anemia.md (6596B)
1 # Anemia 2 3 **Anemia – Margaret Wheless** 4 5 General Approach to Diagnosis 6 7 - First evaluate RI (decreased production) vs ↑RI (loss vs hemolysis) 8 - Reticulocyte index > 2%: see below 9 - RI < 2%: hypoproliferative stratify based on RBC size 10 - Microcytic vs. Normocytic vs. Macrocytic 11 - Exception to ↓RI is thalassemia where RI can be slightly ↑ 12 13 Presentation 14 15 - Symptoms: fatigue/malaise, DOE, angina (if CAD) 16 - Hx of systemic illness, ETOH abuse, Family History 17 - Signs: 18 - Pallor, tachycardia, orthostatic hypotension, purpura, glossitis, koilonychia (IDA) 19 - Jaundice (2/2 hemolysis) 20 - Splenomegaly: suggests extramedullary hematopoiesis or sequestration 21 - Neurologic symptoms: suggests B12 deficiency 22 23 Evaluation 24 25 - CBC w/diff, reticulocyte count, peripheral blood smear, Iron studies (TIBC, Ferritin) 26 - Hemolysis labs: Bilirubin, LDH, haptoglobin 27 - Nutritional studies: B12, folate 28 29 **Reticulocyte Index > 2%** 30 31 Background 32 33 - Consumption vs Blood loss 34 - Loss: acute bleed vs iatrogenic from labs 35 - Hemolysis: Microangiopathic hemolytic anemia (MAHA), autoimmune hemolytic anemia, intrinsic RBC defects 36 37 Evaluation 38 39 - LDH, ↑indirect bilirubin, ↓haptoglobin, PT/PTT 40 - Peripheral blood smear: looking for schistocytes 41 - Consider direct antiglobulin test (DAT) if suspicion for autoimmune cause 42 43 Extrinsic RBC causes: 44 45 - If schistocytes ± thrombocytopenia = MAHA: TTP, DIC, HUS, HELLP, mechanical valves, malignant HTN, cocaine, scleroderma renal crisis 46 - Check Cr and Plt count to evaluate for TTP 47 - mechanical valves, malignant HTN, cocaine, scleroderma renal crisis 48 - If DAT positive = AIHA 49 - Order cold agglutinin titer 50 51 Intrinsic RBC causes: 52 53 - Sickle cell disease: chronic hemolysis + splenic sequestration crisis where RI is↑ vs aplastic crisis where RI is↓ (see sickle cell section) 54 - Hereditary spherocytosis 55 - Hereditary elliptocytosis 56 - PNH (generally see pancytopenia, RI is lower than expected for severity of anemia) 57 - G6PD: bite cells, Heinz bodies on PBS: Usually precipitated by drugs: nitrofurantoin, dapsone, sulfonamides, rasburicase, primaquine 58 59 Management 60 61 - MAHA: Caused by DIC, TTP, HUS 62 - DIC: sepsis, malignancy, pregnancy 63 - Treat underlying cause 64 - If active bleeding: FFP, cryoprecipitate (to keep fibrinogen>100) and platelets 65 - TTP: Order ADAMTS13 66 - Will need PLEX 67 - If concern for TTP you should immediately consult Heme and NephrologyHUS: + shiga toxin, AKI, diarrhea 68 - Other: mechanical valves, malignant HTN, cocaine, scleroderma renal crisis 69 - Treat underlying cause 70 - Autoimmune hemolytic anemia (AIHA): 71 - Cold: IgM binds at temp <37 72 - Caused by lymphoproliferative disorder (Waldenstrom’s), mycoplasma, EBV, HIV 73 - Consult heme. Treat underlying. Consider rituximab (steroids don’t work) 74 - Warm: IgG 75 - Idiopathic or associated with lymphoma, SLE, drugs, babesiosis, HIV 76 - Can use steroids, IVIG, ritux 77 78 **RBC Size Framework** 79 80 **Normocytic Anemia: MCV 80-100** 81 82 - Look for pancytopenia (eg. something else may be happening in the BM, splenic sequestration, PNH, etc) 83 - Anemia of chronic disease may also be microcytic 84 - Mixed macrocytic/microcytic disease: look for ↑RDW 85 - CKD: low Erythropoietin (EPO) levels 86 - Endocrine disease: ↓metabolic demand/O2 requirement 87 - Pure red cell aplasia: