Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

POM Haematology > Haemostasis > Flashcards

Haemostasis Flashcards

1
Q

What factors are balanced in normal haemostasis?

A

Fibrinolytic factors, anticoagulant proteins and coagulation factors, platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the balance of haemostasis very important for?

A

Allow the stimulation of blood clotting processes following injury, in which blood changes from its liquid state (coagulation)

Limit the extent of the response to the area of injury to prevent excessive or generalised blood clotting (thrombosis)

Start the process that eventually leads to the breakdown of the clot as part of the process of healing (fibrinolysis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What does haemostasis describe?

A

‘Halting of blood’ following trauma to blood vessels and results from three intertwined processes:
Vasoconstriction
Formation of an unstable platelet plug at the site of the vessel wall damage (primary haemostasis)
Formation of a stable fibrin clot (secondary haemostasis/coagulation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is primary haemostasis?

A

Formation of a platelet plug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How are platelets formed?

A

Formed in bone marrow by the fragmentation of megakaryocyte cytoplasm and have a circulating lifespan of around 10 days.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Outline platelet adhesion

A

The plasma membrane contains glycoproteins (GPs) that are important for the platelet’s interactions. Following injury to the vessel wall platelets stick to the damaged endothelium, either directly to collagen via the platelet GPIa receptor or indirectly via von Willebrand factor (VWF), which binds to the platelet GPIb receptor. This adhesion of platelets causes them to become activated and changes their shape from a disc to a more rounded form with spicules to encourage platelet-platelet interaction.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Outline platelet release action

A

The adhesion of platelets initiates their activation and the release of the contents of their storage granules. There are two main types of granules: α-granules and dense granules. The platelet membrane is invaginated to form a surface-connected cannalicular system through which the contents of platelet granules are released. Important components of these contents include ADP, fibrinogen and von Willebrand factor.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

2 types of platelet granules?

A

Alpha and dense;

release ADP, fibrinogen and VWF.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Outline thromboxane A2 synthesis

A

Platelets are stimulated to produce the prostaglandin thromboxane A2 from arachidonic acid that is derived from the cell membrane.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is TA2?

A

Prostaglandin; also a known vasoconstrictor, which is especially important during tissue injury and inflammation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Outline platelet aggregation

A

Granular release of ADP and generation of TA2 have positive feedback effects resulting in further platelet recruitment activation and aggregation. They do this by binding respectively to the P2Y12 and thromboxane A2 receptor. Platelet activation also causes a conformational change in the GPIIb/IIIa receptor (known as ‘inside-out’ or ‘flip-flopping’) to provide binding sites for fibrinogen. Fibrinogen binding to GPIIb/IIIa causes ‘outside-in’ signalling which further activates the platelets. Fibrinogen has a key role in linking platelets together to form the platelet plug. These effects are normally counterbalanced by the active flow of blood and the release of prostacyclin (PGI2) from endothelial cells; prostacyclin is a powerful vasodilator and suppresses platelet activation, thus preventing inappropriate platelet aggregation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Name 2 of the most commonly used antiplatelet drugs

A

Aspirin and clopidogrel

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What are antiplatelet drugs used for?

A

Prevention and treatment of cardiovascular and cerebrovascular disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Outline the action of aspirin

A

Aspirin inhibits the production of TA2 by irreversibly blocking the action of cyclo-oxygenase (COX), resulting in a reduction in platelet aggregation. Although prostacyclin production is also inhibited by cyclo-oxygenase, endothelial cells can synthesise more COX whereas the non-nuclear platelet cannot.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How long does a single dose of aspirin persist?

A

7 days, until most of the platelets present at the time of aspirin ingestion have been replaced by new platelets.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Outline the action of clopidogrel as antiplatelet drug

A

Clopidogrel works by irreversibly blocking the ADP receptor (P2Y12) on the platelet cell membrane. Therefore the effect of clopidogrel ingestion also lasts for 7 days until new platelets have been produced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

What is VWF?

A

GP that is synthesised by endothelial cells and megakaryocytes and circulates in plasma as multimers of different sizes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

VWF is a specific carrier for which factor?

