Haemostasis + thrombosis Flashcards
What are the 2 stages of haemostasis?
- Primary → formation of the primary platelet plug
* Secondary →formation of insoluble, cross-linked fibrin
What is the first step in primary haemostasis?
Vasoconstriction
What causes vasoconstriction post trauma to the endothelium of a blood vessel?
- Smooth muscle contraction
* Release of endothelin → causes vasoconstriction
If endothelin constricts the smooth muscle of vessels, what 2 agents dilate smooth muscle in vessel walls?
- Nitric oxide
* prostacyclin
What is the second step of primary homeostasis?
Platelet adhesion
vWF
What are the 2 main glycoprotein receptors on the platelet surface?
- GlycoProtein 1b
* GlycoProtein 2b/3a
What does von Willebrand factor do?
- primary function is binding to other proteins
- Particular strong binding to factor VIII
- It is important in PLATELET ADHESION to the wound.
•It binds to collagen in the wound and GP1b on the platelet.
When do platelets degranulate and change shape?
- Once they have been bound by vWF
* once they are activated and both degranulate and change shape.
What do platelet Alpha granules contain?
- Fibrinogen
* von wilebrand factor
What do platelet dense granules contain?
Serotonin → constricts smooth muscle cells
ADP → activates platelets and promotes aggregation
Ca++ → Needed for secondary haemostasis
SAC
what are the 2 granules inside platelets called?
- alpha granules
* dense granules
what does the gp2/3a receptor do?
It binds fibrinogen
what does the GP1a receptor do?
It binds to vWF
What happens in the second phase of haemostasis?
Fibrin aggregates over the clot.
What is haemophilia A
Clotting Factor 8 deficiency
What is Haemophilia B
Clotting factor 9 deficiency
Where is fibrinogen sythesized?
In the liver
what is the extrinsic pathway?
- Tissue damage releases tissue factor,
- this and factor 7 activate factor 10 → 10a
- which then cleaves prothrombrin → thrombrin
What is the intrinsic pathway?
- 11 →11a
- 11a activates 9 →9a
- 9a activates 8 →8a
- 8a activates 10
What is responsible for haemolysis?
Plasmin
What is cleaved to become plasmin?
plasminogen
What happens when fibrin is degraded?
It is picked up by macrophages that recycle the component parts in the spleen and the liver.
What are the 5 tests for clotting?
- Clotting time
- Prothrombrin time → extrinsic pathway
- thrombrin time
- APTT activated partial prothrombrin time →intrinsic pathway
- fibrinogen concentration
Coagulation failure is linked to which pathway?
The intrinsic pathway
Primary homeostatic failure is linked to which pathway?
The extrinsic pathway
What are the symptoms of primary homeostatic failure?
- Immediate bleeding
- mucocutaneous bleeding → mouth/gut
- Purpura
What are the symptoms of coagulation failure?
- Delayed bleeding after trauma
- Muscle and joint bleeding
- Bruising
What are 5 diseases associated with associated with clotting disorders?
- Haemophilia
- Von Willebrand’s disease
- Thrombocytopenia
- Liver disease
- Disseminated intravascular coagulation (DIC).
What is haemophilia A?
- X-linked
- Lack of intrinsic factors 8
•APPT prolonged
What is haemophilia B?
- X-linked
- Lack of intrinsic factors 9
•APPT prolonged
What is the treatment for Haemophilia?
- Factor 8 or 9 replacement
- Desmopressin
- transexemic acid
What is current thought on managing haemophilia?
Phrophylaxis as a way of preserving quality of life.
What is von willebrandts disease?
- This is a deficiency or lack of functionality of vWF
- Mucosal bleeding
- ↑APPT and ↑bleeding time. prolonged as vWF binds to intrinsic factor 8
What is liver disease?
- Destruction of hepatocytes and failure to produce clotting factors.
