Haemostasis

Question 1

What is haemostasis?

Answer 1

The stopping of blood flow.

Question 2

Requirements for haemostasis?

Answer 2

Permanent state of readiness

Prompt response

Localised response

Protection against unwanted thrombosis

Question 3

What are the components of the normal haemostatic system?

Answer 3

Formation of platelet plug
- Primary Haemostasis

Formation of fibrin clot
- Secondary Haemostasis

Fibrinolysis (the enzymatic breakdown of the fibrin in blood clots)

Anticoagulant Defences

Question 4

Structure and lifespan of platelets?

Answer 4

Platelets are small anucleate discs with a mean lifespan of 7-10 days.

Question 5

How are platelets formed?

Answer 5

Formed in the marrow by “budding” from megakaryocytes

Question 6

Mechanism behind platelet adhesion at site of injury?

Answer 6

Endothelial (vessel wall) damage exposes collagen and releases Von Willebrand factor (VWF) and other proteins to which the platelets have receptors.

There is then secretion of various chemicals from the platelets, this leads to aggregation of platelets at the site of injury.

Question 7

What are the 3 main groups that cause failure of platelet plug formation?

Answer 7

Vascular

Platelets

Von Willebrand factor deficiency

Question 8

Vascular causes of platelet plug formation failure?

Answer 8

Can be hereditary e.g. Marfan’s

Can be acquired e.g. HSP vasculitis, age-related, vitamin C deficiency

Question 9

Platelet causes of platelet plug formation failure?

Answer 9

Reduced number (thrombocytopenia) - majority of cases are acquired

• Reduced production — marrow problem
• Increased destruction — coagulopathy (impaired clot formation) e.g. DIC (disseminated intravascular coagulation), autoimmune e.g. Immune thrombocytopenic purpura

Reduced function - majority of cases are acquired
- Drugs e.g. aspirin or NSAID’s, renal failure

Question 10

Can Von Willebrand factor deficiency lead to platelet plug formation failure?

Answer 10

Yes

Can be acquired but most commonly hereditary - autosomal dominant. Varies in severity.

Question 11

What are the consequences of failure of platelet plug formation?

Answer 11

Spontaneous Bruising and Purpura

Mucosal Bleeding
- Epistaxis (nosebleeds)
- Gastrointestinal
- Conjunctival
- Menorrhagia

Intracranial haemorrhage

Retinal haemorrhages

Question 12

What are the screening tests for primary haemostasis?

Answer 12

Platelet count

No simple screening tests for other components of primary haemostasis

Question 13

How many pathways is there for the formation of a fibrin clot?

Answer 13

3 pathways

• Intrinsic pathway
• Extrinsic pathway
• Final common pathway

Question 14

Features of intrinsic pathway for fibrin clot formation?

Answer 14

Initiation: The intrinsic pathway is activated by trauma inside the vascular system. This could be due to injury or damage to the blood vessel.

Activation of Factor XII: The intrinsic pathway starts with the activation of Factor XII (Hageman factor) by contact with exposed collagen in the damaged vessel.

Cascade of Activations: Activated Factor XII triggers a cascade of activations involving various clotting factors, including Factor XI, Factor IX, and Factor VIII.

Activation of Factor X: The cascade culminates in the activation of Factor X.

Question 15

Features of extrinsic pathway for fibrin clot formation?

Answer 15

Initiation: The extrinsic pathway is activated by external trauma leading to blood leakage outside the vascular system.

Release of Tissue Factor (TF): Tissue Factor, a substance released by damaged tissue, combines with Factor VII.

Activation of Factor VII: The TF-Factor VII complex activates Factor X.

Question 16

Final common pathway for fibrin clot formation?

Answer 16

Convergence: Both intrinsic and extrinsic pathways converge at Factor X, which is activated to Factor Xa. Proceeds intrinsic/extrinsic pathways.

Formation of Prothrombinase: Factor Xa combines with Factor V and phospholipids to form the prothrombinase complex.

Prothrombin Activation: Prothrombin (Factor II) is converted into thrombin (Factor IIa) by the prothrombinase complex.

Fibrin Formation: Thrombin activates fibrinogen (Factor I) into fibrin monomers.

Fibrin Polymerization: Fibrin monomers polymerize to form a stable fibrin clot.

Clot Retraction and Repair: The clot contracts (retracts), bringing wound edges together for tissue repair.

Question 17

What are the causes of failure of fibrin clot formation?

Answer 17

Single clotting factor deficiency
- usually hereditary
- eg Haemophilia

Multiple clotting factor deficiencies
- usually acquired
- eg Disseminated Intravascular Coagulation (DIC)

Increased fibrinolysis
- usually part of complex coagulopathy

Question 18

What are the consequences of failure of fibrin clot formation?

Answer 18

No characteristic clinical syndrome

May be combined primary/secondary haemostatic failure

Pattern of bleeding depends on
- Single/multiple abnormalities
- The clotting factors involved

Question 19

What are tests for fibrin clot formation deficiency?

Answer 19

Prothrombin time for extrinsic pathway
- Since factor VII pathology is rare, better used as a measure for overall clotting.
- Affected in anti-coagulant use, liver failure and DIC.

Activated partial thromboplastin time for intrinsic pathway
- Measures factors VIII (and vWF), IX, XI and XI.
- Most common causes of increased APTT are haemophilia A and possibly von Willebrand’s disease.

Question 20

What could be affected if both prothrombin time and activated partial thromboplastin time are increased?

Answer 20

factor V, X, II or I could be affected, however most commonly due to multiple clotting factor deficiencies (e.g. liver disease, anticoagulants).

Question 21

PT vs aPTT, what do they measure?

Answer 21

PT measures the time it takes for blood to clot through the extrinsic and common coagulation pathways.

aPTT measures the time it takes for blood to clot through the intrinsic and common coagulation pathways.

Question 22

Initiation of PT and aPTT?

Answer 22

PT - It primarily assesses the activity of the clotting factors in the extrinsic pathway (Factors I, II, V, VII, and X).

aPTT - It primarily assesses the activity of the clotting factors in the intrinsic pathway (Factors I, II, V, VIII, IX, X, XI, and XII).

Question 23

Uses for PT and aPTT?

Answer 23

PT is often used to monitor the effectiveness of anticoagulant medications like warfarin, which primarily affects the extrinsic pathway.

aPTT is frequently used to monitor the effectiveness of heparin, an anticoagulant that affects the intrinsic pathway. It is also used in the investigation of bleeding disorders.

Question 24

What are the causes of vitamin K deficiency?

Answer 24

Poor dietary intake (leafy green vegetables contain vitamin K or fruits like blueberries, figs and canned pumpkin)

Malabsorption

Obstructive jaundice

Vitamin K antagonists (warfarin)

Haemorrhagic disease of the new-born

Question 25

What coagulation factors are carboxylated by vitamin K?

Answer 25

Factors II, VII, IX & X aka factors 2, 7, 9 and 10

Question 26

Where are all the coagulation factors synthesised?

Answer 26

Hepatocytes hence why there is a reduction in liver failure

Question 27

What are the main acquired causes of multiple factor deficiency?

Answer 27

Liver disease

Vitamin K deficiency

DIC

Question 28

Causes of single factor deficiency?

Answer 28

Haemophilia A and B

Isolated prolonged APTT