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208 Cards in this Set
- Front
- Back
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RBC form: Acanthocyte (spur cell)
associated with what pathology (2) |
Liver disease
Abetalipoproteinemia |
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RBC form: Basophilic Stippling
associated with what pathology (4) |
Thalessemia, Anemia of chronic disease, Iron deficiency, Lead poisoning
BASte the ox TAIL |
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RBC form: Bite cell
associated with what pathology |
G6PD deficiency
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RBC form: Elliptocyte
associated with what pathology |
Hereditary elliptocytosis
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RBC form: Macro-ovalocyte
associated with what pathology (2) |
Megaloblastic anemia (also hypersegmented PMNs), Marrow failure
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RBC form: Ringed sideroblasts
associated with what pathology |
Sideroblastic anemia
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RBC form: Schistocyte, helmet cell
associated with what pathology (3) |
DIC
TTP/HUS Traumatic hemolysis |
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RBC form: sickle cell
associated with what pathology |
Sickle Cell anemia
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RBC form: Spherocyte (2)
associated with what pathology |
Hereditary spherocytosis
Autoimmune hemolysis |
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RBC form: Teardrop cell
associated with what pathology |
Bone marrow infiltration (eg myelofibrosis)
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RBC form: Target cell
associated with what pathology |
HbC disease, Asplenia, Liver disease, Thalassemia
HALT said the hunter to his TARGET |
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RBC form: Heinz bodies
associated with what pathology (2) what causes it |
a-thalessemia, G6PD deficiency
oxidation of Fe (2+ --> 3+) --> denatures Hb precipitation, damage to RBC membrane --> bite cells |
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RBC form: Howwel jolly body
associated with what pathology process? |
functional hyposplenia or asplenia
Basophilic nuclear remnants in RBCs |
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5 etiologies of microcytic, hypochromic (MCV < 80) anemia
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Iron deficiency
a-thaleesemia b-thalassemia Lead poisoning Sideroblastic anemia |
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Iron defiency anemia
a. description of anemia b. causes (3) |
a. microcytic, hypochromic
b. decreased Fe in chronic bleeding, malnutrition, or high demand (pregnancy) |
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Patient has
-Iron deficiency anemia -Dysphagia due to esophageal webs -atrophic glossitis dx? What would you see on blood smear? |
Plummer-Vinson syndrome (Fe deficiency)
Microcytic, hypochromic anemia |
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a-thalassemia
what is the defect? what populations is it endemic to? |
alpha-globin (component of Hb) gene mutation --> low a-globin synthesis, buildup of beta and gamma chains
Endemic in Asia and Africa |
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a-thalassemeia
what forms if there is a 4-gene deletion of a-globin gene |
Formation of Hb barts (lots of gamma chains) --> hydrops fetalis (death)
see microcytic, hypochromic anemia |
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a-thalassemeia
what forms if there is a 3-gene deletion of a-globin gene 1-2 gene deletion |
HbH disease (buildup of beta 4)
-see microcytic, hypochromic anemia no anemia |
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Beta thalessemia
what is the defect? prevalent in what population |
point mutations in splicing sites and promoter sequences of beta chain of Hb
Mediterranean popultions |
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B-thalassemia minor (heterozygote)
a. pathological b. clinical c. diagnosis how? |
a. Beta chain is underproduced
b. asymptomatic c. high HbA2 (>3.5%) on electrophoresis |
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B-thalessemia major (homozygote)
a. pathological b. what do you see on blood smear (2) c. what do you see on skull xray and face d. treat |
a. beta chain absent (homozygotic for mutations)
b. severe microcytic, hypochromic anemia, target cells c. marrow expansion (crew cut on xray) --> skeletal deformities, chipmunk facies d. blood transfusion (can cause secondary hemochromatosis) |
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What happens to HbF (a2g2) in beta-thalassemia?
