Hematology and Coagulation PDF

Hematology and Coagulation PPR 6340 Clinical Laboratory Medicine Don Branam, Pharm.D., BCPS, FASHP Objectives Define red blood cell indices and their interpretation for common anemias Describe the coagulation cascade Define common laboratory tests for coagulation Understand common situ...

Hematology and Coagulation PPR 6340 Clinical Laboratory Medicine Don Branam, Pharm.D., BCPS, FASHP Objectives Define red blood cell indices and their interpretation for common anemias Describe the coagulation cascade Define common laboratory tests for coagulation Understand common situations that would require specific testing (ie, which laboratory assay for a particular drug) Hematology Red Blood Cells, Hemoglobin, and Hematocrit Another name for red blood cell is “corpuscle” Oxygen transport Normal range – men 4.7-6.1 x 106, women 4.2-5.4 x106 Hgb – molecule that carries oxygen Normal range – men 13.8-17.2 g/dL, women 12.1-15.1 g/dL Hematocrit - percentage of RBC that is Hgb Normal range – men 40.7-50.3%, women 36.1-44.3% RBCs https://images.app.goo.gl/2G7Z2vvEMEmHYYKx7 Hemoglobi n Made in bone marrow along with red blood cells https://images.app.goo.gl/evEazaEJPCdNoGvz9 Red Blood Cell Indices Mean Corpuscular Volume (MCV) – an estimate of the average volume of RBCs Attempt to describe the volume of blood that is taken up by a single RBC Normal range – 80-96 fL/cell Directly measured, but can also be estimated by dividing the hematocrit by the RBC count Most clinically useful Mean Corpuscular Hemoglobin Not used clinically Average amount of Hgb in RBCs Normal range 27-33 pg/cell Mean Corpuscular Hemoglobin Concentration Hemoglobin divided by the hematocrit Anemia Low hemoglobin Associated with symptoms of weakness, fatigue, shortness of breath Reticulocyte count Immature RBCs Increased in acute blood loss and hemolysis Decreased in untreated iron, folate, or Vitamin B12 deficiencies 0.5-2.5% of RBCs Next step - look at MCV < 80 = microcytic anemia Commonly caused by iron deficiency > 96 = macrocytic anemia Folate or cyanocobalamin deficiency (Vitamin B12) Folate deficiency is most common B12 deficiency less common Case AB is 32-year-old woman who presents to her primary care clinic complaining of persistent fatigue. After a careful history and examination, the results from the CBCWBC are reviewed: 8000 RBC 3.5 Hgb 8 Hct 25 Plts 300k MCV 110 MCH 30 MCHC 33.3% Reticulocyte count 0.4% Coagulation http://neurobio.drexel.edu/GalloWeb/blood%20clotting%20cascade.gif Accessed Ju Activated Partial Thromboplastin Time aPTT May be referred to as “PTT” Measures activity of intrinsic pathway (factors VIII, IX, XI, XII) and common pathway (factors II, V, and X) Used as a surrogate marker to monitor heparin (which inhibits factors II, IX, X, XI, and XII) and certain direct thrombin (factor II) inhibitors Measured in seconds High variability between labs aPTT Normal and therapeutic ranges must be established for each lab and for each lot of reagent High degree of error possible; thus, correct interpretation is essential Typical normal aPTT ~ 30 secs (control value) Historically, patients on IV heparin would have their infusions titrated for an aPTT goal of 1.5-2.5 times the control value (45-75 secs) However, may not always correlate with a therapeutic anticoagulation Each hospital will have its own therapeutic range (may be referred to as a “heparin curve”) and heparin infusion rates will be titrated for that goal, and NOT the historical standard Obtain at baseline, and 6 hours after initiation of infusion, or 6 hours after any infusion rate change or discontinuation N Engl J Med 1997; 337:688-69 But What About Low Molecular Weight Heparins (LMWHs)? Unlike heparin, LMWHs (exps, enoxaparin, dalteparin) preferentially inhibit factor X Thus, activity cannot be measured by aPTT Anti-Xa levels are used, but aren’t routinely ordered Should be ordered for patients with acute kidney injury, morbid obesity, or who are pregnant) Range 0.5-1 IU/mL (for twice daily dosing of LMWH) or 1-2 IU/mL (once daily dosing) Draw levels 4 hours after LMWH dosing D-Dimer Breakdown product in clot formation Normal range < 0.5 mcg/mL Used for suspected blood clots Venous thromboembolism Deep vein thrombosis (DVT) Pulmonary embolism (PE) Highly sensitive but nonspecific Make sure you know what this means! “Rolling the dimer dice” Prothrombin Time May be referred to as “Protime” PT Measures activity of factors II, V, VII, and X Measured in seconds Normal range ~ 12 secs (control value) Used in assessing and adjusting the therapeutic effect of warfarin (Coumadin) Historic goal was 2 times control Wide variability between labs due to different types of reagents and testing equipment International Normalized Ratio (INR) Developed to standardize the results of the PT regardless of lab, reagent, or equipment ISI – International Sensitivity Index – comes from the maker of each lot of reagent This is calculated and reported by the lab (in other words, you will NEVER calculate this yourself) Unitless value A normal INR is 1 Therapeutic ranges depend on indication Common 2-3 Rarely, 2.5-3.5 Case BR is a 45-year-old man who presents to the emergency department complaining of severe pain in his left leg. His past medical history is significant for morbid obesity and hypertension. He smokes 2 packs of cigarettes per day. On examination, his vital signs are normal. His left leg is swollen and erythematous. The physician orders standard labs including a CBC, CMP (the results of which were within normal limits,) and d-dimer, which was elevated at 1.5 mcg/mL. An ultrasound confirms a deep vein thrombosis in the left leg. The physician orders an LMWH (enoxaparin) at 1mg/kg every 12 hours and consults the pharmacist for monitoring. Along with standard labs, which specific test should be considered to evaluate the therapeutic effect of enoxaparin? Questions?