- Intrinsic and extrinsic pathways both compromised
- Fibrinogen no longer produced.
Tests show ↑TT, ↑PT , ↑APPT, ↓fibrinogen
What is the treatment for von Willebrand disease?
Treatment – vWF replacement or Tranexamic Acid
What are the tests for von willebrands disease?
↑APPT ↑TT ↑PT ↑bleeding time ↓fibrinogen
What is disseminated intravascular coagulation (DIC)?
•Is the widespread activation of the clotting cascade that results in the formation of blood clots in the small blood vessels throughout the body.
•Clotting factors, platelets consumed leading to
prolonged coagulation times
What are the tests for disseminated intravascular coagulation (DIC)?
lab tests normal BUT! ↑bleeding time
What condition is associated with disseminated intravascular coagulation (DIC)?
Microangiopathic hemolytic anemia (MAHA)
What are the tests and what is the treatment for disseminated intravascular coagulation (DIC)?
↓platelets
↑PT
↑APPT
↓fibrinogen
•centres on treating the underlying condition
What are the causes of DIC?
- Sepsis
- malignancy
- Trauma
- obstetric events
What is thrombocytopenia
This is a deficiency of platelets in the blood. This causes bleeding into the tissues, bruising, and slow blood clotting after injury
What 2 diseases are as a result of primary haemostasis failure?
- von Willebrand Disease
* Thrombocytopenia
What 3 diseases are a coagulation failure?
- Haemophilia
- liver disease
- DIC(?)
What are the causes of thrombocytopenia?
•Can be due to decreased platelet production
→Marrow failure
→Hpyoplasia
→Infiltration
•Or can be due to increased consumption of platelets
→Immune
What would you expect to find in screening tests for thrombocytopenia?
↑bleeding time
All other clotting times would be normal
What factors does warfarin inhibit?
10,9,7,2
What factors does Dabigatran inhibit?
Anti-thrombin
What factor does riveroxiban and apixiban inhibit?
10a
What is a tissue plasminogen activator?
Alteplase
How does clopidogrel work?
Inhibits ADP dependent activation of glycoprotein
receptors
What is factor 1?
Fibrinogen
What is factor 2?
Prothrombin
What are the 2 competeing factors in Heamostasis?
Bleeding and thrombosis
What are the 2 endogenous inhibitors of blood coagulation?
- Anti-thrombin
* Protein-c system → vitamin K dependent
Which factors does the protein-C system inhibit?
5a +8a
name 5 examples of arterial thromosis?
•Coronary thrombosis
→MI
→unstable angina
•cerebrovascular thromboembolism
→Stroke
→transient eschemia
•Perihpheral embolism
→limb eschemia
What is the rare Heritable form of thrombophilia that about 5% of caucasians posess?
Factor 5 Leiden
What are the main risk factors in venous thrombosis?
- Immobility
- Tauma
- Pregnancy
- Oral contraceptive pill
- Obesty
- malignancy
What is virchow’s triad?
- Stasis of blood flow
- endothelial injury
- Hypercoaguability
What are the sypmtoms of a PE?
- Acute breathlessness
- pleuritic chest pain
- haemoptysis
- diziness
- syncopy
What is the treatment for a PE?
- LMW Heparin
- Start warfarin
- Stop LMW Heparin when INR is >2
- Continue warfarin for minimum 3 months
• in Event of Massive PE conside a Vena caval filter during thrombolysis
What are the tests for a PE?
- Modified Wells score
- only use D-dimer in cases without high probability of PE
- Gold standard diagnostic test is a CT pulmonary angiogram
Give 3 examples of LMW heparins?
Gives a more stable predictable ad longer lasting effct than unfractioned heparin
- Deltaparin
- Tinzeparin
- Enoxaparin
What is unfractioned Heparin called?
Heparin sodium or heparin calcium
what is the treatment for a DVT?
- LMW heparin or fondaparinux
* start warfarin simultaneously
