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haemostasis Flashcards

1
Q

What is haemostasis?

A

Haemostasis is the mechanism by which the body ensures that blood remains fluid while damaged vessels are quickly fixed to stop excess loss.

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2
Q

Why is haemostasis important?

A

Haemostasis is important because bleeding due to injury must stop quickly to minimise blood loss. Problems with haemostasis can lead to either haemorrhage or excessive blood clot formation, both of which can be extremely dangerous and can lead to death if not treated quickly.

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3
Q

What is primary haemostasis?

A

Primary haemostasis is the initial response to blood vessel injury and involves interactions between platelets and vascular endothelial cells.

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4
Q

What is secondary haemostasis?

A

Secondary haemostasis involves the coagulation cascade and the activation of clotting factors that leads to the formation of a fibrin clot, which helps to stabilise the platelet plug and prevent further blood loss.

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5
Q

What are the two main stages of haemostasis?

A

The two main stages of haemostasis are primary haemostasis and secondary haemostasis.

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6
Q

What is the coagulation cascade?

A

The coagulation cascade is a series of reactions that involves the activation of clotting factors and the formation of a fibrin clot, which helps to stabilise the platelet plug and prevent further blood loss.

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7
Q

What are the consequences of problems with haemostasis?

A

Problems with haemostasis can lead to either haemorrhage or excessive blood clot formation, both of which can be extremely dangerous and can lead to death if not treated quickly.

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8
Q

How can haemostasis be managed?

A

Haemostasis can be managed through a variety of methods, including medications that prevent excessive blood clot formation, blood transfusions to replace lost blood, and surgery to repair damaged blood vessels.

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9
Q

What is the process of erythropoiesis?

A

Erythropoiesis is the process by which red blood cells are produced in the bone marrow.

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10
Q

What hormone stimulates erythropoiesis?

A

The hormone erythropoietin (EPO) stimulates erythropoiesis.

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11
Q

What is the process of thrombopoiesis?

A

Thrombopoiesis is the process by which platelets are produced in the bone marrow.

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12
Q

What hormone stimulates thrombopoiesis?

A

The hormone thrombopoietin (TPO) stimulates thrombopoiesis.

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13
Q

What is the role of von Willebrand factor (vWF) in primary hemostasis?

A

vWF is a protein that helps platelets adhere to the site of vascular injury and form a platelet plug.

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14
Q

What is the role of fibrinogen in secondary hemostasis?

A

Fibrinogen is a protein that is converted to fibrin through the coagulation cascade, which forms the structural basis of a blood clot.

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15
Q

What is the function of megakaryocytes in haemostasis?

A

Megakaryocytes are responsible for forming platelets via endomitosis in the bone marrow.

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16
Q

What is endomitosis?

A

Endomitosis is a type of cell division in which DNA replication occurs without cell division. This results in a cell with a large, complicated nucleus containing multiple copies of DNA.

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17
Q

How are platelets formed from megakaryocytes?

A

The megakaryocyte cytoskeleton rearranges and pro-platelet extensions are formed in the periphery of the megakaryocyte. Microtubules facilitate the movement of organelles in the pro-platelets extensions, which consist of part of the megakaryocyte cytoplasm.

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18
Q

What are the membrane glycoproteins involved in platelet function?

A

The membrane glycoproteins involved in platelet function include Glycoprotein Ib, Glycoproteins Ia – IIa and VI, and Glycoproteins IIb/IIIa.

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19
Q

What is the function of Glycoprotein Ib in platelet function?

A

Glycoprotein Ib plays a role in initial platelet attachment to von Willebrand factor and the vascular endothelium.

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20
Q

What is the function of Glycoproteins Ia – IIa and VI in platelet function?

A

Glycoproteins Ia – IIa and VI facilitate platelet adhesion to collagen.

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21
Q

What is the function of Glycoproteins IIb/IIIa in platelet function?

A

Glycoproteins IIb/IIIa are involved in adhesion to fibrinogen and additional adhesion to von Willebrand factor, as well as platelet-to-platelet adhesion.

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22
Q

What are the contents of electron dense granules in platelets?

A
  • Nucleotides (ADP)
  • Serotonin
  • Ca2+
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23
Q

What are the contents of alpha granules in platelets?