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HbF increases (both major and minor)
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What is the result of an HbS/B-thalassemia heterozygote
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Mild to moderate sickle cell disease depending on amount of b-globin production
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Lead poisoning
what 2 things does it inhibit to decrease heme synthesis? Why do you see basophilic stippling? |
inhibits ferrochelatase and ALA dehydratase --> decreases heme synth
Inhibits rRNA degradation --> buildup of ribosomes --> basophilic stippling |
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On blood smear, you see
-microcytic, hypochromic anemia -ringed sideroblasts with iron-laden macrophages Labs: -high iron, normal TIBC, high ferritin dx? 2 possible causes? treat? |
Sideroblastic anemia = defect in heme synthesis
Hereditary (x-linked defect in aminolevulinic acid synthase), or reversible (alcohol, lead) Treat with B6 |
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4 symptoms of Lead poisoning
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LEAD
-Lead lines in gingivae and on long bone epiphyses (xray) - Burton's lines -Encephalopathy and Erythrocyte basophilic stippling -Abdominal colic and sideroblastic Anemia -Drops of wrist and foot |
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Treatment for lead poisoning in
a. adults b. kids |
a. Dimercaprol and EDTA
b. succimer it 'sucks' to be a kid who eats lead |
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Macrocytic anemia
MCV > ? Cause? |
MCV > 100
Impaired DNA sythesis --> maturation of cytoplasm > maturation of nucleus --> ineffective erythropoiesis --> pancytpenia |
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Patient has macrocytic anemia
-hypersegmented PMNs -glossitis -low folate -high homocysteine -normal methylmalonic acid dx? |
Megaloblastic anemia caused by folate deficiency
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-Malnutrition (alcoholic)
-Malabsorption -Impaired metabolism (eg. methotrexate, trimethoprim) -Hemolytic anemia, pregnancy (increased requirement) what can these cause? what would you see on blood smear? |
folate deficiency
macrocytic, megaloblastic anemia |
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Patient has Macrocytiic anemia +
-Hypersegmented PMNs -glossitis -low B12 -high homocysteine -high methylmalonic acid 4 possible etiologies dx? |
Megaloblastic anemia caused by B12 deficiency
1. insufficient intake (vegans) 2. malabsorption (Crohns) 3. pernicious anemia 4. Diphyllobothrium latum (fish tapeworm) |
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Patient has neurologic symptoms:
-peripheral neuropathy with sensorimotor dysfunction - Loss of Posterior columns (vibration and proprioception) -Loss of lateral corticospinal tract (spasticity) -Dementia See macrocytic anemia dx? cause? |
Subacute combined degeneration due to B12 deficiency
(fatty acid synthesis pathways disrupted by B12 loss) |
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-Liver Disease
-Alcoholism -Reticulocytosis -Congenital metaobolic deficiencies of purine or pyrimidine -5-FU, AZT, hydroxyurea All cause what? |
Nonmegaloblastic, macrocytic anemia
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What is reticulocytosis?
Seen in what kind of anemia? |
reticulocytes (immature RBCs) are bigger than mature RBCs --> increased MCV
seen in nonmegaloblastic, macrocytic anemia |
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3 drugs that cause non megaloblastic macrocytic anemia
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5-FU, AZT, hydroxyurea
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Patient has anemia
You find: low haptoglobin, high LDH, hemoglobin in urine what is happening |
intravascular hemolysis --> normochromic, normocytic anemia
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-Paroxysmal nocturnal hemoglobinuria
-Aortic stenosis -Prosthetic valve -G6PD deficiency all cause what |
intravascular hemolysis --> normochromic, normocytic anemia
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Patient with anemia has
-High LDH, high unconjugated bilirubin --> jaundice what is happening what cells clean it up? |
extravascular hemolysis
(macrophages in spleen clear up RBCs) |
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Hereditary spherocytosis
Sickle cell anemia type of anemia |
extravascular hemolysis --> normochromic, normocytic anemia
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Patient with a chronic infection develops non-hemolytic, normocytic anemia
what is the pathophysiology? What would you expect the levels of Fe, TIBC, and ferritin to be? What can happen over time? |
inflammation --> high hepcidin --> decreased release of iron from macrophages
low iron low TIBC high ferritin Can become microcytic, hypochromic if long-standing |
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Patient has
-fatigue -malaise -pallor -purpura -mucosal bleeding -petechiae -infection blood smear: normal cell morphology BM biopsy: hypocelular, fatty infiltrate dx? treat? |
aplastic anemia (pancytopenia)
Treat: -withdraw agent -immunosuppression (antithymocyte globin, cyclosporin) -allogeneic BM transplant -RBC and patelet transfusion -G-CSF or GM-CSF |
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How can kidney disease cause normocytic anemia?
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decreased erythropoietin --> decreased hematopoiesis
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Patient presents with anemia symptoms, splenomegaly
-On blood smear, you see increased MCHC (Hb conc), increased RDW (anisocytosis) -RBCs look small and round, without a central pallor -positive osmotic fragility test dx? treat? what might you see on a blood smear after treatment? pathogenesis? |
Hereditary spherocytosis (extravacular normocytic anemia)
Splenectomy May see howell-jolly bodies (basophilic nuclear remnants normally removed by spleen) |
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Patient has a defect in proteins interacting with RBC membrane cytoskeleton and plasma membrane (ankyrin, band 4.1, spectrin)
dx? Type of anemia? what would happen in B19 infection? |
hereditary spherocytosis --> premature removal of RBCs by spleen
intrinsic hemolytic normocytic anemia Aplastic crisis |
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Patient is exposed to sulfa drugs/infections/fava beans, experiences
-back pain hemogloiburia a few days later labs: you see RBCs with Heinz bodies and bite cells dx? Why are these stimuli destroying cells? genetics? |
G6PD deficiency (intravascular homolytic normocytic anemia)
Defect in G6PD --> low glutathione --> increased RBC susceptibility to oxidant stress X-linked |
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What causes hemolytic anemia in a newborn?
genetics? |
Pyruvate kinase deficinecy (extravascular hemolytic, normocytic anemia) --> low ATP --> rigid RBCs
autosomal recessive |
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Sickle cell anemia
a. type of anemia b. intra or extravascular |
a. normocytic, hemolytic
b. extravascular |
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Sickle cell
rate of trait carrying in African Americans? rate of disease |
8% have HbS trait
0.2% have the disease |
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Sickle cell disease
a. what would you see on skull xray b. what would you see on blood smear |
a. "crewcut" from marrow expansion from increased erythropoiesis
b. anisocytosis, poiklocytosis, nucleated RBCs, crescent-shaped RBCs |
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2 conditions where you see "crew cut" look of skull on Xray and why
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sickle cell and thalaessemias
due to BM expansion due to increased erythropoiesis |
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What is the pathogenesis in sickle cell disease?
