Secondary Hemostasis: Intrinsic Pathway

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to Lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

Which of the following mechanisms prevents inappropriate primary hemostasis?

  • Inhibition of antithrombin III by heparin sulfate
  • Secretion of nitric oxide and prostacyclin by endothelial cells (correct)
  • Decreased expression of thrombomodulin on endothelial cells
  • Increased production of thromboxane A2 by endothelial cells

What is the role of Factor XIIIa in the context of the intrinsic pathway?

  • Initiating the cascade by binding to collagen
  • Cross-linking fibrin to stabilize the clot (correct)
  • Inhibiting the activation of Factor XII
  • Activating Factor X to Factor Xa

Which of the following is the first factor to join the intrinsic cascade?

  • Factor XI
  • Factor VIII
  • Factor XII (correct)
  • Factor IX

What is the function of von Willebrand factor (vWF) in secondary hemostasis?

<p>Binding to platelets and promoting platelet plug formation (C)</p> Signup and view all the answers

Which of the following is the result of Factor IXa interacting with Factor VIII and Platelet Factor 3 (PF3) in the intrinsic pathway?

<p>Activation of Factor X to Xa (B)</p> Signup and view all the answers

What is the role of Factor Xa in the conversion of fibrinogen to fibrin?

<p>It activates Factor II (prothrombin) into thrombin (Factor IIa), which then activates fibrinogen. (D)</p> Signup and view all the answers

In the extrinsic pathway, what is the role of tissue factor (TF)?

<p>It binds to Factor VII and initiates the pathway. (A)</p> Signup and view all the answers

What is the role of Vitamin K in the coagulation cascade?

<p>It serves as a cofactor for the carboxylation of glutamate residues on certain clotting factors. (B)</p> Signup and view all the answers

Which of the following best describes the common pathway in the coagulation cascade?

<p>It represents the final steps leading to fibrin formation. (D)</p> Signup and view all the answers

What is the significance of the prothrombinase complex in the common pathway?

<p>It activates thousands of thrombin molecules. (A)</p> Signup and view all the answers

What role does calcium play in the coagulation cascade?

<p>It is essential for the function of several coagulation complexes. (D)</p> Signup and view all the answers

Which of the following is a function of thrombin?

<p>Activation of platelets and cleavage of fibrinogen (B)</p> Signup and view all the answers

Why is Vitamin K important for coagulation?

<p>It is required for the gamma-carboxylation of certain clotting factors (A)</p> Signup and view all the answers

What are the three conditions that can make individuals susceptible to Vitamin K deficiency?

<p>Malabsorption, broad-spectrum antibiotics, and premature birth (D)</p> Signup and view all the answers

Which of the following is a direct thrombin inhibitor?

<p>Dabigatran (A)</p> Signup and view all the answers

What role do Proteins C and S play in coagulation?

<p>Prevent clotting (B)</p> Signup and view all the answers

What happens when thrombin interacts with thrombomodulin in coagulation?

<p>Activation of Protein C (C)</p> Signup and view all the answers

Which of the following is a defining characteristic of the extrinsic pathway of coagulation?

<p>It is triggered by exposing blood to a factor found outside of the blood vessel. (A)</p> Signup and view all the answers

How does the body regulate clot formation to prevent it from becoming too extensive?

<p>Through anticoagulation mechanisms that occur after thrombin production (C)</p> Signup and view all the answers

Deficiencies in Proteins C or S can cause which of the following?

<p>Cause thrombosis (A)</p> Signup and view all the answers

What is the role of heparin sulfate in preventing inappropriate blood clotting?

<p>It activates antithrombin III. (D)</p> Signup and view all the answers

Which of the factors are vitamin k dependent serine proteases?

<p>Factors Xa and IIa (A)</p> Signup and view all the answers

What needs to happen in order for vitamin K epoxide to keep working?

<p>Needs to get reduced in order to keep working. (D)</p> Signup and view all the answers

What clotting factors need Ca2+ cofactor in order to function?

<p>Factors II, VII, VIII, IX, X, XI and XIII (A)</p> Signup and view all the answers

How are the intrinsic and extrinsic pathways linked?

<p>Through prothrombinase complex (A)</p> Signup and view all the answers

At which point does antiocoagulation occur?