A

Factor VIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Why is secondary haemostasis (coagulation) required?

A

The primary platelet plug is sufficient for small vessel injury. However, in larger vessels it will fall apart. Fibrin formation stabilises the platelet plug.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What does thrombin do?

A

Cleaves fibrinogen to generate a fibrin clot that stabilises the platelet plug at sites of vascular injury.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Where are most clotting factors synthesised and what are the 2 exceptions?

A

Liver; except FVIII and VWF (both are made by endothelial cells; VWF is also made in megakaryocytes and incorporated into platelet granules)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Which factors are dependent on Vitamin K for carboxylation of their glutamic acid residues?

A

Factors II, VII, IX and X; this is essential for the function of these clotting factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What is each step in in coagulation characterised by?

A

Each step is characterised by the conversion of an inactive zymogen (proenzyme) into an active clotting factor by the splitting of one or more peptide bones and exposure of the active enzyme site.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Which clotting factors are co-factors?

A

V and VIII

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What is the role of calcium ions in coagulation?

A

Important role in the binding of activated clotting factors to the phospholipid surfaces of platelets.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Outline the process of coagulation (Secondary haemostasis)

A

The trigger to initiate coagulation at the site of injury is the tissue factor (TF) exposed on the surface of endothelial cells and leukocytes and on most extravascular cells in an area of tissue damage. TF is mainly located at sites that are not usually exposed to the blood under normal physiological conditions. As a result, blood only encounters TF at sites of vascular injury. The binding of TF to factor VIIa leads to the activation of factors IX to IXa and X to Xa. This leads to the activation of prothrombin (factor II) to generate a small initial amount of thrombin (factor IIa). This phase is known as the Initiation phase.

This small amount of thrombin mediates the activation of the co-factors V and VIII, the zymogen factor XI and platelets (Amplification phase).

Factor XI converts more factor IX to IXa, which in concert with factor VIIIa, amplifies the conversion of factor X to Xa, and there is consequently a rapid burst in thrombin generation (Propagation phase), which cleaves the circulating fibrinogen (soluble) to form the insoluble fibrin clot.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What are the most important natural anti-coagulant pathways?

A

Protein C, protein S and antithrombin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Outline the mechanism of protein C as a natural anticoagulant

A

Thrombin binds to thrombomodulin on the endothelial cell surface leading to activation of protein C to activated protein C (APC). APC inactivates factors Va and VIIIa in the presence of a co-factor protein S.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Outline the mechanism of antithrombin

A

Thrombin and factor Xa are inactivated by the circulating inhibitor antithrombin. The action of antithrombin is markedly potentiated by heparin: this occurs physiologically by the binding of antithrombin to endothelial cell-associated heparins.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

What are the main anticoagulant drugs?

A

Heparin, warfarin and DOACs

31
Q

What is heparin?

A

Heparin is a mixture of glycosaminylglycan chains extracted from porcine mucosa

32
Q

How does heparin work as an anticoagulant?

A

Heparin works indirectly by potentiating the action of antithrombin leading to the inactivation of factors Xa and IIa (prothrombin).
Inactivation of thrombin requires longer chains of heparin, which are able to wrap around both the antithrombin and thrombin
Heparin is administered intravenously or by subcutaneous injection.

33
Q

How does warfarin work as an anticoagulant?

A

Warfarin, derived from coumarin, is a vitamin K antagonist that works by interfering with protein carboxylation. It therefore reduces synthesis of functional factors II, VII, IX and X by the liver.

34
Q

How is warfarin administered?

A

Warfarin is given as an oral tablet and its anticoagulant effect needs to be monitored by regular blood testing

35
Q

Why does warfarin take several days to have an effect?

A

Because it reduces synthesis of coagulation factors rather than inhibiting existing factor molecules

36
Q

What are DOACs?

A

Orally available drugs that directly inhibit either thrombin or factor Xa (i.e. without the involvement of antithrombin)
​These do not usually require monitoring

37
Q

What is the activation of plasmin mediated by?

A

tissue plasminogen factor (t-PA)
However, t-PA does not activate plasminogen until these are both brought together by binding to lysine residues on fibrin.

