Anemia¶
Margaret Wheless
Presentation¶
- Symptoms:
- Fatigue/malaise, dyspnea on exertion, angina (if history of CAD)
- Signs:
- Pallor, tachycardia, orthostatic hypotension, purpura, glossitis, koilonychia (in IDA)
- Jaundice (if 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)
- RI > 2%: blood loss vs hemolysis; see below
- Hemolysis labs: Bilirubin, LDH, haptoglobin
- RI < 2%: hypoproliferative stratify based on RBC size
- Microcytic (<80) vs. Normocytic (80-100) vs. Macrocytic (>100)
Reticulocyte Index >2%¶
Background¶
- Etiology: Consumption vs Blood loss
- Loss: acute bleed vs iatrogenic from labs
- Hemolysis: Microangiopathic hemolytic anemia (MAHA), autoimmune hemolytic anemia (AIHA), intrinsic RBC defects
Evaluation¶
- LDH, ↑indirect bilirubin, ↓haptoglobin, PT/PTT
- Peripheral blood smear: evaluated for schistocytes, bite cells, spur cells, spherocytes, etc.
- Direct antiglobulin test (DAT) to evaluate for autoimmune hemolytic anemia
Extrinsic RBC causes¶
- If schistocytes ± thrombocytopenia = MAHA: TTP, DIC, HUS, HELLP, mechanical valves, malignant HTN, cocaine, scleroderma renal crisis
- If DAT positive = AIHA
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
- G6PD: bite cells, Heinz bodies
- Usually precipitated by drugs: nitrofurantoin, dapsone, sulfonamides, rasburicase, primaquine
Management¶
- MAHA
- DIC: sepsis, malignancy, pregnancy
- Treat underlying cause
- If active bleeding: FFP, cryoprecipitate (to keep fibrinogen >100) and platelets
- TTP: Order ADAMTS13 (prior to plasma transfusion or exchange)
- If concern for TTP you should immediately consult Heme and Nephrology
- HUS: + shiga toxin, AKI, diarrhea
- AIHA:
- Cold (rare): IgM binds at temp <37
- Caused by lymphoproliferative disorder (Waldenström Macroglobulinemia), mycoplasma, EBV, HIV
- Consult heme. Treat underlying. Consider rituximab (steroids ineffective)
- Warm: IgG
- Idiopathic or associated with lymphoma, SLE, drugs, babesiosis, HIV
- Can use steroids, IVIG, rituximab
- Cold (rare): IgM binds at temp <37
Reticulocyte Index <2% (RBC Size Framework)¶
Normocytic Anemia: MCV 80-100¶
- Etiologies
- Anemia of inflammation: (may also be microcytic)
- Anemia of CKD: low Erythropoietin (EPO) levels
- Endocrine disease (hypothyroidism, adrenal insufficiency): ↓metabolic demand/O2 requirement
- Mixed macrocytic/microcytic disease may have a normal MCV: look for ↑RDW
- Pure red cell aplasia: associated with destructive Ab (CLL, thymoma, parvovirus, autoimmune)
- Paroxysmal nocturnal hemoglobinuria (PNH)
- Bone marrow failure or infiltration (typically will see pancytopenia)
- Bone marrow biopsy may be indicated if no identifiable cause or anemia is associated with other cytopenia’s
Microcytic anemia: MCV <80 (mnemonic: SALTI)¶
- Sideroblastic, Anemia of chronic disease, Lead poisoning, Thalassemia and Iron-deficiency
| Disease | Etiology | Evaluation | Considerations |
|---|---|---|---|
| Sideroblastic | MDS Idiopathic EtOH, Lead, Isoniazid Cu deficiency |
Social hx, TB, consider Lead level Fe: ↑↑ Ferritin: ↑ to nL TIBC: nL Smear: basophilic stippling BMBx: ringed sideroblasts |
In clinical practice this is usually acquired; either due to alcohol (can resolved with cessation) or primary bone marrow disorder (e.g. MDS-RARS) |
| Anemia of Inflammation (formerly chronic disease) | Chronic inflammation, malignancy, HIV, autoimmune dz, heart failure, etc. | Fe/TIBC >18% Fe: ↓↓ Ferritin: ↑↑ TIBC: ↓↓ |
Treat underlying disease Replete Fe if ferritin <100 or TIBC <20% EPO if Hgb <10 and serum EPO <10 |
| Thalassemia | ↓ synthesis of α or β chains leads to ↓ erythropoiesis and ↑ hemolysis Family Hx of anemia |
Mentzer’s index: MCV/RBC <13 = thalassemia Normal Fe studies; can mimic microcytic anemia and Fe overload from transfusions Diagnosis: Hb electrophoresis (α will be normal) |
α-thal more common in Asian/African descent β thal common in Mediterranean descent Tx: transfusions, folate, Fe chelator depending on severity |
| Iron (Fe) deficiency | Chronic bleeding: colon cancer, heavy menstrual periods, cirrhosis (portal gastropathy) Supply: malnutrition, Crohn’s dz, Celiac dz, subtotal gastrectomy Demand: pregnancy |
Fe/TIBC <18% Fe:↓↓ TIBC:↑ nl to ↑ Ferritin: < 100 Mentzer’s index: >13 Consider celiac testing based on clinical suspicion Investigate for GIB or source of blood loss |
Oral Fe: 6wks to correct anemia, 6mo to replete stores; dose every other day (↑ absorption w/ ↓ GI side effects); add Vit C for ↑ absorption If can’t tolerate PO consider IV Fe (Avoid when bacteremic) HFrEF: IV Fe if ferritin <100 OR 100-300 w/ Fe sat <20% |
Macrocytic Anemia: MCV >100¶
-
Non-megaloblastic
- ETOH, liver disease, hypothyroidism, MDS
- Medications that impair DNA synthesis: zidovudine, 5-FU, hydroxyurea, ara-C, AZT, MTX
-
Megaloblastic
- B12 deficiency
- Presentation: neurologic changes (subacute combined degeneration), paresthesia, ataxia, dementia (reversible with early treatment)
- Etiology: malnutrition (alcoholics, vegan), pernicious anemia, gastrectomy, Crohn’s disease, chronic pancreatitis, celiac disease
- Diagnosis: ↓B12, ↑MMA, ↑homocysteine
- Treatment: either monthly IM or sublingual B12 (oral not absorbed if no IF)
- Folate deficiency
- Etiology: malnutrition, decreased absorption (e.g. Celiac disease), impaired metabolism (MTX, TMP), ↑requirement (hemolysis, malignancy, dialysis)
- Diagnosis: ↓folate, ↑homocysteine, MMA will be normal
- Treatment: PO folate 1-4 mg daily
- B12 deficiency