Lecture 8 Thrombosis Flashcards
Define briefly described thrombosis
it is a pathological formation of an intravascular blood clot
Can occur in a vein or an artery
it is characterised by the lines of Zhan and attachment to a vessel wall
what is Virchow’s triad?
It is things that cause thrombosis
Suggest one example of each of the three components of Virchow’s triad
Disruption of blood flow (stasis)
Endothelial cell damage
Hypercoagulable states
what are examples of disruption of blood flow?
immobilisation
Cardiac wall dysfunction
Aneurysm
Atrial fibrillation
Left atrial dilation due to mitral stenosis
What are examples of endothelial cell damage?
atherosclerosis
Vasculitis of any cause
High levels of homocysteine
Turbulence blood flow at atrial bifurcation
Oxidised LDL
Cigarette smoke
Cytokines
How are hypercoagulable states caused?
excessive procoagulant factors or defective anticoagulant
May be inherited(AT3 deficiency) or acquired (DIC)
Classic presentation is recurrent DVTs or DVT is at a young age
What are the main features of Venus thrombus?
Most common cause stasis of blood
Most common site is veins in lower limbs
Red swollen, painful leg with skin discolouration
Can dislodge to the lungs causing pulmonary embolism
what are the treatments for Venous thrombus?
warfarin or other anticoagulant E.g Rivarocaban, Apixaban
how do the treatments of Venous thrombus work?
they do not dissolve the cloth they prevent further formation
The fibrinolytic system breaks down the clot
What are the main features of arterial thrombosis?
Commonly due to endothelial damage related to turbulent flow at bifurcation or over atherosclerotic plaques in high velocity vessels
Some case cases have mixed thrombi composed of platelets and with RBCs held together by fibrin
Hypercoagulability and stasis are rare causes of arterial thrombosis
what are the properties of arterial thrombi?
They are adherent and usually occlusive
Grey or white fibrin cloth primarily composed of platelets
inhibitors of platelet aggregation prevent their formation (aspirin)
In which instances will arterial thrombosis occur?
Myocardial infarction
Small bowel infarction
Stroke
What are the three stages of platelet activation when forming a platelet plug?
Adhesion
Release reaction
Aggregation
which mediators allow platelets to undergo shape change and degranulation?
release mediators ADP
Thromboxane A2 - derivative of platelet COX
Calcium
What is the function of release mediators ADP?
it induces the expression of GP2b/3a (receptor essential for aggregation of platelets) and fibrinogen which acts as a linker molecule in the developing clot
What is thromboxane A2?
it is a vasoconstrictor that also promotes platelet aggregation
what is thrombin?
Acts on fibrinogen to produce fibrin monomers
Activates fibrin stabilising factor 13
Acts in a feedback loop to activate several other coagulation factors
what is fibrin stabilising factor 13?
Converts monomer to cross-linked to fibrin
Strengthen blood clot
how is thrombin switched off?
By the natural anticoagulant antithrombin3 which limits clot formation
what is plasmin?
breaks down clot
Cleves firing and fibrinogen into fibrinogen degradation products (FDPs)
Degrade some clotting factors
Blocks platelet aggregation
What is formed when fibrinogen and fibrin are cleaved into fibrinogen degradation products?
fragments are formed known as D–dimers
what is the prothrombin time (PT)?
It evaluates the extrinsic coagulation system down to the formation of the fibrin clot
Which factors are evaluated in prothrombin time?
7, 10, 5, 2 and 1
what is the normal reference range for prothrombin time?
Normal reference range is 11 to 15 seconds however this varies
Time is only prolonged when clotting factor level is 30 to 40% of normal, hence the test is not very sensitive
What are the uses of prothrombin time?
monitoring persons taking warfarin for anticoagulant
evaluate liver synthetic function (increased PT indicated liver disease, chronic hepatitis, cirrhosis of any cause etc.)
What is INR?
International normalised ratio (INR)
Standardised the PT between laboratories for use in monitoring warfarin anticoagulant therapy
Normalised = results the same irrespective of agency used, normal range is 2–3 for therapy
What is target INR?
An INR which is within 0.5 units of the target value is generally satisfactory, larger deviations required dosage adjustment
INR 2.5: treatment of DVT or pulmonary, atrial fibrillation, acute arterial embolism and myocardial infarction
INR 3.5: treatment of recurring DVT or pulmonary embolism