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point mutation in b-chain of HbS (position 6, Glu--> Val) --> sickled HbS --> deoxygenated HbS polymerizes --> anemia, veno-occlusion
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2 instances the precipitate sickle cell symptoms?
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low oxygen, dehydration
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Heterozygoes to sickle cell have resistance to what disease?
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malaria
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-parvovirus B19 --> aplastic crisis
-high risk of encapsulated organism infection -salmonella osteomyelitis -pain -renal papillary necrosis, microhematuria -splenic sequestration crisis all caused by what |
sickle cell anemia
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Why do newborns have few symptoms of sickle cell disease
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have low HbS, high HbF
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African american patient gets dehydrated, experiences
-extreme pain -lots of infections blood smear shows: anisocytosis, poiklocytosis, nucleated RBCs dx? treat? |
Sickle cell anemia (leads to splenic dysfunction)
treat with hydroxyurea (to increase HbF) and BM transplant |
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genetic defect in
a. sickle cell b. HbC defect |
a. Position 6 in HbS beta chain (Glu --> Val)
b. Mutation in position 6 (Glu --> Lys) |
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HbC
how does the course of HbSC differ from HbSS? |
HbSC (1 of each mutant gene - HbS and HbC) have a milder disease than HbSS patients
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Paroxysmal nocturnal hemoglobinuria
a. type of anemia b. what happens c. what do you see in urine |
a. Hemolytic, normocytic anemia, intravascular
b. Impaired synthesis of GPI --> loss of DAF, other GPI linked proteins that prevent complement destruction of RBCs c. increase in urine hemosiderin |
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4 types of extrinsic hemolytic normocytic anemia
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1. autoimmune hemolytic anemia
2. microangiopathic anemia 3. macroangiopathic anemia 4. infection |
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2 types of autoimmune hemolytic anemia
what are some conditions associated with each of these |
Warm agglutinin (IgG) - chronic anemia caused by SLE, CLL, drugs
Cold agglutinin (IgM) - acute anemia seen in cold, CLL, Mycoplasma pneumoniae, infectious mono |
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What is the pathogenesis of erythroblastosis fetalis
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in newborns, Rh or other blood antigen incompatibility --> mother's antibodies attack fetal RBCs
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Coombs test - what does it test for?
what is the difference between direct and indirect? |
tests for autoimmune hemolytic anemia
direct: add anti-Ig Ab to patient's RBCs --> if they agglutinate, it means RBCs have Ig on them Indirect: add normal RBCs to patient's serum --> agglutinate if serum has anti-RBC surface Ig |
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Microagniopathic anemia
a. intra or extravascular b. pathogenesis c. associated with what conditions (4) |
a. intra
b. RBCs damaged when passing through an obstruction or narrow vessel --> schistocytes c. DIC, TTP-HUS, SLE, malignant HTN |
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Cause of macroangiopathic anemia
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prosthetic heart valves, aortic stenosis --> mechanical destruction
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Type of anemia that shows
-low serum iron -high transferrin/TIBC -low ferritin -%transferrin saturation is way down |
Iron deficiency
(primary defect is low serum Fe) |
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Type of anemia that shows
-low serum Fe -low transferrin/TIBC -high ferritin -no change in transferrin saturation |
anemia of chronic disease (primary defect is high ferritin)
Low transferrin due to a adaptation by body to store iron in cells to deprive pathogens of circulating iron |
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Type of anemia that shows
-normal serum iron and ferritin -high transferrin/TIBC -low transferrin saturation |
Pregnancy/OCP
primary defect is in increased transferrin/TIBC) |
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Type of anemia that shows
-high serum rion -low transferrin/TIBC -high ferritin -very high transferrin sat |
hemochromatosis
primary defect is high serum iron |
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Type of anemia that shows
-high serum iron -low transferrin -normal ferritin -high transferrin saturation |
lead poisoning
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what are porphyrias
lead poisoning? |
porphyrias = defect in heme synthesis --> acumulation of heme precursors
lead --> inhibits enzymes needed in heme synthesis |
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Child exposed to lead paint has mental retardation
-microcytic anemia, GI sympotms, kidney disease condition? affected enzyme? accumulated substrate? |
lead poisoning
ferrochelatase and ALA dehydratase protoporphyrin (blood) |
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Patient is exposed to battery/ammunition/radiator factory
condition? affected enzyme? accumulated substrate? |
lead poisoning
ferrochelatase and ALA dehydratase protoporphyrin (blood) |
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Patient has
-painful abdomen -red wine-colored urine -polyneuropathy -psychological disturbances -precipitated by drugs condition? affected enzyme? accumulated substrate? treat? |
acute intermittent porphyria
Porphobilinogen deaminase (uroporphyrinogen I synthetase) Porphobilinogen, d-ALA, uroporphyrin (urine) glucose and heme (inhibits ALA synthase) |
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Most common porphyria that causes blistering cutaneous photosensitivity, tea-colored urine
condition? affected enzyme? accumulated substrate? |
porphyria cutanea tarda
uroporphyrinogen decarboxylase uroporphyrin |
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Sideroblastic anemia
a. genetics b. what enzyme does it inhibit |
x-linked
g-ALA synthetase (rate limiting step of heme synth) |
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effect of heme on ALA synthase activity
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increased heme --> decreased ALA synthase acitivity
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What does the prothrombin time test?
