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Haemostasis Flashcards

1
Q

Haemostasis

A

the balance of blood flow in the body, between hypercoagulability and bleeding disorders.

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2
Q

What are the stages of haemostasis?

A
  1. Primary: initial response to endothelial damage; local vasoconstriction and formation of the platelet plug.
  2. Secondary: strengthening and reinforcement of the plug. Formation of a stable fibrin clot.
  3. Tertiary: removal of fibrin and restoration of vessel patency.

All these stages interlink and influence one another.

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3
Q

How can you assess primary haemostasis?

A
  • Buccal mucosal bleeding time
  • EDTA Sample
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4
Q

How can you assess secondary haemostasis?

A
  • Prothrombin time
  • Activated partial thromboplastin time (activated clotting time)
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5
Q

How are platelets produced?

A
  • Stimulus: thrombopoietin (TPO) from the liver (and small amount kidney)
  • Platelets originate from stem cells in bone marrow. These develop into megakaryocytes under influence of TPO and then form platelets.
  • There is negative feedback: platelets bind to TPO and remove it from circulation.
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6
Q

What is the key aim of primary haemostasis?

A

The formation of a platelet plug

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7
Q

Describe the initial response to endothelial damage in primary haemostasis?

A
  • Local neural reflexes (pain receptors)
  • Muscle contraction (direct mechanical impact on smooth muscle cells)
  • Thromboxane A produced by activated platelets
  • Serotonin released from delta granules in platelets
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8
Q

Describe the formation of the platelet plug (primary haemostasis).

A
  • Platelets bind to von Willebrand factor (vWF) in the exposed sub-endothelium. This is via the GPIb-IX-V receptor.
  • Platelets change shape due to GPIIB/IIIa receptor activation.
  • Agonists are released which result in increased platelet stickiness. Agonists include: alpha and beta granule contents, ADP, serotonin, platelet-activating factor, Thromboxane A2.
  • This is primarily mediated by fibrinogen binding to glycoproteins (IIb/IIIa)
  • This is enhanced by the generation of thrombin (which links to secondary haemostasis)
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9
Q

What is this image showing?

A

Formation of the platelet plug in primary haemostasis.

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10
Q

What is the significance of fibrinogen in this image?

A

Fibrinogen binding to glycoproteins is the primary mediator of the formation of the platelet plug (primary haemostasis)

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11
Q

What is the objective of secondary haemostasis?

A
  • The strengthening and reinforcement of the platelet plug
  • The formation of a stable fibrin clot
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12
Q

What are the two pathways within the coagulation cascade?

A
  • Extrinsic pathway: this initiates the coagulation.
  • Intrinsic pathway: this sustains the coagulation.
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13
Q

Factor VII is crucial to which pathway in the coagulation cascade?

A

Extrinsic pathway

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14
Q

In which stage of haemostasis does the coagulation cascade fall?

A

Secondary

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15
Q

What substances are necessary to secondary haemostasis and where are they formed?

A
  • Coagulation factors are required for secondary haemostasis.
  • Several of them are synthesised in the liver in a process that requires Vitamin K.
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16
Q

Describe the process illustrated in this image

A
  • Several coagulation factors are synthesised in the liver. This requires Vitamin K.
  • Rat poison/warfarin interferes with Vitamin K reductase activity. This inhibits coagulation factor synthesis.
  • Factor VII has the shortest half life so is eradicated first in the case of this happening.
  • Modern poisons have long half-lives so it is harder to treat newer poisons.
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17
Q

Where does cell-based coagulation fit into haemostasis?

A

Cell-based coagulation is part of secondary haemostasis. It describes the actions and results of both intrinsic and extrinsic pathways in the coagulation cascade.

18
Q

What is achieved at the end of secondary haemostasis?

A

The formation of a stable fibrin clot

19
Q

What are the stages of cell-based coagulation (secondary haemostasis)?

A
  1. Initiation
  2. Amplification
  3. Propagation
20
Q

Describe the first step in cell-based coagulation (secondary haemostasis)

A

Initiation

  • Intrinsic and extrinsic systems generate Factor Xa in parallel on different cell surfaces.
  • Injury exposes tissue factor-bearing cells to flowing blood. This generates a small amount of Factor IXa and thrombin.
21
Q

Describe the second step in cell-based coagulation (secondary haemostasis).

A

Amplification

  • Thrombin activates platelets creating a sticky surface and localised what is happening to the site of injury
  • vWF is released and tethers platelets to site of injury (by binding to GPIb/Factor IX receptor on one hand and sub endothelial collagen on the other)
  • This leads to the generation of Factors V, VIII, XI.
22
Q

Describe the third stage of cell-based coagulation (secondary haemostasis)

A

Propagation

  • Factors assemble on the activated platelet to form intrinsic tenase (Factor VIIIa + Factor IXa + Ca2+)
  • This results in Factor Xa generation on the platelet surface
  • Prothrombinase complex (Factor Va + Factor Xa + Ca2+) forms and results in a burst of thrombin generation directly on the platelet = stabilisation.
23
Q

Why do coagulation inhibitors exist? Give some examples.

A

They exist to prevent inappropriate clot formation

e.g. Tissue factor pathway inhibitor (TFPI), antithrombin (III)

24
Q

Describe tertiary haemostasis

A
  • Fibrin clot removed via fibrinolysis
    • Tissue plasminogen → plasmin
    • Plasmin breaks down fibrin fibres to FDP (fibrinogen degradation products)
    • Smallest FDPs = D-dimers
    • FDPs act as anticoagulants and integer with platelet aggregation and fibrin polymerisation
  • Vessel patency is restored
25
Q

Describe some disorders of primary haemostasis.

A
  • Thrombocytopenia: decreased production of platelets/platelets are destroyed/consumed at increased rate.
  • Thrombocytopathy: abnormal platelet function e.g. von Willebrand’s disease
  • Vascular defects
26
Q

What test is shown here?

A

Buccal mucosal bleeding time (BMBT)

Time taken for bleeding to stop after making small incision. This is quick, but does not determine the cause of the abnormality.

This assess primary haemostasis.

27
Q

How can you use an EDTA sample assess primary haemostasis?

A
  • Perform a count ASAP
  • Can use various methods including automated cell count/blood smear.
  • If blood smear: check for clumping in the feathered region = pseudothrombocytopenia
28
Q

What does activated partial thromboplastin time test?

A

The intrinsic pathway of secondary haemostasis.

May suggest a deficiency in Factor VIII, IX, XI, XII.

29
Q

What does prothrombin time test?

A

The extrinsic and common pathway of coagulation in secondary haemostasis.

May suggest a deficiency in Factor VII.

30
Q

What test measures tertiary haemostasis?

A

Thrombin clot time

This measures the conversion of fibrin to fibrinogen

31
Q

What does a latex agglutination test for FDPs/D-dimers measure?

A

It measures whether blood clotting is being switched off at the end of the process.

32
Q

What does flow cytometry (type of platelet test done at special lab) measure?

A

The expression of surface molecules

33
Q

What does an adhesion assay (type of platelet function test done at special lab) measure?

A

The expression of surface molecules

34
Q

1

A

Intrinsic pathway

35
Q

2

A

Extrinsic pathway

36
Q

3

A

Thrombin

37
Q

4

A

Fibrinogen

38
Q

5

A

Plasminogen

39
Q

6

A

FDPs (fibrinogen degradation products)

40
Q

7

A

Vitamin K epoxide

CAR (17 decks)

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