The Irony of Anemia How to interpret the CBC

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Jaideep Shenoi MD Hematology Oncology Northwest Medical Specialities Tacoma, WA The Irony of Anemia How to interpret the CBC March 10 th, 2018

Disclosures: Advisory Board for Pharmacyclics, Janssen, Takeda, Oncopeptides AB, UptoDate No Conflicts :

Objectives: Provide an overview of the use of CBC in primary care. Anemias- how to diagnose and classify. To highlight mechanisms in anemia To improve understanding of iron metabolism in humans To help address common referral questions Polycythemia

Source: Caro J and Erslev AJ. Erythropoietin assays and their use in the study of anemias. Contrib Nephrol 1988; 66:54-62. Review.

https://www.healthcare.uiowa.edu/path_handbook/handbook/test 2328.html

Clinical Case: A 45-year-old W/F Fatigue 1 month. No CP. SOB/DOE. No Hematochezia, No Melena. Heavy menstrual periods 1 year. Past medical history: Postpartum Anemia - 10 years ago. Not on any meds except ASA 81mg Family history: Parents were born in Italy and died when she was in grade school. She does not know their medical history. Habits: Vegetarian who eats a lot of cereal. She does not have an urge to eat ice.

PHYSICAL EXAM General appearance: Pale female in no acute distress. Vital signs: BP - 125/90, HR - 88 regular, RR - 12/min. Pale conjunctiva. Gr I/VI systolic ejection murmur. Heme negative brown stool was present.

WBC 8.2 4.8-14.8K/ ul RBC 4 X 10^6 3.8-5 X10^6/ul Hg% 8 12-15.6g% Hct 24 35-46% Plt 500 150-400K MCV 60 80-96.1 fl/rbc RDW 16.5 Retics 3 0.5-1.7% Ab Retics 40K 25-75K/ul LDH 210 0-304 U/L Correction of Reticulocyte Count [Hct/normal Hct for age and gender] x reticulocyte % [24%/40%] x 3% = 1.8% The corrected reticulocyte count in this case is less than 2%. Ab Retic count- calculated according to the formula: Reticulocyte count in % x RBC count in 10 6 /μl

Macrocytic Microcytic Normocytic Aplastic Anemia Blood loss Iron Def Anemia of Chronic Disease Thalassemia Sideroblastic Anemia Pernicious Anemia Liver Disease Folate Deficiency Iron Def Anemia -Transferrin Sat % or Iron/TIBC ratio <15% Anemia of Chronic Disease - Transferrin sat % or iron/tibc ratio > 15%.

Hyperproliferative Anemias ( destruction of RBC) Hemolysis Hypersplenism Hypoproliferative Anemias Aplastic Anemia Nutritional Anemia Iron Deficiency Anemia

Factors that may affect CBC parameters: iron deficiency thalassaemia medication alcohol minor infections ethnic differences gender pregnancy

Importance of Clinical Examination: pallor, jaundice fever, lymphadenopathy bleeding/bruising hepatomegaly, splenomegaly frequency and severity of infections, mouth ulcers, recent viral illness exposure to drugs and toxins fatigue/weight loss

The absolute count of each of the cell types is more useful than the total WBC. The total count may be misleading, eg: low neutrophils with an elevated lymphocyte count may produce a total white count that falls within the reference range.

Neutrophils Low Significant levels < 0.5 x 10 9 /L (high risk infection) Most common causes viral (overt or occult) autoimmune/idiopathic drugs Red flags person particularly unwell severity rate of change of neutropenia lymphadenopathy, hepatosplenomegaly

Neutrophils High Most common causes infection/inflammation Sinuses/Dental disease Necrosis/malignancy any stressor/heavy exercise Drugs/smoking pregnancy CML Red flags person particularly unwell severity rate of change of neutrophilia presence of left shift

Lymphocytes Lymphocyte Low not usually clinically significant Lymphocyte High isolated elevated count not usually significant Causes acute infection (viral, bacterial) smoking hyposplenism acute stress response autoimmune thyroiditis CLL

Monocytes Low not clinically significant Monocytes High usually not significant watch levels > 1.5 x10 9 /L more closely

Eosinophils Low no real cause for concern Eosinophils High Most common causes: allergy/atopy: asthma/hayfever parasites (less common in developed countries) Rarer causes: Hodgkins Myeloproliferative disorders Churg-Strauss syndrome

Basophils Low difficult to demonstrate Basophils High Associated with Myeloproliferative disorders other rare causes

Useful to use MCV to classify the Anemia Microcytic, MCV < 80 fl Normocytic, MCV 80 100 fl Macrocytic, MCV > 100 fl

Microcytic Anemia The three most common causes for microcytic anaemia are: Iron deficiency Thalassemia Anemia of Chronic disease (20%)

Oral Iron Challenge Test Baseline Iron 31 TIBC 381 % Sat 8 Transferrin 298 Ferritin 20 1 hr Iron 335 TIBC 386 % Sat 87 Transferrin 308 2hr Iron 361 TIBC 378 % Saturation 96, Transferrin 304

Normocytic Anemia Common Causes : Bleeding Early Nutritional Anemia (Iron, B12, Folate Def) Anemia of renal insufficiency Anemia of chronic disease/chronic inflammation Hemolysis Primary bone marrow disorder

Macrocytic Anemia Common causes Alcohol Liver disease B12 or Folate Deficiency Thyroid disease Some Drugs (especially Hydroxyurea)

High Hemoglobin / Polycythemia / Erthrocytosis Hb often accompanied by PCV Can reflect decreased plasma volume (eg: dehydration, alcohol, cigarette smoking, diuretics) or Increased RBC mass (eg polycythemia)

83 y W/M h/o Testicular Lymphoma 1/2006, s/p Rt Orchiectomy, RCHOP X4 cycles and IT MTX X1 & XRT Lt Testicle, Stage IIB Prostate CA-Gleason 3+3=6 s/p Radical Prostatectomy 6/2003

Major Causes of Erythrocytosis Autonomous (inappropriate high) increase of Epo Erythropoietin-producing neoplasms Renal cell carcinoma Hepatocellular carcinoma Hemangioblastoma Uterine fibroids Erythropoietin-producing renal lesions (eg, cysts, hydronephrosis) Following renal transplantation

Appropriate increases in Erythropoietin Hypoxemia secondary to: COPD Right-to-left cardiac shunts Sleep apnea Massive obesity (Pickwickian syndrome) High altitude Red cell defects Some cases of congenital methemoglobinemia Chronic carbon monoxide poisoning (including heavy smoking) Polycythemia vera Idiopathic familial polycythemia High oxygen affinity hemoglobins

Miscellaneous causes Use of androgens or anabolic steroids Blood doping in athletes Self-injection of erythropoietin

Take Home Pearls: -Patients to hydrate before a blood draw -Transfusion don t order CMV neg blood, all blood is LR -All patients on Epo need Iron supplements -Thresholds for PRBC Hct 22 and Plt Transfusions 10K -Ferrous Gluconate -324mg ( 38mg elemental iron) -Ferrous Sulfate -325mg ( 65mg elemental iron) -Prenatal Vitamin- 28mg iron, Folate 800mcg, Vit B12-8mcg -others like Iron glycinate, iron fumarate