Hematology Lecture Notes PDF

Hematology Week #3 Hanzely, DMSc, PA-C, RD South College Where Dreams Find Direction  Instructional Objectives 1. Inventory the components of a CBC, including RBC indices: MCV, MCH, and MCHC. (LO4) 2. Compare...

Hematology Week #3 Hanzely, DMSc, PA-C, RD South College Where Dreams Find Direction  Instructional Objectives 1. Inventory the components of a CBC, including RBC indices: MCV, MCH, and MCHC. (LO4) 2. Compare common causes of anemia and polycythemia. (LO4) 3. Debate the importance of the reticulocyte count. (LO4) 4. Contrast ferritin, iron, total iron binding capacity, and transferrin and indications of each. (LO9) 5. Inspect the relationship between B12, folate and megaloblastic anemia. (LO9) 6. Inventory the main function of the segmented neutrophil, lymphocyte, monocyte, eosinophil, basophil and thrombocyte and causes for their increase or decrease. (LO4) 7. Inspect white blood cell inclusions and at least one indication of each. (LO4) 8. Contrast the differences between Hodgkin’s and non-Hodgkin’s lymphoma. (LO4) 9. Compare CLL, ALL, CML and AML and list the differences in lab findings. (LO4) The ability to find joy in Dr. Hanzély’s memes Fishbone Diagrams  Complete Blood Count (CBC) Series of tests of the blood that provides information about RBCs, platelets, and WBCs Easy, quick, inexpensive Includes RBC Hemoglobin Hematocrit Platelets RBC indices MCV, MCH, MCHC, RDW WBC count and differential- The five white blood cell types: neutrophils, lymphocytes, monocytes, eosinophils, and basophils. (Blood smear-WBC, RBC, PLT)-not on CBC  Erythrocyte count (RBCs) Reference range: male: 4.7 – 6.1; female: 4.2 – 5.4 (x1012/L) Measures the number of RBCs in 1mm3 of peripheral blood Females have lower values than males and RBC count decreases with age Decreased =anemia Conditions that decrease production by bone marrow Myelofibrosis, leukemia, renal disease, dietary deficiencies Conditions that involve increased loss Hemorrhage, hemolysis Dilution of body fluids i.e., pregnancy CBC example  Erythrocyte count (RBCs) Increased =polycythemia Physiologically induced due to increased O2 requirements i.e., living at high altitudes Chronic hypoxia Dehydration factitiously increases RBCs  Anemias Macrocytic anemia Megaloblastic anemia DNA synthesis impairment during RBC production RBCs continue growing without dividing Larger RBCs but fewer of them Many causes but usually Vit B12 or folate deficiency Folate = natural B9; folic acid = synthetic B9 Microcytic anemia Small RBCs many causes, Fe intake is most common cause Insufficient intake, increased need, insufficient absorption, or increased blood loss Stored iron is eventually depleted, Hgb drops. Pancytopenia (leukopenia, anemia, thrombocytopenia) Aplastic anemia most common cause Deficiency of all blood cell types Toxin exposure, hereditary, autoimmune disorder. Often idiopathic.  Reticulocytes Aka “retic count” Reference range in adults: 0.5% - 2.0% Percent of immature RBCs Increased Indicates that marrow is putting more RBCs into circulation Causes consistent with ongoing loss of RBCs (hemolysis, hemorrhage) Body attempts to compensate by increasing RBC production, which pushes out immature RBCs “retic-ing”) Low (or even normal) retic count in patient with anemia indicates inadequate bone marrow response to the anemia if anemia is still present, bone marrow should be correcting it or pushing out retics trying to correct it Chemotherapy, aplastic anemia (body stops producing new blood cells)  Hemoglobin (Hgb) Reference range: male: 14- 18; female: 12-16 g/dL Critical values: less than 5 or greater than 20 RBC protein that carries oxygen (and CO2) Reflects the number of RBCs in the blood Increased and decreased levels of Hgb point to similar causes as RBCs Low hemoglobin is also called “anemia”  Hematocrit (Hct) Reference range: male: 42-52%; female: 37-47% /“crit” Critical values: less than 15% or greater than 60% Percent of total blood volume made up of RBCs Closely reflects RBC values Normally 3x Hgb value Altered values reflect same pathologic states and are affected by hydration in the same manner Extremely elevated WBC can decrease Hct  Platelet Count (Plt) Reference range: 150,000-400,000/mm3 Critical values: less than 50k or greater than 1 million Number of thrombocytes per cubic mm Essential for blood clotting Decreased (thrombocytopenia) Reduced production (bone marrow failure, cancer) Hypersplenism sequestration (platelets trapped in spleen) Increased destruction (antibodies, infections, drugs, prosthetic heart valves) Consumption (DIC) Hemorrhage  Platelet Count (Plt) Increased thrombocytosis thrombocythemia Iron deficiency anemia Cancer Various hematologic conditions  Mean Platelet Volume (MPV) Measurement of the average size of platelets Bone marrow will release