What you need to know about CBC and coagulation profile By Prof Ahmed Abdelwarith

Slide credits to many contributors Including PPT & Text Books

Introduction

Hematology Study of normal and pathologic aspects of different blood components 1-complete blood count (CBC) reports 2- Bone Marrow 3- coagulation and hemeostasis

Blood &Plasma Suspension of cells in a solute of water, proteins, and electrolytes Average volume is 5 liters 70mL per kg body weight

Blood &Plasma Plasma Blood from which the cellular components (RBCs, WBCs, platelets) have been removed by centrifuge Color is yellow Contains coagulation proteins (clotting factors)

Hematopoiesis Development of blood cells and other formed elements Sites vary throughout development Fetal: yolk sac, liver, spleen Pediatric: axial and appendicular skeleton Adult: axial skeleton (sternum and pelvis)

Hematopoiesis Stem cells Primitive; self-replicate and differentiate to become increasingly specialized progenitor cells which form mature cells Process regulated by growth factors (interleukins, erythropoietin, thrombopoietin, G-CSF) Early lineage division between progenitors for lymphoid and myeloid cells

B lymphocyte development markers CELL ARREST X CLONAL EXPANSION

Complete Blood Count White blood cells (WBC) Differential Neutrophils, lymphocytes, monocytes, eosinophils, basophils, bands Must specify whether to include with CBC order Red blood cells (RBC, HGB, HCT) Platelets Mean corpuscular volume (MCV) Red cell distribution width (RDW)

Fish bone diagram

Hemoglobin & Hematocrit Hematocrit : (packed cell volume) It is ratio of the volume of red cell to the volume of whole blood. M: 40.7 to 50.3 % F: 36.1 to 44.3 %

Red Blood Cells Transport oxygen via hemoglobin from lungs to peripheral tissues and organs Normal lifespan = 120 days Electron microscope of RBC – Biconcave disc

Red Blood Cells Peripheral blood smear Normal

Anemia Almost 1/3 of the world population is anemic! Condition resulting from decrease in total body erythrocyte mass Defined by measurement of hemoglobin concentration Normal range Males 14-16 g/dL Females 12-14 g/dL Almost 1/3 of the world population is anemic! Increase in hgb that occurs in men is mostly related to effect of androgens on release of erythropoietin ; gender disparity becomes less significant in advanced age HGB x 3 = Rough HCT

Manifestations related to duration and severity of anemia Body has physiologic responses to chronic anemia such that many patients are asymptomatic until hgb < 8 g/dL

Anemia Symptoms Signs Easy fatigue Headache Dyspnea on exertion Pallor Tachycardia Systolic ejection murmur Orthostatic hypotension

Anemia Decrease production -No raw material -Malfunction of the factory Increase destruction Hemolysis Sequestration Blood loss Acute , chronic External , internal

Determining reticulocyte count and MCV are first steps in determining etiology

Reticulocytes 1- Reticulocyte Count Immature red blood cells Measurement assists in determining cause of anemia Normal = 1-2% Must correct for degree of anemia Observed retic count (Actual HCT/Normal HCT) = Corrected retic count

Reticulocyte Count Low suggests decreased production (i.e. nutritional or bone marrow problem) High suggests bleeding or premature destruction of red blood cells (i.e. hemolysis)

2- Check the MCV

MCV&MCHC MCV = mean corpuscular volume HCT/RBC count= 80-100fL small = microcytic normal = normocytic large = macrocytic MCHC= mean corpuscular hemoglobin concentration HB/RBC count= 26-34% decreased = hypochromic normal = normochromic

Microcytic Anemia Microcytosis – small cells (MCV <80) Most common type of anemia encountered in primary care Differential diagnosis Hemoglobinopathy (inherited) Iron deficiency Chronic disease (may also be normocytic) Inflammation Lead poisoning Check iron studies for clarification Be familiar with interpretation (see next slide)

Microcytic Anemia Microcytosis – small cells (MCV <80) Most common type of anemia encountered in primary care Differential diagnosis Hemoglobinopathy (inherited) Iron deficiency Chronic disease (may also be normocytic) Inflammation Lead poisoning Check iron studies for clarification

Microcytic Anemia Peripheral blood smear Microcytosis, Hypochromic

RDW ( RBCs distribution width)= 6–8 um Dx RDW MCV Iron deficiency   FOLATE &VIT B12  RECENT Hge NORMAL . High RDW -Iron Deficiency Anemia: usually presents with high RDW with low MCV -Folate and vitamin B12 deficiency anemia: usually presents with high RDW and high MCV -Recent Hemorrhage: typical presentation is high RDW with normal MCV

Macrocytic Anemia Fasting homocysteine, and methylmalonic acid (MMA) Macrocytosis – large cells (MCV >100) Differential diagnosis B12 deficiency Pernicious anemia Folate deficiency Myelodysplasia (pre-leukemia) Medication effect Check vitamin B12, RBC folate, Fasting homocysteine, and methylmalonic acid (MMA) are elevated in subclinical B12 and folate deficiency Medications associated with elevated MCV include…

Hemolytic Anemia History and physical findings Lab findings Review PMH, FH, and medications Jaundice Abdominal discomfort Lab findings Elevated reticulocyte count Reflects bone marrow compensating for peripheral RBC destruction Elevated LDH Elevated total bilirubin (indirect/unconjugated) Decreased haptoglobin Abnormal cells on peripheral blood smear examination

Hemolytic Anemia Membrane defects Enzyme defects Congenital Hereditary spherocytosis Splenectomy is curative Hereditary elliptocytosis Enzyme defects G6PD deficiency Affects 10% of world population Common in patients of African descent Precipitated by stress, infection, drugs, and fava beans Hemolysis mostly extravascular but may be intravascular if severe case

