Coagulation- normal and abnormal

Question 1

Define Haemostasis

Answer 1

The stopping of blood flow

Question 2

What are the 5 main constituents of coagulation

Answer 2

Vessels lined by endothelium
Platelets 
Coagulation factors
inhibitors of coagulation
Fibrinolytic system and inhibitors

Question 3

Describe some of the features of endothelium

Answer 3

• Produce thrombomodulin and heparin sylphate to inhibit thrombin production.
• Enzymes breakdown platelet derived molecules
• Produce prostacyclin and nitric oxide to reduce platelet adhesion.

Question 4

Describe some of the features of Platelets

Answer 4

• They are derived from fragments megakaryocyte cytoplasm
• Production is stimulated by thrombopoetin
• Form a plug when attracted by lower prostacyclin and collagen exposure
• Produce thromboxane A2 and serotonin to cause vasoconstriction.

Question 5

How do platelets adhere to the vessel wall and to each other?

Answer 5

Wall - Von Willibrand’s factor and Glycoprotein 1b

Each other - Glycoprotein 2b-3a and fibrinogen

Question 6

Outline the major steps in the coagulation pathway

Answer 6

Two pathways; Intrinsic and Extrinsic pathway which undergo several steps before both making Xa (factor 10a)
Xa and Va activate thrombin, in the Common Pathway, which produces fibrin, the end product of the coagulation cascade.

Question 7

Name some of the inhibitors of the coagulation cascade

Answer 7

• Protein C with its co-factor, Factor S

- Antithrombin and Heparin cofactor II which are both stimulated by heparin.

Question 8

What is the fibrinolytic system and describe briefly the ways in how it works.

Answer 8

-System that allows for clots to be dissolved.
Plasminogen which gets activated into plasmin by tPA can dissolve fibrin, or fibrin can be broken down into products, including one called D Dimers (used to measure blood clotting)

Question 9

Name some of the methods for measuring platelet count

Answer 9

Full blood count (includes platelet count, size, granules but poor assessment of function)
Bleeding time - Poorly controlled variables so not done often.
Prothrombin Time - Measure of extrinsic and common pathway and how much warfarin someone has.
Activated Partial Thromboplastin test (APTT) - measure of intrinsic and common pathway

Question 10

How can you measure fibrinogen?

Answer 10

Clot density or thrombin time

Question 11

Describe the mutation in Haemophilia A and B and some of its features

Answer 11

• Haemophilia A and B- X linked defect in VIII or IX gene
• Commonly (1/3) a new mutation so no family history
• Approx 1:5000 of males
• Female heterozygotes (carriers) not affected
• Can be very mild- chance finding or issue for surgery
• Severe (<1% VIII level)- frequent bleeds into joints and soft tissues

Question 12

If PT or APTT is prolonged what can you do?

Answer 12

A correction test

Question 13

What are some of the features of Von Willibrand’s disease?

Answer 13

• Usually autosomal dominant
• Defect in platelet adhesion and binding of
  VIII
• Up to 1% of population
• Mild disease- easy bruising, heavy periods
• Severe disease- similar to haemophilia

Question 14

Describe some of the features of acquired coagulation disorder

Answer 14

Through damage to liver, e.g. alcohol, autoimmune or hepatitis and this is because all coagulation factors are produced in the liver.
Causes bleeding due to abnormal clotting and low platelets.

Question 15

Describe some of the features of disseminated intra-vascular disease? What is is and some causes

Answer 15

• It is a condition where activation of the coagulation cascade results in small blood clots develop in vessels, blocking smaller blood vessels.
  Causes - Trauma, malignancy, sepsis or amniotic fluid embolism

Question 16

Describe why people get thrombocytopenia (low platelet count)

Answer 16

It could be due to; Under production, increased use or abnormal distribution

Question 17

Describe how Thrombocytopenia arises from under production

Answer 17

From abnormal marrow function, side effects of chemotherapy and drugs side as some co-trimoxazole or anti-inflammatories

Question 18

Describe how thrombocytopenia arises from increased use

Answer 18

The autoimmune disease called autoimmune thrombocytopenia

Question 19

Describe the mechanism of thrombophilia and the acquired problems

Answer 19

• Inherited defects in coagulation inhibitors and factor V.
  Results in abnormal - vessels walls (atheroma/plaque, varicose veins and Aneurysm) , blood flow (AF and varicose veins) and blood component (increase haemoglobin, WBC, platelets, viscosity of plasma and reduced coagulation factor inhibitors)