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Biochemistry LE 1: Hemostasis, Thrombosis, and Coagulation

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42 Questions

What is Factor III more commonly known as?

Tissue Factor

What is the main function of cofactors in the clotting mechanism?

To serve as binding sites for other factors

Which factor is regulated by proteolytic cleavage?

Protein C

What is the outcome of the activation of Factor VIIa?

Activation of both Factor X and Factor IX

What is the time it takes to form a clot in the extrinsic pathway?

12 seconds

What is the trigger for the extrinsic pathway?

Trauma

What is the role of Tissue Factor in the extrinsic pathway?

To bind with Factor VII

What is the sequential activation of serine proteases in the clotting cascade result in?

Amplification and acceleration of the response

What is the result of Thrombin formation in the Coagulation Cascade?

It feeds itself by promoting activation of the factors needed for its own formation

What is the role of the intrinsic pathway in the Coagulation Cascade?

It sustains the coagulation response

What is the major substrate of Thrombin?

Fibrinogen

What is the result of the conversion of fibrin monomers to fibrin clot?

A soft clot is formed

What is the role of Vitamin K in the Coagulation Cascade?

It is required for the carboxylation of Glutamate residues

What is the function of Factor XIII in the Coagulation Cascade?

It cross-links fibrin molecules to form a hard and stable clot

What is the purpose of the extrinsic pathway in the Coagulation Cascade?

It initiates the coagulation response

What is the function of the Vit-K dependent carboxylase?

It carboxylates Glutamate residues

What is the normal value of Prothrombin Time (PT)?

11-12.5 seconds

Which pathway is measured by the Partial Thromboplastin Time (PTT)?

Intrinsic Pathway

What is the normal value of Platelet Count?

150,000-400,000/mm3

What is the result of a low Platelet Count?

Thrombocytopenia

What is the purpose of the Coagulation Factor Assay?

To diagnose deficiencies in coagulation factors

Which disease is associated with a prolonged Partial Thromboplastin Time (PTT)?

All of the above

What is the purpose of the Platelet Function Assay?

To diagnose Platelet dysfunction

What does the mnemonic ❗️HELPFUL stand for?

Playing Table Tennis (PTT) INdoors: Test for the Intrinsic Pathway

A mutation in which proenzyme would lead to uncontrolled blood clotting?

Factor XIII

Which factor is directly activated by factor Xa?

Factor II

What is the primary cause of classical hemophilia A?

Absence of factor VIII

Which factor is necessary for the activation of factor X by factor IXa?

Factor VIII

Warfarin inhibits the reduction of which vitamin?

Vitamin K

What is the result of an inability to form clotting factor complexes on cell membranes?

Bleeding disorder

Which factor is directly activated by factor XIa?

Factor IX

What is the primary cause of the bleeding disorder in the infant?

Decreased levels of circulating vWF

Why is the patient at risk for further clots?

Due to the increased vitamin K in the patient's diet and circulation

What is the function of Streptokinase?

Activating plasminogen to plasmin

What is the role of Protein C in the body?

Inhibiting the clotting cascade

Why is the liver important in hemostasis?

It is the site of synthesis of many clotting factors

What is the function of Urokinase?

Activating plasminogen to plasmin

What is the effect of Warfarin on the body?

It acts as a vitamin K antagonist

What is the role of PAI-1 in the body?

It inhibits plasminogen activator

What is the function of t-PA in the body?

It activates plasminogen to plasmin

Why is the liver important for vitamin K absorption?

It is the site of vitamin K absorption from the diet

What is the effect of green leafy vegetables on Warfarin?

It reduces the action of Warfarin

Study Notes

Blood Coagulation Cascade

  • Intrinsic Pathway: triggered by internal stimuli, involves serine proteases that cleave the next proenzyme in the cascade, resulting in a rapid response
  • Extrinsic Pathway: triggered by trauma, involves Tissue Factor (Factor III) and Factor VII, leading to the activation of Factor X and the coagulation cascade

Factors and Cofactors

  • Factor II (Prothrombin): a key factor in the coagulation cascade
  • Factor III (Tissue Factor): an integral membrane protein that does not require cleavage for activation
  • Factor VII: binds to Tissue Factor to auto-catalyze its activation to VIIa
  • Factor X: activated by Factor VIIa, leads to the formation of Thrombin (Factor IIa)
  • Calcium (Ca2+): a cofactor that facilitates the clotting mechanism
  • Protein C: a regulatory protein that is activated by proteolytic cleavage and inhibits the clotting cascade

Coagulation Cascade

  • Tissue Factor and VIIa: key process involved in the initiation of blood coagulation in vivo
  • Steps of Extrinsic Pathway:
    • Trauma causes damaged tissues to present Tissue Factor (Factor III) to blood at injured site
    • Factor VII binds to Tissue Factor to auto-catalyze its activation to VIIa
    • Factor VIIa activates Factor X (to Xa) and Factor IX (to IXa)
  • Activation of Factor IIa (Thrombin): leads to the formation of a "soft" clot, which is then cross-linked to form a "hard and stable" fibrin clot

Vitamin K Dependence

  • Factors VII, IX, X, and II: require Vitamin K for their activation
  • Vitamin K-dependent carboxylase: necessary for the activation of these factors
  • HELPFUL MNEMONIC: 1972 → Factor X, II

Coagulation Assays

  • Coagulation Factor Assay: measures the extrinsic pathway (III, VII) and common pathway (X, V, II, I)
  • Prothrombin Time (PT): measures the extrinsic pathway
  • Partial Thromboplastin Time (PTT): measures the intrinsic pathway
  • Platelet Function Assay: measures platelet function and counts

Pathology and Disease

  • Prolonged PT and aPTT: indicative of acquired or congenital deficiency of coagulation factors, Vitamin K deficiency, or liver disease
  • Hemophilia A: results from a deficiency in Factor VIII
  • Hemophilia B: results from a deficiency in Factor IX
  • Von Willebrand Disease: a bleeding disorder characterized by a deficiency in von Willebrand Factor (vWF)

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