A
  • Fibrinogen
  • Factor V
  • Heparin antagonist
  • Platelet Derived Growth Factor (PDGF)
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24
Q

How does vascular injury lead to platelet adhesion and activation?

A
  • Vascular injury exposes collagen fibres which causes platelet adhesion and activation.
  • The endothelial damage and exposure of collagen triggers the platelet adhesion.
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25
Q

What is the role of serotonin in haemostasis?

A

Serotonin causes vasoconstriction and reduces blood flow.

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26
Q

What is the role of nitric oxide in haemostasis?

A

Endothelial cells and macrophages secrete nitric oxide (NO) inhibiting platelet activation and promoting vasodilation.

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27
Q

What is the role of platelet aggregation in haemostasis?

A

Platelet aggregation with their phospholipid surface offers a “platform” for the coagulation cascade.

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28
Q

What is the role of platelets in haemostasis?

A

Platelets play a vital role in haemostasis by facilitating primary haemostasis, which involves the interaction between platelets and vascular endothelial cells. Platelets adhere to collagen fibres, become activated, and release their granule contents, which includes nucleotides (ADP), serotonin, Ca2+, fibrinogen, factor V, heparin antagonist, and platelet-derived growth factor (PDGF). The phospholipid surface of the aggregated platelets serves as a “platform” for the coagulation cascade, which leads to the formation of a blood clot.

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29
Q

What is the function of von Willebrand factor in platelet function?

A

Von Willebrand factor (VWF) is a large multimeric glycoprotein that is synthesised by endothelial cells and megakaryocytes. In platelets, VWF is stored in alpha granules and is released upon activation. The multimers of VWF bind strongly to platelets and subendothelial collagen, facilitating platelet adhesion and aggregation. In addition, VWF stabilises factor VIII of the coagulation cascade. The cleavage of large VWF multimers by the metalloproteinase ADAMTS13 is crucial for its function. In Von Willebrand disease, which is a blood clotting disorder, excessive bleeding is observed due to the deficiency of VWF.

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30
Q

What is the role of nitric oxide in platelet function?

A

Nitric oxide (NO) is a molecule that is secreted by endothelial cells and macrophages, which inhibits platelet activation and promotes vasodilation. The release of NO by endothelial cells prevents platelet adhesion and aggregation, which helps to maintain the fluidity of the blood. In addition, NO plays a crucial role in regulating blood pressure by promoting vasodilation.

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31
Q

What initiates the coagulation cascade in the extrinsic pathway?

A

The interaction between Tissue Factor and Factor VII.

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32
Q

Which factors are activated by the Tissue Factor-Factor VII complex in the extrinsic pathway?

A

Factor X, Factor IX, and Factor XI.

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33
Q

Is the amount of thrombin formed during the extrinsic pathway sufficient for the conversion of fibrinogen to fibrin?

A

No, only a small amount of thrombin is formed.

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34
Q

What is the purpose of the intrinsic pathway in the coagulation cascade?

A

To amplify the coagulation cascade signalling pathway.

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35
Q

What factors are activated by thrombin during the intrinsic pathway?

A

Factor VIII and Factor V.

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36
Q

What is the role of Ca2+ in the intrinsic pathway?

A

Ca2+ is required for the intrinsic pathway to occur.

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37
Q

What is the ultimate goal of the common pathway in the coagulation cascade?

A

To stop bleeding and clot formation.

38
Q

What does thrombin do during the common pathway?

A

Thrombin hydrolyses fibrinogen and releases fibrin monomers.

39
Q

What is the function of fibrin monomers in the coagulation cascade?

A

Fibrin monomers form a fibrin polymer, which is important for platelet aggregation and the formation of a haemostatic plug.

40
Q

Which factors are necessary for the common pathway?

A

Factor X and Factor V.

41
Q

What is Factor I and what is its function in the coagulation cascade?

A

Factor I is also called fibrinogen and its function is to serve as a fibrin subunit in the formation of a haemostatic plug.
Its half life is 90 hours.

42
Q

What is Factor II and what is its function in the coagulation cascade?

A
  • Factor II is also called prothrombin and is a serine protease.
  • Its function is to be converted to thrombin during the coagulation cascade.
  • Its half life is 65 hours.
43
Q

What is Factor III and what is its function in the coagulation cascade?

