T2 L2: Haemostasis Flashcards
What is extravasation?
Movement of fluid and molecules out of vessels
What is the first stage of wound healing?
Haemostasis
What does the endothelium secrete when it’s injured?
It stops secreting inhibitors and starts secreting von Willebrand factor
What does von Willebrand factor (vWF) do?
A multi-subunit protein that serves both to anchor the platelets to the subendothelial collagen and as a carrier protein for Factor VIII in plasma
What is the 3 step platelet-based pathways for repair of blood vessels?
- Platelets form a haemostatic plug by adhesion, activation and aggregation.
- Coagulation using the enzyme cascade
- Vasoconstriction by release of vasoconstrictors and pro-thrombotic agents `
Give 3 examples of molecules used for vasoconstriction
Serotonin, ADP, and Thomboxane A2
What are the 3 points of Virchow’s triad?
Venous stasis, activation of blood coagulation, and vein damage.
What white blood cells develop from the common lymphoid progenitor?
NK cells, T-cells, and B-cells
What do plasma cells develop from?
B-cells
What common progenitor do megakaryocytes develop from?
The common myeloid progenitor
What cell do thrombocytes develop from?
A megakaryocyte
What is thrombocytopaenia?
Low platelet count
How many platelets can 1 megakaryocyte produce?
About 4000
What does exocytose mean?
Excrete
What 3 changes occur to platelets once they’re activated?
They start to exocytose, they change shape and their respiratory rate increases
Describe the shape of an activated platelet
Irregular shape with many protruding pseudopodia
What do platelets adhere to during the first step of activation?
To exposed collagen
What do platelets exocytose once they’re activated?
Dense granules like serotonin, ADP, calcium, and Thromboxane A2 (TXA2)
What molecule stimulates platelet aggregation?
ADP
Which drug blocks platelet aggregation?
Prasugrel via fibrinogen
What happens during platelet activation in detail?
Extracellular ADP activates P2Y12 receptors and cause a cation flow
Which 2 clotting factors are not enzymes?
Factor V and factor VIII (they’re co-factors)
Where are tissue factors in terms of the endothelium?
Behind the endothelium, it’s revealed when the endothelium is damaged which causes coagulation
Where are clotting factor precursors found?
In the blood
What is the difference between the intrinsic and extrinsic coagulation pathway?
Extrinsic begins with trauma, intrinsic begins with a damaged surface within
What factor does factor 5 develop from?
Factor 10
How does Prothrombin (II) turn into fibrin?
Prothrombin (II) turns into Thrombin (IIa) by factor 5. Thrombin (IIa) then turns Fibrinogen (I) into Fibrin (Ia). This is the common pathway of the coagulation cascade
What do labs use to stop clotting?
Citrate, heparin or EDTA
What is the difference between plasma and serum?
Plasma in blood without the white or red cells. Serum is the fluid after clotting has occurred
What is thrombosis?
Abnormal formation of a clot locally
What 2 molecules are needed to make fibrin cross-linked?
cross-linked fibrin is made with the interaction of factor XIII (fibrin stabilising factor) and Ca2+
What is Factor Xa co-factor and why is it needed to activate thrombin?
Va is needed because factor Xa activated thrombin poorly
What are the 3 ways to activate factor X into factor Xa?
Extrinsic Xase, Intrinsic Xase, and thrombin by positive feedback
What factors are involved in Extrinsic Xase?
Tissue factor and factor VIIa
What factors are involved in intrinsic Xase?
Factor VIIIa and Factor IXa
Describe an example of positive feedback in the coagulation cascade
Thrombin. I activates factor V and Factor XIII that activate thrombin later on in the cascade.
Describe the prothrombin group of the coagulation cascade
Includes factors II, VII, IX, and X. They’re enzymes that turn prothrombin into thrombin. Vitamin K is needed for their synthesis and Ca2+ for their activation. They’re stable
Describe the thrombin group of the coagulation cascade
Includes factors I, V, and VIII. They’re activated by thrombin. factor V and VIII are co-factors, and factor I is fibrinogen
When are thrombin group factors increased?
Inflammation, pregnancy and oral contraceptives
What does factor IX do?
Without it you get Haemophilia B
What does factor X do?
It clotting factor
Where are clotting factors produced?
Liver
What is the role of vitamin K in clotting?
It enables gamma carboxylation of clotting enzymes
What is factor 2 also known as?
Prothrombin
What is the function of plasmin?
It lyses fibrin
What does plasmin develop from and how?
Starts as plasminogen and is made by the liver. It then requires plasminogen activator (tPA) to mature
Where can tPA be found?
On the surface of endothelial cells
What is the function of protein C?
It’s a coagulation inhibitor for factor Va and VIIIa. Co-factor protein S is also needed to inactivate Va
Where is protein C found?
Starts as an inactive enzyme on the surface of endothelial cells
What is antithrombin III (ATIII)?
A peptide made in the liver that blocks activity of thrombin along with factors Xa and IXa
What does Heparin do to antithrombin III?
It increases its activity
How can the effects of Heparin be reversed?
protamine sulfate
What does antithrombin III deficiency cause?
Unwanted clotting
How is vitamin K made in the body?
By bacteria in the large intestine but its also found in leafy green veg
How does Warfarin work?
It prevents recycling of vitamin K but takes a couple of days
How can vitamin K deficiency occur?
By GI disease or no fat absorption. Liver disease can prevent bile salt production so fat won’t be absorbed
What is Haemophillia A?
A clotting disorder caused by congenital lack of factor VIII. It’s X-linked so only males have symptoms
What is the treatment for Haemophilia A?
Purified factor VIII injections
What is haemophilia B?
A clotting disorder caused by lack of factor IX
What was Polly the sheep meant for?
So scientists could derive recombinant factor IX out of her milk
Describe the process of atherogenesis
Injury to the endothelium from a plaque rupture causes monocytes to enter the lesion where they become macrophages. They consume the cholesterol esters and become foam cells. When the macrophages die, they release their contents which attracts more monocytes. This results in inflammation and therefore haemostasis
What are cholesterol esters oxidised into?
Into oxygen radicles which makes them immunogenic. The oxidised lipids are then consumed by macrophages
What does immunogenic mean?
The ability for a foreign substance to produce an immune response
Why can’t vessels control their dilation when damaged?
During injury, the endothelium is stripped away which would usually produce NO
What do antiplatelet agents do?
Block platelet activation. Good for treating arterial disease especially acute coronary syndromes
What do anticoagulants do?
They block the production or activity of clotting factors. Used to treat venous disease
What are fibrinolytics used for?
Used to dissolve fibrin in arterial disease
How does aspirin work?
It’s a cyclo-oxygenase (COX) inhibitor that blocks the formation of thromboxane A2 in platelets. It lengthens bleeding time but doesn’t increase coagulation time
Which drug is used for prophylaxis for MI?
Aspirin
What does prasugrel do?
It’s an antiplatelet drug that blocks ADP receptors
What does Clopidogrel do?
It’s an antiplatelet drug that blocks ADP receptors
What drug class is used for prophylaxis for deep vein thrombosis and pulmonary embolism?
Anticoagulants
What do Heparins do?
They inhibit coagulation (with ATIII) by inhibiting factor Xa. These drugs have to be injected
What kind of drug is Dabigatron and how does it work?
A novel oral anti-coagulant (NOAC) that inhibits thrombin
What kind of drug is Rivaroxaban and how does it work?
A novel oral anti-coagulant (NOAC) that inhibits factor Xa
What type of drug is streptkinase?
A fibrolytic
What type of drug is Urokinase?
A fibrolytic
