Haemostasis Flashcards Preview

Year 3: CSP & PH > Haemostasis > Flashcards

Flashcards in Haemostasis Deck (30)
1

What is the lifespan of platelets?

8-14 days

2

Outline the structure and function of platelets

The cell membrane hosts glycoproteins for receptor binding and the phospholipid bilayer is associated with PG synthesis and calcium mobilisation; the granules contain VWF, fibrinogen and platelet derived growth factor;

3

Outline primary haemostasis

Formation of primary platelet plug:
Damaged endothelium -->exposed collagen --> vWF binds to exposed collagen --> platelets bind to the bound vWF (as GP1b on platelets membrane can bind to the vWF, leading to the exposure of a GP2b and GP3a molecules on the platelet membrane, secondary sites for platelet to bind to vWF allowing platelet aggregation and stimulates release of thromboxane, ADP and serotonin)

4

Outline secondary haemostasis

Coagulation cascade:
Intrinsic pathway (secondary haemostasis): 12-11-9-8-7
1. Factor XII is activated to become factor XIIa
2. Factor XI is activated to become factor Xia
3. Factor IX is activated to become factor IXa
4. Factor IXa and factor VIII combine to form intrinsic ten-ase complex
5. The formed factor X (intrinsic ten-ase complex) is then activated to become factor Xa which acts to cleave prothrombin into thrombin with the aid of factor V
Extrinsic pathway (secondary haemostasis): 3+7=10
1. Factor III (tissue factor) is found in the sub-endothelial tissue and is exposed in vascular injury causing it to be activated to Factor IIIa
2. Factor IIIa (activated tissue factor) then activates factor VII
3. Factor IIIa (tissue factor) and factor VIIa combine to form the extrinsic ten-ase complex to form factor X
4. Factor X is then activated to form factor Xa and this acts to cleave prothrombin into thrombin with the help of factor V (which can then cleave fibrin from fibrinogen and lead to the formation of a stable mesh and a stable clot)
Common pathway of secondary haemostasis (after extrinsic/intrinsic):
Both the extrinsic and intrinsic pathways converge when factor Xa cleaves prothrombin into thrombin
1. Factor X is activated to become factor Xa (sum of 8 and 9 in intrinsic and 7 + 3 in extrinsic)
2. Factor Xa then causes the cleavage of prothrombin to form thrombin, with the aid of factor V
a. Thrombin production also stimulates the activation of factor XIII
3. Thrombin then allows the cleavage of fibrinogen and fibrin with the aid of factor XIIIa
Thrombin enhances the activity of: factor V, VIII, IX and XIII i.e. the two factors involved in producing the intrinsic ten-ase complex, the molecule that aids in the cleavage of prothrombin to thrombin and the factor which aids in the formation of a stable fibrin clot from fibrin.

5

Outline the intrinsic pathway of the coagulation cascade

Intrinsic pathway (secondary haemostasis): 12-11-9-8-7
1. Factor XII is activated to become factor XIIa
2. Factor XI is activated to become factor Xia
3. Factor IX is activated to become factor IXa
4. Factor IXa and factor VIII combine to form intrinsic ten-ase complex
5. The formed factor X (intrinsic ten-ase complex) is then activated to become factor Xa which acts to cleave prothrombin into thrombin with the aid of factor V

6

Outline the extrinsic pathway of the coagulation cascade

Extrinsic pathway (secondary haemostasis): 3+7=10
1. Factor III (tissue factor) is found in the sub-endothelial tissue and is exposed in vascular injury causing it to be activated to Factor IIIa
2. Factor IIIa (activated tissue factor) then activates factor VII
3. Factor IIIa (tissue factor) and factor VIIa combine to form the extrinsic ten-ase complex to form factor X
4. Factor X is then activated to form factor Xa and this acts to cleave prothrombin into thrombin with the help of factor V (which can then cleave fibrin from fibrinogen and lead to the formation of a stable mesh and a stable clot)

7

Outline the common pathway of the coagulation cascade

Both the extrinsic and intrinsic pathways converge when factor Xa cleaves prothrombin into thrombin
1. Factor X is activated to become factor Xa (sum of 8 and 9 in intrinsic and 7 + 3 in extrinsic)
2. Factor Xa then causes the cleavage of prothrombin to form thrombin, with the aid of factor V
a. Thrombin production also stimulates the activation of factor XIII
3. Thrombin then allows the cleavage of fibrinogen and fibrin with the aid of factor XIIIa
Thrombin enhances the activity of: factor V, VIII, IX and XIII i.e. the two factors involved in producing the intrinsic ten-ase complex, the molecule that aids in the cleavage of prothrombin to thrombin and the factor which aids in the formation of a stable fibrin clot from fibrin.