A
  • Factor III is also called tissue factor and is a receptor/cofactor.
  • Its exact function in the coagulation cascade is not fully understood.
  • Its half life is not specified.
44
Q

What is Factor V and what is its function in the coagulation cascade?

A
  • Factor V is also called labile factor and is a cofactor.
  • Its function is to amplify the coagulation cascade signalling pathway.
  • Its half life is 15 hours.
45
Q

What is Factor VII and what is its function in the coagulation cascade?

A
  • Factor VII is also called proconvertin and is a serine protease.
  • Its function is to initiate the coagulation cascade by interacting with Tissue Factor.
  • Its half life is 5 hours.
46
Q

What is Factor VIII and what is its function in the coagulation cascade?

A
  • Factor VIII is also called antihemophilic factor and is a cofactor.
  • Its function is to be activated by thrombin and Factor IX to amplify the coagulation cascade.
  • Its half life is 10 hours.
47
Q

What is Factor IX and what is its function in the coagulation cascade?

A
  • Factor IX is also called Christmas factor and is a serine protease.
  • Its function is to amplify the coagulation cascade by activating Factor X.
  • Its half life is 25 hours
48
Q

What is Factor X and what is its function in the coagulation cascade?

A
  • Factor X is also called Stuart-Prower factor and is a serine protease.
  • Its function is to be activated by both the extrinsic and intrinsic pathways to generate thrombin.
  • Its half life is 40 hours.
49
Q

What is Factor XI and what is its function in the coagulation cascade?

A
  • Factor XI is also called plasma thromboplastin antecedent and is a serine protease.
  • Its function is to amplify the coagulation cascade by activating Factor IX.
  • Its half life is 45 hours.
50
Q

What is Factor XII and what is its function in the coagulation cascade?

A
  • Factor XII is also called Hageman factor and is a serine protease.
  • Its function is to initiate the intrinsic pathway of the coagulation cascade.
  • It also serves as a cofactor for the activation of fibrin stabilizing factor (transglutaminase).
  • Its half life is not specified.
51
Q

What is vitamin K?

A

Vitamin K is a fat-soluble vitamin present in green vegetables and synthesised by gut bacteria.

52
Q

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

A

Vitamin K is essential for the activity of Factors II (Prothrombin), VII, IX and X, as it is required for the synthesis of the active forms.

53
Q

Where is vitamin K deficiency seen?

A

Vitamin K deficiency is seen in newborns or adults due to dietary restrictions.

54
Q

What is the mechanism of action of warfarin?

A

Warfarin stops the activity of vitamin K reductase, which recycles vitamin K.

55
Q

How does liver disease affect vitamin K absorption?

A

Liver disease affects (decreases) the absorption of vitamin K.

56
Q

What is thrombosis?

A

Thrombosis is the formation of blood clots (thrombi) in the blood vessels, which can obstruct blood flow.

57
Q

What are some examples of thrombosis?

A

Examples of thrombosis include arterial thrombosis and venous thrombosis.

58
Q

What can thrombosis cause?

A

Thrombosis can cause myocardial infarction (heart attack), cerebrovascular disease (stroke), and other serious health problems.

59
Q

What is an embolus?

A

An embolus is a clot that breaks free and travels through the blood vessels, risking embolism in another part of the body.

60
Q

What are some hereditary risk factors for thrombosis?

A

Some hereditary risk factors for thrombosis include Factor V Leiden gene mutation, hereditary antithrombin deficiency, Protein C or Protein S deficiency, hereditary elevated levels of plasma prothrombin, and elevated levels of von Willebrand factor.

61
Q

What is the Factor V Leiden gene mutation?

A

The Factor V Leiden gene mutation is a genetic mutation that changes an arginine to a glutamine on Factor V, leading to incomplete inactivation of Factor V by Protein C.

62
Q

What is hereditary antithrombin deficiency?

A

Hereditary antithrombin deficiency is a genetic disorder that results in reduced levels of antithrombin, a protein that inhibits blood clotting.

63
Q

What is Protein C deficiency?

A

Protein C deficiency is a genetic disorder that results in reduced levels of Protein C, a protein that inhibits blood clotting.

64
Q

What is Protein S deficiency?

A

Protein S deficiency is a genetic disorder that results in reduced levels of Protein S, a protein that helps Protein C inhibit blood clotting.

