Lecture 2b Flashcards
Define aplastic anemia.
Failure of hematopoietic bone marrow due to suppression of injury to stem cells
What are the main causes of aplastic anemia?
Autoimmune supression
Benzene
Chemo
Hepatitis
Radiation exposure
Pregnancy
What are some symptoms of aplastic anemia?
Decreased WBC, RBC, and platelets
Leads to…
Infections
Anemia
Bruising, bleeding
Whats special about petechia and purpura?
They don’t blanch when pressure is put on it
Why are there no or very few reticulocytes in aplastic anemia?
The bone marrow isn’t functioning
What do you typically not see in aplastic anemia?
Hepatomegaly and spelnomegaly
What test do we use to check aplastic anemia?
Bone marrow biopsy
What are some treatments for aplastic anemia?
Remove underlying etiology
Red cell transfusion
Platelet transfusion
Multilineage: eltrombopag
Erthyropoietic: epoetin, darbepoetin
Myeloid: filgrastim, sargramostim
Bone marrow transplant
Triple therapy (immunosuppression, for those who can’t go through bone marrow transplant)
What is triple therapy?
Giving pts equine antithymocyte globulin(ATG), cyclosporine, and eltrombopag(promacta) for severe treatment of aplastic anemia
Steroids given along to reduce ATG side effects
How does Epoetin or Darbepoetin work?
EPO made with recombinate DNA that stimulates the erythroid precursors causing reticulocyte and RBC release
Rise in Hbg and Hct, dose-dependent (peaks 2-6weeks)
What is the different between Epoetin and Darbepoetin?
Darbepoetin has 3x the half life
Can be dosed weekly or Q 2 weeks
What are Epoetin and Darbepoetin indicated for?
Anemia from CKD
Chemotherapy
Myelodysplasia
What are the contraindications of Epoetin and Darbepoetin?
Allergy to drug
Uncontrolled HTN
Pure red cell aplasia after any EPO tx
What are some SE of Epoetin and Darbepoetin?
HTN
Thrombosis
Rash
Seizures
Pruritus
Fever
Edema
Dyspnea
Cough
Abdominal pain
What are the BBW for Epoetin and Darbepoetin?
Risk of death from thrombosis related issues
Increase Stoke in CKD with Hgb >11
Tumor progression of cancers
Increase risk of DVT after surgery
What do we need to monitor for patients on Epoetin and Darbepoetin?
Iron status
Hgb
BP
What is sideroblastic anemia?
Decrease of Hgb synthesis because of inability to make heme since it impairs the ability to incorporate iron into protoporhyrin IX(precursor to heme)
How is sideroblastic anemia inherited?
X-linked
Autosomal recessive
Mitochondrially inherited
How is sideroblastic anemia acquired?
Part of myelodysplastic syndrome
Alcoholism
Lead poisioning
Copper deficiency
Infection/inflammation
Medications: Isoniazid, Linezolid, Chloramphenicol
What other SE appears in sideroblastic anemia other than the normal anemic symptoms?
Palmar creases if Hgb <8-9 (also appears in iron deficient anemia)
May also see S/S with myelodysplastic syndrome
Why are reticulocytes decreased in sideroblastic anemia?
Pts have issue producing RBC
What shows up on a peripheral smear for sideroblastic anemia?
Basophilic stippling
Poikilocytosis
Anisocytosis
Polychromasia
What do we need to order before making a diagnosis of sideroblastic anemia?
Bone marrow aspirate
What does bone marrow aspirate show?
Erythroid hyperplasia: indicates effectiveness of erythropoiesis
Prussian blue stain: shows ringed sideroblasts and increase of iron stores
What are some treatments of sideroblastic anemia?
Transfusion
B6 (pyridoxine) or B1 (thiamine)
Stopping medication (isoniazid)
Genetic counseling
Phlebotomies, chelation (to prevent iron overload)
What is the main cause of anemia worldwide?
Iron deficient anemia
How much iron do we need to intake a day?
10-15mg
How much iron do we absorb?
10%
What is the role of ferroportin?
Iron transporter that release iron from cells
What dos Hepcidin do to ferroportin?
Promotes ferroportin breakdown which inhibits iron release
How much iron do we lose a day?
Lose 1 mg from skin/mucosa
So we absorb ~1mg and lose 1mg
What are some causes of iron deficiency anemia?
Deficient diet
Increased iron requirements
Chronic blood loss
Decreased absorption
Iron sequestration
When do we need an increase of iron consumption?
Pregnancy
Lactation
Growth spurt
What can cause a decreased absorption of iron?
Gastritis
Chronic disease
Gastric surgery
Zinc deficiency
Hereditary iron-deficency anemia
What are the S/S of iron deficient anemia?
Normal anemic symptoms
Smooth tongue
Brittle nails
Koilonychia
Cheilosis
Plummer-Vinson syndrome
Restless leg
Neurodevelopmental delay
What is Pica?
Craving for substances not rich in iron (ice, clay, dirt)
What are the stages of iron deficiency?
Low iron without anemia
Normocytic anemia
Microcytic anemia
What shows up on a peripheral smear in iron deficiency anemia?
Hypochromic microcytic cells
Target cells
Poikilocytosis
Anisocytosis
Increased platelets
What are some treatments for iron deficiency anemia?
Supplements (Ferrous sulfate)
Transfusion
Iron replacement therapy (parenteral, IV)
What can you add to increase absorption of ferrous sulfate?
Vitamin C
What are the SE and dosage of ferrous sulfate?
325mg 3x/day on empty stomach
SE:
N/V
Constipation
Abdominal pain
Dark stool
Rare SE:
Diarrhea
Urine discoloration
Teeth staining
What is contraindicated for ferrous sulfate?
