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Author: Beau <cbeauhilton@gmail.com>
Date: Mon, 27 Sep 2021 21:36:13 -0500
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+# Anemia
+
+**Anemia – Margaret Wheless**
+
+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
+
+**Reticulocyte Index > 2%**
+
+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
+
+**RBC Size Framework**
+
+**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
+
+| **Disease** | **Etiology** | **Evaluation** | **Considerations** |
+| --- | --- | --- | --- |
+| **Sideroblastic** | MDS
+
+Idiopathic
+
+ETOH, Lead, Isoniazid,
+
+Cu deficiency | Social hx, work, TB,
+
+consider Lead level
+
+Fe:↑↑ ferritin:↑nl or ↑
+
+TIBC: nl
+
+Smear: basophilic stippling
+
+BMbx: ringed sideroblasts | |
+| **Anemia of chronic disease** | Chronic inflammation, malignancy, HIV autoimmune dz, Inflammation (IL6, TNF α)↓ | Fe/TIBC >18%
+
+Fe: ↓↓ ferritin:↑↑ TIBC:↓↓ | Tx: underlying dz
+
+EPO if Hgb <10 and serum EPO <500
+
+Replete Fe if ferritin <100 or TIBC <20% |
+| **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 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: < 15, <41 w/co-morb.
+
+Mentzer’s index: >13
+
+Consider celiac testing based on clinical suspicion
+
+Investigate for GIB or sources 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: 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
+
+- Megaloblastic
+ - B12 deficiency
+ - Total body stores last 2-3 yr; absorbed in terminal ileum, requires IF
+ - Can have neurologic changes (subacute combined degeneration); paresthesias, ataxia, dementia (reversible with early treatment)
+ - Etiology: malnutrition (alcoholics, vegan), pernicious anemia, gastrectomy, Crohn’s disease, chronic pancreatitis, celiac disease (8-41% of pt)
+ - Dx: ↓B12, ↑MMA, ↑homocysteine
+ - If B12 low normal but have neuro sx, can get MMA to help confirm dx
+ - Tx: either monthly IM or sublingual B12 (oral not absorbed if no IF)
+ - Folate deficiency
+ - Total body stores last 2-3 mo; absorbed mostly in jejunum
+ - Etiology: malnutrition, decreased absorption (celiac disease 2/2 damaged jejunum), impaired metabolism (MTX, TMP), ↑requirement (hemolysis, malignancy, dialysis)
+ - Dx: ↓folate, ↑homocysteine but wnl MMA
+ - Tx: PO folate 1-4 mg daily
+
