Thrombosis- Haemostatis In The Wrong Place Flashcards
What is primary haemostasis?
Aggregation of platelets
What is secondary haemostasis?
The conversion of fibrinogen into fibrin
What are the three basic steps of fibrinolysis?
1- aggregation of platelets
2- fibrinogen -> fibrin mesh by thrombin
3- thrombin is itself converted from prothrombin
What do anticoagulants do?
Prevent thrombosis
What does fibrinolysis do?
Reverses thrombosis
What are the three main features of arterial thrombosis?
Mostly result from atheroma rupture or damage to the endothelium.
Mostly primary, platelet rich ‘white’ thrombosis
May block downstream arteries
What are the main features of venous thrombosis?
Often results from stasis or a hypercoagulant state
Mostly secondary, platelet poor ‘red’ thrombus
May move to lungs
What happens if the endothelial cells get damaged and the subendothelial cells get exposed?
The blood may either coalesce around it and form a clot or von willebrand factors will bind to platelets and start a clot
What does heparin bind to?
Antithrombin
What do antithrombin and heperan do?
Inhibit clotting prostaglandins, platelets and nitric oxide
What does tissue plasminogen activator cause?
Plasminogen to be converted to plasmin, which acts in the clot to give D-dimers
What are d-dimers?
Breakdown products of a clot
What are the components of Virchows triad?
Stasis, endothelial damage and the hypercoagulant state
How does stasis cause clotting?
Static blood lacks kinetic energy and tends to clot
How does endothelial damage lead to clotting?
When you have surgery or a cannula you are exposing the subendothelial cells
When may you be in a hypercoagulant state?
In infection/ sepsis, drugs or if you have a genetic predisposition
Why is there an increased risk of stasis around venous valves?
The blood eddys around them so doesn’t move as efficiently
What happens if venous return is blocked?
The affected organ becomes congested with fluid and there is an increased pressure so more filtration
What are the four fates for a thrombus?
Resolution, embolism, organised or recanalised and organised
What happens when a thrombus is resolved?
Thrombolysis
What happens when a thrombus embolises?
Moves to another location and blocks the vessel
What happens when a thrombus is organised?
Becomes covered by the endothelium
What are the risks with a proximal DVT?
Higher risk of pulmonary embolism and post-thrombotic syndrome
What are symptoms of proximal DVT?
Pain, swelling and maybe even ulcers
Where are proximal DVTs found?
Upper leg
Where are distal DVTs found?
Lower leg
What are the risks of distal DVT?
Not much- they rarely cause PE or post-thrombotic syndrome
What is post-thrombotic syndrome?
Inflammation along with damage to the venous valves from the thrombus itself
What causes post thrombotic syndrome?
Valvular incompetence combined with a persistent venous obstruction
What does post thrombotic syndrome induce?
Rupture of small superficial veins, subcutaneous haemorrhage and an increase of tissue permeability
What symptoms follow post-thrombotic syndrome?
Pain, swelling, discolouration and even ulceration
What causes pulmonary embolus?
Small venous thrombolus getting through the heart and caught in the lung
What happens in platelet adherence?
- von willebrand factors on subendothelial cells activate platelets
- circulating von willebrand factors may bind to exposed subendothelial cells
- activated endothelial cells can also express von willebrand factors
What happens in platelet activation?
- activated platelets release thromboxane A2 and adenosine disphosphate which induce receptors for fibrinogen
- bind to receptors and increase expression of GPIIb/IIIa
- platelets can also be activated by thrombin, collagen and many other mediators
What happens in platelet aggregation?
Fibrinogen acts as a tether holding platelets together- it is the soluble precursor to fibrin and is in the circulation
What happens in platelet substrate for coagulation?
- clumps of platelet form a negatively charged surface
- coagulation involves the conversion of fibrinogen to fibrin and then cross linking the fibrin clot
What are the 7 steps in the common coagulation pathway?
1- factor IXa activates factor X by proteolysis to create factor Xa
2- factor Xa cleaves prothrombin to form thrombin (IIa)
3- thrombin cleaves fibrinogen into fibrin
4- fibrinogen promotes blood clotting by forming bridges between (and activating) blood platelets through binding to their GPIIb/IIIa surface membrane fibrinogen receptor
5- thrombin cleaves factors V and VIII to give Va and VIIIa
6- Va and VIII together with Ca2+ form a tenase complex and a prothrombinase complex
7- once enough thrombin has been generated, XIII is activated, which cross links the fibrin fibres into a solid clot
What do VIIIa and Va amplify?
The existing reactions making them hard to overpower
What is a GLA domain?
10-12 glutamic acids on the N-terminus of the molecule converted to gamma carboxy glutamic acid
What is the GLA domain dependant on?
Vitamin K
What is the extrinsic pathway?
Tissue factor is a receptor for VIIa which is bound to negatively charged platelet phospholipid surface along with calcium. Then VIIa activated Xa and the common pathway starts
What is the extrinsic pathway triggered by?
Transcription factors which activates factor VII
When is the intrinsic pathway activated?
When you put blood onto a charged surface (like glass)
What do lab tests distinguish between?
Activating the intrinsic or extrinsic pathways in order to assess where a defect may be
What is antithrombin expressed by?
Endothelial cells
What does antithrombin inhibit?
A lot of the enzymes in the coagulation cascade
