haemostasis

Question 1

What is haemostasis?

Answer 1

Haemostasis is the mechanism that ensures blood remains fluid while damaged vessels are quickly fixed to stop excess loss. It prevents excessive bleeding or clot formation.

Question 2

What are the two components of haemostasis?

Answer 2

The two components of haemostasis are primary haemostasis and secondary haemostasis.

Question 3

What is the role of platelets in haemostasis?

Answer 3

Platelets play a crucial role in haemostasis by forming blood clots to stop bleeding. They interact with vascular endothelial cells and release various factors to initiate clot formation.

Question 4

What is thrombopoiesis?

Answer 4

Thrombopoiesis is the process of platelet production from megakaryocytes in the bone marrow.

Question 5

What are megakaryocytes?

Answer 5

Megakaryocytes are large cells found in the bone marrow that give rise to platelets. They undergo endomitosis, where DNA replication and organelle formation occur without cell division.

Question 6

How do megakaryocytes produce platelets?

Answer 6

Megakaryocytes produce platelets by forming pro-platelet extensions in their periphery. These extensions contain part of the megakaryocyte cytoplasm and are facilitated by microtubules for organelle movement.

Question 7

What is the chromosomal characteristic of megakaryocytes?

Answer 7

Megakaryocytes have large complicated nuclei with up to 368 chromosomes.

Question 8

What are the main membrane glycoproteins found on platelets?

Answer 8

The main membrane glycoproteins found on platelets are:

Glycoprotein Ib: involved in initial platelet attachment to von Willebrand factor and the vascular endothelium.
Glycoproteins Ia – IIa and VI: responsible for platelet adhesion to collagen.
Glycoproteins IIb/IIIa: mediate adhesion to fibrinogen and additional adhesion to von Willebrand factor, facilitating platelet-to-platelet adhesion.

Question 9

What is the function of glycoprotein Ib?

Answer 9

Glycoprotein Ib plays a role in the initial attachment of platelets to von Willebrand factor and the vascular endothelium.

Question 10

What is the function of glycoproteins Ia – IIa and VI?

Answer 10

Glycoproteins Ia – IIa and VI are involved in platelet adhesion to collagen.

Question 11

What is the function of glycoproteins IIb/IIIa?

Answer 11

Glycoproteins IIb/IIIa are responsible for platelet adhesion to fibrinogen and additional adhesion to von Willebrand factor, facilitating platelet-to-platelet adhesion.

Question 12

What are the contents of platelet electron dense granules?

Answer 12

Platelet electron dense granules contain:

Nucleotides (ADP)
Serotonin
Ca2+, which is essential for the coagulation cascade.

Question 13

What are the contents of platelet alpha granules?

Answer 13

Platelet alpha granules contain:

Fibrinogen, a precursor of fibrin and von Willebrand factor.
Factor V, which is involved in the coagulation cascade.
Heparin antagonist.
Platelet-Derived Growth Factor (PDGF), which is important for vascular repair.

Question 14

How does vascular injury and damage to the endothelium contribute to clot formation?

Answer 14

Vascular injury and damage to the endothelium expose collagen fibers, leading to platelet adhesion and activation. This results in platelet shape change, secretion of granule contents, and platelet aggregation. The activated platelets provide a surface for the coagulation cascade to occur.

Question 15

What role does serotonin play in clot formation?

Answer 15

Serotonin released by activated platelets causes vasoconstriction and reduces blood flow at the site of injury.

Question 16

How do endothelial cells and macrophages contribute to clot formation?

Answer 16

Endothelial cells and macrophages secrete nitric oxide (NO), which inhibits platelet activation and promotes vasodilation, helping to prevent excessive clot formation.

Question 17

What is the coagulation cascade?

Answer 17

The coagulation cascade is a series of enzymatic reactions that leads to the formation of a fibrin clot. It involves the activation and interaction of various coagulation factors.

Question 18

What are the different pathways in the coagulation cascade?

Answer 18

The coagulation cascade consists of the intrinsic pathway, extrinsic pathway, and common pathway. The intrinsic pathway is initiated by factors within the blood, while the extrinsic pathway is triggered by tissue factor released from damaged tissues. Both pathways converge into the common pathway, which leads to the formation of fibrin.

Question 19

What is the role of vitamin K in the coagulation cascade?

Answer 19

Vitamin K is essential for the synthesis of several coagulation factors, including factors II, VII, IX, and X. It helps modify these factors, allowing them to bind to calcium ions and form a functional clot.

Question 20

What is von Willebrand factor (VWF), and what is its role in clotting?

Answer 20

Von Willebrand factor is a large multimeric glycoprotein. It is synthesized by endothelial cells and megakaryocytes. VWF circulates in plasma and is stored in alpha granules of platelets. It plays a crucial role in platelet adhesion and aggregation by binding strongly to platelets and subendothelial collagen. It also stabilizes factor VIII of the coagulation cascade.

Question 21

What happens in Von Willebrand disease?

