blood coagulation

what is haemostasis

body’s natural process for stopping bleeding after an injury which involves forming clot and seal damaged blood vessel

what is the main purpose of haemostasis

to control blood loss following vascular injury

what happens if haemostasis is overactive

thrombosis (blood clot)

what happens if haemostasis is underactive

haemorrhage (excessive bleeding)

difference between thrombosis and haemorrhage

• thrombosis is blockage of blood flow from within blood vessel (blood clot inside blood vessel)

• haemorrhage is loss of blood from blood vessel (leakage of blood)

what are the main stages in haemostatic process after vascular injury

1) Local vasoconstriction

2) Platelet plug formation

3) Stabilisation of platelet plug by fibrin (thrombus formation)

4) Thrombus dissolution (fibrinolysis)

1) local vasoconstriction - why does the injured blood vessel immediately narrow

to reduce blood flow to damaged area

2) platelet plug formation - how do platelets stick together in the site of injury to exposed collagen

they stick by a protein called von Willebrand factor (vWF) which forms a bridge between collagen platelets

3) thrombus formation - what happens

fibrin forms from the coagulation cascade which is a tough sticky protein 

the fibrin mesh turns soft platelet plug into stable clot (thrombus)

4) thrombus dissolution - how is the clot removed once healed

• enzyme plasmin breaks down fibrin into soluble fragments

• plasmin is made from plasminogen and activated by tPA 

• prevents clots from blocking blood vessel permanently

what drug classes can modulate haemostasis

• Antiplatelet drugs

• Anticoagulant drugs

• Fibrinolytic/thrombolytic drugs

• Anti-fibrinolytic drugs (e.g. tranexamic acid)

what triggers platelet adhesion

• exposure of collagen

• von Willebrand factor (vWF acts as a bridge)

name key substances that activate platelets

• thrombin

• thromboxane A2

• ADP

• fibrinogen

what are the main functions of platelets in haemostasis

• adhere to exposed collagen via vWF

• aggregate with other platelts

• provide surface for coagulation cascade

what is contained in platelet dense granules

ADP and serotonin

what is contained in platelet alpha granules

vWF, fibrinogen, Factor V, fibronectin, platelet factor 4, platelet-derived growth factor

true or false: there is only a single layer of endothelium cells so when damaged, this exposes underlying structures to the blood. via vWF, tethering between structures and surface of platelets

true

what is the purpose of coagulation cascade

production of fibrin to stabilise clot

what triggers the intrinsic pathway (intrinsic = internal damage to blood vessel)

contact with a negatively charged surface e.g. collagen, glass

what triggers extrinsic pathway (extrinsic = external injury releasing tissue factor)

exposure to tissue factor during vascular injury

which factor marks start of common pathway

factor Xa

which ion is essential for coagulation reactions

Ca2+

what activates factor V and factor VIII

thrombin

why is there no factor IV and factor VI

“Factor IV” was found to be Ca²⁺ and “Factor VI” is actually Va

what is inactive precursor of plasmin

plasminogen

how is plasminogen activated

by tissue plasminogen activator (tPA) released from damaged endothelium

what does plasmin do

digests fibrin into soluble degradation products

what is the mechanism of fibrinolytic drugs

activate plasminogen to plasmin promoting fibrin breakdown

examples of fibrinolytic agents

• Streptokinase: Antigenic; can cause allergic reactions (1–4% incidence).

• Alteplase: Recombinant tPA; used in MI and ischaemic stroke.

• Reteplase: Longer-acting tPA mutant; bolus administration (MI).

• Tenecteplase: Longer-acting tPA mutant; bolus administration (MI).

antiplatelet drugs

• aspirin 

• clopidogrel

• tirofiban

what enzyme does aspirin inhibit

cyclooxygenase (COX)

true or false: aspirin’s inhibition is reversible

false - irreversible

how does aspirin reduce platelet activation

inhibits thromboxane AT synthesis → less platelet activation and vasoconstriction

what receptor does clopidogrel block

P2Y12 receptor (ADP receptor)

what effect does clopidogrel have on platelets

Inhibits ADP-induced platelet aggregation and GPIIb/IIIa expression

what drug class does clopidogrel belong to

thienopyridines (same as prasugrel)

what other drug has similar mechanism to clopidogrel

ticagrelor

what is the target of tirofiban

GPIIb/IIIa complex on platelets

what is the role of GPIIb/IIIa complex

platelet receptor for fibrinogen binding — crucial for platelet aggregation

name other drugs that inhibit GPIIb/IIIa

• eptifibatide (peptide inhibitor)

• bciximab (monoclonal antibody; no longer available)

what is the GPIIb/IIIa complex

glycoprotein receptor found on the surface of platelets important for platelet aggregation

true or false: haemophilia is X-chromosome linked

true

which sex is usually affect by haemphilia

males because females are usually carriers

what factor is deficient in haemophilia A

factor VIII

which factor is deficient in haemmophilia B

factor IX

which factor deficiency has less clinical significance

factor XI deficiency

what is the main clinical problem in untreated haemophilia

internal bleeding