Hemostasis Flashcards
(32 cards)
Define Hemostasis
the process of blood clot formation at the site of vessel injury.
Hemostasis is a complex process & depends on interactions between the?
- vessel wall
- platelets
- coagulation & fibrinolytic mechanisms
Antithrombic factors
- thrombomodulin
- heparin sulphate
- prostacyclin
- nitric oxide
- plasminogen activator
Platelets
1) Exposure
2) Platelet adhesion
intimal injury & exposure of subendothelial elements leads to platelet adherence via platelet membrane receptor glycoprotein Ib (GpIb), to collagen & vWF in the subendothelial matrix.
Platelets
4 stages of Hemostasis
1) constriction of the blood vessel
2) formation of a temporary platelet plug
3) activation of the coagulation cascade
4) formation of fibrin plug or final clot
Vaso-constriction
- injury to vessels leads to immediate vasoconstriction = reducing blood flow to the injured area & endothelial damage results in loss of antithrombotic properties = leading to extracellular matrix/collagen exposure to the blood components.
Platelet Adhesion
- ECM releases cytokines & inflammatory markers that lead to adhesion of the platelets & their aggregation at that site = which leads to the formation of a platelet plug & sealing of the defect.
- The platelet adhesion is a complex process mediated by interactions between various receptors and proteins including tyrosine kinase receptors, glycoprotein receptors, other G-protein receptors as well as the von Willebrand Factor (vWF) (functions via binding to the Gp 1b-9 within the platelets).
Platelet Activation
The platelets that have adhered undergo very specific changes:
= they release their cytoplasmic granules that include ADP, thromboxane A2, serotonin, & multiple other activation factors.
= they also undergo a transformation of their shape into a pseudopodal shape which in-turn leads to release reactions of various chemokines. P2Y1 receptors help in the conformational changes in platelets.
Platelet Aggregation
- various platelets are activated, adhered to each other & the damaged endothelial surface leading to the formation of a primary platelet plug.
Coagulation
- involves a series of enzymatic reactions leading to the conversion of soluble plasma fibrinogen to fibrin clot.
- initiated by tissue damage
- local generation of fibrin enmeshes & reinforces the platelet plug.
Extrinsic Pathway
Intrinsic Pathway
Fibrin Clot Formation
- conversion of fibrinogen to fibrin monomers which polymerizes & forms fibrin polymer mesh and result in a cross-linked fibrin clot.
- this reaction is catalyzed by activated factor XIII (factor XIIIa) that stimulates the lysine and the glutamic acid side chains causing cross-linking of the fibrin molecules and formation of a stabilized clot.
Clot Resolution (Tertiary Hemostasis)
- activated platelets contract their internal actin and myosin fibrils in their cytoskeleton, which leads to shrinkage of the clot volume.
- plasminogen then activates to plasmin, which promotes lysis of the fibrin clot; this restores the flow of blood in the damaged/obstructed blood vessels.
Physiological limitation of coagulation
- could lead to dangerous occlusion of blood vessels if it’s not limited to the site of injury by protective mechanisms.
- activity is increased by Heparin.
- antithrombin binds to & forms complexes with coagulation factors thereby inactivating them.
- activated protein C inactivates factors V & VIII = enhanced by the cofactor protein S.
- venous thromboembolism = inherited deficiencies of natural anticoagulant proteins places patient at increased risk of venous thromboembolism.
Deficiency of
- platelet membrane receptor glycoprotein 1b (Gp1b)
or
- vWF
leads to congenital bleeding disorders…
- Bernard–Soulier disease
- von Willebrand’s disease
Aneurysms
- occurs when a weak blood vessel begins to swell or blow up like a balloon.
- most dangerous cases = aneurysm can burst, causing blood to spill on the surface of the brain.
- ruptured brain aneurysm = most common & most deadly vascular brain abnormality, with a 50% fatality rate.
Arteriovenous Malformation (AVM)
- believed to a congenital condition.
- happens when tangle of blood vessels either irritates another part of the brain, causing a stroke, or ruptures and causes bleeding within the brain.
- AVM patient can continue to re-bleed over time & develop serious neurological problems.
Difference between Arteriovenous Malformation (AVM) & Cavernous Malformation
- AVM holds blood flowing at high pressure.
- AVM described as a tangle but CVM described as small balls of blood vessels.
Cavernous Malformation
- small ball of blood vessels that carries low BP blood.
- least lethal
- can lead to seizures, brain bleeds & serious neurological deficits.
Symptoms of vascular abnormalities
- most patients are asymptomatic until a rupture occurs.
- minor symptoms = difficulty seeing, enlarged pupils.
- Aneurysm = moment of rupture = worst headache of a lifetime.
Risk factors for vascular abnormalities
- Family history
- High BP = puts extra strain on blood vessel walls.
- Medical history
- Sex = women
- Smoking
Treatment options for vascular abnormalities
- Craniotomy (removing a section of the skull) = to stop the bleeding before damage is done.
- Endovascular surgery = allows the surgeon can make an incision in a patient’s leg andsnake a very narrow catheter up through the blood vessels to the brain = when the catheter reaches the brain, the surgeon can then fill the aneurysm with ametallic thread called coils, which prevent blood from getting into the aneurysm & protect the patient from another rupture.