Answer 21

Von Willebrand disease is a blood clotting disorder characterized by a deficiency or dysfunction of von Willebrand factor. This results in impaired platelet adhesion and aggregation, leading to excessive bleeding.

Question 22

What is the coagulation cascade?

Answer 22

The coagulation cascade is a series of enzymatic reactions that leads to the formation of a fibrin clot. It involves the activation and interaction of various coagulation factors.

Question 23

What is the extrinsic pathway of the coagulation cascade?

Answer 23

The extrinsic pathway of the coagulation cascade is initiated by the interaction between tissue factor and factor VII. This complex activates factor X, as well as factors IX and XI. However, the amount of thrombin produced in this pathway is not sufficient for the conversion of fibrinogen to fibrin.

Question 24

What is the purpose of the intrinsic pathway in the coagulation cascade?

Answer 24

The intrinsic pathway amplifies the coagulation cascade signaling pathway. Thrombin, which is produced during the extrinsic pathway, activates factor VIII and factor V, creating a positive feedback loop. The intrinsic pathway relies on the presence of calcium ions (Ca2+), which are also found in platelet dense granules.

Question 25

What role does the intrinsic pathway play in the coagulation cascade?

Answer 25

The intrinsic pathway contributes to increased generation of thrombin, an enzyme that plays a central role in the conversion of fibrinogen to fibrin.

Question 26

How does the extrinsic pathway of the coagulation cascade initiate?

Answer 26

The extrinsic pathway begins with the interaction between tissue factor and factor VII. This interaction leads to the activation of factor X, as well as factors IX and XI.

Question 27

What is the consequence of the extrinsic pathway activation in terms of thrombin production?

Answer 27

The extrinsic pathway produces a small amount of thrombin, which is not sufficient for the conversion of fibrinogen to fibrin.

Question 28

What is the function of the common pathway in the coagulation cascade?

Answer 28

The common pathway stops bleeding and clot formation. Thrombin, produced in the pathway, breaks down fibrinogen into fibrin monomers, which then polymerize to form a fibrin clot. This clot is important for platelet aggregation and the formation of a haemostatic plug.

Question 29

Which factors are involved in the common pathway of the coagulation cascade?

Answer 29

The common pathway depends on factor X and factor V, both of which circulate in the plasma.

Question 30

What are the main coagulation factors and their functions?

Answer 30

Factor I (Fibrinogen): Fibrin subunit involved in the formation of fibrin clot.
Factor II (Prothrombin): Serine protease that is converted into thrombin, a key enzyme in the coagulation cascade.
Factor III (Tissue Factor): Receptor/cofactor involved in initiating the extrinsic pathway.
Factor V (Labile Factor): Cofactor that works together with factor X in the intrinsic pathway.
Factor VII (Proconvertin): Serine protease involved in the extrinsic pathway.
Factor VIII (Antihemophilic Factor): Cofactor that assists in the intrinsic pathway and is deficient in individuals with hemophilia A.
Factor IX (Christmas Factor): Serine protease involved in the intrinsic pathway and deficient in individuals with hemophilia B.
Factor X (Stuart-Prower Factor): Serine protease that plays a key role in the common pathway.
Factor XI (Plasma Thromboplastin Antecedent): Serine protease involved in the intrinsic pathway.
Factor XII (Hageman Factor): Serine protease involved in the intrinsic pathway.
Fibrin Stabilizing Factor: Transglutaminase serine protease that cross-links fibrin molecules to stabilize the clot.
HMWK (High Molecular Weight Kininogen): Cofactor involved in the intrinsic pathway.

Question 31

What is the role of vitamin K in the coagulation cascade?

Answer 31

Vitamin K is essential for the synthesis of active forms of factors II (Prothrombin), VII, IX, and X. It is required for their proper functioning in the coagulation cascade.

Question 32

How can vitamin K deficiency occur?

Answer 32

Vitamin K deficiency can occur in newborns or adults due to dietary restrictions. It can also be caused by liver disease, which affects the absorption of vitamin K. Additionally, the anticoagulant medication warfarin inhibits the activity of vitamin K reductase, which recycles vitamin K.

Question 33

What is clotting?

Answer 33

Clotting, also known as coagulation, is the process by which blood forms a clot to stop bleeding. It involves the activation of various factors and the conversion of fibrinogen into fibrin, which forms a mesh to trap blood cells and form a clot.

Question 34

What is thrombosis?

Answer 34

Thrombosis refers to the formation of a blood clot (thrombus) within a blood vessel. It occurs when platelets and fibrin form clots at sites of injury or inflammation, leading to blood flow obstruction. Examples of thrombosis include arterial thrombosis (in arteries) and venous thrombosis (in veins).

Question 35

What can thrombosis cause?

Answer 35

Thrombosis can cause various conditions such as myocardial infarction (heart attack) when the clot blocks blood flow to the heart, and cerebrovascular disease when it affects blood flow to the brain, leading to a stroke.

