Anemias Flashcards
Iron deficiency anemia
Microcytic
hypochromic
Poor iron intake
Blood loss: menstruation, colon cancer, peptic ulcer
Increased iron demand in pregnancy
Assoc: plummer vinson sn -iron deficiency anemia -esophageal webs -dysphagia \+/- atrophic glossitis
Alpha thalassemia
Defect in globin synthesis
Alpha on Chr 16, 4 alleles
1 abnl allele – no anemia
2 abnormal alleles
- a-thalaseemia trait/minor
- no anemia
3 abnl alleles – 1 normal alpha gene
-> HbH – beta 4
4 abnl allels – incompatible with life
Fetus: hemoglobin Barts (gamma 4)
-> generalized fetal edema – hydrops fetalis
-> death
Beta thalassemia
Defect in beta globin gene – 2 alleles
Mediterranean populations
Minor: decreased beta globin
- minimal anemia
- increased HbA2 – a2delta2
Major: absent beta globin
- severe anemia
- blood transfusion -> hemochromatosis (tx: deferoxamine – iron chelator)
- Peripheral smear: target cells
- BM hyperplasia
- XR: crew cut on skull XR
- > chipmunk facies
- increased HbF (alpha 2 gamma 2)
Anemia of chronic disease
Defective iron utilization Assoc w/ chronic inflammation -RA -Chronic infections -Malignancy
iron trapped in M0
normal or elevated ferritin
low serum iron
Normocytic first -> microcytic hypochromic
Iron deficiency anemia iron studies
Serum Iron: low
TIBC: high
Ferritin: low
% transferrin saturation: low (below 12%)
Anemia of chronic disease iron studies
Serum Iron: low
TIBC: not iron deficient - low
Ferritin: nl or high
% transferrin saturation: nl (above 18%)
Hemochromatosis iron studies
Serum Iron: high
TIBC: low
Ferritin: high (normal r/o hemochromatosis)
% transferrin saturation: high
Sideroblastic anemia iron studies
Serum Iron: high
TIBC: low
Ferritin: high
% transferrin saturation: nl or high
Megaloblastic anemia
B12 deficiency (vegans, malabsorption (pernicious anemia, crohn’s dz), diphyllobothrium latum)
Folate deficiency (malnutrition, malabsorption, MTX, TMP, high folate req (hemolytic anemia, pregnancy))
Impaired DNA synthesis
Hypersegmented neutrophils >6 lobes
Glossitis
Elevated homocysteine
B12: neurologic defects -> high methylmelonic acid (MMA)
Other cause:
Orotic aciduria: deficient UMP synthesis -> pyrimidine synthesis impaired
-orotic acid in urine
no hyperammonemia
Nonmegaloblastic macrocytic anemia
Liver dz
Alcoholism
Drugs – 5FU, zidovudine, hydroxyurea
Causes of non-hemolytic normocytic anemia
Anemia of chronic disease
Renal failure
Aplastic anemia
non-hemolytic normocytic anemia - Renal failure
No EPO production
EPO injections needed
non-hemolytic normocytic anemia – anemia of chronic dz
Inflammatory mediates (IL6)
- > liver production of hepcidin
- inhibits ferroportin
- iron trapped in M0
labs:
low serum iorn
lower TIBC
nl or high ferritin
Non-hemolytic normocytic anemia – aplastic anemia
Pancytopenia
Histo: hypocellular BM w/ fatty infiltration
Anemia: fatigue, malaise, palor
Thrombocytopenia: purpura, petechiae, bleeding
Leukopenia: infections
d/t radiation, benzene Chloramphenicol Cancer drugs Parvo B19, EBV, HIV, esp sickle cell Fanconi anemia Idiopathic after acute hepatitis
Tx: stop offending agent Immunosuppresants Transfusions G-CSF, GM-CSF BM transplant
Intravascular hemolysis
Low haptoglobin
High LDH – high in RBCs
Autoimmune hemolytic anemia
Paroxysmal nocturnal hemoglobinuria
Mechanical destruction of RBCs
G6PD deficiency
Extravascular hemolysis
High LDH High unconjugated (indirect) bilirubin
Hereditary spherocytosis G6PD deficiency Pyruvate kinase deficiency Sickle cell dz Hemoglobin C dz
Hereditary spherocytosis
Ankryin
Spectrin
Band 3, Protein 4.2 : link ankryin to cytoskeleton to membrane
Lack central pallor, smaller
Increased MCHC – same amount of Hb in smaller cell = more concentrated
High RDW – vary in size
Spleen removes abnl cells -> splenomegaly
Jaundice
Pigmented gallstones
Aplastic crisis d/t Parvovirus B19 infection
Test: omotic fragility test
-lyse more readily in hypotonic solution at any given [NaCl]
eosin 5 maleimide: normally binds band 3, reduced binding = band 3 deficiency
Tx: Supportive Folic acid RBC transfusion Splectomy -> Howell –Jolly bodies
G6PD deficiency
Sensitive to oxidative stress -> hemolysis and back pain
Heinz body -> bite cells
Drugs: Fava beans Isoniazid Nitrofurantoin Dapsone Sulfonamides Primaquine Aspirin – high dose Ibuprofen Napthalene Chloroquine
Pyruvate kinase deficiency
Glycolytic enzyme deficiency
Can’t generate ATP, no Na+/K+ ATPase activity -> swelling and hemolysis
Paroxysmal nocturnal hemoglobinuria
