Approach to Anemia: Recap!

Anemia: a reduction in one or more of the major RBC measurements obtained as part of the CBC (i.e. Hemoglobin concentration, hematocrit, or RBC count)

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Always consider the patient's volume status: concentrations (i.e. hemoglobin, hematocrit, RBC count) are all dependent on red blood cell mass (RCM) and plasma volume. Thus, the values of all three masses will be reduced if the RCM is decreased and/or the plasma volume is increased. 

Examples:

• Acute UGIB: a 70 kg adult with a UGIB from a peptic ulcer, with 750 mL hematemesis (i.e. 15% normal total blood volume) within the last 30 minutesà likely to have postural hypotension due to acute volume depletion, but he/she will have normal hemoglobin (Hb) & hematocrit (Hct). Over the next 48 hours, most of the total blood volume deficit will be repaired by movement of fluid from extra-vascular into the intra-vascular spaceà only during these later times will the Hb and Hct reflect blood loss!!
• Pregnancy: in the third trimester (T3), the RBC mass and plasma volume are expanded by 25 and 50% respectively, resulting in reductions in Hb, Hct and RBC count
• Volume depletion: initial Hb may appear normal, due to hemoconcentration

Special Populations to consider in Anemia: Altitude (higher values), Smokers (carboxy-hemoglobin & polycythemia), ethnic differences (lower Hb values in African Americans vs Caucasians), Chronic Disease, Athletes

RBC lifespan: Erythropoiesis in the BM (influence: cytokines, erythroid specific growth factors, EPO); mature RBCs circulate for 110-120 daysà then they are removed from the circulation via macrophages

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    Under steady-state conditions: Rate of RBC production= rate of RBC loss

APPROACH & CAUSES: Kinetic (mechanistic) vs Morphological (MCV)

·        Morphological Approach

Microcytic Anemia: MCV<80 fl; most commonly iron (Fe) deficiency, thalassemia minor, ACD. Think "TAILS"...

Thalassemias: decrease synthesis of alpha or beta globin chains of Hb, leading to destruction of RBCs & erythroid precursors

• MCV is usually quite low (<70), normal Fe, more narrow RDW then Fe deficiency
• Thalassemia index: MCV/RBC; <13 suggests Thalassemia, >13 Fe deficiency
•  Target cells, basophilic stipling
• Order Hb Electrophoresis

Anemia of chronic inflammation: impaired Fe utilization and reduction in EPO responsiveness due to hepcidin and cytokine increase in the setting of autoimmune diseae, chronic infection, inflammation, malignancy, etc

• High/Normal Ferritin, TIBC low, Fe low

Iron Deficiency: you always must determine how and where the iron is being lost. Considerations include chronic GI bleeding, menstrual loss (i.e. menorrhagia), reduced supply (cases of malnutrition, poor absorption, high gastric pH), increased demand (i.e. pregnancy)

• Low ferritin, increase in TIBC (transferrin), low Fe

·       Lead Poisoning

      

      Sideroblastic: defective heme biosynthesis within RBC precursors

•       Causes: hereditary, idiopathic (MDS), Reversible (EtOH, lead, isoniazid). Fe increased, ferritin increased, normal TIBC. Smear may show basophilic stippling and ringed sideroblasts.
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Normocytic Anemia: MCV 80-100 fL

Acute Blood Loss: GI, GU, pelvis/abdomen, skin, CNS

Decreased Production

• Primary BM disorder: Bone marrow (BM) suppression from drugs (Chemotherpay), MM, Myelodysplasia, Myeloproliferative disorders, lymphoma, mets, infections (i.e. TB)
•  Decreased EPO: CKD
• Anemia of Chronic Disease

Sequestration: Splenomegaly

Increased Destruction

• Immune: AI hemolytic anemia (Warm & Cold agglutinins)
•  Non-immune

o   RBC membrane: spherocytosis

o   RBC enzyme: G6PD, pyruvate kinase deficiency

o   RBC HB: Sickle Cell Anemia

o   MAHA: DIC, HUS/TTP, HTN (malignant), drugs

o   Blood: toxins, infections (malaria)

Mixed Picture: combined microcytic and macrocytic

Macrocytic Anemia: MCV> 100 fL (femtoliters)

·       Reticultocytosis

·       Impaired DNA synthesis: Vitamin B12 and Folate deficiency

•        Low folate: malnutrition (EtOH, anorexic, elderly), decrease in absorption (celiac), impaired metabolism (MTX, TMP, hydroxyurea)
•       Low Vitamin B12: this vitamin is found in foods of animal origin. Normally, vitamin B12 binds intrinsic factor (IF), which is secreted from gastric parietal cells; absorption of vitamin B12 occurs in the terminal ileum (TI)
•  Malnutrition (vegans, EtOH), pernicious anemia (AI disease against gastric parietal cells), dec abs (celiac, Crohn’s), bacterial overgrowth

·       EtOH use/abuse

·       Liver disease

·       Hypothyroidism

·         Drugs: Chemo (hydroxyurea, MTX, azathioprine), AEDs (phenytoin), Abx (TMP-SMX)

·         MDS, Acute Leukemia

·       Paroxysmal Nocturnal Hemoglobinuria (PNH)

Clinical

 Symptoms: more profound with a more rapid onset vs. a slow evolution of anemia.  Symptoms are due to decreased O2 delivery to tissues +/- hypovolemia. Reduction in O2 deliveryà fatigue, exertional dyspnea, increased cardiac demand (may have angina, bounding pulses, palpitations), CHF, confusion, arrhythmia

-Inquire about GIB (hematemesis, hematochezia, melena), Gyne (menorrhagia); constitutional symptoms, chronic infections, rheumatological conditions, diet, meds (NSAIDs, ASA, anticoagulation), FHx (thalassemia), fatigue

- Ethnicity: thalassemias & other hemoglobinopathies—more common in Mediterranean, Middle East, sub-Saharan Africa & SE Asia

-Acute bleed: volume depletion can cause fatigue, muscle cramps, dizziness, lethargy, syncope, persistent hypotension, shock and death

Physical Exam Signs

•  VS: postural drop, hypotensive, tachycardia
• Pallor (mucous membranes, palmer creases, conjunctiva), jaundice (Bili>40) tachycardia, orthostatic hypotension; LAD, consider DRE with FOBT, HSM, Bone pain
• Nail changes, atrophic glossitis; petechiae, ecchymoses

Diagnostic Work-up

• CBC (always track down and compare to recent previous CBC), peripheral smear
• Reticulocytes
• Fe studies: Fe, Ferritin, TIBC (transferrin), % saturation
•  Hemolysis evaluation (smear- fragments/spherocytes), increase LDH, indirect bilirubin and reduction in haptoglobin. A  combination of increased LDH & reduced Haptoglobin= 90% SPECIFIC for hemolysis
• Intravascular hemolysis: plasma & urinary Hb, urinary hemosiderin (? PNH)
• May need to consider bone marrow aspirate and biopsy, SPEP & UPEP (if ? Multiple Myeloma)