Hemostasis Flashcards
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.
Define Thrombocytopenia
- defined as = platelet count below the lower limit of the reference range.
Thrombocytopenia severity can be further subdivided by platelet count:
- Mild = 100,000 to 149,000/microL
- Moderate = 50,000 to 99,000/microL
- Severe = <50,000/microL
True or False
Correlation between platelet count & bleeding risk is relatively weak
True
Give an example to explain how the correlation between platelet count & bleeding risk is relatively weak
- surgical bleeding is generally not a concern with platelet counts >50,000 micro/L = some procedures may be safely performed at lower platelet counts e.g. cataract surgery, bone marrow aspiration.
Explain this comment:
Bleeding risk in Immune thrombocytopenia may be slightly lower compared with other conditions for the same platelet count.
We are less concerned about bleeding in an individual with Immune thrombocytopenia and a platelet count of 30,000 micro/L than we are about bleeding in an individual with aplastic anemia and a platelet count of 30,000 micro/L.
Heparin-induced thrombocytopenia (HIT)
- an uncommon complication of heparin exposure in which antibodies to a platelet factor 4 epitope induced by heparin can cause thrombocytopenia & platelet activation, leading to life-threatening venous &/or arterial thrombosis.
- should be considered in a patient recently exposed to heparin who develops thrombocytopenia, thrombosis, anaphylaxis, or skin reactions.
- treatment involves immediate discontinuation of heparin & administration of a non-heparin anticoagulant.
Vaccine-induced immune thrombotic thrombocytopenia (VITT)
- rare syndrome that occurs after vaccination with a coronavirus disease 2019 adenoviral vector vaccine.
- resemble spontaneous Heparin-induced thrombocytopenia.
Paroxysmal nocturnal hemoglobinuria (PNH)
- rare condition caused by loss of glycosylphosphatidylinositol from cell membranes.
- thrombosis often involves unusual locations such as intraabdominal or cerebral veins.
