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 Guide Editors
 Editor In Chief
    Joel E. Gallant, MD, MPH

Pharmacology Editor
    Paul Pham, PharmD, BCPS

Zambia Guideline Team
   Peter Mwaba MMed PhD FRCP
   Alywn Mwinga MMed
   Isaac Zulu MMed MPH
   Velepie Mtonga MMed
   Albert Mwango MBChB
   Jabbin Mulwanda MMed FCS
 

 

 

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Anemia

Richard D. Moore, M.D.
12-17-2008

  • Based on large Zambian cohort study, anemia common among HIV+ Zambians.
  • In appropriate clinical scenarios, consider malaria as potential cause of anemia.
  • Hgb measurement required prior to starting AZT-containing ART regimens.
  • Initiation of AZT-containing regimen may worsen anemia because of bone marrow suppression.
  • AZT not recommended in patient with pre-ART Hgb <10 gm/dl.
  • Delay ART until anemia treated or use alternative NRTI in patients with baseline anemia.
  • For severe anemia (Hgb <6.5 gm/dl)in patient on AZT, first exclude malaria in endemic areas. Substitute TDF or ABC.
  • Parvovirus B19 PCR, DNA blot, IVIG, erythropoietin, and darbepoetin not readily available in Zambia.
Zambia Information Author: Larry William Chang, MD, MPH

CLINICAL

  • Prevalence 1-10% in asymptomatic HIV, 10-25% with CD4-defined AIDS, 30-60% with AIDS-defining illness
  • Hypoproliferative anemia more common than hemolytic anemia
  • Earliest Sx affect functional status: easy fatigue, weakness, exertional dyspnea, slowed cognition (Hgb 10-12)
  • Later Sx include rapid heart rate, bounding pulse, dyspnea, severe fatigue, confusion, angina, CHF (Hbg <8-9)
  • HIV can directly cause suppression of hematopoietic precursor cells in marrow through inflammatory cytokine suppression, inhibition of endogenous erythropoietin response
  • Low testosterone level can cause anemia.
  • Anemia a prognostic factor for worse survival in HIV, but association unlikely to be causal.

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DIAGNOSIS

  • Hgb <12 (HCT <36) in women and <13 (HCT <41) in men (WHO criteria).
  • Reticulocyte count, indirect bilirubin, MCV can help assess cause
  • Decreased RBC production: Low retic. count, normal indirect bili, normal MCV, except low in iron-deficiency, anemia of chronic disease, MCV high with certain drugs (e.g., AZT). Includes: 1. HIV-induced (pattern of anemia of chronic disease, MCV low-normal; normal Fe stores, but laboratory appearance of Fe deficiency anemia with Fe <60 ug/dL, transferrin <300, ferritin <100) 2. Iron-deficiency (Fe <60, transferrin <300, ferritin <80; chronic blood loss, most commonly GI) 3.Neoplasm infiltrating bone marrow (lymphoma, KS) 4. Infection in marrow (MAC, MTb, CMV, fungal) 5. Parvovirus B19 (Severe anemia, typically with normal neutrophils and platelets; PCR or DNA dot blot for parvovirus B19) 5. Drugs (zidovudine, cancer chemotherapy, interferon-alpha, gancyclovir, pyrimethamine, amphotericin, phenytoin)
  • Ineffective RBC production: Low retic, high indirect bili, high MCV. Includes:1. Folic acid deficiency (RBC folate <150-200, GI malabsorption in 20% of AIDS pts) 2. B12 deficiency (serum B12 <125-200, GI malabsorption in 20% of AIDS patients)
  • RBC destruction (hemolysis): High retic, high indirect bili, high LDH, low haptoglobin, peripheral smear may have fragmented RBCs, spherocytes, schistocytes. Includes: 1. Coomb's positive hemolytic anemia 2. TTP 3. DIC 4. Drugs: sulfonamides, oxidant drugs such as dapsone, primaquine with G6PD deficiency, ribavirin.