65
Q

What is von Willebrand factor?

A

Von Willebrand factor is a protein in the blood that plays a role in blood clotting. Elevated levels of von Willebrand factor can increase the risk of thrombosis.

66
Q

What is the anti-coagulation mechanism?

A

It is a mechanism aimed at preventing excessive clot formation that acts in balance with blood coagulation.

67
Q

What is plasminogen?

A

It is an inactivated proenzyme that is converted to plasmin by thrombin.

68
Q

What is plasmin?

A

Plasmin is a serine protease that limits the growth of a thrombus by degrading fibrin polymers

69
Q

What is the process of inhibition of coagulation?

A

Thrombin binds on the endothelial cell receptor thrombomodulin, leading to the activation of the endothelial cell bound protein C. Protein C destroys factors V and VIII. No more thrombin is produced, and the coagulation cascade ends.

70
Q

What is tissue factor pathway inhibitor (TFPI)?

A

It is a small (40 kDa) protein produced by endothelial cells, present in platelets, and circulates in the plasma.

71
Q

What does TFPI inhibit?

A

TFPI inhibits Xa, VIIa, and Tissue Factor, thereby limiting thrombin activity to the site of injury only.

72
Q

What is the role of protein C and protein S in coagulation?

A

Protein C, made in the liver, is a serine protease that destroys factors V and VIII, effectively halting the coagulation cascade. Its activity depends on the presence of protein S, which assists in its binding on the surface of platelets.

73
Q

What is antithrombin?

A

Antithrombin is a small glycoprotein that is synthesised by endothelial cells and enters circulation. It inhibits serine proteases, which are involved in coagulation.

74
Q

How does heparin enhance the activity of antithrombin?

A

Heparin is an anti-coagulant that enhances the activity of antithrombin by increasing its ability to bind to and inhibit serine proteases.

75
Q

What is the role of thrombomodulin in coagulation?

A

Thrombomodulin is an endothelial cell receptor that binds to thrombin, resulting in the activation of protein C.

76
Q

How does protein C halt the coagulation cascade?

A

Protein C destroys factors V and VIII, which are necessary for the continuation of the coagulation cascade.

77
Q

What is the role of protein S in coagulation?

A

Protein S assists in the binding of protein C on the surface of platelets, thereby enhancing its activity.

78
Q

What is the function of antithrombin?

A

Antithrombin inhibits serine proteases, which are involved in coagulation.

79
Q

What is heparin?

A

Heparin is an anti-coagulant that enhances the activity of antithrombin by increasing its ability to bind to and inhibit serine proteases.

80
Q

What is the relationship between protein C and vitamin K?

A

Protein C, like many other coagulation factors, is dependent on vitamin K for its activity.

81
Q

What is the role of thrombin in coagulation?

A

Thrombin is a serine protease that converts fibrinogen to fibrin, which forms the basis of a blood clot. It is also involved in the activation of protein C.

82
Q

What is thrombocytopenia?

A

Thrombocytopenia is a condition characterized by low platelet numbers in the blood.

83
Q

What can be a possible sign of bone marrow failure?

A

Thrombocytopenia can be a possible sign of bone marrow failure.

84
Q

What is haemophilia A?

A

Haemophilia A is a hereditary disease characterized by a deficiency in Factor VIII.

85
Q

How is haemophilia A inherited?

A

Haemophilia A is inherited through X-linked inheritance, which means the disease is passed from the mother to the son.

86
Q

What is the prevalence of haemophilia A in the general population?

A

The prevalence of haemophilia A in the general population is 30-100/106.

87
Q

What is haemophilia B?

A

Haemophilia B, also known as Christmas disease, is a hereditary disease characterized by a deficiency in Factor IX.

88
Q

How is haemophilia B different from haemophilia A?

A

Haemophilia B is very similar to haemophilia A, but it has a lower prevalence (1/5 of haemophilia A cases).

89
Q

What is Von Willebrand disease?

A

Von Willebrand disease is a bleeding disorder caused by mutations that reduce the function of VWF or limit its synthesis.

90
Q

How is Von Willebrand disease inherited?

A

Von Willebrand disease is inherited through autosomal dominant inheritance.

91
Q

What is the prevalence of Von Willebrand disease in females?

A

Von Willebrand disease is more prevalent in females.

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