38
Q

What does the breakdown of fibrin produce?

A

Fibrin-degradation products (FDPs)

39
Q

What is the principle fibrinolytic enzyme?

A

Plasmin, which circulates in its inactive zymogen form plasminogen

40
Q

What inhibits plasmin?

A

Anti-plasmin

41
Q

Is plasmin specific to fibrin?

A

Plasmin is not specific for fibrin and can also break down other protein components of plasma, including fibrinogen and the clotting factors Va and VIIIa.

42
Q

Give an example of a thrombolytic agent?

A

Recombinant t-PA

43
Q

How does thrombolytic therapy work?

A

Generating plasmin to lyse clots and are administered intravenously to selected patients presenting with ischaemic stroke. The benefit is time-dependent and so t-PA needs to be given to eligible patients as quickly as possible, preferably within one hour of the onset of symptoms. There is a high risk of bleeding associated with its use.

44
Q

Why is thrombolytic therapy no longer used in patients with myocardial infarction?

A

It has largely been replaced with angioplasty and the insertion of stents to open the diseased coronary vessels.

45
Q

How does tranexamic acid act as an antifibrinolytic drug?

A

Binds to plasminogen and preventing it from binding to the lysine residues of fibrin. Competitive inhibition.
This prevents the activation of plasminogen to plasmin, which would otherwise result in fibrinolysis

46
Q

What is tranexamic acid?

A

Synthetic derivative of amino acid lysine that works by binding to plasminogen.

47
Q

What is tranexamic acid used to treat?

A

Tranexamic acid is used widely to treat bleeding in trauma and surgical patients as well as in patients with inherited bleeding disorders.

48
Q

What do the extrinsic and intrinsic pathway refer to?

A

Intrinsic refers to a system in which all components are in the plasma (factors 9, 10, 11, 12 and co-factors 5 and 8), while the ‘extrinsic’ system comprises TF and factors 7, 10, and co-factor 5.

49
Q

What doe the prothrombin time measure?

A

Integrity of the extrinsic pathway

50
Q

How is blood for PT collected and processed?

A

​Blood is collected into a bottle containing sodium citrate (usually blue-topped), which chelates calcium thus preventing the blood from clotting in the bottle
The sample is spun to produce platelet-poor plasma
A source of TF and phospholipid is added to the citrated plasma sample, together with calcium to start the reaction; the length of time taken for the mixture to clot is recorded.

51
Q

Why might the PT be prolonged?

A

Reduction in the activity of factors 2, 5, 7, 10 or fibrinogen

52
Q

What is used as the source of both TF and phospholipid nowadays?

A

Recombinant thromboplastin

53
Q

When the PT is used to monitor vitamin K antagonist anticoagulant therapy such as warfarin how are the results expressed?

A

As the INR (international normalised ratio)

This involves a correction for the different thromboplastin reagents used by different laboratories and means that all laboratories would be expected to obtain the same INR result for a given sample irrespective of the source of thromboplastin.

54
Q

Which test measures the integrity of the intrinsic pathway?

A

Activated partial thromboplastin time (APTT)

55
Q

How is the APTT performed?

What is added to the citrated plasma?

A

By the contact activation of factor XII by a surface such as glass, or using a contact activator such as silica or kaolin.

Contact activator and phospholipid followed by calcium and the time taken for this mixture to clot is measured.

56
Q

In which situations is a prolonged APTT seen?

A

When there is a reduction in a single or multiple clotting factors; in the latter there may also be an associated prolonged PT.

57
Q

In which patients is an isolated prolonged APTT seen?

A 
Haemophilia A (factor VIII deficiency) and haemophilia B (factor IX deficiency).
Factor XI and XII deficiency.

(Factor 8, 9, 11, 12 deficiency)

58
Q

Deficiency in which factor doesn’t lead to bleeding?

A

Factor XII (XII doesn’t appear in the coagulation - formation of the stable fibrin clot and isn’t important for clotting in vivo)

59
Q

What are the 3 causes of bleeding?

A

Reduction in platelet number or function (platelet plug)
Reduction in coagulation factors (fibrin clot)
Increased fibrinolysis

60
Q

What causes thrombocytopenia?