Hemolytic Anemia Acquired Classified according to site of RBC destruction and whether mediated by immune system Intravascular Extravascular Autoimmune Non-immune Many causes… be aware of these – Transfusion of incompatible blood (details later) Warm (IgG-mediated) ; most common Cold (IgM-mediated) Prosthetic valves TTP/HUS DIC Cancer Drugs

Hemolytic Anemia Coomb’s Test (DAT) Used to screen for autoimmune hemolytic anemia

Polycythemia / Erythrocytosis Abnormal elevation of hemoglobin Rule out “relative” polcythemia caused by contraction of plasma volume, e.g. dehydration Primary Polycythemia Vera Secondary RBC production in response to increased EPO production EPO level is usually high

White Blood Cells Differential Neutrophils 45-65% Lymphocytes 15-40% “Segs” / “Polys” Lymphocytes 15-40% Monocytes 2-8% Eosinophils 0-5% Basophils 0-3% Do you remember the physiologic role of each type of WBC?

Leukopenia Neutropenia is most common cause Many causes Absolute neutrophil count (ANC) < 1.5 x 109 cells/L Many causes Viral infections Epstein-Barr, Hepatitis B, HIV Drugs * Careful review of medications ; Splenomegaly Autoimmune disorders = SLE (lupus), Rheumatoid Bone marrow disorders

Neutropenia Common Medicinal Causes of Neutropenia Cytotoxic agents Antibiotics (Penicillins, Cephalosporins, Sulfonamides) Anticonvulsants NSAIDs Antithyroid agents (Methimazole, PTU) Phenothiazines Allopurinol Cimetidine Diuretics (HCTZ, Spironolactone)

Leukocytosis WBC count > 11,000 Determine which type of WBC is leading to the leukocytosis Neutrophilia = most common Infection Connective tissue disorders Medications (especially steroids, growth factors) Cancer (CML and solid tumors) Myeloproliferative disorders Cigarette smoking Stress (physiologic) Pain, seizure, trauma Idiopathic

Leukocytosis Patients with acute bacterial infection often present with neutrophilia and band formation ; i.e. “left shift” Bands = young neutrophils Viral infections are usually associated with low WBCs ; leukocytosis may suggest complications Ex: bacterial pneumonia with underlying influenza infection

Chronic Leukemia Chronic myelogenous leukemia (CML) Translocation between long arms of chromosomes 9 and 22 ; “Philadelphia Chromosome” ; bcr/abl protein Patients usually middle-age at diagnosis, average age 55 years Fatigue, fever, night sweats, abdominal fullness (splenomegaly) Symptoms of leukostasis may be present if WBC > 500,000 Blurred vision, respiratory distress, priapism Three phases of disease Early / Chronic phase Accelerated Blast crisis

Chronic Leukemia CML, Vs leukomoid reaction Can you recognize early CML from infection? WBC usually < 50,000 with infection WBC average 150,000 at time of diagnosis with CML LAP score is decreased with CML Splenomegaly NOT present with infection Chromosomal abnormality and detection of bcr/abl protein by peripheral blood PCR is diagnostic of CML

Acute Leukemia Myeloblast

Bleeding Disorders Coagulation cascade

Bleeding Disorders Review coagulation cascade ; general understanding is essential for clinical practice Prothrombin time (PT) evaluates extrinsic system Factors I, II, V, X, VII Activated partial thromboplastin time (PTT) evaluates intrinsic system Factors I, II, V, X, VIII, IX, XI, XII Bleeding time reflects platelet number and function Factor I is also called fibrinogen

Bleeding Disorders General approach Prolonged PT only Warfarin (Coumadin®) therapy Factor VII deficiency Fibrinogen abnormality Prolonged PTT only Heparin therapy Factor VIII deficiency Congenital Hemophilia A (X-linked) 1:5000 male births Male and female carriers ; no racial predilection Acquired Factor IX deficiency – Hemophilia B / Christmas disease Lupus anticoagulant * Antiphospholipid antibodies * Prolonged PT and PTT Usually reflective of general medical condition such as DIC, vitamin K deficiency, or liver disease Disorders of common pathway (rare) * See page Schmaier p. 82

Bleeding Disorders Approach to patient History of trauma? Time between injury and bleeding? Ask about bleeding at times of life events Circumcision Tooth eruption Dental extraction Ear piercing Childbirth Menstrual cycles Family history Did you know 30% of patients with hemophilia have unremarkable family history? Spontaneous mutation of X chromosome

Primary hemostasis – platelet and vascular function Bleeding Disorders Patterns of bleeding Primary hemostasis – platelet and vascular function Secondary hemostasis – clotting factors CNS bleeding is leading cause of death among hemophilia patients

Bleeding Disorders Characteristic Primary hemostasis Secondary hemostasis Onset Spontaneous and immediate Delayed after trauma Usual site Skin, mucous membranes Deep tissues / hemarthrosis Other sites Rare Retroperitoneum, CNS Examples Thrombocytopenia, platelet defects (vWD) Factor deficiency or inhibitor CNS bleeding is leading cause of death among hemophilia patients

Bleeding Disorders Acute hemarthrosis

Bleeding Disorders Petechiae in patient with acute ITP ; platelet count = 10,000

Heparin-Induced Thrombocytopenia (HIT) Occurs in 3% of patients exposed to UFH ; 0.6% with LMWH Drop in platelet count ≥ 50% within 5-10 days of heparin exposure May occur within 48 hours of exposure in those previously exposed to drugs Thrombosis (NOT bleeding) is of great clinical concern Thrombotic events detected in about half of HIT patients Must STOP heparin and consult hematology Direct thrombin inhibitor (alternative anticoagulant) may be started Argatroban® Refludan®