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Measures serum coagulation time --> tests factors I, II, V, VII, and X (extrinsic coagulation pathway)
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What does PTT test for?
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Tests function of all coagulation factors except VII and XIII (intrinsic and extrinsic)
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Difference between Prothromin time and partial prothrombin time as far as procedure?
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PT - add tissue factor
PTT - don't add tissue factor |
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Hemophilia A vs. B
what are the defects? What test would you see an abnormality in? |
A = factor VIII (increased PTT)
B = factor IX (increased PTT) both are defects in the intrinsic clotting pathway |
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Macorhemorrhage in hemophilia
what does it cause? |
hemarthroses (bleed into joints), easy bruising, PTT
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Vitamin K deficiency
a. what is the effect b, what tests would you see an abnormality in |
a. factors II, VII, IX, X, protein C, S
increase in PT, PTT |
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Patient experiences
-mucous membrane bleeding -epistaxis -petechiae -purpura -increased bleeding time -decreased platelet count what is defective |
platelets
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disease in which there is a deficiency of Gp1b --> defective platelet to collagen adhesion
effect on platelet count, bleeding time? |
Bernard-Soulier Syndrome
low platelet count, high bleeding time |
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Patient has high bleeding time, blood smear shows no platelet clumping
-normal platelet count dx? what is happening? |
Glanzmann's thrombasthenia
low GpIIb/IIIa --> defect in platelet to platelet adhesion |
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Patient has defect in anti-GpIIb/IIIa antibodies --> peripheral platelet destruction
labs show increase in megakaryocytes dx? effect on platelet count, bleeding time? |
idiopathic thrombocytopenic purpura (ITP)
low platelet count, high bleeding time |
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Patient experiences
-neurological symptoms -renal symptoms -fever -thrombocytopenia -microangiopathic hemolytic anemia labs: schistocytes, increased LDH dx? what is going on? effect on platelet count, bleeding time? |
Thrombotic thrombocytopenic Purpura
deficiency of ADAMTS 13 (vWF metalloprotase) -->decreased degradation of vWF multimers --> platelet aggregation, thrombosis --> decreased platelet survival low platelet count, high bleeding time |
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What is the difference between leukemia and lymphoma
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leukemia = lymphoid neoplasm with widespread BM involvement, see tumor cells in peripheral blood
lymphoma = discrete tumor mases arising from LNs |
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Patient has an infection
-you see high WBC count with a left shift -high leukocyte alkaline phosphatase what is going on |
leukemoid reaction
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Patient is a young/old man who comes in with fever, night sweats, wt. loss
-you see mediastinal lymphadenopathy -on LN biopsy, you see binucleate giant cells (2 owl eyes) dx? patholog? virus association? prognosis? |
Hodgkin's lymphoma
localized, single group of nodes, contiguous spread 50% associated with EBV good prognosis if high lymphocytes, fewer RS cells |
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who is affected most
hodkin's vs. non-hodgkins |
Hodgkin's = young and old (bimodal), men
Non-Hodgkin's = 20-40 yo |
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What occurs in Non-Hodgkin's Lymphoma
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Multiple peripheral LNs have tumors, non-contiguous spread, extranodal involvement occurs
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Type of cells seen mostly in Non-Hodgkin's lymphoma
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B cells (except if lymphoblastic T origin)
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Associated conditions/virus
Hodgkin's vs non-hodgkins |
Hodgkin's = EBV (50%)
Non-Hodgkins = HIV, immunosuppression |
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What is a Reed Sternberg cell?