8

Which clotting test reflects the intrinsic pathway?

Activated partial thrombin time (APTT)

9

Which clotting test reflects the extrinsic pathway?

Prothrombin time (PT)

10

Which clotting test reflects the common pathway?

Thrombin time (TT)

11

Which compounds are involved in regulating the clotting cascade?

• Tissue factor pathway inhibitor (TFPI) – this is a drug which inhibits factor Xa
• Protein C – t’s production is stimulated by thrombin and thrombomodulin, it inhibits factor Va (which cleaves prothrombin to thrombin) and factor VIIIa (to prevent formation of intrinsic ten-ase complex)
• Antithrombin – inhibits factor VIIa, IXa, Xa and factor IIa/thrombin (prevents the cleavage of fibrinogen to fibrin)
• Plasmin – breaks down fibrin and degrades clot as a result of tissue plasminogen activator-1 cleaving plasminogen

12

What's the role of tissue factor pathway inhibitor (TFPI) in secondary haemostasis?

Inhibits factor Xa --> prevents common pathway

13

What's the role of protein C in secondary haemostasis?

Stimulated by thrombin and thrombomodulin --> inhibits factor Va (prevents cleavage of prothrombin) and VIIa (prevents formation of extrinsic Xa complex)

14

What's the role of antithrombin in secondary haemostasis?

Inhibits factor VIIa, IXa, Xa and factor IIa/thrombin (prevents the cleavage of fibrinogen to fibrin)

15

What's the role of plasmin in secondary haemostasis?

Breaks down fibrin and degrades clot as a result of tissue plasminogen activator-1 cleaving plasminogen

16

What is Bernard Soulier syndrome?

Lack GP1b (prevents platelets from binding to VWF). The platelets will be morphologically large and reduced in number, PFA will be abnormal and the flow cytometry will demonstrate absent GP1b.

17

How is Bernard Soulier syndrome treated?

Can be treated with platelets, recombinant factor VIIa, tranexamic acid, COCP or bone marrow transplantation.

18

What is Glanzmann’s syndrome?

lack GP2b/3a (prevents the activity of the secondary binding site to allow aggregation and binding of fibrinogen to aid coagulation). PFA will be grossly abnormal and flow cytometry will demonstrate absent GP2b/3a

19

How is Glanzmann’s syndrome treated?

Can be treated with platelets, recombinant factor VIIa, tranexamic acid, COCP or bone marrow transplantation.

20

What is Von Willebrand Disease?

Autosomal disease due to a deficient or defective vWF disease. There are three main types of this disease; 1 is mild-moderate, 2 is where the protein is present but defective and type 3 is where vWF is completely absent.

Type 1 & 2 = autosomal dominant
Type 3 = autosomal recessive

21

How is Von Willebrand Disease treated?

Desmopressin stimulates the release of vWF from the Weibel-Palade bodies of endothelial cells, thereby increasing the levels of vWF (as well as coagulant factor VIII)

22

What is haemophilia A and how is it treated?

Haemophilia A, is a recessive X-linked genetic disorder resulting in a deficiency of functional clotting Factor VIII. Replace clotting factors and tranexamic acid may be used for surgeries.

23

What is haemophilia B and how is it treated?

Haemophilia B, is also a recessive X-linked genetic disorder involving a lack of functional clotting Factor IX. Replace clotting factors and tranexamic acid may be used for surgeries.

24

What is factor XI deficiency?

affects the intrinsic pathway of coagulation and affects Ashkenazi Jewish population in particular; the severity of the condition often doesn’t correlate with the level of the factor, treated with concentrated factor from plasma

25

What is factor VII deficiency?

Affects the extrinsic pathway of coagulation; factor VII levels may rise during pregnancy

26

What is factor V deficiency?

Affects the common pathway, and there is no concentrated factor available so plasma with solvent detergence FFP (octaplas) is administered in severe cases instead

27

What is fibrinogen (factor I) deficiency?

quantitative deficiency is known as afibrinogenaemia or hypofibrinogenaemia, a qualitative deficiency is known as dysfibrinogenaemia. This is treated either with a cryoprecipitate (which isn’t inactivated by pathogens) or fibrinogen concentrate (which is inactivated by heat). In pregnancy fibrinogen deficiency can lead to recurrent miscarriage.

28

What is factor X deficiency?

there is some bleeding correlation with severity

29

What is factor XII deficiency?

the numerical severity often reflects the bleeding risk, and those affected tend to present with bleeding symptoms from birth with prolonged umbilical cord bleeding or poor wound healing. A conventional bleeding test will not detect this condition

30

What's the mechanism of action of tranexamic acid?

Antifibrinolytic that competitively inhibits the activation of plasminogen to plasmin (which would usually break down clots)