A 
Drugs
Viruses
Immune thrombocytopenia
BM infiltration
Hereditary thrombocytopenia 
Increased splenic pooling
Megaloblastic anaemia
DIC
61
Q

What is a reduction in platelet function due to?

A

Antiplatelet drugs e.g. aspirin

Inherited causes

62
Q

What are the 2 types of causes for a reduction in coagulation factors?

A

Congenital

Acquired

63
Q

List and explain congenital causes for a reduction on coagulation factors.

A

VWD - Reductions in level or function of VWF. Most common inherited bleeding disorder - autosomally inherited therefore affects both males and females

Haemophilia A - factor VIII deficiency.

Haemophilia B - factor IX deficiency

(Around 1% of patients have deficiencies of one of the other clotting factors. These usually follow an autosomal recessive inheritance pattern and are more common in areas with high levels of consanguinity.)

64
Q

How do you treat a reduction in coagulation factors?

A

Replacement of the missing clotting factor with specific clotting factor concentrates forms the mainstay of treatment for patients with congenital forms of bleeding disorders: many of the factor concentrates now used in the Western world are recombinant and are synthesised in cell lines. This eliminates the risk of pathogen transmission in plasma-derived concentrates.

65
Q

Are acquired causes of reduced coagulation factors more common than congenital?

A

Yes

66
Q

List the acquired causes for a reduction in coagulation factors?

A

Liver disease
Anticoagulant drugs
DIC (disseminated intravascular coagulation)

67
Q

Explain DIC (don’t need to know all of it)

A

Describes a process in which there is generalised and uncontrolled activation of coagulation followed by marked activation of the fibrinolytic system. This activation results from the expression of TF within the circulation and leads to the generation and dissemination of large amounts of thrombin, the activation and consumption of platelets (leading to thrombocytopenia) and the widespread formation of thrombi in the small blood vessels (microcirculation). The clotting factors and fibrinogen in the plasma become depleted, which impairs haemostatic activity and may result in severe and life-threatening bleeding. There are high levels of fibrin degradation products (FDPs) as a result of fibrinolysis activation. The thrombi in the small blood vessels may cause shearing of the circulating red blood cells, leading to their fragmentation; red cell fragments (also known as schistocytes) may be seen on the blood film.

68
Q

What are the causes of DIC?

A

There are many causes of DIC including bacterial sepsis, advanced cancer and a variety of obstetric emergencies. While replacement of missing clotting factors and platelets may help control the bleeding symptoms, the underlying cause needs to be addressed in order to switch off the unregulated coagulation activation.

69
Q

What can cause increased fibrinolysis?

A

DIC or administration of thrombolytic therapy.

70
Q

Define thrombosis

A

Formation of a blood clot within an intact blood vessel resulting in the obstruction of blood flow with serious and possibly fatal consequences.

71
Q

What is Virchow’s Triad?

A

3 contributory factors to pathological clotting (thrombosis):

  • Blood - dominant in venous thrombosis
  • Vessel wall - dominant in arterial thrombosis
  • Blood flow - complex, contributes to both arterial and venous thrombosis
72
Q

What are the changes in blood that increase the risk of venous thrombosis?

A

Reduced anticoagulant proteins (usually have a genetic basis, e.g. inherited antithrombin deficiency, an example of an inherited thrombophilia)

Reduced fibrinolytic activity (e.g. pregnancy where there is inhibition of plasminogen activation through the production of a specific inhibitor by the placenta (PAI-2))

73
Q

Increases in levels of which clotting factors/platelets can increase the risk of venous thrombosis?

A

Cofactors V and VIII

Increased factor VIII during pregnancy
Activity of factor V is increased by asingle point mutation in the factor V gene, known as factor V Leiden > makes factor V more resistant to inactivation by protein C. ~7% of the population are carriers (heterozygotes) for Factor V Leiden, making it the most common of the inherited thrombophilias.
Platelets are increased in number in some myeloproliferative disorders, where the bone marrow output is increased.

74
Q

How is heparin administered?

A

IV or subcutaneous injection

POM Haematology (10 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions