HEMA2_Prelim_Lec: Coagulation pathway / Secondary hemostasis

What is secondary hemostasis?

The enzymatic activation of plasma coagulation proteins that produces a fibrin meshwork to stabilize the platelet plug.

What is coagulation?

A cascade in which plasma proteins, tissue factor, and calcium interact to form a stable fibrin clot.

What is the main purpose of secondary hemostasis?

To convert the temporary platelet plug into a stable platelet-fibrin clot.

What is a zymogen?

An inactive precursor of an enzyme that must be activated before it has biological activity.

What type of enzymes are primarily involved in the coagulation cascade?

Serine proteases.

What are the two major stages of secondary hemostasis emphasized in the lecture?

Fibrin-platelet plug formation and fibrin stabilization.

What coagulation factor stabilizes the fibrin clot?

Factor XIIIa.

What does thrombin do to fibrinogen?

Converts fibrinogen into fibrin.

Why is fibrin important in secondary hemostasis?

Fibrin forms an insoluble meshwork that stabilizes the platelet plug.

What is Factor I?

Fibrinogen.

What is Factor II?

Prothrombin.

What is Factor III?

Tissue factor/tissue thromboplastin.

What is Factor IV?

Calcium ions.

What is Factor V?

Proaccelerin/Labile factor.

What is Factor VII?

Proconvertin/Stable factor.

What is Factor VIII?

Antihemophilic factor A.

What is Factor IX?

Christmas factor/Antihemophilic factor B.

What is Factor X?

Stuart-Prower factor.

What is Factor XI?

Plasma thromboplastin antecedent.

What is Factor XII?

Hageman factor/contact factor.

What is Factor XIII?

Fibrin-stabilizing factor.

What is the function of Factor III/tissue factor?

It initiates the extrinsic pathway and works with Factor VII.

Which factor initiates the extrinsic pathway?

Factor VII, after activation by tissue factor.

Which factor initiates the intrinsic pathway?

Factor XII.

Which factor begins the common pathway?

Factor X.

Which factor is the substrate of thrombin?

Fibrinogen (Factor I).

Which factor is the precursor of thrombin?

Prothrombin (Factor II).

Which factor activates Factor X in the extrinsic pathway?

Factor VIIa with tissue factor and calcium.

Which factors activate Factor X in the intrinsic pathway?

Factor IXa with Factor VIIIa, calcium, and phospholipid.

What activates Factor II/prothrombin?

Factor Xa with Factor Va.

What does Factor IIa (thrombin) activate?

Fibrinogen to fibrin and Factor XIII to XIIIa; it also enhances Factors V and VIII and promotes platelet aggregation.

What is the function of Factor XIIIa?

Cross-links/stabilizes fibrin to produce a stable clot.

Which coagulation factors are vitamin K-dependent?

Factors II, VII, IX, and X.

What are the contact group factors?

Factors XII, XI, prekallikrein, and HMWK.

What are the fibrinogen group factors?

Factors I, V, VIII, and XIII.

What is the prothrombin group?

Factors II, VII, IX, and X; they are vitamin K-dependent.

What is the substrate in the coagulation cascade?

Fibrinogen (Factor I).

What are coagulation cofactors?

Proteins that assist in the activation of coagulation factors rather than functioning primarily as enzymes.

What are important coagulation cofactors?

Factors V and VIII, tissue factor, and HMWK.

Which coagulation factors are serine proteases?

Activated Factors II, VII, IX, X, XI, and XII, among others identified in the lecture.

Which coagulation group is most labile?

The fibrinogen group.

Which coagulation group is consumed during clotting?

The fibrinogen group.

Which coagulation group is vitamin K-dependent?

The prothrombin group.

Which coagulation group can be found in both serum and plasma?

The contact and prothrombin groups.

Which coagulation group is found only in plasma?

The fibrinogen group.

Why are fibrinogen-group factors difficult to preserve in stored specimens?

They are labile and Factors V and VIII deteriorate during storage.

Which factor has the shortest half-life according to the lecture?

Factor VII, approximately 6 hours.

Which factors have among the longest half-lives?

Factors I and XIII.

What is the intrinsic pathway?

A coagulation pathway initiated by contact with exposed subendothelial surfaces/collagen.

What is the sequence of the intrinsic pathway?

XII → XIIa → XI → XIa → IX → IXa; IXa works with VIIIa, calcium, and phospholipid to activate X.

What is the extrinsic pathway?

A rapid pathway initiated by tissue injury and exposure/release of tissue factor.

What is the sequence of the extrinsic pathway?

Tissue factor + VII → VIIa → activation of X to Xa.

What is the common pathway?