origin? (cell type, surface markers) What does it indicate? |
Binucleate or bilobed "owl's eye"
CD30 and CD15 positive B cell origin indicates Hodgkin's (but not sufficient to diagnose) |
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What type of RS cell variant is seen in nodular sclerosis type of Hodgkin's lymphoma
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Lacunar cell
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Hodgkin's lymphoma types
most common? 2nd? 3rd? rare? |
nodular slcerosing (65-75%)
Mixed cellularity (25%) Lymphocyte predominant (6%) Lymphocyte depleted |
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Young woman comes in with fever, night sweats, wt loss
-has LN involvement in anterior mediastinum and another LN above the diaphragm -You can see collagen banding, lacunar cells, and lymphocytes > RS cells dx? prognosis? |
Nodular sclerosing Hodgkin's
Excellent |
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Older man comes in with fever, night sweats, and wt. loss
-mediastinal lymphadenopathy -You see Lymphocytes = RS cells dx? prognosis? |
Mixed cellularity Hodgkin's Lymphoma
Intermediate |
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Type of Hodgkin's lymphoma affecting males <35 yo, see far more lymphocytes than RS cells
dx? prog? |
Lymphocyte predominant Hodgkin's lymphoma
Excellent |
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Patient is an older male with fever, night sweats, and wt. loss
-see mediastinal lymphadenopathy -see very few lymphocytes and even less RS cells dx? Prog? What would indicate a better prognosis? |
Lymphocyte depleted Hodgkin's (rare)
poor prog better prog if increased lymphocyte to RS cell ratio |
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population affected
a. Burkitt's Lymphoma b. Diffuse Large B cell lymphoma c. Mantle cell lymphoma d. follicular lympohoma |
a. adolescents or young adults
b. older adults, 20% in children c. older males d. adults |
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genetic mutation
a. Burkitt's Lymphoma b. Diffuse Large B cell lymphoma c. Mantle cell lymphoma d. follicular lympohoma |
a. t(8;14) c-myc moves next to heavy chain Ig (14)
b. c. t(11;14) d. t(14;18) bcl2 expression |
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Patient is a young adult with HIV, presents with a pelvic/abdomen lesion that is unresponsive to antibiotics
Patient has an EBV infection See starry sky appearance on biopsy (sheets of lymphocytes interspersed w/macrophages) dx? genetics? |
Burkitt's (non Hodgkin's, neoplasm of B cells)
t(8;14) cmyc to heavy chain Ig |
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Type of Burkitt's
a. with jaw lesion b. with pelvic or abdomen lesion |
a. endemic (Africa)
b. sporadic |
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Most common adult Non-Hodgkin's Lymphoma
type of cells |
Diffuse large B cell lymphoma
Mature B cells, 20% mature T cells |
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Type of lymphoma with predominant CD5+ antigen naive pregerminal center B cells
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Mantle cell (non Hodgkin's)
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Type of lymphoma that centers in follicle center B cells
Most common indolent non -hodgkin's lymphoma what is the genetic variant? |
Follicular lymphoma
t(14;18), bcl2 expression inhibits apoptosis |
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2 Non hodgkins lymphomas of mature T cells
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Adult T cell lympohoma and Mycosis fungoides/sezary syndrome
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Cause of adult T cell lymphoma
How do adults present? What countries? Course? |
HTLV-1
Adults with cutaneous lesions Japan, W. Africa, Carribean Aggressive |
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Most common form of cutaneous T cell lymphoma?
How does it present? Types of cells? |
mycosis fungoides/sezary syndrome
adults present with cutaneous patches/nodules indolent CD4+ T cells |
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What is the most common primary tumor arising within bone in the elderly (>40-50yo)
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multiple myeloma
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Multiple myeloma
a. what is overproliferating? appearance? b. what do these produce? (which Ab's) c. what should you see on protein electrophoresis? |
plasma cell (fried egg appearance)
IgG or IgA see M spike of gamma globulins |
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Patient has
-hyperCalcemia -Renal insufficiency -Anemia -Bone lytic lesions/Back pain See Bence Jones protein in urine, rouleuax formation of RBCs in blood smear dx? |
multiple myeloma
CRAB hyperCalcemia Renal insuff. Anemia Bone lesions |
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Increased susceptibility to infection
Primary amyloidosis Punched out lesions on bone xray type of tumor association |
Multiple myeloma
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How is Waldenstrom's macroglobulinemia different from multiple myeloma?
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M spike --> IgM, hyperviscosity symptoms
No lytic bone lesions |
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What is monoclonal gammopathy of undetermined significance
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monoclonal plasma cell expansion without the symptoms of multiple myeloma
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Leukemia
what grows? effects? |
unregulated growth of leukocytes in BM --> anemia (RBCs), infections (WBCs low), hemorrhage (platelets low), can get leukemic infiltrates in liver, spleen, and LNs
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Type of lymphoid neoplasm most responsive to surgery
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ALL
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Type of lymphoid neoplasm that affect children primarily?
How does it present? |
ALL
BM involvment (childhood) or mediastinal mass (adolescent males) |
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ALL
what is happening? where might it spread? |
Bone Marrow replaced by lymphoblasts
may spread to testes and CNS |
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2 markers that are used to diagnose ALL
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TdT, CALLA
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ALL what genetic variant confers a better prognosis
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t(12;21)
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What leukemia?
