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122 Cards in this Set
- Front
- Back
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Clopidogrel and Ticlopidine: mech of action
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Irreversibly block ADP receptors
Inhibit fibrinogen binding: prevent glycoprotein IIb/IIIa expression |
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Glycoprotein IIB/IIIA receptor antagonist (2)
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Abciximab
Eptifibatide |
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Antiplatelet effect of Aspirin
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Inhibit COX-1 --> Dec platelet production of TXA2 (platelet activator and vasoconstrictor)
Note: Also dec endothelial cell production of PGI2 (platelet aggregation inhibitor and vasodilator) but endothelial cells can resynthesize COX |
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Heparin: Adverse effects (2)
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Bleeding
Heparin-induced thrombocytopenia (HIT) - heparin binds to platelets, binds to PF4 which is immunogenic --> Heparin-PF4 complexes activate Fc receptors: 1. damaged platelets --> thrombocytopenia 2. platelet activation & thrombin generation --> thrombosis |
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Lepirudin: mechanism
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directly inhibit thrombin
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Lepirudin: clinical use
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Alternative to heparin for patients with HIT
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Warfarin: mechanism
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inhibits epoxide reductase --> prevent vitamin K from being converted to active form
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Hemophilia A: deficiency of...
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Factor VIII
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Hemophilia B: deficiency of...
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Factor IX
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Sickle cell mutation
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Hemoglobin S - substitution of valine for glutamine in the gene coding for the B-globin chain of hemoglobin
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Sickle cell: pathogenesis
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HbS polymerizes in hypoxic environments (infection, exercise, dehydration) --> RBC becomes distorted
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Sickle cell: lab findings
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- crescent shaped RBCs
- Howell-Jolly bodies |
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Most common inherited bleeding disorder
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von Willebrand's disease (AD)
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von Willebrand disease: pathogenesis (2)
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1. impaired platelet adhesion to subendothelium --> deficient platelet plug formation
2. Deficient protection/carrying of factor VIII --> impaired intrinsic pathway of coagulation |
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VHL gene:
- encodes - location |
Protein involved in inhibiting RNA synthesis
- mutation --> vascular malformations, tumors Chromosome 3p |
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Erythrocyte lifespan
Limited by: |
120 days
Limited by energy supply |
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Erythrocytosis
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inc # RBCs
AKA polycythemia |
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Anisocytosis
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varying sizes of RBCs
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Poikilocytosis
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varying shapes of RBCs
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Neutrophil lifespan in blood
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6-12 hours
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Neutrophil granules contain...
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- hydrolytic enzymes
- lysozyme - myeloperoxidase - lactoferrin |
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Basophil granules contain...
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- heparin (anticoagulant)
- histamine (vasodilator) - vasoactive amines - leukotrienes |
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Causes of eosinophilia
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NAACP
Neoplastic Asthma Allergy Collagen vascular disease Parasites (invasive) |
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Eosinophil granules contain...
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- histaminase
- arylsulfatase (help limit reaction following mast cell degranulation) |
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Platelet granules contain...
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Dense granules:
- ADP - calcium alpha-granules - vWF - fibrinogen |
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Bortezomib: mechanism
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Inhibits 26S subunit of the proteasome--> cell death
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Bortezomib: clinical use
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multiple myeloma
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Trastuzumab: mechanism
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Monoclonal antibody targeting HER2 (human EGF receptor 2) --> prevent activation of HER2 tyrosine kinase domain --> block tumor growth, survival, VEGF production
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Trastuzumab: clinical use
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HER2 overexpressing breast cancer
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Heinz Body: process
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Denatured hemoglobin precipitation
Damaged RBC membrane Hemolytic anemia |
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Heinz Body: associated with...
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G6PD deficiency
a-thalassemia |
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Sideroblastic anemia: inability to...
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synthesize heme
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Anemia of chronic disease: mechanism
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Inflammation
--> inc hepcidin --> dec release of iron from MPhage |
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Main iron sensor is....
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Hepatocyte
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Main iron feedback effector molecule is...
