Chapter 142 - Arterial and Venous Thrombosis Flashcards Preview

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Flashcards in Chapter 142 - Arterial and Venous Thrombosis Deck (32):

Which of the following was estimated as more common in 2009 in the United States - coronary artery non-silent new events or new or recorrent cerebral stroke?

"In 2009 in the United States, an estimated 785 000 people had a new coronary thrombotic event (...) approximately 795 000 people had a new or recurrent stroke."


Name the differences in arterial and venous thrombosis.

"In venous thrombosis, primary hypercoagulable states reflecting defects in the proteins governing coagulation and/or fibrinolysis or secondary hypercoagulable states involving abnormalities of blood vessels and blood flow or stasis lead to thrombosis. By contrast, arterial thrombosis is highly dependent on the state of the vessel wall, the platelet, and factors related to blood flow."


Give examples of platetet functions that are not related to its primary function of regulation of hemostasis.

"In addition (...) our understanding of their role in other processes, such as immunity, wound healing, and inflammation, continues to grow."


What is the estimation death rate for coronary artery disease and stroke in the United States?

Coronary artery disease - "about 1 of every 5 deaths"
Stroke - "it is estimated that 1 of every 18 deaths"


What is the normal lifespan of a healthy platelet?

7 to 10 days.


What are the differences between alpha and dense granules of the platelets?

"The two major types of platelet granules, alpha and dense, are distinguished by their size, abundance, and content. Alpha-granules contain soluble coagulation proteins, adhesion molecules, growth factors, integrins, cytokines, and inflammatory modulators. Platelet dense-granules are smaller than alpha-granules and less abundant. Whereas alpha-granules contain proteins that may be more important in the inflammatory response, dense-granules contain high concentration of small molecules, including adenosine diphosphate (ADP) and serotonin, that influence platelet aggregation."


Which subendothelial molecules might be responsible for the adhesion of platetelet to the vessel wall?

"Damage exposes subendothelial components responsible for triggering platelet reactivity, including collagen, von Willebrand factor, fibronectin, and other adhesive proteins, such as vitronectin and thrombospondin."


Collagen-induced platelet adhesion is dependent on the platelet receptor glycoprotein (GP) IV, GPVI and integrin alpha2-beta1.
True or False?



Which platelet receptors are involved in the adhesion to von Willebrand factor?



What is the platelet ligand for fibrinogen? How come platelets in innactive state do not ligate to fibrinogen?

"von Willebrand factor-bound GPIb-IX-V promotes a calcium-dependent conformational change in the GPIIb/IIIa receptor, transforming it from an inactive low-affinity state to an active high-affinity receptor for fibrinogen."
This conformational change might be mediated by many other receptor-ligand complexes.


The platelet membrane is both enriched with thrombotic and nonthrombotic receptors.
True or False?



Which platelet receptors are the most abundant?

Thrombin receptors.


What is the main function of PAR1 Receptor?

PAR1 is responsible for the cleavage of the N-terminus of thrombin which, in turn, serves as a ligand to this platelet receptor. It is the main receptor for thrombin.


Name the main receptors responsible for platelet aggregability dependent on ADP.

P2Y12 and P2Y1 are the most important ones.
(the other receptor for ADP is P2X1)


PSGL1, present in platelets, serves as a ligand to P-selectin (CD62P) presente in leukocytes.
True or False?

"Platelets bind via P-selectin (CD62P) expressed on the surface of activated platelets to the leukocyte receptor, P-selectin glycoprotein ligand 1 (PSGL-1)."


Platelets express CD40 ligand, which might have a role both in thrombosis and inflamattion.
True or False?

"While many immunologic and vascular cells have been found to express CD40 and/or CD40 ligand, in platelets, CD40 ligand is rapidly translocated to the surface after stimulation and is upregulated in the newly formed thrombus."


Explain one possible molecular link between specific bacteria and platelet-dependent thrombosis.

Platelets have Toll Like Receptors (TLR) in its membrane, such as TLR2, TLR3 and TLR4. Specific bacteria "induce a proinflammatory response in platelets in a TLR2-dependent manner, suggesting a mechanism by which specific bacteria and bacterial components can directly activate platelet-dependente thrombosis."


Prasugrel is superior to clopidogrel because the last drug needs hepatic metabolization by CYP450 and CYP2C19 polymorphisms explain 100% of the variability of response to this drug.
True or False?

"although the loss-of-function polymorphisms in CYP2C19 is the strongest individual variable affecting pharmacokinetics and antiplatelet response to clopidogrel, it only accounts for 5-12% of the variability in ADP-induced platelet aggregation on clopidogrel. In addition, genetic variables do not appear to significantly contribue to the clinical outcomes of patients treated with P2Y12 receptor antagonists prasugrel or ticagrelor."


What percentage of patients die of tromboembolic venous disease in the first 30 days?



What percentage of patients have recorrent tromboembolic disease within 10 years of the establishment of the first event?



How many patients who suffer a tromboembolic venous event have sudden death?



Which of the following condition is associated with higher mortality rate? Deep vein Thrombosis or Pulmonary Embolism? (ARIC study)

Pulmonary Embolism.
"(ARIC) study reported a 9% 28-day fatality rate from DVT and a 15% rate from pulmonary embolism. Pulmonary embolism in the setting of cancer has a 25% mortality rate."


Besides the classic Virchow's tryad (hypercoagulopathy, stasis, and vascular dysfunction) as known risk factors for thrombosis, which newer factors have been identified?

"newer areas of research have identified contributions from procoagulant microparticles, inflammatory cells, microvesicles, and fibrin structure."


What is the cofactor for factor IXa in the coagulation cascade? What is the main function of this complex?

The cofactor is factor VIIIa. The complex IXa-VIIIa activates the factor X.


Factor XIII is responsible for the clot stabilization.
True or False?

"Thrombin also activate FXIII to FXIIIa, a transglutaminase that covalently cross-links and stabilizes the fibrin clot."


Name the main anticoagulant factors.

Tissue factor pathway inhibitor (TFPI), antithrombin III, heparin cofactor II, and protein C/protein S.


What is the percentage of the U.S. population that has a genetic risk factor for venous thrombosis?



The most feared consequence of protein C/protein S homozygous deficiency is thromboembolic venous events.
True or False?

The most feared consequence is fatal purpura fulminans.
"heterozygous deficiencies are associated with a moderate risk of thrombosis."


Factor V Leiden is the so called FV with a pontual mutation in its gene, localized in chromossome 1.
True or False?



Name the folate metabolism alterations that constitute individual risk factors for both venous thrombosis aswell as arterial vascular disease.

Elevated levels of methylene tetrahydrofolate reductase and hyperhomocysteinemia.


What might be the molecular link between metabolic syndrome and hypofibrinolytic state?

"One of the most frequently documented prothrombotic abnormalities reported in this syndrome is an increase in plasma levels of PAI-1."
PAI-1 - Plasminogen Activator Inhibitor type 1


Inflammation plays a role in both formation and resolution of thrombosis.
True or False?