immature platelets to maintain normal count Immature platelets are larger (“reticulated platelets”) Increased MPV (larger average platelets) Massive hemorrhage, leukemia Decreased MPV Bone marrow underproducing platelets, fewer immature platelets too Chemotherapy, myelosuppression, aplastic anemia  Red Blood Cell Indices Provide information about the size of RBCs, their hemoglobin content, and the concentration of hemoglobin Cell size Normocytic, microcytic, macrocytic Hemoglobin content Normochromic, hypochromic, hyperchromic RBC indices MCV, MCH, MCHC, RDW RBCs MCV MCH, MCHC, RDW  Red Blood Cell Indices Mean corpuscular volume (MCV) RBC version of MPV Average size of a single RBC. Useful in classifying anemias. Increased MCV (macrocytic) Megaloblastic anemias like B12 or folic acid deficiency Decreased MCV (microcytic) Iron deficiency anemia or thalassemia Red blood cell distribution width (RDW) Variation of RBC sizes in the sample Useful in classifying anemias  Red Blood Cell Indices Mean corpuscular hemoglobin (MCH) Average amount of hemoglobin in an RBC Macrocytic cells have more Hgb than microcytic cells so values consistent with MCV Mean corpuscular hemoglobin concentration (MCHC) Average concentration of Hgb in 1 RBC relative to volume of the cell Hypochromic RBCs: hgb deficiency Hyperchromic RBCs: probably a machine error or hemolyzed sample Could indicate altered RBC shape which allows them to fit more Hgb  White Blood Cell Count Two components to the leukocyte portion of the CBC WBC count WBC differential WBC count (reference range: 5,000-10,000/mm3) “white count” “5” Critical values: less than 2,500 or greater than 30,000 Routinely used to diagnose and track infections Increased (leukocytosis) Infection, inflammation, cancer, leukemia, necrosis Trauma, emotional stress, physical stress, pain Decreased (leukopenia) Bone marrow failure, cancer treatment, autoimmune diseases, cancer Overwhelming infections IN REAL LIFE WBC DOES NOT GUARANTEE INFECTION* Typically, an assumption on assessments  White Blood Cell Differential Percent of each type of leukocyte Neutrophils (55-70%) Phagocytize bacteria. Increased values indicate bacterial infection. Significant production can lead to immature neutrophils =bands This is called “left shift” and represents an ongoing bacterial infection “Right shift” represents return towards normal values Neutrophilia without bands could be due to inflammation without infection Lymphocytes (20-40%) WBC differential combines T and B lymphocytes Chronic bacterial or acute viral infections  White Blood Cell Differential Monocytes (2-8%) Fight bacteria like neutrophils Remain in circulation longer and are produced more rapidly Eosinophils (1-4%) and basophils (0.5-1%) Represent a response to parasite or allergens Do not respond to bacterial or viral infections Basophilia on its own might indicate leukemia  Blood Smear Part of the CBC-ordered separately Manual microscopic examination of RBCs, platelets, and WBCs by pathologist or technician Often done when automated cytometer detects abnormal values Verifies Quantities of RBCs, platelets, WBCs Size, shape, color of RBCs Size and granulation of platelets WBC counts  WBC Inclusions Hypersegmented neutrophils Neutrophils with 6 or more lobes Highly sensitive and specific for megaloblastic anemias (B12/folic acid deficiency) Dohle bodies Oval inclusions due to severe stress (like burns)causing improper Dohl maturation e Auer rods Acute myeloid leukemia  Leukemia WBC cancer in the blood Divided into acute and chronic Chronic Difficult to tell from normal mature leukocyte except that there are many Presentation is asymptomatic with severely elevated WBC WBC differential: PMNs (neutrophils, eosinophils, basophils, mast cells) chronic myeloid leukemia (CML*) Lymphocytes: chronic lymphocytic leukemia (CLL) Next step is bone marrow biopsy anyway Both geriatric cancers  Leukemia Acute Blast cells (type of immature WBC) cause bone marrow dysfunction Symptomatic presentation Infections and fever (no WBCs), anemia (no RBCs), bleeding (no platelets), bone pain Blood smear PMNs: acute myeloid leukemia (AML) Lymphocytes: acute lymphoBLASTIC leukemia (ALL) Next step is still bone marrow biopsy ALL pediatric A; AML more geriatric (peds can get it too)  Lymphomas Cancers arising from lymphocytes Many subtypes. Two main categories: Distinction is important because their treatments are effective but only if correct type is identified Non-Hodgkin’s lymphoma (NHL) 90% *Hodgkin’s lymphoma (HL) 10% Marked by the presence of Reed-Sternberg cells on biopsy Mutated B-cells with “moth-eaten” appearance *Better prognosis  Iron Panel Consists of serum iron, TIBC/transferrin, transferrin saturation, and ferritin (often separate) Serum iron 70% of iron is in Hgb of RBCs, remaining 30% stored as ferritin (and