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Hepcidin
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Ferritin is (high/low) in Fe deficiency
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Fe deficiency --> low ferritin
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Best test for iron deficiency anemia
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Absent iron stores in BM macrophages
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Lead poisoning: enzymes affected
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Ferrochelatase (heme synthesis)
ALA dehydratase (heme synthesis) Pyrimidine 5' nucleotidase (RNA breakdown) |
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Basophilic stippling of RBCs (2)
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BASte the ox TAIL
Thalassemias Anemia of chronic disease Iron deficiency Lead poisoning |
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Paroxysmal nocturnal hemoglobinuria (PNH): defect
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Impaired ability to add glucosylphosphatidylinositol (GPI) anchors posttranslationally to DAF for the surface of RBCs
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Paroxysmal nocturnal hemoglobinuria: consequence
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Bouts of hemolytic anemia, hemoglobinuria
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Vincristine: mechanism
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Alkaloid, binds tubulin in M phase
--> block microtubule polymerization --> mitotic spindle cannot form |
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Vincristine: toxicity
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Neurotoxicity
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Paclitaxel: mechanism
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Hyperstabilize polymerized microtubules in M phase
--> mitotic spindle cannot break down (anaphase cannot occur) it is TAXing to stay polymerized |
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Viruses that can cause aplastic anemia (3)
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HIV
EBV Parvovirus B19 HCV |
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Which AIHA has a C3b RBC coating?
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Cold
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Common causes of warm AIHA (3)
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SLE
AIDS CLL |
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Common causes of cold AIHA (3)
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Lymphoma
M. pneumoniae EBV CLL |
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Thrombotic Thrombocytopenic Purpura: pentad
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1. Fever
2. Microangiopathic hemolytic anemia 3. Thrombocytopenia 4. Renal dysfunction 5. Neurological abnormalities |
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Antithrombin inhibits:
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Thrombin
IXa, Xa, XIa, XIIa |
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Heparin: mechanism
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Activates antithrombin
--> inactivate thrombin |
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Vitamin K deficiency:
Decreased synthesis of.... |
II, VII, IX, X
Protein C Protein S |
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Most common hereditary thrombosis syndrome
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Factor V Leiden
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Warfarin: possible complication
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Short half life of Protein C --> level can dec first --> procoagulant (b/c increased activity of V and VIII)
Avoid this in patients with an existing thrombus - administer heparin first |
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Monitor Heparin:
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Follow PTT
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Monitor Warfarin:
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Follow PT
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Platelet lifespan
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8-10 days
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Platelet vWF receptor
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Gp1b
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Platelet Fibrinogen receptor
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GpIIb/IIIa
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Bernard-Soulier disease: defect
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dec Gp1b --> defect in platelet-to-collagen adhesion
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Glanzmann's thrombasthenia: defect
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dec GpIIb/IIIa --> defect in platelet-to-platelet aggregation
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Acute promyelocytic leukemia: translocation
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t(15;17)
(acute --> close together) |
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CML: translocation
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t(9;22)
(Philadelphia CreaML cheese bagel at 9:22am) |
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Follicular lymphoma: translocation
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t(14;18)
(F = 4) |
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Burkitt's lymphoma: translocation
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t(8;14)
(8 = B) |
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Ewing's sarcoma: translocation
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t(11;22)
(must be perfect to fly - eWINGS) |
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Mantle cell lymphoma: translocation
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t(11;14)
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bcl-2 activation
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Follicular lymphoma
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c-myc activation
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Burkitt's lymphoma
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bcr-abl hybrid
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CML
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Ovalocyte: when would you see?