Question 36

What is an embolus?

Answer 36

An embolus is a clot that breaks free from its site of formation and travels through the bloodstream. It can potentially cause an embolism by blocking a blood vessel at a distant site. For example, a pulmonary embolism occurs when an embolus blocks a blood vessel in the lungs.

Question 37

What are some hereditary risk factors for thrombosis?

Answer 37

Some hereditary risk factors for thrombosis include:

Factor V Leiden gene mutation: This mutation affects Factor V, reducing its inactivation by Protein C, leading to an increased risk of clot formation.
Hereditary antithrombin deficiency: Deficiency in the antithrombin protein, which inhibits clotting factors, can increase the risk of thrombosis.
Protein C or Protein S deficiency: Deficiencies in these proteins, which play a role in regulating clotting, can increase the risk of thrombosis.
Hereditary elevated levels of plasma prothrombin: Higher levels of prothrombin, a clotting factor, can increase the risk of thrombosis.
Elevated levels of von Willebrand factor: Some blood groups may have higher levels of von Willebrand factor, which can increase the risk of thrombosis.

Question 38

What is fibrinolysis?

Answer 38

Fibrinolysis is an anti-coagulant mechanism that works in balance with blood coagulation. It involves the breakdown of fibrin, the protein that forms blood clots, and aims to prevent excessive clot formation.

Question 39

How is plasmin generated in fibrinolysis?

Answer 39

Plasminogen, an inactivated proenzyme, is converted to plasmin by thrombin. Plasmin is a serine protease that plays a key role in fibrinolysis by degrading fibrin polymers, limiting the growth of a thrombus (blood clot).

Question 40

How is coagulation inhibited?

Answer 40

Coagulation is inhibited through a process involving thrombin, endothelial cells, and protein C. Thrombin binds to the endothelial cell receptor thrombomodulin, which activates endothelial cell-bound protein C. Activated protein C then destroys factors V and VIII, inhibiting further thrombin production and effectively ending the coagulation cascade.

Question 41

What is tissue factor pathway inhibitor (TFPI)?

Answer 41

TFPI is a small protein (40 kDa) produced by endothelial cells. It is present in platelets and circulates in the plasma. TFPI inhibits factor Xa, factor VIIa, and tissue factor. By inhibiting these factors, TFPI helps limit the activity of thrombin to the site of injury only.

Question 42

What is the relationship between protein C, protein S, and vitamin K?

Answer 42

The activity of protein C, which is synthesized in the liver, relies on the presence of the protein S cofactor. Both protein C and protein S are dependent on vitamin K for their proper functioning.

Question 43

What is the role of protein S in coagulation?

Answer 43

Protein S assists in the binding of protein C on the surface of platelets. It acts as a cofactor for protein C, enhancing its anticoagulant activity.

Question 44

What type of protein is protein C?

Answer 44

Protein C is a serine protease, belonging to the same class as other coagulation factors involved in the coagulation cascade.

Question 45

What is the role of antithrombin in coagulation?

Answer 45

Antithrombin is a small glycoprotein that is synthesized by endothelial cells and enters circulation. It inhibits serine proteases, including several factors involved in the coagulation cascade. Antithrombin helps regulate the coagulation process by inhibiting excessive clot formation.

Question 46

How does heparin enhance the activity of antithrombin?

Answer 46

Heparin is an anticoagulant that enhances the activity of antithrombin. Heparin binds to antithrombin and induces a conformational change, allowing antithrombin to more effectively inhibit serine proteases involved in coagulation.

Question 47

What is thrombocytopenia?

Answer 47

Thrombocytopenia is a condition characterized by a low platelet count, which can lead to impaired clotting. It can be a possible sign of bone marrow failure or result from autoimmune destruction of platelets.

Question 48

What is Haemophilia A?

Answer 48

Haemophilia A is a hereditary bleeding disorder caused by a deficiency in Factor VIII, a clotting factor. It is an X-linked inheritance disorder, commonly passed from mother to son. While the prevalence in the general population is 30-100 cases per 1 million individuals, around one-third of cases have no family history due to gene mutations or deletions.

Question 49

What is Haemophilia B (Christmas disease)?

Answer 49

Haemophilia B is a bleeding disorder similar to Haemophilia A but caused by a deficiency in Factor IX, another clotting factor. It is less prevalent than Haemophilia A, accounting for about one-fifth of Haemophilia A cases.

Question 50

What is Von Willebrand disease?

Answer 50

Von Willebrand disease is a bleeding disorder caused by various mutations that reduce the function or limit the synthesis of von Willebrand factor (VWF), a protein involved in platelet adhesion and clotting. It has an autosomal dominant inheritance pattern and is more prevalent in females. The severity of bleeding can vary among patients.

Question 51

What are other coagulation factor deficiencies?

Answer 51

There are rare disorders characterized by deficiencies in other coagulation factors. An example is Factor XI deficiency, which is more common in the Ashkenazi Jewish population.