->60 yo -smudge cells in peripheral blood smear -warm Ab autoimmune hemolytic anemia (IgG) dx? what if there is more peripheral blood lympocytosis |
Small Lymphocytic lymphoma/ Chronic lymphocytic lymphoma
chronic has more peripheral blood lymphocytosis |
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Mature B cell lymphoma in the elderly
cells have filamentous, hairlike projections stains TRAP pos |
Hairy cell luekemia
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Pateint is an adult, experiences fatigue, SOB, bleeding, and lots of infections
-on blood smear, you see auer rods, lots of circulating myeloblasts dx? treat? |
Acute myelogenous leukemia
Responds to all-trans retinoic acid (vitamin A) --> induces differentiation of myeloblasts |
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Patient is 30-60yo, has lots of PMNs, metamyelocytes, basophils, splenomegaly
-very low leukocyte alkaline phosphatase type of leukemia? Cause? treat? |
Chronic Myelogenous elukemia
Philadelphia chromosome t[9;22], bcr-abl (myeloid stem cell proliferation) responds to imatinib (anti-bcr-abl tyrosine kinase) |
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What happens to CML in a blast crisis
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accelerates to transform to AML or ALL
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How do you differentiate CML from leukemoid rxn
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CML has very low leukocyte alkaline phosphatase
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Age associations
a. ALL b. AML c. CML d. CLL |
a. < 15yo
b. about 60 yo c. 30-60yo d. > 60yo |
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Acute vs. chromic leukemias
a. type of cell b. age c. course |
acute - blasts, children/elderly, short and drastic course
chronic - mature cells, midlife, longer and less devestating |
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2 types of acute leukemias
what type of cells |
ALL - preB or preT lymphoblasts
AML - myeloblasts |
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2 types of chronic leukemias
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CLL - lymphocytes, non-Ab-producing B cells
CML - myeloid stem cells, blast crisis |
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What are auer bodies?
Where do you see them? One danger with treatment? |
Peroxidase-positive cytoplasmic inclusios in granuloctes and myeloblasts
seen in acute promyelocytic leukemia --> treatment can release Auer rods, cause DIC |
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Chromosomal translocation
a. CML b. Burkitt's c. follicular lymphoma d. M3 AML e. Ewing's f. Mantle Cell lymphoma |
a. t(9;22) Philadelphia
b. t(8;14) cmyc c. t(14;18) bcl-2 d. t(15;17) e. t(11;22) f. t(11;14) |
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Birbeck granules (tennis rackets on EM
what are the defective cells and what do they express |
Histiocytosis (Langerhans)
proliferative disorder of dendritic (langerhan's) express S-100 and CD1a |
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Chronic myeloproliferative disorders
-high RBC, WBC, platelet -Philadelphia chromosome neg -JAK2 pos |
Polycythemia vera = abnormal clone of hematopoietic stem cells, increasingly sensitive to growth factors
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Chronic myeloproliferative disorders
-RBC, WBC normal, no philly chromosome -high platelets -30-50% pos for JAK2 mutation |
Essential thrombocytosis
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Chronic myeloproliferative disorders
-low RBCs -variable WBCs and platelets -negative philly chromosome -positive JAK2 mutation (30-50%) |
Myelofibrosis = fibrotic obliteration of bone marrow, tear drop cell
"BM is crying because it is fibrosed) |
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Chronic myeloproliferative disorders
-low RBCS -high WBCs, platelets -positive philly chromosome -negative JAK2 mutation |
CML
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What is JAK 2?
What kinds of disorders are seen when it is mutated? |
hematopoietic growth factor signaling
myeloproliferative disorders other than CML |
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Types of polycythemia
low plasma volume -normal RBC mass, O2 sat, EPO |
Relative
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Type of polycythemia
-high RBC mass, low O2 sat, high EPO -normal plasma volume associated w/ lung disease, congenital heart disease, high altitude |
appropriate absolute
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Type of polycythemia
High RBC mass, high EP due to ectopic EPO |
inappropriate absolute
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Type of polycythemia
High plasma volume, very high RBC mass, high EPO associated with RCC, Wlms' tumor, cyst, HCC, hydronephrosis |
Polycythemia vera
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Anticoagulant used for immediate use in
-pulmonary embolism -stroke -acute coronary syndrome -MI -DVT -used in pregnancy what is the drug? How does it work? How do you track its effectiveness |
Heparin
Activates antithrombin --> lowers thrombin and factor Xa (short half life) measure PTT |
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Patient was given heparin and is now bleeding too much
how do you reverse its affects |
protamine sulfate = positively charged molecule that binds negatively charged heparin
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4 negative side effects of heparin
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Bleeding
Thrombocytopenia (HIT) Osteoperosis Drug-Drug interaction |
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4 benefits of using newer, low molecular weight heparins
1 negative |
-act more on Xa
-better bioavail. -2-4 times longer half life -subcut. injection, don't need to monitor -hard to reverse |
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what occurs in heparin-induced thrombocytopenia
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Heparin binds platelet factor IV --> Ab production that binds to and activates platelets --> hypercoagulable state, but also thrombocytopenia (increased platelet clearance)
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2 Drugs used as an alternative to heparin for anticoagulating patients with HIT
derived from what? MOA? |
Lepirudin, Bivalirudin
hirundin directly inhibits thrombin |
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Drug used for chronic anticoagulation
-can cross the placenta, so don't use if pregnant MOA? How is it metabolized? How should you monitor the affect? |
Warfarin
Interferes with synth and carboxylation of vit K-dependent clotting factors II, VII, IX, X, protein C, S Metabolized by Cyt p450 Follow PT/INR, has effect on EXtrinsic pathway "EX PresidenT went to WAR" Extrinsic, PT, Warfarin |
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4 negative effects of warfarin
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bleeding
teratogenic skin/tissue necrosis (acquired protein C deficiency) --> uninhibited factor V/VIII --> clotting drug-drug interaction |
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You give warfarin and now the patient is bleeding too much. How do you reverse?