TREATMENT

General

  • Iron deficiency: Ferrous sulfate 300 mg 3 times daily; oral iron may not correct deficit in setting of erythropoietin use and frequent phlebotomy, consider IV ferric gluconate in sucrose (Ferrlecit) 125 mg (10 cc) in 100 cc 0.9% NaCl infused over 1 hr until total body replacement (5-20 doses). Initial test dose, 2 mL IV (25 mg elemental iron) in 50 mL NS, over 60 min recommended due to risk of hypersensitively reaction.
  • Folate deficiency: Folate 1-5 mg/d for 1-4 mos
  • B12 deficiency: B12 1 mg/d IM x 7 days, then q wk x 4, then monthly until malabsorption resolved
  • Parvovirus B19: IVIG 0.4 g/kg/d x5 days. If relapse in <6 mos, consider 2g/kg over 2 days. Consider maintenance dosing of 0.4g/kg q4wks for relapse.
  • Marrow infiltration by tumor or infection: Bone marrow Bx. Treat specific cause (e.g. MAC, MTb, CMV, fungal)
  • Drug-induced anemia: For G6PD deficiency and oxidant drugs such as dapsone, primaquine, discontinue drug. Severe methemoglobinemia (in pts without G6PD deficiency) can be treated with IV methylene blue (1 mg/kg)
  • HIV induced: ART may improve Hgb by 1-2 g/dL over 6 mos. Can use hematopoietic growth factor while waiting for response to ART (see subheading for dosing). Improvement may be slower with AZT-containing regimens
  • Transfuse only for acute blood loss or severe anemia with potential cardiovascular compromise. Evidence that repeated transfusions may compromise immune system recovery, increase viral load
Hematopoietic growth factors

  • Erythropoietin-alfa:effective when serum EPO level <500 u/mL. Do not start growth factors unless Hgb < 10-11. Start with at 10,000 U SQ q wk or 20,000 U SQ q 2 weeks (based on anemia of chronic kidney disease).. If Hgb increase <1g by 4-6 wks, increase dose by 25-50% q wk.
  • Aim for Hgb of 11-12. Decrease dose by 25% increments or decrease frequency of dosing (e.g., to q2wks, then q3wks, etc.) to maintain hemoglobin 11-12. A clinical trial showed that dosing every 2-4 wks is effective in maintaining Hgb.
  • Darbepoetin-alpha: erythropoiesis-stimulating protein with longer half-life. Initial dose of 0.45 mcg per kg SC q2wk (based on studies in anemia of ckd. Increase by 25% if increase in Hgb <1 by 4-6 wks. Decrease frequency of dosing (e.g., to q3-4 wks, etc.) or decrease dose by 25% increments to maintain Hgb 10-12.
  • Maintain use of growth factors for at least several mos. Taper dose slowly as tolerated to maintain Hgb 11-12
  • Monitor Hgb q 2 wks during titration, and no less frequently than q4 wks thereafter
  • Maintain adequate iron stores with iron supplementation. Inadequate iron stores most common reason for non-response to growth factors.
  • Treatment with EPO improves QOL, correlated with Hgb improvement
  • Treatment with weekly darbepoetin-alfa (1 mcg = "200" IU EPO conversion) shown to be as effective as 3x/wk erythropoietin for anemia in hemodialysis in HIV+ persons, though erythropoieting now given weekly.
  • Erythropoietin  corrects anemia in HIV/HCV-coinfected patients treated with IFN/RBV, including those taking AZT.
  • Complete correction of anemia with erythropoietin in patients with chronic kidney disease increases risk of CV events and death. Relevance to HIV unknown, but suggests that correction of Hgb to >12.0 g/dL should not be goal of treatment.

Drug Comments

DrugRecommendations/Comments
Darbepoetin Second choice after erythropoietin. Effective for anemia from cancer chemotherapy and renal failure. Currently no data for HIV.
Erythropoietin First choice of hematopoietic growth factors, pending clinical data that darbepoetin as effective in HIV+ pts. Do not increase Hgb to >12 g/dL due to increased risk for CV events.
intravenous immune globulin IVIG 0.4 g/kg once-daily over 5 days for Parvovirus B19

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