Heme Meds Flashcards
Normal HGB levels
Male: 14-17.5
Female:12.3-15.3
women < men due to menstrual cycle
S/sxs of Anemia
- fatigue, lethargy dizziness
- SOB, HA, tachycardia
- edema, dry skin, chapped lips
- nail brittleness
- hunger for ice (pagophagia) , starch, or clay (pica)
Distribution of Fe in the body
- absorbed intake: 1-2mg/day
- myoglobin (muscle): 300mg
- Bone Marrow: 300mg
- Reticuloendothelial macrophages: 600mg
- Liver: 1000mg
- circulating erythrocytes (hemoglobin): 1800mg
- avg. iron loss/day: 1-2 mg
Types of Macrocytic Anemia
MCV >100
- Megaloblastic (immature RBCs)
- folate deficiency
- Cobalamin (Vitamin B12) deficiency
- Drug-Induced
- Non-Megaloblastic
- alcohol use disorder
- liver disease
*
Types of Microcytic Anemias
MCV <80fL
- Iron deficiency
- anemia of chronic disease
- thalassemias
- lead poisoning
Types of Normocytic Anemia
MCV: 80-100fL
- Hemolytic:
- Intrinsic:
- hereditary spherocytosis
- paroxsymal nocturnal hemoglobinuria
- G6PD deficiency
- Sick cell anemia
- Extrinsic:
- micro/macroangiopathic hemolytic anemia
- autoimmune hemolytic anemia
- Intrinsic:
- Non-Hemolytic
- iron deficiency
- anemia of chronic disease
- CKD
- aplastic anemia
When to transfuse pts without significant CV disease?
- hgb = 7gm/dL
- pt with acute sxs (i.e. dyspnea, CP) + hgb 7-9
Tx of Iron Deficiency Anemia
- Provide 150-200mg/day of elemental iron
- should increased hgb by 1g/dL/week
- if proper tx will see reticulocytes in 7-10 days
- if HGB increases <2 g/dL/3weeks → should reassess
Overview of Tx of B12/Folic Acid Anemia
B12/Folic Acid Supplement
Overview of Tx of Anemia of Chronic Disease
- tx the chronic disease
- ESA (erythropoietin stimulating agent)
Fe Treatment
- 50-65 elemental Fe PO BID-TID on empty stomach to maximize absorption
- 20% elemental iron in 325 ferrous sulfate = 65mg
- ferrous fumarate (33%)
- ferrous gluconate = 12 %
- 20% elemental iron in 325 ferrous sulfate = 65mg
- SEs: abdominal pain, nausea, heartburn, constipation, dark stools
-
DDI: vitamin C, orange juice can decrease stomach pH = more absorption
-
fluoroquinolones, TCN, & macrolides, mycophenolate mofetil can chelate with iron and decrease absorption
- ****give iron 2 hours before or 4 hours after***
-
fluoroquinolones, TCN, & macrolides, mycophenolate mofetil can chelate with iron and decrease absorption
Parenteral FE
- iron dextrose: hypersensitivity black box warning
- sodium ferric gluconate complex
- iron sucrose
-
Indications:
- Pts cannot tolerate PO formulations
- non-compliant
- malabsorption syndromes
B12 (Cyanocobalamin)
needed for RBC production and maturation
-
PO & parenteral = equally effective
- PO poorly absorbed
- Dose: B12 1000mcg Qday IM x 1 week, then 1000mcg Qweek x 1 month or until hgb normalizes
-
Lifelong tx:
- 1000mcg Qmonth for pernicious anemia/surgical resection of ileum
- SEs: injection site rxn, pruritus, rash
Folic Acid
- Dose: 1mg POQday
- if malabsorption: may need up to 5mg Qday
- hgb should rise after 2 weeks
- should have resolution of sxs and reticulocytosis within a few days
- SEs: allergic rxn, flushing, malaise, rash
- DDI: no significant interactions
Tx for Anemia of Chronic Disease
- Goals: reduced requirement for transfusion
-
ESA:
- binds to EPO receptors on RBC precursor cells in Bone Marrow → increased RBC production
- do not use if hgb >10g/dL
- Epoetin
-
Darbepoetin
- synthetic analog of Epoetin
- longer t½ → longer dosing interval
- Drugs that are biosimilar (not generics, but similar) for anemia:
-
Retacrit (epoetin alfa-apbx)
- first approved biosimilar to epoetin alpha
-
Retacrit (epoetin alfa-apbx)
ESA monitoring in CKD
-
Dialysis:
- start 50-100units/kg SC/IV 3x/week
- hgb <10
- use lowest dose
-
may increase dose q 4 weeks
- if no/inadequate response by 3 months (12 wks) do not increase dose more
- if hgb response >1 g/dL/2week → decrease dose by 25%
- decrease dose or interrupt tx if hgb near or exceeds 11g/dL
-
Non-dialysis:
- decrease dose or interrupt tx if hgb nears or exceeds 10g/dL
Non-pharmacologic tx of Sickle Cell Anemia
- splenectomy
- screen for:
- ischemic retinopathy, nephropathy, pulmonary HTN, vascular disease, stroke
- blood transfusion for pts with splenic sequestration & O2 sats <90% even with O2 supplementation
- vaccines: flu, menveo, PCV-13, PPSV23
Pharmacologic Tx of Sickle Cell Anemia
-
PCN prophylaxis: 1st line for prevention of pneumococcal sepsis in kids
- can also use amox, erythromycin, azithromycin, cephalosporin or fluoroquinolones (contraindicated in kids <16 due to cartilage damage)
- for mild-mod pain: NSAIDS
- for severe pain: opioids
-
Hydroxyurea:
- inhibits DNA synthesis; increases fetal hgb, increases water content in RBC; alters RBC adhesion to endothelium → makes RBCs “less sticky”
