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24 Cards in this Set

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A. What are the four (or five) stages of hemostasis? Which components contribute to each stage?
1) Arteriolar vasoconstriction (arterioles)
2) Primary hemostasis: platelet adherence, activation, aggregation leading to the hemostatic plug.
3) Secondary hemostasis: activation and progression of the coagulation cascade that consolidates the initial platelet plug.
4) Permanent plug: Polymerization of fibrin and platelet aggregates to form the permanent plug.
5) Activation of the fibrinolytic system to reverse steps 2, 3, and 4.
Which events, forces, or entities activate endothelium to promote thrombosis?
1. Besides trauma, endothelium can be activated by infectious agents, hemodynamic forces, plasma mediators, and cytokines.
2. Activated endothelium can lead to unwanted clots
3. Inflammation is a prominent cause of activated endothelium = unwanted clots.
example of unwanted clot formation
inflammation of atherosclerosis can lead to thrombus in a coronary artery leading to a myocardial infarction.
What are the antiplatelet effects of endothelium that keep blood flowing smoothly?
1) Intact endothelium prevents platelets from engaging the highly thrombogenic subendothelial ECM.
2) Prostacyclin (PGI2) and nitric oxide produced by the endothelial cells impede platelet adhesion.
3. Adenosine diphosphatase
Which anticoagulants does the endothelium produce?
1. Heparin-like molecules
2. thrombomodulin
3. protein C, protein S,
4. tissue factor pathway inhibitor
Which prothrombotic effects and molecules does activated or injured endothelium produce
1) allow latelets to access thrombogenic extracellular matrix
2) Tissue factor, the major activator of the extrinsic clotting cascade
3) augment the catalytic function of activated coagulation factors IXa and Xa.
What are the two contrasting roles of normal endothelium versus activated endothelium?
Intact, nonactivated endothelium inhibits platelet adhesion and blood clotting. Activated endothelium enhances thrombus formation.
Why is heparin used to prevent thrombosis
Heparin activates antithrombin III, which inactivates coagulation factors IIa (thrombin), IXa, Xa, XIa, and XIIa.
What do platelets contribute to hemostasis?
1. They play a critical role in normal hemostasis, by forming the hemostatic plug that initially seals vascular defects, and by providing a surface that recruits and concentrates activated coagulation factors
What do platelet granules contribute to platelet function
1. α-Granules have the adhesion molecule P-selectin on their membranes and contain fibrinogen, fibronectin, factors V and VIII, platelet factor 4 (a heparin-binding chemokine), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β).
2. Dense (or δ) granules contain ADP and ATP, ionized calcium, histamine, serotonin, and epinephrine
Which two proteins are crucial for successful platelet adhesion
GpIb receptor on platelets and von Willebrand factor sticking to ECM
What is the genetic deficiency of von Willebrand factor (vWF) called? What is the phenotype
1. von Willebrand disease.
2. Excessive bleeding (hemophilia) is the phenotype because platelet GpIb cannot stick to the ECM in the absence of vWF.
What is Bernard-Soulier syndrome? What is the phenotype?
Deficiency of GpIb receptor protein on platelets
The outcome is similar to von Willebrand disease: hemophilia (i.e., too much bleeding).
Platelets do not have the receptor they need for sticking to von Willebrand factor on the ECM. You need to associate the disease name with the mutated protein and vice-versa.
Which substance activates platelet aggregation? Where is the substance found?
ADP, which is found in gamma-granules of platelets.
Which substance counteracts thromboxane (TxA2)
Prostacyclin (PGI2), which is a potent vasodilator and inhibitor of platelet aggregation and is produced by endothelium.
Prostacyclin (PGI2) is antithrombotic.
Where is TxA2 produced?
Platelets.
TxA2 is prothrombotic.
Which drug inhibited the production of PGI2 and led to an increased risk of myocardial
The COX2- inhibitor rofecoxib (Vioxx®).
What results from genetic mutation of GpIIb-IIIa?
Glanzmann thrombasthenia.
Platelets fail to aggregate because GpIIb-IIIa is needed to link platelet-to-platelet through fibrinogen.
What is the most important coagulation factor?
1. Thrombin is the most important coagulation factor and can act at numerous stages in the process
2. its both prothromic and antithromic
Which pathway of the coagulation cascade does prothrombin time assess?
Which pathway of the coagulation cascade does partial thromboplastin time measure?
1. Protein time uses tissue factor, a component of the extrinsic pathway, and measures the extrinsic pathway. PTT measures the intrinsic pathway.
(Note that thromboplastin is another name for tissue factor)
Which molecule activates antithrombin III?
Heparin provided by the medical team or a heparin-like molecule on the surface of endothelium. Heparin must be administered by injection (intravenous or subcutaneous).
Which molecules activate protein C?
Thrombin complexed to thrombomodulin at the endothelial surface.
Protein C is a key anticoagulant enzyme along with its cofactor protein S (protein S does not have enzymatic activity).
Which clinical conditions are monitored by measuring fibrin split products?
1. Elevated levels of FSPs (most notably fibrin-derived D-dimers) can be used in diagnosing abnormal thrombotic states including disseminated intravascular coagulation (DIC), deep venous thrombosis, or pulmonary embolism.
What substance is given intravenously to lyse thrombus during the early stages of a myocardial infarction or ischemic stroke?
Recombinant tissue plasminogen activator: alteplase, reteplase, and tenecteplase.
These drugs differ in structure and the indications for their clinical use