what if you need rapid reversal? |
vitamin K
fresh frozen plasma |
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Heparin vs. Warfarin
structure |
H = large, anionic, acidic polymer
W = small, lipid-soluble |
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Heparin vs. Warfarin
Route of administration |
H = parenteral (IV, SC)
W = oral |
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Heparin vs. Warfarin
site of action |
H = blood
W = liver |
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Heparin vs. Warfarin
Onset of action |
H = rapid (sec)
W = slow (depends on half lives of normal clotting factors) |
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Heparin vs. Warfarin
MOA |
H = activates antithrombin --> decreased thrombin, Xa
W = impairs synth of vitamin K-dependent clotting factors II, VII, IX X (antagonizes vit K) |
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Heparin vs. Warfarin
Duration |
H = acute (hrs)
W = chronic (days) |
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Heparin vs. Warfarin
Inhibits coagulation in vitro? |
H = yes
W = no |
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Heparin vs. Warfarin
Treatment of acute OD |
H = protamine sulfate
W = IV vitamin K and fresh frozen plasma |
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Heparin vs. Warfarin
Monitoring |
H = PTT (intrinsic)
W = PT/INR (extrinsic) |
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Heparin vs. Warfarin
Crosses placenta |
H = No
W = Yes (teratogenic) |
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Streptokinase, urokinas, tPA (alteplase), APSAC (anistreplase)
type of drug? used for what? MOA? |
thrombolytic
Early MI, early ischemic stroke Aids in conversion of plasminogen to plasmin --> cleaves thrombin and fibrin clots |
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Patient is given thrombolytics
what should happen to PT, PTT, and platelet count |
PT up
PTT up Platelet count normal |
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Thrombolytics
toxicity? contraindications? |
tox = bleeding
-active bleeding -hx of intracranial bleed, severe HTN, or known bleeding diathesis -recent surgery |
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Patient was given thrombolytics and is now bleeding too much
how do you reverse |
aminocaproic acid (inhibits fibrinolysis)
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Effect of thrombolytics on
a. fibrin b. fibrinogen |
a. fiberin --> D dimers (fibrin split products)
b. fibrinogen --> degradation products |
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Asprin
MOA? Use? tox (5)? |
Inhibits COX1 and 2 (irreversibly acetylates) --> prevent TxA2 --> increases bleeding time (no effect on PT or PTT)
antipyretic, analgesic anti-inflamm, antiplatelet gastric ulcer, bleeding, hyperventilation, Reye's, tinnitus |
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Drug used in acute coronary syndrome, coronary syndrome to decrease the incidence of recurrence of thrombotic stroke
MOA tox |
clopidogrel, ticlopidine
inhibtits platelet agg by irreversibly blocking ADP receptors --> no IIb/IIIa expression --> inhibited fibrinogen cross linking of platelets ticlopidine causes neutropenia |
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Monoclonal Ab that binds to glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
use? tox? |
abciximab
acute coronary syndrome, percutaneous transluminal coronary angioplasty bleeding, thromboycytopenia |
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Cancer drugs - where in the cell cycle do these work?
Vinca alkaloids and taxols |
M
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Cancer drugs - where in the cell cycle do these work?
Antimetabolites |
DNA synth
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Cancer drugs - where in the cell cycle do these work?
Etoposide |
DNA synth, G2
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Cancer drugs - where in the cell cycle do these work?
Bleomycin |
G2 (synth components needed for mitosis)
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Antineoplastics
decrease thymine synthesis (2) |
methotrexate, 5-FU
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Antineoplastics
decrease purine synthesis |
6-MP
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Antineoplastics
cross link DNA (2) |
alkylating agents, cisplatin
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Antineoplastics
intercalate DNA (2) |
dactinomycin, doxorubicin
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Antineoplastics
inhibit topoisomerase II |
etoposide
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Antineoplastics
inhibit microtubules (inhibits cell division) |
vinca alkaloids
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Antineoplastics
inhibits microtubule dissassembly |
paclitaxel
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Antimetabolits
drug used for: Leukemia, lymphoma choriocarcinoma, sarcoma + abortion, ectopic pregnancy, RA, psoriasis MOA tox (4) |
Methotrexate
Folic acid analog that inhibits DHFR --> low dTMP --> low DNA and protein synth 1. myelosuppression (save w/leucovorin) 2. fatty change in liver (macrovesicular) 3. Mucositis 4. teratogenic |
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Drug to treat colon cancer and other solid tumors, basal cell carcinoma (topical)
synergy with MTX MOA tox |
5-FU
pyrimidine analog, activated to 5F-dUMP --> complexes with folinic acid, inhibits thymidylate synthase --> low dTMP --> low DNA and protein synth myelosuppression (not reversible by leucovorin), photosensitivty |
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Overdose treatment
methotrexate vs. 5-FU |
Myelosuppression
meth = leucovorin 5-FU = thymidine |
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Drug to treat Leukemia or lymphoma, but NOT CLL or Hodgkin's
Purine analog MOA? toxicity |
6-MP
purine analog activated by HGPRTase --> decreased de novo purine synth Bone marrow, GI, liver |
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What is the effect of allopurinol on 6-MP and why?
