Flashcards in Deck XXI Deck (33):
What occurs in clotting after platelet activation?
Release of mediators (such as ADP and thromboxane A2) and conformational change of glycoprotein IIb/IIIa to bind fibrinogen and form a crosslinked plug.
What is the mechanism of action of Abciximab?
A glycoprotein IIb/IIIa inhibitor. It inhibits its binding to fibrinogen.
What conditions is Abciximab used to treat?
Unstable angina, acute coronary syndrome (esp in patients undergoing percutaneous coronary intervention).
What is Glanzmann thrombasthenia?
Disorder characterized by defective glycoprotein IIb/IIIa on platelet surfaces causing mucocutaneous bleeding. No platelet clumping on peripheral smear.
Which proteins drive angiogenesis?
Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Proinflammatory cytokines (like IGF-1 and INF-y) can indirectly promote angiogenesis through increased VEGF expression.
What does ki-67 fraction measure?
Proliferation index (ie mitotic index)
What condition is characterized by burr cells, helmet cells, and RBC fragments?
Traumatic hemolysis which can result from either microangiopathic hemolytic anemia or mechanical damage (i.e. prosthetic valve).
What are Burr cells?
Erythrocytes with short, evenly spaced projections. They can occur as an artifact or in association with uremia, pyruvate kinase deficiency, microangiopathic hemolytic anemia, or mechanical damage.
What distinguishes benign lymph node enlargement from malignant enlargement?
Benign enlargement in response to antigenic stimulation is associated with a polyclonal proliferation of lymphocytes; malignancy is associated with a monoclonal lymphocytic proliferation.
What findings are seen on light microscopy of GBM?
Pseudopalisading tumor cells around areas of necrosis. Necrosis and hemorrhage are also seen on gross examination.
What is the key metabolic difference between methotrexate and 5-FU?
Methotrexate prevents reduction of folic acid to tetrahydrofolate while 5-FU binds tetrahydrofolate and thymidylate synthetase in a stable reaction intermediate form thereby decreasing the amount of thymidylate synthetase available for thymidine synthesis.
How does leucovorin (N5-formyl-tetrahydrofolate) rescue cells from MTX toxicity?
It is a tetrahydrofolate derivative that does not require reduction by dihydrofolate reductase before acting as a cofactor for thymidylate synthase. It thus bypasses the dihydrofolate reductase step inhibited by methotrexate.
What is a common point in the mechanism of action of MTX and 5-FU?
Both effectively inhibit thymidylate formation. The effects of methotrexate can be overcome by folinic acid or leucovorin supplementation however.
Myeloblasts stain positive for what?
Peroxidase (or myeloperoxidase) in auer rods.
Describe the appearance of a myeloblast nucleus.
Folded/ bilobed nuclei containing multiple nucleoli. They contain auer rods.
What are the clinical manifestations associated with hereditary spherocytosis?
Anemia, jaundice, splenomeagly with increased risk of pigmented gallstones and aplastic crisis (parvovirus B19 infection). These sx are caused by splenic sequestration.
What test is diagnostic for hereditary spherocytosis?
Osmotic Fragility Test.
What is the pattern of inheritance for hereditary spherocytosis?
What types of proteins are BRCA1 and BRCA2?
DNA repair genes.
What laboratory abnormalities are characteristic of multiple myeloma?
Erythrocyte rouleaux formation on peripheral smear and Bence-Jones proteins in the urine.
What reduces the risk of non-hereditary ovarian cancer?
OCPs. They decrease the total number of times that a woman ovulates in her lifetime and thus with fewer ovulatory cycles, there is less need for ovarian surface repair
What is the most prominent adverse effect of Cisplatin?
Nephrotoxicity (acute tubular injury)
What preventative measures must be undertaken for a patient on cisplatin?
Amifostine- a thiol based cytoprotective free radical scavenging agent used to decrease cumulative nephrotoxicity. Also, chloride diuresis (via IV NS) keeps cisplatin in the nonreactive state.
Hemolytic anemia due to intravascular erythrocyte destruction results in what laboratory findings?
Increased serum indirect bilirubin, free hemoglobin in serum and urine, and increased LDH. It also causes decreased serum haptoglobin.
What is haptoglobin?
A serum protein that binds to free hemoglobin and promotes its uptake by the reticuloendothelial system.
When do haptoglobin levels characteristically decrease?
When significant quantities of hemoglobin are released into circulation (ex. intravascular hemolysis).
What are the lymphoblast types in precursor B-ALL?
TdT+, CD10+, CD19+.
What are the lymphoblast types in precursor T-ALL?
CD2, CD3, CD4, CD5, CD7, CD8, TdT, CD1a
What disorders characteristically present with petechial lesions?
How does Desmopressin acetate (DDAVP) ameliorate symptoms of hemophilia A?
Stimulates release of factor VIII and vWF from endothelial cells which temporarily increases factor VIII. It has no effect in hemophilia B.
What symptoms are associated with hemorrhagic disease of the newborn?
Cutaneous, GI, and intracranial bleeding due to vitamin K deficiency.
Patients with Polycythemia Vera have increased incidence of what conditions?
Peptic ulceration, itching, gouty arthritis, reversible moderate hypertension.