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Sophie - Principles of Pathology - Year 2 > 41.1 Haemostasis > Flashcards

41.1 Haemostasis Flashcards

1
Q

What is a blood clot?

A

Semisolid mass composed of both platelets and fibrin entrapped in a mesh of fibrin and blood cells

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2
Q

Define haemostasis

A

Process that prevents excessive blood loss (haemorrhage)

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3
Q

How does a breach of the endothelium lead to platelet adhesion?

A

Exposes platelet receptors to ligands that are components of the subendothelial matrix: collagen (Ia), fibronectin and laminin (Ic)

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4
Q

How does AT III work?

A

Binds and inhibits factor Xa and thrombin

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5
Q

How does the endothelial lining of blood vessels prevent thrombosis?

A

-Physical barrier separating platelets and coagulation factors from stimulatory collagen
-Secretion of heparan sulphate to activate AT II
-Synthesis of inhibitors of platelet activation (prostacyclin, NO)

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6
Q

How does the extrinsic pathway occur if factor VII is inside the vascular system and tissue factor is on non vascular cells?

A

Injury to endothelium allows for Factor VII to come in contact with tissue factor which non proteolytically activates Factor VII to VIIa

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7
Q

How does thrombomodulin work?

A

Forms a complex with thrombin and removes it from circulation

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8
Q

How is haemostasis achieved (4)?

A

-Vasoconstriction
-Increased tissue pressure
-Platlet plug
-Coagulation (clot formation)

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9
Q

List the factors that inhibit clotting

A

-Blood flow
-TFPI (Tissue factor pathway inhibitor)
-Antithrombin III
-Thrombomdulin
-Activated protein C
-Clot degradation (fibrinolysis)

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10
Q

Other than adhesion, what does binding of platelet receptors to ligands cause?

A

Causes a conformational change in the receptor that initiates an intracellular signalling cascade leading to PLATELET ACTIVATION

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11
Q

State the intrinsic pathway

A
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12
Q

What activates the conversion of plasminogen to plasmin?

A

t-Pa (tissue plasminogen activator) (increased levels of t-Pa by caetcholamines)

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13
Q

What are platelets?

A

Thrombocytes: small colourless cell fragments of megakaryocytes made in bone marrow
Life spand of 8-10 days
Secrete vasoactive mediators (TXA2, 5-HT)

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14
Q

What are the ‘factors’?

A

Most are serine proteases- once activated it catalyses a specific proteolytic event in the subsequent factor

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15
Q

What are the three processes that occur when a platlet plug is formed?

A

-Adhesion
-Activation
-Aggregation

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16
Q

What are the two pathways in the coagulation cascade?

A

Intrinsic and extrinisic pathway that converge to a common pathway

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17
Q

What causes haemophilia?

A

Inability to synthesis clotting factors (VIII) (IX)

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18
Q

What causes the cleavage of X to Xa in the extrinsic pathway?

A

Tissue factor + Ca + Factor VIIa

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19
Q

What complex is required to convert X to Xa from the intrinsic pathway?

A

VIIIa and IXa (and Ca2+) complex

20
Q

What does thrombin do?

A

Proteolysis of soluble fibrinogen to insoluble fibrin monomers that spontaneously polymerise to form a gel of fibrin polymers that traps blood cells

21
Q

What does vWF bind to?

A

Platelet receptor glycoprotein Ib/Ia

22
Q

What does Xa do?

A

With Va converts plasma protein prothromobin to thrombin (protease)

23
Q

What follows platelet activation?

A

Aggregation

24
Q

What form does plasmin circulate as?

A

Inactive plasminogen

25
Q

What generates VIIa?

A

VII –> VIIa
-Thrombin: feedback activation (downstream product)
VIIa is a crucial modifier of X –> Xa

26
Q

What helps to stabilise the platelet plug?

A

Conformational change in Gp IIb/IIIa exposes it and allows it to bind fibrinogen
-Fibrinogen in blood forms bridges between platelets
-stabilises platelet plug

27
Q

What is the cause of platelet adhesion?

A

Increase in SHEARING force in response to injury causes platelets to adhere to themselves and other components (vascualr wall)

28
Q

What is the purpose of a cascade?

A

Amplifies a signal = only a small amount of one factor generates large amounts of the downstream factors

29
Q

What is tissue factor?

A

An integral membrane protein that is a receptor for Factor VII

30
Q

What is vasospasm? When does it occur?

A

Narrowing of the arteries caused by persistent contraction of blood vessels (prevents haemorrhage)

31
Q

What makes anti thrombin III?

A

Endothelial cells and the liver

32
Q

What mediates platelet adhesion?

A

Platelet receptors - integrall membrane glycoproteins in the platelet membrane belonging to a class of receptors known as integrins

33
Q

What reaction activates the common pathway?

A

X –> Xa
Xa is the first protease of the common pathway

34
Q

What signal transduction cascade does platelet activation involve? What are the consequences of platelet activation?

A

-Activation of PLC
-Increase in intracellular Ca2+
-Exocytosis of dense storage granules (ADP, serotonin, vasoconstrictors: 5-HT, adrenaline)
-Exocytosis of alpha granules (vWF, Clotting factor V, PDGF (platelet activating factor) and fibrinogen deposition)
-Cyclooxyenease breaks down arachidonic aid to thromboxane A2 which is released
-Cytoskeletal morphological change: pseudopodia emerge (finger like projections) to increase surface area and adhesiveness of platelets

35
Q

What stimulates the intrinsic coagulation cascade?

A

Abnormal surfaces:
-Negatively charged surfaces (activated platelet)

36
Q

What triggers the extrinsic pathway?

A

Factors outside the vascular system: TISSUE FACTOR (factor III, thromboplastin) binding to factor VII
Initiates a cascade that occurs outside the vascular system
Responsible for initating clotting

37
Q

What unites the extrinsic and intrinsic pathways?

A

The common pathway

38
Q

Where is positive feedback in the clotting cascade?

A

Thrombin catalyses the formation of cofactors Va and VIIIa (and more)

39
Q

Where is vWF found?

A

-secreted by endothelium in response to injury (hypoxia, high shear)
-found in alpha granules of platelets (released upon platelet activation)

40
Q

Which cascade occurs alongside the platelet activation cascade?

A

Blood clotting/coagulation cascade

41
Q

Which enzyme breaks down fibrin?

A

Plasmin (serine protease)

42
Q

Which factor becomes activated at the beginning of the intrinsic cascade?

A

Factor XII (plasma protein) becomes factor XIIa

43
Q

Which factors require vitamin K?

A

Factor X
Prothrombin
Factor VII
Factor IX
Protein C

44
Q

Which platelet receptor ligand is found in plasma?

A

von Willebrand factor (vWF)

45
Q

Why do platelets not normally adhere to endothelial cells?

A

Due to the negative charge on both surfaces:
-Endothelial cells have proteoglycans (heparan sulphate)

46
Q

Why must the clotting cascade be regulated?

A

Too slow –> excessive bleeding
Too efficient –> excessive coagulation

Sophie - Principles of Pathology - Year 2 (43 decks)

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