Anemia Dr. Bossaer Exam 4 Flashcards
What is the lifespan of RBCs and neutrophils?
-RBC: 120 days
-Neutrophils: 7 days
(Hematoposies: blood cell production of RBCs, neutrophils, platelets)
What are the materials needed for blood cell production?
What is anemia?
-Iron
-Cobal, Copper
-Folic acid
-Vitamin B12, B6, C, B2 (Riboflavin)
Anemia: increased erythrocytosis
What is the function of Erythropoietin and Thrombopoietin?
Erythropoietin: promotes stem cell differentiation into mature red blood cells (RBCs)
Thrombopoietin: promotes stem cell differentiation of megakaryocytes into platelets
Where are erythropoietin and thrombopoietin produced?
erythropoietin: Kidney
thrombopoietin: Liver
Which hormone stimulates granulocyte production?
Granulocyte colony-stimulating factor (G-CSF)
Granulocyte: Neutrophils, Basophils, Eosinophils
What is Iron used for?
-RBC production
-Myoglobin (muscle metabolism)
-Enzymes: cytochromes, catalase, peroxidase, xanthine oxidase
In what form and in which organs is iron stored?
Ferritin
in the liver and the heart
What are the two types of Iron?
Which one has better absorption?
Heme-Iron (from meat)
Nonheme-iron (from plants, grains) - absorbed via DMT1)
better absorption with Heme-Iron (via heme transporter)
What decreases Iron absorption?
-Food
-high pH -> PPIs
-Ca2+
-Polyphenols (tea, coffee)
What helps with the absorption of non-heme Iron?
Vitamin C
Which hormone reduces the absorption of Iron from the small intestine?
Hepcidin
by inhibiting Ferroportin 1 (transporter)
What is the function of the reticuloendothelial system?
destruction of RBCs by phagocytic cells (macrophages)
-spleen
-liver
-in the blood, lymphatics
What is the function of Hepcidin in macrophages in an immune response?
helps to keep Iron in the macrophage (inhibits Iron transporter)
also inhibits iron transport (absorption) from the small intestine to the blood (less iron for bacteria in an infection)
What is required for Vitamin B12 absorption?
Vitamin B12 (Cobalamin)
-intrinsic Factor B12 (secreted from gastric parietal cells)
-> gastric bypass or removing parts of the stomach can cause Vitamin B12 deficiency
-acidic environment -> PPIs can cause Vitamin B12 deficiency
Which drugs are Granulocyte stimulating factor analogs?
Filgrastim (short-acting)
Pegfilgrastim (pegylated, long half-life)
stimulates neutophil production
Which drugs are Thrombopoietin mimetics?
Romiplostim
Eltombopag
Avatrombopag
stimulates megakaryocyte production -> more platelets
What Hemoglobin level is indicative of anemia?
Hgb <13 for men
Hgb <12 for women
What are the symptoms of acute and chronic anemia?
acute:
-tachycardia
-lightheadedness
-dyspnea
chronic:
-fatigue, weakness
-pallor
-headache
-vertigo
Which lab is the best for diagnosing Iron deficiency?
-Ferritin (iron storage)
CAUTION: it reacts to acute conditions (pneumonia) and can look high
-Tsat (% of transferrin occupied by Fe)
If ferritin and Tsat are low, it is considered anemia (regardless of the iron level)
What is the site of RBC destruction?
Spleen
What happens to Iron after RBC destruction?
- bind to Transferrin for transport
- kept in storage or reused in the bone marrow
What happens to Hemoglobin after RBC destruction?
- Hemoglobin is degraded to Heme -> then Bilirubin
- Bilirubin is toxic, so it must be glucuronidated in the liver for excretion
Which organ and which labs are affected by the increased destruction of RBCs?
Splenomegaly
elevated Bilirubin
What are typical issues of RBC production causing Anemia?
Lack of material:
-Fe, folic acid, Vitamin B12 deficiency (5yr metformin) due to:
heavy period, GI bleed, cancer
-> use supplements, but also clarify sources of bleeding !!!
Lack of Epo (CKD): Epo drugs
Physiologic stress (ICU, sepsis): treat the cause
Myelodysplasia (cancer): RBC transfusion
Hypothyroidism: use levothyroxine
What are the common causes of increased RBC destruction?
-Splenomegaly (hepatosplenomegaly)
-hemolytic anemia with Coombs
autoimmune or drug-induced
-hemolytic anemia without Coombs
microangiopathic or drug-induced
What type of anemia and what type of deficiency is associated with low MCV?
What are the causes?
Microcytic anemia -> Fe deficiency
causes:
-Fe malabsorption (gastric bypass or PPIs (acidic environment needed for absorption)
-blood loss (rule out!!)
-increased iron use (pregnancy)
How much Iron can we absorb?
200 mg daily
Know how much elemental Iron we need based on different Iron formulations
What is the elemental amount of Fe in Ferrous sulfate?
OBJECTIVE
65 mg (20%)
know the other ones too
How much elemental Iron is in Ferrous Gluconate?
36 mg (12%)
How much elemental Iron is in Ferrous Fumarate?
106 mg (33%)
How much elemental Iron is in 150 mg of Polysaccharide Fe Complex?
150 mg (100%)
What happens to Hepcidin when taking Fe supplements?
upregulation of hepcidin, which increases Iron retention in the cells and reduces Fe absorption
What are the side effects of oral Fe supplements?
What might help with side effects?
-GI upset and abdominal pain
-constipation, N/V
-dark stool, hard stool (docusate helps)
improve tolerability
-take it every other day (titrate dose)
-take it with food (but food decreases absorption)
How long does it take to complete Fe stores?
1-2 months
What are the DDIs associated with oral Fe supplements?
What mechanism causes the DDI?
