Anemia
Definition Erythropoiesis (RBC Synthesis)
 ↓ number of circulating RBCs
 Low Hgb, HCT, RBC measured on
CBC:
-Surrogate Markers
Pathophysiology
 ↓ RBC production
o Nutrition deficiencies –B12, Fe
o BM failure - (chemo, radiation)
o Tumor into marrow
o Endocrine deficiency –EPO synth.
o Chronic DZ – renal, liver,
infection
 Blood loss – most common**
o Trauma, Ulcers, NSAIDs
 RBC destruction
o Hemolysis
o Drug-Induced
Classifications:
 Based on MCV – size of RBC
o Microcytic: ↓ than normal
o Normocytic
o Macrocytic:  than normal
 Based on Hgb content
o Hypochromic – ↓normal
o Normochromic
o Hyperchromic –  normal
Causes
 Blood loss:
o Menstruation, GI bleed, Trauma
 ↓ absorption:
o Gastrectomy, Inflammation, Poor diet
 ↑ requirement: Pregnancy
 Impaired utilization: Heredity
PO Supplementation
 Recommended: 200 mg elemental Fe daily
 Tx for 3-6 months to replete stores
 Dosed based on tolerability
Counseling Points:
 AEs: dark stools, N/V/D/C
 Give with Vit C to ↑ absorption
 Take 1 hr before meals
o milk & tea ↓ absorption
 Take 2 hr before or 4 hr after antacid
Symptoms Compensatory Mechanisms
 Starts in bone marrow w: Asymptomatic mostly  ↑ cardiac output
o Folate, Vit. B12, Iron  Fatigue** – hallmark  ↑ coronary flow
o Cytokines  Dyspnea  Altered blood viscosity
o EPO  Hyperdynamic  Changes in O₂ consumption &
 EPO release o Bounding pulses extraction
o Due to hypoxia (not RBC level) o Palpitations
o  growth /differentiation of RBCs o Roaring in ears
-Normoblasts: slightly mature RBCs
-Reticulocytesmature RBCs  Symptoms due to:
 4 days to mature o Hypoxia
 RBC circulate for 120 days o Hypovolemia (bleeds)
Evaluation Evaluation
 Hgb < 11g/dL 1. Kinetic Approach
 Hgb > 2 below baseline  Focuses on underlying mechanism of anemia
 CBC w/ indicies  Primary featurereticulocyte count
 Blood smear morphology o Corrected against degree of anemia
 Evaluate possible causes o Normal RI = 1.0-2.0
Reticulocyte count & MCV  Low RI = ↓RBC production
 High RI = ↑ or normal RBC
Additional Cues or Tests 2. Morphologic Approach size of RBC
 Iron deficiency  Microcytic: <80 - Fe deficiency
o TIBC- reflects Fe storage seen in hepatocellular carcinoma or renal cell carcinoma
o TSAT- bound Fe in serum  Normocytic: MCV 80-100 - Blood loss
o Ferritin- Fe storage protein also hemolysis, BM failure, chronic inflam, renal insufficiency
 Hemorrhage: + stool guaiac key follow up test: reticulocyte count
 Hemolysis: + coombs test, ↑LDH  Macrocytic: MCV >100 - B12/folate deficiency
also abnormal RBC maturation
or indirect bilirubin
 CKD: GFR <60 for >3 months, ↓EPO
Vitamin B12:
level  Abnormal DNA metabolism: Releases large, immature RBCs
 Often Drug Induced: MTX, 6-MP
 Treatment:
o Cyanocobalamin 1000mcg IM/SQ weekly X 4-6 weeks
o Cyanocobalamin PO daily X 1 month
 Maintenance: Cyanocobalamin IM/SQ monthly or PO QD
Folic Acid:
 Poor intake or drug induced: 5-FU, 6-MP, MTX
 Txt: Folic Acid 1 mg PO daily X 4 months
Iron Deficiency anemia
Fe Storage and Requirements Lab Results
 Stored as Ferritin in:
o Liver, Spleen, Marrow
 Absorbed as Ferrous (Fe 2+) in:
o Duodenum, Upper Jejunum
 Nutritional requirements:
o Adult M /Post-menopause Fem – 8 mg
o Pre-menopausal women – 18 mg
Iron Treatments
IV Supplementation
Indications: Iron Wk 1: Test dose 25 mg Anaphylactic type rxn
 Intolerance to PO Dextran (slow IV push); 1 hr -uneventful test dose
 Malabsorption later 75 mg over 5 min DOES NOT ensure rxn
 Sig blood loss Week2-10: 100 mg will not occur w.
over 5 min QW therapeutic dose
 CKD
Ferric IV infusion:125 mg Hypersensitivity rxn
 Chemo pt on ESAsGluconat over 1 hr Avoid rapid admin
e Repeat dose QW x 8wk Dilute in 100 ml NS
trial showed Hgb (Ferrlecit)
increase is greater in Iron Diff doses for CKD & Anaphylactic type rxn
IV iron than PO iron Sucrose
chemo-assoc anemia Dilute doses
(Venofer)
 Anemia of Chronic Kidney Disease
Caused by:
 Chemotherapy
 Infections (e.g. HIV)
 Inflammatory disease
 CKD
Treatments
PRBCs ESAs
About  Preferred for immediate correction  Takes weeks to elicit Hgb response
o Rapid ↑ in Hgb & Hct  Was popular in early 2000s for cancer
o 1 unit PRBC (300 mL)  ↑Hgb 1g/dL  Allows for 16% reduction in transfusions
 Neutropenic pts may need CMV (-) PRBCs o Mostly just improves QOL
 Used when Hgb > 10g/dL (or >7-8 via AABB)  Dosed differently for CKD or chemo related anemia
 May enhance OS  High risks, minimal benefit
Survival  Retrospective study of 56 unresectable esophageal cancer pts N/A
on
RT w/ cisplatin & 5-FU
 5 yr OS 65% compared to 21% in placebo
Risks  Transfusion rxn (type & test for cross reactivity first)  ↑ mortality & tumor progression
 CHF  Thromboembolism (strong link)
 Bacterial contamination/viral infect. (rare)  HTN & seizures
 Fe overload (w/ numerous transfusions)  Pure red cell aplasia
 VTE  **REMS PROGRAM due to multitude of risks!