<p>The most important regulation happens after production of thrombin. (C)</p> Signup and view all the answers

What is the function of Fibrinolysis?

<p>To dissolve the fibrin (B)</p> Signup and view all the answers

What is the definition of Factor XIII?

<p>A fibrin stabilizing factor (A)</p> Signup and view all the answers

What happens to individuals who are deficient in FXIII?

<p>They formed an initial fibrin clot but the clot dissolves and the person can hemorrhage (C)</p> Signup and view all the answers

Flashcards

What is fibrinogen?

A plasma protein that is converted into fibrin by thrombin to form a stable clot.

What is Factor XIIIa?

A transamidase that crosslinks fibrin molecules to stabilize the clot.

What is the Common Pathway?

The final steps in the coagulation cascade, leading to clot formation.

What are Factors Xa and IIa?

Serine proteases that require vitamin K for their synthesis, playing a key role in coagulation.

Signup and view all the flashcards

What is Heparin Sulfate?

A glycosaminoglycan that activates antithrombin III, inhibiting coagulation.

Signup and view all the flashcards

What is Thrombomodulin?

Binds thrombin, activating protein C, which inhibits factors V and VIII.

Signup and view all the flashcards

What happens if you are deficient in FXIII?

Are deficient in patients who form an initial fibrin clot, but then the clot dissolves and the person hemorrhages.

Signup and view all the flashcards

What is von Willebrand's factor (vWF)?

Produced by damaged cells and binds to platelets, promoting platelet plug formation.

Signup and view all the flashcards

What is Factor XIIa?

Activates Factor XI to XIa in the intrinsic pathway.

Signup and view all the flashcards

Why is has Calcium (Ca2+) needed in secondary hemostasis?

Needed for the interaction and formation of the complex that then activates Factor X to Xa

Signup and view all the flashcards

What does Thrombin (Factor IIa) do?

Cleaves fibrinogen into fibrin.

Signup and view all the flashcards

Why is the Extrinsic pathway extrinsic?

Tissue factor it requires is outside of the blood.

Signup and view all the flashcards

Why is Calcium so vital?

Is vital for coagulation!

Signup and view all the flashcards

What are some facts about vitamin K?

Synthesized by intestinal bacteria and is a fat soluble vitamin.

Signup and view all the flashcards

What happens during absence of Vitamin K?

Leads to uncontrolled bleeding!

Signup and view all the flashcards

What does Vitamin K epoxide reductase do?

Reduces vitamin K epoxide back to Vitamin K quinone.

Signup and view all the flashcards

What happens if there is no gamma (y)-carboxylation?

The non-carboxylated factors are unable to bind to activating Ca2+ ions or to phospholipid membranes.

Signup and view all the flashcards

What is Proteins C?

A serine protease that destroys the activated cofactors Va and VIIIa.

Signup and view all the flashcards

When does anticoagulation happen?

Primary and secondary hemostasis happens during coagulation.

Signup and view all the flashcards

When does Clot retraction and Fibrinolysis?

Primary and secondary hemostasis happens after retraction and Fibrinolysis.

Signup and view all the flashcards

Study Notes

Learning Objectives

  • Fibrinogen is converted to fibrin by thrombin (Factor II)
  • Factor XIIIa is a transamidase fibrin stabilizing factor
  • The common pathway consists of the final steps in the coagulation cascade
  • Vitamin K-dependent serine proteases Factors Xa and IIa must be described

Prevention of Inappropriate Primary Hemostasis

  • Endothelial cells secrete nitric oxide (NO), a vasodilator, and prostacyclin (PGI2) which inhibits platelet aggregation
  • Heparin Sulfate activates anti-thrombin 3 (AT III), which inactivates factors II, IX, and X and acts as an anti-coagulant
  • Thrombomodulin binds thrombin (Factor II) on endothelial cells, activating Protein C, which inhibits Factors V and VIII
  • Protein C stops coagulation

Secondary Hemostasis: Intrinsic Pathway

  • Clotting factors are present within the blood
  • Negatively charged surfaces such as activated platelets, collagen, or glass trigger it
  • The liver constantly produces coagulation factors (zymogens)
  • Factor XII is the first factor to join the intrinsic cascade
  • Damaged cells produce von Willebrand's factor (vWF) to bind platelets and promote platelet plug formation
  • Platelets also bind fibrinogen via GpIIb/IIIa

