Haemostasis and Vascular Pathology Flashcards Preview

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Define haemostasis

A precisely orchestrated sequence of regulatory processes that culminate in the formation of a blood clot to limit bleeding from a site of vascular injury.


What are the roles of haemostasis?


-Blood to be in a fluid state in a normal vessel

-Formtion of a localised haemostatic clot at sites of vascular injury

-Prevents haemorrhage


What are the 3 components of haemostasis?

Vascular Wall


Coagulation cascade


Explain the structure of basic blood vessel histology

1: Tunica Intima (inner most layer)

  • Endothelium (single layer of squamous cells)
  • Basement membrane
  • Connective tissue (subendothelium)
  • Internal elastic lamina

2: Tunica Media

  • Circumferentially arranged smooth muscle

3: Tunica Adventitia

  • Connective tissue containing vascular and neural supply


What layers of the tunica intima are significant in haemostasis?


Connective tissue (subendothelium)


What is the role of the endothelium?

Endothelial cells are:

  • Antiplatelet
  • Anticoagulant
  • Fibrinolytic

Act as a barrier between thrombogenic subendothelium and coagulation factors in the blood.

Express factors which prevent thrombosis in undamaged vessels and limit clot formation to sites of vascular injury.


What is the role of platelets in haemostasis?

How do they carry out this role?

Formation of initial platelet plug

Provide a surface for the recruitment and concentration of coagulation factors

Does this in 3 stages:

  • Adhesion to extracellular matrix at sites of vascular injury
  • Activation by secretion of granules
  • Aggregation of platelets


What components does the clotting cascade require?

  • Coagulation factors (pro-enzymes)
    • Converted to activate coagulation factors:
      • Factors XII, XI, IX, X, VII and prothrombin
  • Cofactors (reaction accelerators)
    • Factors V and VIII
  • Negatively charged phospholipid surface (platelet activation)
  • Calcium Ions
  • Vitamin K: factors VII, IX, X and prothrombin are dependent on vit K for correct production.



What are the 4 stages of haemostasis?


Primary Haemostasis

Secondary Haemostasis

Clot Stabilisation and Resorption



What is the purpose of the vasoconstriction phase of haemostasis?

Minimise blood loss

Maximises interactions between platelets, clotting factors, and vessel wall


What is the vasoconstriction stage mediated by?

Reflex neurogenic mechanisms

Release of endothelin


Explain the process of primary haemostasis

  1.  Damage to the vessel wall releases Von Willebrand Factors (vWF) and collagen from the exposed subendothelium.
  2. vWF binds to and activates platelets.
  3. Platelets grow spiky projections which allows platelet-platelet interaction.
  4. Platelets also release secretory granules which causes further platelet recruitment and aggregation.
  5. This process forms a primary platelet plug.



What occurs in secondary haemostasis?

Reinforcement of platelet plug

  1. Tissue Factor (expressed on smooth muscle cells and fibroblasts in subendothelium in response to damage) binds to and activates Factor VII and initiates the clotting cascade.
  2. Clotting cascade generates thrombin
  3. Thrombin claeves circulating fibrinogen into fibrin (insoluble)
  4. Fibrin meshwork is formed 
  5. Fibrin binds more platelets
  6. Consolidates initial platelet plug


What is the purpose of the clotting cascade?

Production of thrombin which converts fibrinogen to fibrin, stabilising blood clot


What measures the extrinsic pathway?

Prothrombin time


Describe the process of the extrinsic pathway of the coagulation cascade

  1. Initiated by tissue factor (TF)
  2. TF activates FVII to FVIIa 
  3. TF forms a complex with FVIIa and Ca2+ ions
  4. This complex activates FX and FIX
  5. This leads to the final common pathway


What measures the intrinsic pathway of the coagulation cascade?

Partial thromboplastin time (PTT)


Describe the process of the intrinsic pathway of the coagulation cascade

  1. Initiated when FXII comes into contact with a negatively charged surface (i.e. activated platelets) and is activated to FXIIa
  2. FXIIa activates FXI to FXIa
  3. FXIa activates FIX to FIXa
  4. FIXa activates FVIII to FVIIIa
  5. FIXa, FVIIIa and Ca2+ form a complex which activates FX
  6. This leads to the final common pathway


Describe the process of the final common pathway of the coagulation cascade

  1. FXa, cofactor Va and Ca2+ ions form prothrombinase complex.
  2. Prothrombnase activates prothrombin and converts it to thrombin
  3. Thrombin converts fibrinogen to fibrin
  4. Fibrin monomers spontaneously polymerise to form long fibres which form an insoluble network around the primary platelet plug.
  5. The clot is further stabilised by FXIIIa which is activated by thrombin which forms stronger cross links between e fibrin polymers.


What are the actions of thrombin?

  • Conversion of fibrinogen to fibrin
  • Amplifies coagulation process by activating:
    • FXI
    • FV
    • FVIII
  • Stabilises secondary haemostatic plug by activating FXIII
  • Further platelet activation
  • Pro-inflammatory effects: contributes to tissue repair and angiogenesis
  • Anticoagulant effects: when interacting with normal endothelium, helps limit clots to site of injury


What occurs in the clot stabilisation and reabsorption stage of haemostasis?

Fibrin and platelet aggregates undergo contraction to form a permanent plug

Counter-regulatory mechanisms limit the clotting to the site of injury

Clot reabsorption and tissue repair

Involves the fibrinolytic system


Describe the process of the coagulation cascade in vivo

  1. TF forms complex with FVIIa
  2. TF-VIIa complex activates FIX and FX
  3. Activated platelet membrane catalyses prothrombin conversion to thrombin by FXa on its own.
  4. Thrombin activates V, VIII and XI
  5. IXa forms complex with VIIIa and Ca2+:  much more potent activator of X than TF-VIIa complex
  6. Xa forms complex with Va and Ca2+: much more potent convertor of prothrombin to thrombin than Xa alone.
  7. Lots more thrombin is produced


Which factors limit coagulation?

  • Dilution: blood flowing past the clot dilutes the clotting factors.
  • Intact endothelium expresses anti-coagulation factors
  • Circulating inhibitors:
    • Antithrombin III- actively augmented by heparin-like molecules on intact endothelium: inhibits thrombin, FIXa, FXa, FXIa and FXIIa
  • Fibrinolytic cascade


What drugs affect coagulation?


  • LMWH
  • Unfractioned heparin



Describe the process of the fibronolytic cascade

Inactive, circulating plasminogen is converted to plasmin by:

  • FXII-dependent pathway OR
  • Plasminogen activators: e.g. tissue plasminogen activator- releassed by endothelial cells near site of injury

Plasmin breaks down fibrin:

  • Limits clot size
  • Contributes to its later dissolution

Fibrin degradation products formed circulate in the blood, can be measured via D-dimer


What blood test is used to measure breakdown products from fibrin degradation?

What does it indicate if raised?


Indicates hypercoagulable state due to formation of clot


Define haemorrhage

Extravasation of blood into the extravascular space


What factors affect the clinical significance of haemorrhage?

Volume of blood lost

Location (e.g. small bleed in brain= significant; small bleed from skin=insignificant)

Rate of blood lost (ability to compensate)

Patient's condition: age, comorbidities



Define thrombosis

Pathological formation of a solid mass of blood products in a blood vessel lumen

Can lead to vascular occlusion, ischaemia and infarction


Virchow's Triad:

What factors increase the risk of thrombosis?

Endothelial injury


Abnormal blood flow