Hemostasis and the role of thrombocytes Flashcards
Hemostasis definition
The arrest of bleeding after injury, involving a large variety of pro- and anticoagulants that allow repair while also avoiding thrombosis and bleeding disorders
Hemostasis mechanism
- Vasoconstriction
- Platelet aggregation
- Blood coagulation
Primary hemostasis: the immediate vasoconstriction, the platelet activation that follows, blood coagulation that occurs minutes after that
Secondary hemostasis: The later formation of the fibrin meshwork that stabilized the clot. And fibrinolysis
Vasoconstriction mechanism
Evoked due to endothelin release and neurogenic reflex.
Locally-released vasoconstrictor substances: thromboxane A2, serotonin, adrenaline, extracellular K+ ions
Platelet adhesion, activation, aggregation
Within seconds of injury: Platelets begin to adhere to the injured area, the initial adherence activates the platelets
Activated platelets: release ADP, thromboxane A2, cause additional platelets to adhere
The platelets aggregate to form a thrombus/plug, which causes the injury to be blocked.
**Platelets are prevented from aggregating along a
normal vessel by the action of NO and prostacyclin, which are released from uninjured
endothelial cells and this also keeps the thrombus from getting too big.
The role of thrombocytes/platelets
Platelets (also called thrombocytes, derivatives of megakaryocytes) are the main actor in primary hemostasis.
The major functions of platelets are
(1) adhesion and aggregation with each other
(2) formation of a phospholipid surface for blood coagulation factors,
(3) secretion of granules with biologically-active molecules.
Dense granules containing ADP, serotonin, and polyphosphates to activate platelets
α granules produced by the liver but stored in platelets, contain clotting factors),
Actin/myosin for later contraction to reduce the size of the clot.
Platelet adherence
Adhere to the injured space via glycoprotein-collagen binding with glycoprotein GP VI (6) and GP Ia-IIa.
von Willebrand Factor
Endothelial cells also release the von Willebrand factor
(vWF) that allows another platelet glycoprotein to bind to the injury area and is also used as
part of the coagulation cascade.
There is a weak connection between platelets and collagen via GP VI and GP Ia/IIa to surface integrins
A STRONGER connection via GP Ib-IX-V (1-9-5) and vWF
(know that the connection is made stronger when vWF is involved, and not just the glycoproteins).
von Willebrand factor binds to which GP?
Ib
IX
V
Platelet binding to collagen via glycoprotein
GP VI and Ia-IIa
Platelet activation
Activation substances: Collagen TXA2 - vasoconstrictor 5-HT - vasoconstricotr Adrenaline - activates platelets and aggregates Thrombin PAF
Activated platelets mechanism
When platelets are “activated,” this means that there is a CALCIUM release that allows the thrombocyte cytoskeleton rearrangement, shape change, and secretion of clotting factors.
The shape change of platelets is associated with a disassembly and reassembled cytoskeleton
to make the thrombocyte larger and bind better to other platelets. This increases platelet aggregation.
Another important change in activated platelets is the change to make their cell surface
contain more negative charges. This occurs by flipping phosphatidylserines to the surface,
which leads to plug formation and aids in the formation of the coagulation factors