Intrinsic Pathway Cascade of Activation

  • Factor XIIa activates Factor XI becoming XIa
  • Factor XIa activates Factor IX becoming IXa
  • Factor IXa interacts with Factor VIII and Platelet Factor 3 (PF3) and this complex needs Ca2+
  • The complex activates Factor X to Xa

Thrombin Conversion of Fibrinogen to Fibrin

  • Factor Xa cleaves Factor V to Factor Va, then interacts with Va and Ca2+ to form the prothrombin activator
  • Factor II (prothrombin) gets activated into thrombin (Factor IIa)
  • Thrombin (Factor IIa) activates fibrinogen to fibrin
  • Factor XIII (fibrin stabilizing factor) crosslinks fibrins resulting in a stronger mesh

Secondary Hemostasis: Extrinsic Pathway

  • The extrinsic pathway requires tissue factor, which is outside of the blood
  • The extrinsic pathway is shorter and faster than the intrinsic pathway and can form a clot in ~15 seconds
  • Exposure of blood to a factor found in tissues underneath the damaged endothelium (tissue factor or TF) triggers the pathway. TF is also called Factor III
  • Factor VII is exposed to TF and gets activated to Factor VIIa
  • Factor VIIa binds to TF and Ca2+ which forms a VIIa-TF-Ca2+ complex at the smooth muscle
  • The VIIa-TF-Ca2+ complex cleaves Factor X to Factor Xa

Conversion of Fibrinogen to Fibrin and Factor XIII to Factor XIIIa

  • Prothrombinase complex cleaves prothrombin (Factor II) into thrombin (or Factor IIa)
  • This is the step that gets amplified
  • Thrombin activates platelets and cleaves fibrinogen (Factor I, which is soluble in blood) into fibrin (Factor Ia, which is insoluble)
  • Thrombin activates Factor XIII into XIIIa and 3 cofactors, Factor V of the common pathway, and Factors VIII and IX of the intrinsic pathway
  • Factor XIIIa binds Ca2+ and forms crosslinks between the fibrin chains, further reinforcing the fibrin mesh
  • Fibrin makes the liquid plasma become gel-like and traps formed elements

Fibrin Cross-linking Actions of Factor XIIIa

  • Factor XIIIa results in the formation of a stable fibrin clot that withstands mechanical and enzymatic breakdown
  • Patients deficient in FXIIIa form an initial fibrin clot, but the clot dissolves causing hemorrhage

Common Pathway

  • Once Factor X is activated to Xa, the intrinsic and extrinsic pathways merge
  • Factor X (Stuart-Prower factor) joins Factor Va (plus Ca2+) to form the Prothrombinase complex
  • The prothrombinase complex can activate thousands of thrombin (F II) in the amplification step
  • Thrombin can activate platelets and cleave fibrinogen
  • Factor XIIIa stabilizes the mesh
  • Factors II, VII, VIII, IX, X, XI and XIII need Ca2+ cofactor

Common Pathway Activation

  • Factor X is activated by the intrinsic pathway through the Tenase Complex (VIIIa-IXa-Ca2+)
  • It is activated by the extrinsic pathway through the (TF-VIIa-Ca2+) complex
  • Both pathways lead to Xa-Va-Ca2+ prothrombinase complex
  • The prothrombinase complex cleaves prothrombin (FII) to generate thrombin (FIIa)
  • Amplification happens as thrombin activates proteins of intrinsic and common pathway
  • The process releases more vWF and causes platelet activation resulting in "positive feed back"

Clot Formation

  • The Intrinsic Pathway:
    • Is activated by factors present in blood
    • Starts with Factor XII (Hageman factor)
    • Can be measured via the Partial thromboplastin time (PTT) and the normal range is between 25 and 40 seconds
  • The Extrinsic Pathway:
    • Is activated by muscle cell damage
    • Starts with tissue factor (TF) and Factor VII
    • Can be measured via the Prothrombin Time (PT) and the normal range is between 9.5 and 13 seconds

Clot formation regulation

  • Anticoagulation happens during primary and secondary hemostasis, regulating clot formation
  • Prevents clots from getting too big (embolus)
  • The most important part of this regulation happens after production of thrombin
  • Clot retraction and fibrinolysis happen after primary and secondary hemostasis reducing clot size