-Fluoroquinolones
-tetracyclines
-levothyroxine
-cefdinir !! -> orange stools !!
-levodopa
-methyldopa
-> decreases absorption of these drugs by chelation (Fe is reactive)
What is required before giving IV Fe Dextran?
!!! NAPLEX
0.5 ml test dose to see if the patient has an anaphylactic reaction (Box warning, also with Fe Sucrose)
it is a Fe-sugar formulation
(Fe is very reactive, to reduce the reaction it is formulated with sugar (dextran))
IV iron is used when oral iron is ineffective.
Which IV Fe drug causes hypophosphatemia?
Ferric carboxymaltose
IV iron supplementation is recommended for which patient population?
HFreF (LVEF < 40%) patients in the hospital
AND
with iron deficiency (Ferritin < 100 mcg/L or <300 with Tsat <20%) regardless of their Hbg
What type of anemia is associated with high MCV?
Macrocytic anemia (MCV >100) -> Vitamin B12 deficiency, can also be Folic acid deficiency
What are the causes of Vitamin B12 deficiency?
-gastric bypass
-PPIs
(VitB12 needs gastric acid for absorption)
-Metformin long-term
Which neurological symptoms are associated with Vitamin B12 deficiency?
peripheral neuropathy
paresthesia (pins and needle sensation in the hand)
What is the Vitamin B12 replacement IV regimen?
1mg IM/SC daily 1x week, then
1mg weekly for 1 month, then
1mg monthly for 1 year
-> once replenished may change to oral (IV is preferred over oral to replenish bc they are not absorbing well)
What type of anemia and what type of deficiency is associated with high MCV?
Macrocytic anemia (MCV > 100) and Folic acid or
Vitamin B12 deficiency
-1mg po folic acid daily (may increase up to 5 mg daily)
What causes Anemia in patients with chronic disease or chronic inflammation?
-increased levels of Hepcidin -> keeps Fe in the liver and decreases it from circulating in the blood
-the inflammation suppresses bone marrow production of RBC (also WBC and platelets)
What levels of Tsat and Ferritin do we expect in patients with Anemia of chronic diseases (or chronic inflammation)?
high or normal Ferritin: there is enough Fe in the cells (storage), but not enough in circulation
-> Hepcidin keeps Fe in the cells (liver and macrophages) and less Fe absorption from the GI
low Fe levels
low Tsat: Transferrin saturation is low due to a decreased level of Fe in the blood
What is the goal range of Hbg, Tsat and Ferritin when treating Anemia in patients with CKD?
11-12 g/dl (not normal levels)
-to prevent blood transfusion
Tsat >20%
Ferritin >100 to 200
What should be given when starting treatment with ESA for Anemia in CKD patients?
Iron supplement
bc they need raw materials for producing RBCs
When should ESA treatment be initiated in patients with CKD?
Hgb <10
start Fe if
Tsat <30%
Ferrtiin <500 ng/ml
Which ESA drug can be used for Anemia due to chemotherapy?
Epoetin alfa (only Procrit)
Darbepoetin alfa (Aranesp) -> longer half-life
How fast do we want the Hgb to increase in CKD patients?
What happens if it increases too fast?
1 g/dl over 2 weeks
if too fast:
-risk of blood clots, stroke, MI, hypertension
What are the criteria for using ESA in anemia in cancer patients?
Why?
-currently receiving chemotherapy (in the last 6-8 weeks)
-Hgb < 10g/dL
-palliative therapy (not curative)
-low-risk myelodysplastic syndrome
-has to be chemotherapy with myelosuppression (doxorubicin, cyclophosphamide, not the mAbs)
because Epopoetin stimulates cancer growth, risk for tumor progression (BBW)
What is the BBW for ESA drugs?
NAPLEX
CKD:
-risk of death, CV reactions, and stroke if targeting Hgb > 11
-use the lowest dose of Aranesp to prevent blood transfusion
Cancer: ESAs are rarely used for cancer
-increased risk of tumor progression
-only used for myelosuppressive chemotherapy
-use the lowest dose possible to prevent RBC transfusion
-don’t use if chemotherapy is for cure
-d/c after chemotherapy course
How do you manage immune-mediated hemolytic (destructive) Anemia?
treat with prednisone or immunosuppressants
How would you identify an autoimmune-induced hemolytic anemia?
-positive Coombs test (Antibodies on the surface of RBCs)
-low Haptoglobin (undetectable, it binds to Hbg and comes out of solution)
-LDH (high due to release after lysis of RBCs)
-reticulocyte count (high, premature RBCs and a sign of increased production)
-bilirubin (high, breakdown of more heme)
How do you manage Non-immune-mediated hemolytic Anemia?
if it is due to increased oxidative stress (in G6PD deficiency, less protection of oxidative stress) ->
stop the offending agent (for example Sulfonamide)
-Microangiopathic hemolytic anemia, Hemolytic uremia syndrome (HUS)
Which two drug classes of drugs are often associated with hemolytic anemia?
Anticonvulsants (Phenobarbital, Phenytoin)
Antiinfectives (ß-lactams, FQ,…)
also APAP, NSAIDs
Why are patients with G6PD at higher risk for hemolytic anemia?
What class of drugs puts them at higher risk?
because their RBCs are more susceptible to oxidative stress
-Sulfonamides put them at higher risk,
also
-Metformin
-Ascorbic acid (Vit C)
-Nitrofurantoin
-Dapsone
-rasburicase (TLS treatment)
Which drugs can induce Microangiopathic Hemolytic Anemia?
-Ticlodipine > Clopidogrel
-Tacrolimus
-Cyclosporine
-Gemcitabine (chemo)
-happens in capillaries, snowball through a fence
vWF attracts platelets in the vessel and built a fence -> RBC falls apart when going through