Sickle Cell Anemia

Etiology/Epidemiology Fetal Hgb (HbF) Complications
 Inherited, autosomal recessive Hgb  2 alpha & 2 gamma Hgb subunits  Hemolysis
disorder o Adult Hgb = 2 alpha & 2 beta o Sickle cell life span 10-20 days
o DNA substitution mutation at o <2% of adult Hgb is this form o Shorter life span than normal RBC bc of
beta-globin gene  Inhibits polymerization that results in hemolysis  anemia
o TA substitution results in more sickle shape o ↓NO  vasoconstriction
negative charge  polymerized, o >20% HbF  milder disease  ↑adhesion/coag initiation
sickle-shaped RBCs o If we can induce this, it could be  Obstructed blood flow to
 Sickled RBCs are rigid & cause occlusions in beneficial! spleen  ↑risk of infection
microvasculature  Vaso-occlusion
o Poor oxygenation o Pain
o Excrutiating pain o Stroke
 2.5 mill American carriers o Acute chest syndrome
 70,000 w/ disease  Similar to ARDS
 Survival advantage in malaria areas  Causes cough/dyspnea
o Priapism
o Splenic sequestration
o Osteonecrosis
o Renal insufficiency
o Anemia
o Infection w/ encapsulated organisms
Management
Prevention/Txt of crisis Pain Mgmt (cornerstone) Infection Prevention
 Hydroxyurea:↑HgF synth & ↓ neutrophils  Usually requires opioids (often IV)  PCV13 & PPSV23
 Indicated if:  Hydration w/ D5W ½ NS w/ 20 mEq KCl for  Meningococcal vaccine
o 3+ pain crisises/yr severe crisis  PCN prophylaxis (erythromycin for PCN allergy)
o acute chest syndrome
o severe anemia Txt:
 Monitoring  Common Organisms: S. pneumo, H. flu, S.
o CBC w/ indicies q 2-4 wks aureus, E. coli, EGNR
o Reticulocyte count, HgF, CMP q 3-6 mo.  Ceftriaxone
 AEs:  Vancomycin only if meningitis suspected
o Neutropenia, thrombocytopenia
o Hyperpigmentation & drying of skin/nails
o Teratogenicity (preg. Cat D)
 Hydroxyurea requires dose titration**

SUMMARY:

 Anemias have various etiologies

 Treatment depends on the morphology of the anemia

 Folic acid, Vitamin B12, and iron supplementation is needed for their respective deficient anemias

 ESAs are limited in use due to high risks and minimal benefit

 Sickle cell anemia is an inherited disorder that requires lifelong management of its complications

 Hydroxyurea is the drug of choice to manage sickle cell crisis and it requires dose titration