The pathway beginning with Factor X activation and leading to thrombin formation and fibrin clot formation.

What is the sequence of the common pathway?

X → Xa → II → IIa (thrombin) → fibrinogen → fibrin → XIIIa-mediated fibrin stabilization.

Which pathway is faster?

The extrinsic pathway.

How long does the lecture state the intrinsic pathway takes?

Approximately 4–6 minutes.

How long does the lecture state the extrinsic pathway takes?

Approximately 30 seconds.

What activates Factor XII?

Contact with exposed surfaces such as collagen.

What is the role of prekallikrein?

With HMWK, it participates in activation of Factor XII and contributes to the contact system.

What is HMWK?

High Molecular Weight Kininogen; a contact-system protein that works with prekallikrein.

strengthen the aggregation btwn plts.

What happens in Factor XII deficiency?

aPTT is prolonged, but the patient does not necessarily have increased bleeding tendency.

What is Factor VIII deficiency called?

Hemophilia A.

What is Factor IX deficiency called?

Hemophilia B.

What is Factor XI deficiency called?

Hemophilia C.

What is Factor V deficiency called?

Owren's disease.

What is a major function of thrombin?

It converts fibrinogen to fibrin and coordinates multiple steps of hemostasis.

Why is thrombin considered a key protease?

It promotes coagulation, platelet activation, coagulation control, and regulation of fibrinolysis.

How does thrombin promote platelet formation?

It induces platelet activation and aggregation.

How does thrombin amplify coagulation?

It enhances Factors V and VIII and can promote additional thrombin generation.

How does thrombin participate in anticoagulation?

It binds thrombomodulin, leading to activation of Protein C.

What does activated Protein C do?

Inactivates Factors Va and VIIIa with the assistance of Protein S.

What is the function of Protein S?

It enhances Protein C binding to phospholipid surfaces and increases inactivation of Va and VIIIa.

What is thrombomodulin?

A protein that binds thrombin and activates the Protein C anticoagulant system.

What is antithrombin III?

A major physiologic inhibitor of thrombin and Factor Xa.

What is the role of heparin cofactor?

It inhibits thrombin, with activity enhanced by heparin.

What is alpha-2 macroglobulin?

A protein that forms complexes with thrombin and kallikrein to inhibit their activity.

What is C1 inhibitor?

It inactivates Factor XIIa, plasma kallikrein, Factor XIa, and plasmin.

What is alpha-1 antitrypsin?

A slow-reacting inhibitor that inhibits Factor XIa and Xa.

What is the extrinsic pathway inhibitor?

A lipoprotein-associated inhibitor that inhibits VIIa in the tissue-factor complex.

What is the function of Protein C?

It is a major coagulation inhibitor that inactivates Va and VIIIa with Protein S.

What is the difference between PT and aPTT?

PT evaluates the extrinsic and common pathways, whereas aPTT evaluates the intrinsic and common pathways.

What pathway does PT assess?

Extrinsic and common pathways.

What pathway does aPTT assess?

Intrinsic and common pathways.

Which factor is most associated with an isolated prolonged PT?

Factor VII deficiency.

Which factors are assessed by aPTT in the intrinsic pathway?

XII, XI, IX, and VIII.

Which factors are assessed by PT in the extrinsic pathway?

Primarily VII.

Which factors are assessed in the common pathway by both PT and aPTT?

X, V, II, and fibrinogen.

What happens to both PT and aPTT when a common pathway factor is deficient?

Both may become prolonged.

What conditions can prolong aPTT?

Hemophilia, Factor XII deficiency, heparin therapy, and some liver disease according to the lecture.

What conditions can prolong PT?

Warfarin therapy, vitamin K deficiency, liver disease, and Factor VII deficiency.

Why can vitamin K deficiency affect coagulation?

Vitamin K is required for synthesis of Factors II, VII, IX, and X.

Why does Factor VII deficiency primarily affect PT?

Factor VII belongs to the extrinsic pathway, which is assessed by PT.

Why does Factor VIII deficiency primarily affect aPTT?

Factor VIII belongs to the intrinsic pathway, which is assessed by aPTT.

What happens when Factor X is activated?

The common pathway begins, leading to thrombin generation and fibrin formation.

What happens when Factor V acts with Factor Xa?

They form the complex that activates prothrombin to thrombin.

What is the role of calcium in coagulation?

It is required for several coagulation reactions, including activation of thromboplastin and conversion of prothrombin.

Why is Factor XIII deficiency different from many other factor deficiencies?

It affects fibrin stabilization, so bleeding can be delayed even when initial clot formation occurs.

What does delayed bleeding suggest in Factor XIII deficiency?

The initial fibrin clot may form, but it is inadequately stabilized.