Anemias

→ Anemia: ↓ number of RBCs or ↓ Hb concentration

→ Macrocytic RBCs!vitamin B12 or folate deficiency
→ Microcytic RBCs! iron deficiency anemia: results from acute/chronic blood loss, insufficient intake or in heavily menstruating/pregnant women
→ Normocytic RBCs! acute blood loss & hemolysis
→ Iron is stored as ferritin in intestinal mucosal cells
→ Phlebotomy → for chronic iron overload without anemia
→ Vitamin B12!cofactor for many rxns; deficiency!microcytic megaloblastic anemia and neurologic abnormalities
o Ultimate source: microbial synthesis!not synthesized by plants or animals (found in meat, eggs and dairy)
o stored in the liver; would take about 5 years to develop the anemia from depleting stores requires R Factor & Intrinsic Factor
review o absorbed only after its formed a complex w/ intrinsic factor in the distal ileum via receptor-mediated transport system
notes o deficiency results from malabsorption d/t lack of IF (pernicious anemia) or defective transporter or d/t nutritional deficiency as seen in strict vegetarians, partial or total gastrectomy and any condition that affects the distal ileum
o deficiency prevents synthesis of purines required for DNA synthesis & chronic pancreatitis: cannot cleave RF-B12 complex
o deficiency causes accumulation of homocysteine and methylmalonyl-CoA
o SXS include neurologic syndrome!paresthesia in peripheral nerves, weakness and progresses to spasticity, ataxia and other CNS dysfxn
o admin of folic acid will NOT prevent neurologic SXS even though it will correct the anemia
→ Folic acid! cofactor for many rxns; deficiency!microcytic megaloblastic anemia
o Deficiency can develop within 1-6mon after intake has stopped :fast depletion of stores
o deficiency prevents synthesis of purines required for DNA synthesis dUMP --> dTMP
o deficiency causes accumulation of homocysteine
o deficiency is often caused by inadequate dietary intake (alcoholics and liver disease), increased demand (pregnant women, pts with hemolytic anemia), malabsorption syndromes affecting the jejunum, or certain drugs (methotrexate,
trimethoprim and pyrimethamine or long term therapy with phenytoin) ** phenytoin does not cause megaloblastic changes
Drug Name Class Description Uses Pharmacodynamics Adverse effects
/Contraindications
Nausea
Ferrous Sulfate Iron deficiency anemia!hypochromic microcytic anemia Epigastric discomfort
Ferrous gluconate Oral iron therapy Abdominal cramps
Ferrous iron is most
Ferrous fumarate TXT should continue 3-6mon after correction of the cause of the iron loss Constipation
Iron efficiently absorbed!only
Diarrhea
preparations ferrous salts should be
Iron deficiency anemia!hypochromic microcytic anemia used
Iron dextran

Sodium ferric gluconate complex Parenteral iron therapy
Reserved for pts who can’t tolerate oral iron or in pts w/ chronic anemia who
Iron sucrose
can’t be maintained on oral iron alone
Acute Iron Toxicity: seen in young children who ingest iron pills!necrotizing
Deferoxamine gastroenteritis with vomiting, abdominal pain, and bloody diarrhea followed
by shock, metabolic acidosis coma and death
Binds to iron which has
Chronic Iron Toxicity/Hemochromatosis: XS iron is deposited in the heart,
already been absorbed!
Iron chelator Given parentally liver, pancreas, etc.!organ failure and death; seen in pts with inherited
promotes excretion in
hemochromatosis or pts receiving many red cell transfusions (thalassemia
Deferasirox urine and feces
major pts) & sickle cell
disease
Acute Iron Toxicity
Therapy must be continued for life in
Vitamin B12 deficiency! megaloblastic, macrocytic anemia Two reactions: pts with pernicious anemia
Cyanocobalamin homocysteine →
Parenteral Vitamin B12
Hydroxocobalamin Hydroxocobalamin preferred b/c it is more highly protein-bound and this methionine Deficiency of cobalamin can cause
Vitamins
(inactive) activated to:
remains longer in circulation methylmalonyl → succinyl neurologic abnormalities due to
(macrocytic) • dihydroacetylcobalamin? (Methylmalonyl CoA path)
• methylcobalamin (methionine pathway) increased homocysteine
Folic acid deficiency and B12 deficiency Required for purine
Deficiency is a lot more common than Masking of neurologic deficits in B12
Folic Acid Prevents neural tube defects (spina bifida) in the fetus when given to a synthesis Need B12 to form
B12, but can be easily corrected deficiency
pregnant woman THF → folate trap
Stimulates erythroid proliferation and
• Chronic Renal Disease (intrinsic low EPO)
differentiation via JAK/STAT Produced in the kidney in
Erythropoietin • cannot be used if extra-renal anemia (EPO normal)
cytokine receptor
Anemia with renal disease [can’t produce endogenous EPO → best response to hypoxia
Hyperviscosity → HTN & thrombosis
Induces release of reticulocytes from BM responders] • MI
3x Longer acting than EPO ↓clearance in comparison • stroke
Darbepoetin
Hematopoietic Two CHO chains to erythropoietin
Growth Filgrastim (G-CSF)! production/fxn of neutrophils
Myeloid growth factors with JAK/STAT C-CSF!bone pain
Factors Sargramostin (GM-CSF)! production/fxn of neutrophils +production of other
Filgrastim G-CSF receptors GM-CSF! fever, arthralgia, and
myeloid megakaryocyte progenitors
Sargramostin GM-CSF capillary damage with edema
patients with
(cytokine receptor) Allergic rxns=rare
BM supression Primary and secondary neutropenia; after cancer chemotherapy
along with Txt of pts with prior episode of thrombocytopenia after chemo
IL-11 Megakaryocyte growth factor : platelets
thrombopoeitin Reduced need for platelet transfusions
Sickle cell Anemia + folate supplements
Sickle cell Increases fetal Hb!dilute HbS!relieve Bone marrow suppression aplastic
Hydroxyurea Chronic myelogenous leukemia
Agents painful crisis (less hypoxia) Cutaneous vasculitis crisis
Polycythemia Vera