- if CrCl <60mL/min → reduce dose by 50%
- SEs: myelosuppression; stomatitis (mouth ulcers); n/v/d/c; HA; drowsiness; nail & skin hyperpigmentation/atrophy
- risk of teratogenic effects → need to do a baseline pregnancy test
- DDI: myelosuppressive effects
SEs & DDI of ESA
-
SEs:
- tumor progression
- thromboembolism
- MI, stroke, CHF, HTN
- tachycardia, dyspnea
- seizures, HA, dizziness, N/B
- Hypersensitivity rxn, arthralgia, rash, fever, edema, diarrhea
-
DDI with ESA:
- combined. oral contraceptives → thromboembolism
- droxidopa (Northera) = prodrug of NE → increased supine HTN
- tamoxifen (selective estrogen receptor modulator) ; thalidomide; tranexamic acid → thromboembolism
Thrombocytopenia General Info
- platelets lower than normal (Normal 150-450)
- mild bleeding <50K
- serious bleed <20K
- platelet life span: 8-12 days for humans
- causes:
- bone marrow: under production, damage to stem cells; excessive destruction; splenic sequestration
- Drug induced: diuretics (thiazides); chloramphenicol (50s inhibitor), ASA, ibu, heparin, PCN, phenytoin, vancomycin, rifampin
- EtOH: reduces production of platelets
- Viruses: chickenpox, mumps, rubella, EBV →decreased platelet count
- Risk factors: CA, autoimmune diseases, genetic conditions, infections, medications
S/sxs and Tx of Thrombocytopenia
- Mild-serious bleeding:
- purpura & petechia
- abnormal vaginal bleeding, internal bleeding
- blood in urine, dark tarry stools, HA
- Dx tests: CBC, blood smear, bone marrow tests - aspiration or biopsy, PT, aPTT, spleen U/S
-
Treatments:
- steroids PO or IV (slow platelet destruction)
- IVIG → for immune thrombocytopenia
- rituximab - blocks immune system → reduces B-cell activity
- “-trombags” → eltrombopag, avatrombopag
- romiplostim
- blood or platelet transfusions
- splenectomy
“-trombopag”
MOA: activates thrombopoietin receptors → increased platelet production
“EAL”
-
eltrombopag (promacta):
- SEs: hepatotoxicity, thrombosis, cataracts, URI, UTI, n/v/d, skin discoloration
- Precautions: asian ancestry → start at lower dose (25mg)
- thromboembolism risk
- CI: LFTs > 5x ULN, Albumin <3.5
-
Avatrombopag (Doptelet):
- SEs: hyponatremia, HA, peripheral edema
- Precautions: thromboembolism risk
-
Contraindication:
- breastfeeding, and wait at least 2 weeks after d/c
-
Lusutrombopag (Mulpleta):
- SEs: HA, thromboembolism
- Precautions: thromboembolism risk
- Contraindications: breastfeeding, during and wait at least 28 days (4 weeks) after d/c
Romiplostim (Nplate)
for thrombocytopenia : MOA: activates thrombopoietin receptors → increased platelet production
for chronic immune thrombocytopenia (ITP)
- max dose: 10mcg/kg/wk
- Hold dose if platelets > 400K; d/c if no increase in platelets after 4 weeks
-
SEs: bone marrow collagen fibrosis
- thromboembolism, angioedema, HA, arthralgia, myalgia
- insomnia, dizziness, n/v/d, cough
-
Contraindications:
- breastfeeding; myelodysplastic syndrome; chronic hepatic disease; hematologic malignancy
Populations with High Prevalence of Anemia
elderly (85+ yo)
black, non hispanic
mexican america
females (85+)
Retacrit
used to tx anemia of chronic disease
- biosimilar to EPO (but not identical so not called “generic”
*
Darbepoetin (Aranesp)
synthetic analog of Epoetin
longer ½ life = longer dosing interval
used to tx anemia of chronic disease if hgb <10
Hydroxyurea
- inhibits DNA synthesis; increases fetal hgb, increases water content in RBC; alters RBC adhesion to endothelium → makes RBCs “less sticky”
- if CrCl <60mL/min → reduce dose by 50%
- SEs: myelosuppression; stomatitis (mouth ulcers); n/v/d/c; HA; drowsiness; nail & skin hyperpigmentation/atrophy
- risk of ****TERATOGENIC**** effects → need to do a baseline pregnancy test
- DDI: myelosuppressive effects
Platelet count in mild bleeding vs serious bleeding
Mild bleeding < 50K
Serious Bleeding <20 K
Average lifespan of platelet
8-12 days in humans
Eltrombopag (Promacta)
Activates thrombopoietin receptions and increase platelet production
- SEs: hepatotoxicity, hemorrhage, thrombosis, cataracts, URI, UTI, n/v/d, skin discoloration
- Precautions: asian ancestry → start at lower dose (25mg)
- thromboembolism risk
- CI: LFTs > 5x ULN, Albumin <3.5
Avatrombopag (Doptelet)
Activates thrombopoietin receptions and increase platelet production
- SEs: hyponatremia, HA, peripheral edema
- Precautions: thromboembolism risk
-
Contraindication:
- breastfeeding, and wait at least 2 weeks after d/c
Lusutrombopag (Mulpleta)
Activates thrombopoietin receptions and increase platelet production
- SEs: HA, thromboembolism
- Precautions: thromboembolism risk
- Contraindications: breastfeeding, during and wait at least 28 days (4 weeks) after d/c