Flashcards in Platelets and haemostasis Deck (30)
A myeloid blood cells that produces thrombocytes (platelets).
Each cell produces 4000 platelets
Present in the bone marrow
Platelets- key cell necessary for blood coagulation.
Produced by megakaryocytes.
Very scarce in the blood: less than 50x as much as RBCs
Size- around 1.5 micrometers
State that describes a low platelet count
Extrinsic coagulation pathway
This is the initiating step in the coagulation pathway.
Factor VIIa reacts with Tissue factor (factor III) to form Extrinsic Xase.
Extrinsic Xase activates factor X with Intrinsic Xase.
Formation of fibrin
Fibrinogen is activated by thrombin (Factor IIa) to form fibrin.
Intrinsic coagulation pathway
Thrombin (factor IIa) activates factor VIII to VIIIa.
VIIIa is a coenzyme that activates Factor IXa to form Intrinsic Xase.
Intrinsic Xase activates X to Xa. Whilst thrombin (IIa) activates V to Va.
Va is a co-factor for Xa. Va activates Xa to form thrombinase, used to form thrombin.
Common coagulation pathway
1. Prothrombin (Factor II) is activated by factor Xa to thrombin (IIa).
2. Thrombin activates fibrinogen (I) to fibrin (Ia).
Thrombin also goes to activate VIII in the intrinsic pathway (positive feedback).
3. XIIIa activates fibrin to form a fibrin clot cross link- to stop bleeding.
Factors activated by thrombin
V- co-factor, when activated, reacts with Xa to form thrombinase (activates thrombin)
VIII- co-factor, when activated, reacts with IXa to form intrinsic Xase, which activates X.
Vitamin required for the synthesis of factors, made in livers: II (prothrombin), VII, IX and X (2, 8, 9, 10).
X is a Ca2+ dependant protease.
Vit K is made by bacteria in large intestines or ingested from leafy greens.
Vit K is essential for gamma carboxylation of clotting enzymes
Vitamin K deficiency
Causes inadequate clotting of blood.
Causes: Liver/ GI damage.
New born babies' intestines have not yet been colonised by bacteria which can cause clotting problems due to low Vit K.
Anticoagulant drug that antagonises Vit K.
This prevents the synthesis of clotting factors: II, VIII, IX, X.
Enzyme that inhibits coagulation. Vit K is involved in its synthesis, in the liver.
Activated by thrombin, when there is too much clotting. Activation happens on endothelial surface.
Also inactivates other co-factors. Protein C and co-factor S inactivate Va and VIIIa together.
Enzyme that lyses clots by breaking down fibrin.
Plasminogen is its inactive form, made in the liver. This is activated by the tissue plasminogen activator (tPA)
Peptide made by the liver that inhibits factors: IIa (thrombin), Xa, IXa (2a, 10a, 9a).
A deficiency of this peptide causes a thrombotic disease- increasing risk of stroke, embolisms.
Heparin increases the activity of antithrombin III by inhibiting Xa.
Blocks platelet activation
Used to treat arterial diseases
Drugs that dissolve fibrin (clots). This is used as last resort.
Used for arterial clots
Tissue plasminogen activator
Drugs that block clotting factors: mainly used for venous clots.
Prophylaxis for deep vein thrombosis and pulmonary embolisms.
Low BP in pulmonary circulation.
Novel-oral anticoagulants (NOACs)
Anticoagulant used mainly for venous clots.
Works by inhibiting factor Xa with antithrombin III.
Antiplatelet drug that blocks thromboxane in platelets.
Used for MI prophylaxis.
Anti-platelet drug that is used to prevent arterial clotting.
Works by inhibiting ADP receptors on platelets.
Novel oral anticoagulants (NOACs)
Anticoagulants that inhibit clotting factors.
NOAC that inhibits thrombin, IIa.
NOAC that inhibits factor Xa.
X-linked genetic disease that is characterised by the mutation of factor VIII (8).
VIII is a co-factor that activates IXa in the the intrinsic pathway when activated.
Excessive bleeding of wounds, that bleeds for days.
Affects muscles and joints.
Treatment- injecting purified factor VIII- expensive
Also known as the Christmas disease.
Lack of clotting factor IX.
IX is used to activate the intrinsic Xase, which also activates X to Xa.
Individuals also have the same symptoms as those with haemophilia A.
Monocytes enter endothelium lesions and become macrophages.
Macrophage consume cholesterol esters and become foam cells.
When the foam cells burst and release their content, they attract more monocytes, cytokines and pro-inflammatory molecules.
Atherogenesis caused by lipids
LDL deposits itself in lesions.
Cholesterol is oxidised to oxygen radicals.
Oxidised lipids are eaten by macrophages to form foam cells.
Foam cells die and release their content, causing more inflammation.
Endothelium- cause of atherogenesis
Endothelial cells release these which attract monocytes.
2. Stimulation of coagulation.
When endothelium is lost, this exposes collagen, stimulating coagulation. Also-releases tissue factor.
3. Release of NO
When endothelium is lost, this prevents NO from being released. Therefore vessels cannot dilate.