Anemia

General Approach to Diagnosis

• First evaluate RI (decreased production) vs ↑RI (loss vs hemolysis)
  • Reticulocyte index > 2%: see below 
  • RI < 2%:  hypoproliferative  stratify based on RBC size 
    • Microcytic vs. Normocytic vs. Macrocytic
    • Exception to ↓RI is thalassemia where RI can be slightly ↑

Presentation

• Symptoms: fatigue/malaise, DOE, angina (if CAD)
• Hx of systemic illness, ETOH abuse, Family History
• Signs:
  • Pallor, tachycardia, orthostatic hypotension, purpura, glossitis, koilonychia (IDA)
  • Jaundice (2/2 hemolysis)
  • Splenomegaly: suggests extramedullary hematopoiesis or sequestration
  • Neurologic symptoms: suggests B12 deficiency 

Evaluation

• CBC w/diff, reticulocyte count, peripheral blood smear, Iron studies (TIBC, Ferritin)
• Hemolysis labs: Bilirubin, LDH, haptoglobin
• Nutritional studies: B12, folate

Background

• Consumption vs Blood loss
• Loss: acute bleed vs iatrogenic from labs
• Hemolysis: Microangiopathic hemolytic anemia (MAHA), autoimmune hemolytic anemia, intrinsic RBC defects

Evaluation

• LDH, ↑indirect bilirubin, ↓haptoglobin, PT/PTT
• Peripheral blood smear: looking for schistocytes
• Consider direct antiglobulin test (DAT) if suspicion for autoimmune cause

Extrinsic RBC causes:

• If schistocytes ± thrombocytopenia = MAHA: TTP, DIC, HUS, HELLP, mechanical valves, malignant HTN, cocaine, scleroderma renal crisis
  • Check Cr and Plt count to evaluate for TTP
  • mechanical valves, malignant HTN, cocaine, scleroderma renal crisis
• If DAT positive = AIHA
• Order cold agglutinin titer

Intrinsic RBC causes:

• Sickle cell disease: chronic hemolysis + splenic sequestration crisis where RI is↑ vs aplastic crisis where RI is↓ (see sickle cell section)
• Hereditary spherocytosis
• Hereditary elliptocytosis
• PNH (generally see pancytopenia, RI is lower than expected for severity of anemia)
• G6PD: bite cells, Heinz bodies on PBS: Usually precipitated by drugs: nitrofurantoin, dapsone, sulfonamides, rasburicase, primaquine

Management

• MAHA: Caused by DIC, TTP, HUS
  • DIC: sepsis, malignancy, pregnancy
    • Treat underlying cause
    • If active bleeding: FFP, cryoprecipitate (to keep fibrinogen>100) and platelets
  • TTP: Order ADAMTS13
    • Will need PLEX
  • If concern for TTP you should immediately consult Heme and NephrologyHUS: + shiga toxin, AKI, diarrhea
  • Other: mechanical valves, malignant HTN, cocaine, scleroderma renal crisis
    • Treat underlying cause
       
• Autoimmune hemolytic anemia (AIHA):
  • Cold: IgM binds at temp <37
    • Caused by lymphoproliferative disorder (Waldenstrom’s), mycoplasma, EBV, HIV
    • Consult heme. Treat underlying. Consider rituximab (steroids don’t work)
  • Warm: IgG
    • Idiopathic or associated with lymphoma, SLE, drugs, babesiosis, HIV
    • Can use steroids, IVIG, ritux

Normocytic Anemia: MCV 80-100

• Look for pancytopenia (eg. something else may be happening in the BM, splenic sequestration, PNH, etc)
• Anemia of chronic disease may also be microcytic
• Mixed macrocytic/microcytic disease: look for ↑RDW
• CKD: low Erythropoietin (EPO) levels
• Endocrine disease: ↓metabolic demand/O2 requirement
• Pure red cell aplasia: associated with destructive Ab (CLL, thymoma, parvovirus, autoimmune)
• Bone marrow biopsy may be indicated if normocytic with low RI without an identifiable cause or anemia associated with other cytopenia’s

Microcytic anemia: MCV <80 (Mnemonic: SALTI)

• Sideroblastic, anemia of chronic disease, lead poisoning, thalassemia and iron-deficiency
• See Table

Macrocytic Anemia: MCV >100

• Non-megaloblastic:
  • ETOH: BM suppression, macrocytosis independent from cirrhosis or vitamin deficiency
  • Liver disease
  • Hypothyroidism
  • MDS
  • Medications that impair DNA synthesis: zidovudine, 5-FU, hydroxyurea, ara-C, AZT