associated with destructive Ab (CLL, thymoma, parvovirus, autoimmune) 88 - Bone marrow biopsy may be indicated if normocytic with low RI without an identifiable cause or anemia associated with other cytopenia’s 89 90 **Microcytic anemia: MCV <80**(Mnemonic: SALTI) 91 92 - Sideroblastic, anemia of chronic disease, lead poisoning, thalassemia and iron-deficiency 93 - See Table 94 95 | **Disease** | **Etiology** | **Evaluation** | **Considerations** | 96 | --- | --- | --- | --- | 97 | **Sideroblastic** | MDS 98 99 Idiopathic 100 101 ETOH, Lead, Isoniazid, 102 103 Cu deficiency | Social hx, work, TB, 104 105 consider Lead level 106 107 Fe:↑↑ ferritin:↑nl or ↑ 108 109 TIBC: nl 110 111 Smear: basophilic stippling 112 113 BMbx: ringed sideroblasts | | 114 | **Anemia of chronic disease** | Chronic inflammation, malignancy, HIV autoimmune dz, Inflammation (IL6, TNF α)↓ | Fe/TIBC >18% 115 116 Fe: ↓↓ ferritin:↑↑ TIBC:↓↓ | Tx: underlying dz 117 118 EPO if Hgb <10 and serum EPO <500 119 120 Replete Fe if ferritin <100 or TIBC <20% | 121 | **Thalassemia** | ↓synthesis of α or β chains leads to ↓ 122 123 erythropoiesis and ↑ hemolysis | Family Hx of anemia 124 125 Mentzer’s index: MCV/RBC <13 = thalassemia 126 127 Normal Fe studies; can mimic microcytic anemia and Fe overload from transfusions 128 129 Diagnosis: Hb electrophoresis | α thal more common in Asian/African descent 130 131 β thal common in Mediterranean descent 132 133 Tx: transfusions, folate, Fe chelator depending on severity | 134 | **Iron (Fe) deficiency** | Chronic bleeding: 135 136 colon cancer 137 138 heavy menstrual periods, cirrhosis (portal gastropathy) 139 140 Supply: malnutrition, Crohn’s dz, celiac dz, subtotal gastrectomy 141 142 Demand: pregnancy | Fe/TIBC <18% 143 144 Fe:↓↓ TIBC:↑ nl to ↑ 145 146 ferritin: < 15, <41 w/co-morb. 147 148 Mentzer’s index: >13 149 150 Consider celiac testing based on clinical suspicion 151 152 Investigate for GIB or sources of blood loss | Oral Fe: 6wks to correct anemia, 6mo to replete stores; dose every other day ( ↑ absorption w/ 153 154 ↓ GI side effects); add Vit C for ↑ absorption 155 156 If can’t tolerate PO consider IV Fe (Avoid when bacteremic 157 158 HFrEF: IV Fe if ferritin <100 OR 100-300 w/ Fe sat <20% | 159 160 **Macrocytic Anemia: MCV >100** 161 162 - Non-megaloblastic: 163 - ETOH: BM suppression, macrocytosis independent from cirrhosis or vitamin deficiency 164 - Liver disease 165 - Hypothyroidism 166 - MDS 167 - Medications that impair DNA synthesis: zidovudine, 5-FU, hydroxyurea, ara-C, AZT 168 169 - Megaloblastic 170 - B12 deficiency 171 - Total body stores last 2-3 yr; absorbed in terminal ileum, requires IF 172 - Can have neurologic changes (subacute combined degeneration); paresthesias, ataxia, dementia (reversible with early treatment) 173 - Etiology: malnutrition (alcoholics, vegan), pernicious anemia, gastrectomy, Crohn’s disease, chronic pancreatitis, celiac disease (8-41% of pt) 174 - Dx: ↓B12, ↑MMA, ↑homocysteine 175 - If B12 low normal but have neuro sx, can get MMA to help confirm dx 176 - Tx: either monthly IM or sublingual B12 (oral not absorbed if no IF) 177 - Folate deficiency 178 - Total body stores last 2-3 mo; absorbed mostly in jejunum 179 - Etiology: malnutrition, decreased absorption (celiac disease 2/2 damaged jejunum), impaired metabolism (MTX, TMP), ↑requirement (hemolysis, malignancy, dialysis) 180 - Dx: ↓folate, ↑homocysteine but wnl MMA 181 - Tx: PO folate 1-4 mg daily 182