hemosiderin) Abnormal iron levels are characteristic of many diseases including iron deficiency anemia and hemochromatosis Total iron binding capacity (TIBC) / transferrin Measurement of all proteins available for binding iron (mostly transferrin) High = iron deficiency Transferrin saturation Percentage of TIBC (mostly transferrin) that is saturated with iron Decreased in iron deficiency anemia, increased in other anemias… Also increased with iron overload or poisoning  Iron Panel Ferritin Major storage protein for iron Serum ferritin represents iron stores in the body Decreased ferritin represents depleted stores Iron deficiency anemia Increased ferritin represents iron excess Iron overload, recent blood transfusion, hemosiderosis, hemochromatosis, anemias, hepatitis (and some anemias) Factitiously elevated in chronic disease states Positive acute phase reactant (serum concentration rises significantly with inflammation) Cancer, infection, liver disease, alcoholism  Iron Panel SIMPLIFIED Total iron in body = ferritin (stored iron) + TIBC (transferrin) Balance of iron-out vs iron-in Too much iron-out: ferritin decreases, TIBC increases Too much iron-in: ferritin increases, TIBC decreases  Erythrocyte Sedimentation Rate (ESR) The rate at which RBCs settle Proinflammatory conditions (infection, cancer, necrosis) increase protein content for plasma (positive acute phase reactants) Pushes RBCs closer together, which causes them to stack Stacks of RBCs settle more rapidly than single RBCs Increase sedimentation rate is a sign of inflammation Can be used to detect or track inflammation Real life: focus on the trend, not one number Frequently ordered to detect presence of infection but is very nonspecific  C-reactive Protein (CRP) Commonly ordered with ESR Acute phase reactant protein secreted by liver in the presence of inflammation or bacterial infections Also, nonspecific Does not rise consistently with viral infections More sensitive to ESR and responds more quickly Disappearance of CRP precedes ESR returning to normal Used to determine cardiac risk factors (elevated: 3xs increased risk MI) Disadvantage Many causes for elevated CRP HTN, increased BMI, DM, low HDL, high triglycerides, smoking, chronic gingivitis  Coagulation Panel Combination of tests used to provide broad understanding of hemostatic mechanisms Commonly ordered with CBC (platelets esp important) and LFTs (covered later) Bleeding time PT/INR PTT Fibrinogen  Coagulation Panel Bleeding time Causing superficial puncture wound and blotting skin every 30sec until it stops bleeding Normal time depends on specifics of method. Increased time indicates platelet dysfunction.  Coagulation Panel Protime/prothrombin time (PT) Protein made by the liver Prothrombin is the inactive form of thrombin which turns fibrinogen into fibrin Time it takes for blood to clot via extrinsic clotting pathway Factors I II V VII X Decrease in factors can be due to many causes Liver disease (affects production) Obstructive biliary disease (affects bile secretion which is needed for fat soluble Vit K which is needed for factors II, VII, IX, and X) Anticoagulant administration (warfarin)  Coagulation Panel International normalized ratio (INR) Calculated from PT in order to assess risk of bleeding/coagulation Target INR varies depending on condition being treated Essentially a measure of how much longer it takes for blood to clot 1.5 = 50% longer for blood to clot (blood is “thinner”) PT and INR communicate the same thing 1.0-1.3 reference range INR  Coagulation Panel Partial thromboplastin time (PTT) Measures speed of blood clotting via intrinsic pathway Factors VIII IX XI XII Fibrinogen assay Factor I Common pathway factor Positive acute-phase reactant Bleeding disorders Inflammation or necrosis Also associated with CAD, stroke, MI, PAD Decreased: liver disease, consumptive coagulopathy, recent transfusion (banked blood does not have fibrinogen)  Coagulation Panel PT/INR vs PT can help identify which factors are deficient and associated conditions Elevated: PT only: 7 PTT only: 8, 9, 11, and 12 PT and PTT: 1, 2, 5, and 10  Coagulation Panel PT/INR vs PT can help identify which factors are deficient and associated conditions Elevated: PT: 7 (plus 1,2,5,10) (1 to a lesser extent): extrinsic + common (RED circle) PTT: 8,9,11,12 (plus 1,2,5,10): intrinsic + common PT and PTT: 1,2,5,10: common 1972-vitamin K 1x2x5=1 0  D-dimer Produced by the degradation of fibrin Levels increase when a clot is degrading and therefore elevated d- dimer increases suspicion of a clot in the body (DVT, PE) Cancer, inflammation, infection, COVID-19 Sickle cell disease (sickle cells make fibrin resistant to fibrinolysis) Useful in screening for DVT before sending patient for ultrasound Extremely sensitive (essentially 100%) for clots but notoriously nonspecific