Allergy to drug
Hemochromatosis
Hemolytic anemia
What improved over iron dextran(older parenteral iron)?
New preparations are infused over minutes, not hours
Lower risk of serious reactions(anaphylaxis)
No risk of “iron staining” (cutaneous siderosis)
What causes anemia of inflammation/infection?
Cytokines increased hepcidin which decrease iron absorption and availability
Mimics iron deficiency anemia
75% normocytic 25% microcytic
Define anemia of CKD.
Anemia due to inadequate secretion of EPO by kidneys
Normocytic, normochromic anemia
Normal iron
Pts on dialysis can develop secondary iron/folate deficiency
Define anemia of endocrine disorders.
Decrease EPO secretion
Normocytic, normochromic anemia
Decreased thyroid, testosterone, cortisol
Define anemia of chronic liver disease.
Cholesterol deposits in RBC membrane causing decreased RBC survival and EPO sectretion
Macrocytic anemia due to deposits
Define Anemia of starvation.
Decreased EPO due to decrease of metabolism(protein intake)
Why are elderly susceptible to anemia?
Resistance to EPO
Decreased EPO secretion
Chronic low-level inflammation
What are some treatments for anemia of chronic diseases?
Transfusion
EPO (Poetin, darbepoetin)
What is the role of vitamin B12(cobalamin)?
Converts methylmalonyl-CoA to succinyl-CoA
Converts homocysteine to methionine
DNA synthesis in erythroid precursors
What are sources of vitamin B12?
Animal-based foods, fortified foods
How much B12 do we absorption and use?
Absorb ~5mcg/day
Use 3-5 mcg/day
How much B12 is stored in the liver?
2-5mg
What are some S/S of B12 deficiency?
Fatigue
Anorexia
Nausea
Glossitis
Angular cheilitis
What are some ways that can cause B12 deficiency?
Diet
Decrease intrinsic factor (Pernicious anemia, gastric surgery)
Pancreatic insufficiency
Transcobalamin II deficieny
Medications
Chrohns disease
What medications affect B12 absorption?
Metformin
PPI
Colchicine
What is blind loop syndrome?
Bacterial overgrowth of small bowel (fish tapeworm) that competes for B12
What are neuro symptoms progress in B12 deficiency? (initial, later, severe)
Initial: peripheral paresthesias
Later: balance and proprioception difficulty
Severe: affect cerebral function
Why is MCV elevated in B12 deficiency?
Due to formation of megaloblasts from impaired DNA synthesis
What are present in a peripheral smear for B12 deficiency anemia?
Hypersegmented neutrophils
Macro-ovalocytes
Bizarre RBC shapes
Basophilic stippling
Whats elevated in testing for pernicious anemia in B12 deficiency?
Anti-intrinsic factor antibodies
Anti-parietal cell antibodies
Gastrin levels
What tests do we perform on checking pernicious anemia in B12 deficiency?
Gastric biopsy
Schilling test (old test using radio labeled B12)
What are the treatments for B12 deficiency?
Oral supplements 1mg/day
B12 injection therapy
Folic acid therapy 1mg/day
Transfusion
Dietary counseling
How fast is B12 deficiency treated?
See reticulocytosis in 1 week and normalize in 2 months
What are the SE of Cyanocobalamin?
HA
Paresthesias
GI upset
Glossitis
Worsening edema or HF
Allergic reaction (parenteral)
Muscle soreness/weakness (parenteral)
What do you monitor when pts are on cyanocobalamin?
B12
Hgb/Hct
RBC
Reticulocytes
Iron/folate levels
What is the role of folate?
Coenzyme for conversion of homocysteine to methionine
Involved in DNA synthesis, especially in erythroid precursors
How much folate is absorbed and used daily?
125mcg/day (50% of eaten 250mcg)
Use 50-100mcg/day
What are some causes of folate deficiency?
Dietary deficiency (main)
Increased folate requirement
Inhibition of reduction to active form (methotrexate)
Excess folate loss (hemodialysis)
Decreased absorption of folate
What can decreased absorption of folate?
Tropical sprue
Concurrent B12 deficiency
Phenytion
Sulfasalazine
Trimethoprim-sulfamethoxazole
What causes an increase of folate requirement?
Pregnancy
Chronic hemolytic anemia
Exfoliative skin disease
What is the difference in symptoms of folate and B12 deficiency?
Folate deficiency does not have any neuropathy
What appears on a peripheral smear for folate deficiency anemia?
Hypersegmented neutrophils
Macro-ovalocytes
What are some treatments for folic acid deficiency?
Oral supplement
Levomethylfolate (active form)
Transfusion
What SE appear in taking folic acid?
Malaise
Nausea
Allergic reaction symptoms
What is a myeloproliferative disorder?
Diverse group of disorders categorized by excessive growth of one or more hematopoietic stem cell lines
What are the types of myeloprolilferative disorders?
Polycythemia vera: excessive production of all hematopoietic cells, especially RBCs
Essential thrombocytosis: excessive platelet production
Myelofibrosis: excessive production of collagen or fibrous tissue in the marrow
Chronic myelogenous leukemia(CML): excessive production of granulocytes
What are the S/S of myeloproliferative disorders?
Fatigue
Anorexia
Night sweats
Splenomegaly
Hepatomegaly
Superficial vein thrombosis
Bruising
Petechia
Ruddy facial features, plethora (polycythemia vera)
What work-ups do you need for myeloproliferative disorders?
CBC
Bone marrow biopsy
What treatment do all themyeloproliferative disorders have in common?
All require myelosuppression
Myelofibrosis and CML may need bone marrow transplant
