes ¡ ¡ ¡ Cervical Axillary Inguinal — Most common presenting symptom: ¡ ¡ Nontender, palpable lymphadenopathy in the neck Continuous nodes — Other nonspecific early symptoms ¡ ¡ ¡ ¡ Fever Night sweats Fatigue Unexplained weight loss — Confirmation by lymph node biopsy ¡ Characterized by Reed-Sternberg cells ÷ Mature B-cells; giant multi-nucleated cells Non-Hodgkin’s Lymphoma — Neoplastic tumor of lymph nodes (B cells>T cells) ¡ *No Reed-Sternberg cells present — *Higher incidence/more common than HL ¡ 70k cases annually; ~20k deaths — More likely to affect noncontiguous lymph nodes — Poorer prognosis than HL — 70% -have 5 year survival rate — Tx: ¡ Chemo ¡ Radiation ¡ Medication Sjögren's Syndrome and Non-Hodgkin's Lymphoma — Sjogren’s Syndrome can cause severe dry eyes and lead to dry mouth — Patients with Sjögren's Syndrome are 46x more likely to develop NHL than healthy patients. — Approximately 5% to 8% of all patients with Sjögren's Syndrome will develop NHL ¡ ~1 in 20 Ocular Manifestation of Lymphoma — *Non-Hodgkin’s >> Hodgkin’s ¡ Relatively rare ¡ 2% of all lymphomas ¡ *50% of primary orbital malignancies *60% Orbit — DDX ¡ Squamous papilloma ¡ Pyogenic granuloma ¡ Lymphangiectasis — Dx via biopsy — Tx ¡ Meds, radiation, surgery, chemo 25% Adnexa Questions??? — [email protected] — Office 932 in Tower