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allopurinol --> increased toxicity of 6-MP (BM, GI, liver)
Because 6-MP is metabolized by xanthine oxidase |
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Drug to treat ALL that works just like 6-MP
toxicity? |
6-thioguanine
BM suppression, liver BUT you can give it with allopurinol |
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Drug used to treat AML, ALL, high grade non-Hodgkin's lymphoma
MOA Tox |
cytarabine (ara-C)
pyrimidine antagonist --> inhibits DNA polymerase leukopenia, thrombocytopenia, megaloblastic anemia |
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Drug to use in
-Wilms' tumor -Ewing's sarcoma -Rhabdomyosarcoma -childhood tumors MOA Tox |
Dactinomycin
Intercalates DNA Myelosuppression |
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Drug for Hodgkin's lymphoma, myeloma, sarcoma, and solid tumors (breast, ovary, lung)
MOA Tox |
Doxorubicin (adriamycin), daunorubicin
generates free radicals, intercalates DNA --> breaks--> decreased replication cardiotox, meylosuppression, alopecia, toxic to tissues with extravasation |
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Drug used in testicular cancer, Hodgkin's
MOA tox |
Bleomycin
Induces free radicals --> strand breaks pulm fibrosis, skin changes, but minimal myelosuppression |
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Drug for small cell carcinoma of lung and prostate, testicular carcinoma
MOA tox |
inhibits topoisomerase II --> increased DNA degradation
myelosuppression, GI irritation, alopecia |
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Alkylating agent used in non-Hodgkin's lymphoma, breast, ovarian carcinoma, immunsuppression
MOA Tox |
cyclophosphamide, ifosfamide
activated by liver, covalently links DNA at guanine N-7 Myelosuppression, hemorrhagic cystitis, prevented partially with mesna |
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Alkylating agents
Used for brain tumors (including glioblastoma multiforme) MOA Tox |
Nitrosoureas (carmustine, lomustine, semustine, streptozocin)
Bioactivation, crosses BBB CNS tox (dizzy, ataxia) |
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Alkylating agents
Used for CML and to ablate bone marrow before transplant MOA tox (2) |
Busulfan
alkylates DNA pulm fibrosis, hyperpigmentation |
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Microtubule inhibitors (2)
Used for Hodgkin's, Wilm's, and choriocarcinoma MOA tox |
vincristine, vinblastine
Inhibit tubulin polymerization in M phase -> spindle cannot form vincristine --> neurotox (areflexia, peripheral neuritis), paralytic ileus vinblastine - bone marrow "vinBLASTine BLASTS BM" |
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Microtubule inhibitors
used for ovarian and breast carcinomas MOA tox |
pacliTAXel, TAXols
hyperstabilize polymerized microtubules in M phase --> mitotic spindle cannot break down (no anaphase) Myelosuppression ,hypersensitivity |
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Drug that is used for testicular, bladder, ovary, and lung carcinomas
cross links DNA tox? |
cisplatin, carboplatin
nephrotoxic, acoustic nerve damage |
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Hydroxyurea
MOA Increases level of what substance? use tox |
inhibits ribonucleotide reductase --> decreased DNA synth (s phase)
Melanoma, CML, sickle cell (increases HbF) BM suppression, GI upset |
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Prednisone
USe? Tox? |
CLL, Hodgkin's (MOPP), autoimmune
cushing-like; immunosuppression, cataracts, acne, osteoperosis, HTN, peptic ulcer hyperglycemia, psychosis, insomnia |
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Drug used in breast cancer, to prevent osteoperosis
MOA Tox |
SERM = receptor antagonist in breast, agonist in bone -> blocks binding of estrogen
tamoxifen - increases risk of endometrial carcinoma (agonist effects), hot flashes raloxifene = no increase in endometrial carcinoma (b/c it is an antagonist) |
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Drug used to treat metastatic breast cancer
MOA tox |
Trastuzumab (herceptin)
Monoclonal Ab against HER-2 -> helps kill breast cancer cells that overexpress HER-2 (antibodies?) Cardiotox |
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Drug used for CML, GI stromal tumors
MOA tox |
Imatinib
Philadelphia chromosome bcr-abl tyrosine kinase inhibitor fluid retention |
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Monoclonal Ab for non-hodgkin's lymphoma, RA (w/methotrexate)
MOA |
rituximab
monoclonal Ab against CD20 (found on most B cell neoplasms) |