Missing CD55 and CD59 surface markers
-> complement attack and lyses RBCs
Dx:
“Ham’s Test” – lysis at low pH – complement activates
Flow cytometry
Hemosiderinuria + thrombosis
HbC disease
Point mutation on beta globin gene
Glu -> Lys
-> hexagonal crystals
Heterozygous: asx
Homozygous: milder than sickle cell, hild hemolysis and splenomegalyq
SC disease
Heterozygous mutations
HbS mutation
HbC mutation
Milder than sickle cell dz
Sickle cell disease
HbS mutation
- point mutation on Chr 11 beta globin gene
- Glu -> Val at position 6 -> longer polymerase
sickling triggers:
hypoxemia
dehydration
acidosis
0.2% homozygous
Heterozygous (HbS trait) – 8% AA
-relative resistance to malaria
Newborns asx – more HgF
Complications: Splenic sequestration crisis Salmonella osteomyelitis Aplastic crises w/ Parvo B 19 Pain crisis – vasooclusion -> ischemia Dactylitis Acute Chest Sn Renal papillary necrosis
Skull XR: hair on end of skull, marrow hyperplasia “buzzcut”
Tx: hydroxyurea -> increased HbF
BM transplant
Splenic sequestration crisis
Complication of sickle cell disease
Infants and toddlers 2-3 yo
H and H drops
Wedge shaped infarct
-> autosplenectomy by 3-4 yo
increase risk of infection by encapsulated organisms
Cold agglutinins
Ab against RBCs that interact more strongly at low temp 4C than at body temp
Nearly always IgM Ab
Occur regularly in infections w/ EBV or mycoplasma and with malignancies – CLL
Problems/disease occur when there is circulation to a cold extremity -> IgM binds RBC antigen -> complement fixation -> MAC lysis (and opsonization -> phagocytosis)
Warm agglutinins
Ab that react against RBC protein antigens at body temp – spontaneous
Nearly always IgG
Seen in EBV, HIV Lupus Malignancies – CLL, NHL Congenital immune abnormalities
Direct coombs test
Directed at the RBCs
Ab to anti-RBC Ab cross links RBCs -> agglutination
Ab added to detect Ig already ON the RBC
Positive in:
Hemolytic dz of the newborn
Drug induced autoimmune hemolytic anemia
Hemolytic transfusion reactions
Indirect Coombs Test
Via Serum
Serum incubated w/ normal RBCs to detect presence of Ab in serum
Positive when:
Ab to foreign RBCs present – prior blood transfusion, screen for maternal Ab to fetus blood
Type and screen
Microangiopathic anemia
RBC mechanically damaged as pass through lumen of obstructed or narrowed vessel
DIC, TTP-HUS, lupus, malignant HTN
-> schistocytes
Macroangiopathic anemia
Damage to RBCs by forces in larger vessels
Prosthetic heart valves
Aortic stenosis
Infections -> hemolysis
Malaria
Babesiosis
Autoimmune hemolytic anemia
Auto-Ab bind RBCs -> lysis
- warm agglutinins –IgG
- Cold agglutinins – IgM
- only problems at cold temps
+ Coombs test
Platelets
Derived from megakaryocytes No nucleus Live 8-10 days Several different glycoprotein receptors Contain granules filled w/ various signaling substances
Platelet plug formation
Platelet adhesion
Platelet activation
Platelet aggregation
Von Willebrand factor (vWF)
Subunits liked by disulfide bonds
Synthesized by endothelial cells and megakaryocytes
Complexes w/ and stabilizes factor VIII (deficiency -> elevated PTT)
Platelet adhesion to vessel wall and other platelets (deficiency -> increased bleeding time)
Platelet adhesion
Endothelial damage, vWF, gpIb
Platelet activation
Secretion of ADP, PDGF, serotonin, fibrinogen, lysosomal enzymes, thromboxane A2, calcium (needed for coagulation cascade), thrombin
Thromboxane A2 -> vasoconstriction and platelet aggregation
Thrombin: fibrinogen -> fibrin
Platelet aggregation
Via gpIIb/IIIa
Stimulated by binding of ADP to surface receptors -> expression of GpIIb/IIIa extracellularly
-bind fibrinogen released by platelets
Aspirin
Inhibits COX1 and COX 2
Acetylates
Permanelty blocks conversion of AA to TxA2
Inhibits platelet aggregation
-> prolonged bleeding time
PT/PTT not affected
Uses: Lower fever Pain Anti-inflammatory Antiplatelet drug Kawasaki dz
SE: Bleeding
PUD
Hyperventilations – directly stimulates respiratory centers of brain
-> respiratory alkalosis
tinnitus
Reyes Syndrome in kids
Hepatoencephalopathy – liver problems, encephalopathy, hypoglycemia
ADP receptor inhibitors
Block ADP receptor -> no GpIIb/IIIa to surface -> block platelet aggregation
Clopidogrel
Ticlopidine
Ticagrelor
Prasugrel
Clopidogrel: tx acute MI, post CABG, recurrent stroke prevention
-aspirin allergy
Glycoprotein IIb/IIIa inhibitors
Abciximab
Tirofiban
Eptifibatide
Blocks GpIIb/IIIa – can’t cross link aggregating platelets
Acute coronary sn – NSTEMI
Angioplasty