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Macrocytic anemia
Marrow failure |
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Signs of megaloblastic anemia
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Hypersegmented neutrophils
Macro-ovalocytes |
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Methotrexate: how to reverse myelosuppression
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Leucovorin rescue
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Leucovorin: mechanism
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Folinic acid
Preferentially taken up by normal cells versus tumor cells |
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5-Fluorouracil: how to rescue overdose
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thymidine
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Hydroxyurea: mechanism
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Inhibit ribonucleotide reductase
S-phase specific |
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Tamoxifen, Raloxifene: mechanims
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SERMs - receptor antagonists in breast and agonists in bone
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Tamoxifen, Raloxifene: toxicities
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T - partial agonist in endometrium, hot flashes
R - endometrial antagonist --> no inc in endometrial carcinoma |
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Imanitib: toxicity
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fluid retention
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Waldeyer's ring
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Lymphoid tissue on tonsils and adenoids: Non-Hodgkin's lymphoma
EBV |
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TdT
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Marker of pre-T and Pre-B cells
ALL |
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JAK2
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- Hematopoetic growth factor signaling
- Mutation --> myeloproliferative disorders (except CML) |
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Acute intermittent porphyria: Affected enzyme
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Porphobilinogen deaminase (uroporphyrinogen-I-synthase)
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Acute intermittent porphyria: Symptoms
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5 P's
Painful abdomen Pink urine Polyneuropathy Psychological disturbances Precipitated by drugs |
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Acute intermittent porphyria: Treatment
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glucose and heme
--> inhibit ALA synthase |
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Antigens on Reed-Sternberg cells
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CD15
CD30 |
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Langerhans cell Histiocytosis cells express which tumor markers
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S-100
CD1a |
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Location of heavy chain Ig gene
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Chromosome 14
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Location and function of bcl-2
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Chromosome 18
Inhibits apoptosis |
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Location and function of c-myc
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Chromosome 8
Growth and proliferation |
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Hb Barts
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a-thalassemia
Deletion of 4 alpha genes (gamma 4) Incompatible with life - hydrops fetalis |
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Ristocetin cofactor assay
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test of vWF function
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Lupus anticoagulant: lab findings
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Prolonged PTT that does not correct in mixing studies
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Where does the HMP shunt take place
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RBCs
Places of steroid/fatty acid synth - Lactating mammary glands - Liver - Adrenal cortex |
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Wierd toxicity of Warfarin (2)
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skin/tissue necrosis
Teratogen (bone deformities, fetal hemorrhages, abortion) |
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What purpose does the IgM conformation serve?
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Must bind complement before C1 binding site is exposed
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Effect of lupus anticoagulant on aPTT
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prolong
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Treat heparin toxicity
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Protamine sulfate (positively charged molecule that binds negatively charged heparin)
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Treat tPA, streptokinase toxicity
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Aminocaproic acid (inhibits fibrinolysis)
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What to use for DVT in pregnancy
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Heparin
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Why is Colchicine a second line agent for gout
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GI side effects (nausea, diarhhea, vomiting)
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What to use for gouty arthritis in elderly or those with renal failure
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Intraarticular glucocorticoids
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who expresses COX-2? When
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Inflammatory states
- endothelium - kidney - leukocytes |
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Side effect common to both COX-1 and COX-2
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Kidney effects - inhibit vasodilation
- dec GFR --> fluid retention - exacerbate HTN |
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Hypercoagulable state
Pancytopenia Hemolytic anemia |
Paroxysmal nocturnal hemoglobinuria
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PNH: deficiency of... is diagnostic
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CD55
CD59 |
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Ticlodipine: side effect
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Neutropenia: fever and mouth ulcers
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DIC: decreased factors
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fibrinogen
Factors V, VIII |
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Etiologies of aplastic anemia: viral causes
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parvovirus B19
EBV HIV HCV |
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Etiologies of aplastic anemia: drugs
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alkylating agents
antimetabolites benzene chloramphenicol NSAIDS propylthiouracil, methimazole |
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dec vWF: clinical
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epistaxis
menorrhagia (enough to cause iron deficiency anemia) |
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dec Protein C
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inc DVT
inc hemorrhage, ulcers, necrosis from warfarin |
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Hemophilia: clinical
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hemarthrosis
easy bruising |
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Mantle cell lymphoma: cell markers
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CD5+
Cyclin D1+ |
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Regulation of Fe in body
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Liver (hepcidin)
- inflamm --> inc hepcidin - dec O2, dec Fe --> dec hepcidin |
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Drugs to use in patient with neutropenia to recover the bone marrow (2)
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Filgrastim
Sargramostim (G-CSF) |
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CD markers on macrophage
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CD14
CD40 |
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CD markers on B cell
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CD19
CD20 CD21 CD40 |
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CD markers on NK cells
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CD16 (binds Fc or IgG)
CD56 (unique marker for NK) |
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What to use to prevent cardiotoxicity from Doxorubicin
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Dexrazoxone
(Iron chelator) |
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What to use as cryoprotective with chemotherapy agents
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Amifostine
(free radical scavenger) |
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Cisplatin/carboplatin: toxicity
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Nephrotoxicity (fanconi syndrome)
Prevent with hydration, amifostine |
