clotting and haemostasis

Question 1

Describe the process of haemostasis.

Answer 1

Haemostasis is the stopping of bleeding, involving a complex process with multiple systems in the body.

Question 2

What are the consequences of a dysregulated haemostasis?

Answer 2

Dysregulation of haemostasis can lead to thrombosis if there is too much clotting or excess bleeding (haemorrhage) such as in cases of haemophilia if there is too little.

Question 3

Define thromb and name some causes of venous thrombosis.

Answer 3

Thrombosis is the formation of a blood clot in a blood vessel. Causes of venous thrombosis include genetic defects, surgery, pregnancy, malignancy, and factors like prolonged immobility (e.g., ‘economy class syndrome’).

Question 4

What are the symptoms of venous thrombosis and deep vein thrombosis (DVT)?

Answer 4

Symptoms of venous thrombosis include pain, swelling, redness, itchiness, warm skin, prominent veins, and mild fever. DVT symptoms include pain, tenderness, swelling in the leg, and skin discoloration.

Question 5

Who is Rudolf Virchow and what is Virchow’s triad?

Answer 5

Rudolf Virchow was a late 19th-century physician known as the ‘Father of modern pathology.’ Virchow’s triad consists of circulatory stasis, endothelial injury, and a hypercoagulable state, which are factors contributing to thrombosis.

Question 6

Explain the difference between primary and secondary haemostasis.

Answer 6

Primary haemostasis involves blood vessel constriction, platelet activation, and the formation of a primary haemostatic plug. Secondary haemostasis involves coagulation activation leading to a stable haemostatic plug.

Question 7

What inhibits platelet aggregation in the normal state of endothelium?

Answer 7

Properties of the endothelium normally inhibit platelet aggregation.

Question 8

Describe platelet aggregation in primary haemostasis.

Answer 8

Platelet aggregation involves anuclear cytoplasmic fragments of megakaryocytes that are rapidly activated to form a primary haemostatic plug.

Question 9

What is the role of thrombin in blood clotting/coagulation?

Answer 9

Thrombin plays a crucial role in blood clotting by converting fibrinogen into fibrin, which forms a mesh that helps in clot formation.

Question 10

How does blood clotting occur in the body?

Answer 10

Blood clotting involves a series of steps including platelet activation, coagulation cascade activation, and the formation of a stable clot to stop bleeding.

Question 11

Describe the process of platelet aggregation following exposure to collagen from a damaged blood vessel.

Answer 11

Platelet aggregation is initiated by exposure to collagen, leading to the release of intracellular granules from platelets. These granules include alpha granules containing proteins like von Willebrand factor, and dense granules containing substances like ADP and serotonin.

Question 12

What is the role of fibrinogen receptor GP IIb/IIIa in platelet function?

Answer 12

The fibrinogen receptor GP IIb/IIIa, an integrin on platelet membranes, promotes platelet adhesion.

Question 13

How is blood coagulation promoted by phospholipids?

Answer 13

Phospholipids promote blood coagulation by aiding in the conversion of liquid blood into an insoluble gel clot.

Question 14

Define platelet aggregometry and its significance in platelet function tests.

Answer 14

Platelet aggregometry is a test measuring the time it takes for platelets to aggregate in response to different agonists like ADP. It is a specialist research technique used to assess platelet function.

Question 15

Describe the process of generation of thrombin in blood coagulation cascade.

Answer 15

Thrombin, the final protease in the blood coagulation cascade, is generated through the action of the ‘prothrombinase’ complex, involving Factor Xa as the enzyme, prothrombin as the substrate, and various cofactors like Factor Va and phospholipids.

Question 16

Describe the role of thrombin in fibrin formation.

Answer 16

Thrombin converts fibrinogen into fibrin, a process essential for clot formation.

Question 17

Define fibrinogen and its structure.

Answer 17

Fibrinogen is a large protein in plasma with a symmetrical multi-polypeptide chain structure, consisting of 2 x 3 subunits.

Question 18

How does thrombin convert fibrinogen to fibrin?

Answer 18

Thrombin proteolytically removes a short peptide (fibrinopeptide) from the Aα and Bβ chains of fibrinogen.

Question 19

What is the function of factor XIIIa in fibrin cross-linking?

Answer 19

Factor XIIIa, a transglutaminase, catalyzes the formation of covalent bonds between side-chains of Lys and Glu residues to reinforce fibrin fibrils.

Question 20

Describe the structure of fibrin fibers.

Answer 20

Fibrin fibers have a diameter of approximately 1 μm and consist of several hundred fibrin units, giving them a noodle-like appearance.

Question 21

What are the functions of fibrin in the body?

Answer 21

Fibrin serves as a mechanical meshwork, supports platelet adhesion/aggregation, attracts other cells, provides a provisional matrix for wound repair, and triggers its subsequent dissolution.

Question 22

Explain the process of spontaneous polymerization in fibrin formation.

Answer 22

The α-chain ‘knobs’ spontaneously interact with γ-chain C-terminal binding cavities, leading to the formation of ‘half-staggered overlap’ and end-to-end linear γ-γ associations.

Question 23

What are the mechanisms that inhibit coagulation?

Answer 23

Natural and therapeutic mechanisms, including monitoring of anticoagulation and defects in coagulation, play a role in inhibiting coagulation.

Question 24

Do you need cofactors for the thrombin reaction to be fast?

Answer 24

Yes, in the absence of cofactors, the thrombin reaction is very slow despite its specificity.

Question 25

Define dysfibrinogenaemia and provide an example.

Answer 25

Dysfibrinogenaemia is a condition where there is abnormal fibrinogen function. An example is Fibrinogen Milano IV with the Aα chain mutation Arg16>His.