Calcium and Coagulation

  • Ca2+ is vital for coagulation and is a component of:
    • TF-FVIIa- Ca2+ complex
    • Tenase complex, FVIIIa-FIXa- Ca2+
    • Prothrombinase complex FXa-FVa- Ca2+
  • Individual factors II, VII, IX and X (vitamin K-dependent factors) need Ca2+ as a cofactor for their activation
  • Coagulation is facilitated by platelet granular release of Ca2+ and is markedly impaired in hypocalcemia

Blood clotting factors

  • Most are plasma proteins synthesized in the liver
  • Factor IV is calcium ions
  • Vitamin K is required for synthesis of factors II, VII, IX, and X

Vitamin K-Dependent Serine Proteases, Factors Xa and IIa

  • Vitamin K is a fat-soluble vitamin important for blood clot formation and bone health
  • It must be ingested and metabolized in order to create mature coagulation factors
  • It is used in the production of Factors II, VII, IX and X, particularly from green-leaf vegetables
  • It is also synthesized by intestinal bacteria and is stable in air but decomposes in sunlight
  • Absence of vitamin K leads to uncontrolled bleeding
  • The ingested form of vitamin K is vitamin K quinone, which gets reduced by NADPH to vitamin K hydroquinone and acts as a cofactor to gamma-glutamyl carboxylase which converts Factors II, VII, IX and X into their functional forms

Role of Vitamin K

  • Glutamate carboxylase mediates carboxylation using oxygen, carbon dioxide, water, and protons to produce É£-carboxyglutamate
  • The extra carboxyl group allows the protein to bind calcium, helping blood clotting proteins remain at the injury site
  • Vitamin K is a cofactor for glutamate carboxylase

Recycling of Vitamin K

  • Carboxylation oxidizes (inactivates) vitamin K
  • Inactive form of vitamin K, vitamin K Epoxide, needs to get reduced by Vitamin K epoxide reductase
  • Vitamin K epoxide reductase reduces vitamin K epoxide back to vitamin K Quinone which regenerates active Vitamin K

Vitamin K Recycling Inhibition and Resulting Deficiencies

  • Vitamin K epoxide reductase can be inhibited by blood thinners like warfarin or coumadin (rat poison)
  • Vitamin K deficiencies lead to disordered coagulation from lack of function of Factors II, VII, IX and X, blocking both intrinsic and extrinsic pathways
    • Gamma (γ)-carboxylation is important since Factors that are not carboxylated cannot bind to activating Ca2+ ions or phospholipid membranes
  • Susceptibility to Vitamin K deficiency can be caused by Malabsorption (cystic fibrosis, celiac disease), broad-spectrum antibiotics or being a premature neonate

Anticoagulants

  • Prothrombin time (PT) is important when using anti-coagulants and include drugs like:
    • Heparins (anti-thrombin)
    • Vitamin K Antagonists
    • Direct Oral Anticoagulants (DOACs)
      • Direct Thrombin Inhibitors
      • Factor Xa Inhibitors

Hemostasis Drug Therapies

  • Antiplatelets
  • Anticoagulants
  • Thrombolytics
  • Herbal Supplements

Proteins C and S

  • Protein C and S work together to prevent excessive blood clotting
    • Not enough protein C or S causes increased clotting
  • Protein C is a serine protease that destroys activated cofactors Va and VIIIa
  • It is activated when thrombin binds to thrombomodulin (at the surface of endothelial cells)
  • Protein S is a cofactor for Protein C
  • Both proteins C and S are vitamin K-dependent
  • Undamaged cells ensure coagulation is limited to the injured site

Deficiencies of Proteins C and S

  • Not enough protein C or S may cause more clotting than needed
  • Clinical relevance: hereditary or acquired deficiencies can cause thrombosis/clotting events
    • Such as in deep vein thrombosis
    • Treatment with warfarin can decrease protein C activity

Studying That Suits You

Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

Quiz Team

Related Documents

More Like This

Laboratory Evaluation of Secondary Hemostasis
12 questions
Secondary Hemostasis Quiz
41 questions

Secondary Hemostasis Quiz

DecentBowenite3871 avatar
DecentBowenite3871
Secondary Hemostasis & Coagulation Factors
40 questions
Use Quizgecko on...
Browser
Browser