11. Clinical Haemostasis and Thrombosis Flashcards
What needs to be balanced for haemostasis?
• Fibrinolytic factors + anticoagulant proteins vs. coagulation factors + platelets
How does the balance in haemostasis change during bleeding?
- More coagulation factors + platelets
* Less fibrinolytic factors + anticoagulant proteins
What are the characteristics of abnormal bleeding?
- Spontaneous
- Out of proportion to the injury
- Unduly prolonged
- Restarts after appearing to stop
(prolonged nose bleeds: >15min)
How does the endothelial cell lining respond to injury?
- Vessel constriction (VSMCs contract locally to limit blood flow)
- Primary haemostasis: formation of an unstable platelet plug to limit blood loss and provide a surface for coagulation
- Secondary haemostasis: stabilisation of the plug with fibrin to stop blood loss
- Vessel repair (cell migration/proliferation) and dissolution of the clot (fibrinolysis)
What 3 things can negatively impact the effects of collagen in haemostasis?
- Steroid therapy
- Ageing
- Scurvy
What is thrombocytopenia?
A relative decrease in the number of platelets in the blood
What is Von Willebrand Factor disease?
- Deficiency in Von Willebrand Factor
- Less primary haemostasis
- Platelets pass the damaged endothelium and can’t form a primary plug
What are the patterns of bleeding of a defect in primary haemostasis?
- Immediate
- Easy bruising
- Prolonged nosebleeds
- Prolonged gum bleeding
- Menorrhagia (anaemia)
- Bleeding after trauma/surgery
- Petechiae (specific for thrombocytopenia)
What are petechiae?
- Small spots in people who are thrombocytopenic
- Appear spontaneously
- Normally, platelets constantly plug small holes in blood vessels - continuous repair, but this is made difficult
Briefly outline secondary haemostasis
- Prothrombin => thrombin
- This converts fibrinogen => fibrin
- Fibrin forms an insoluble mesh around the platelets
Why is there are lag in the thrombogram before the rise in thrombin?
Time needed for cofactors and anticoagulant enzymes to be generated
How is haemophilia visualised in a thrombogram and why does the condition lead to prolonged bleeding?
- Factor VIII is missing
- Failure of thrombin burst
- Slower increase in thrombin
- Not as much thrombin is produced
- Failure to produce a fibrin mesh is formed - clot is not stabilised
- Left with a primary platelet plug which can fall apart easily
(• Generally fine when dealing with small cuts - primary haemostasis still works)
Which coagulation factors does a defect of secondary haemostasis involve?
• I to XIII
What are common examples that lead to defects of secondary haemostasis?
- Haemophilia (Factor VIII or IX)
- Liver disease (most coagulation factors are made in the liver)
- Drugs (warfarin inhibits the synthesis of coagulation factors)
- Dilution (volume replacement)
- Consumption (disseminated intravascular coagulation)
What is disseminated intravascular coagulation?
- Acquired coagulation disorder (aka consumptive coagulopathy)
- Generalised activation of coagulation (tissue factor is expressed in the blood when it doesn’t need to be)
- Small clots develop throughout the bloodstream
- Consumes and depletes coagulation factors and platelets
- Activation of fibrinolysis depletes fibrinogen
- Associated with sepsis, major tissue damage and inflammation
What are the patterns of bleeding of a defect in secondary haemostasis?
- Often delayed
- Prolonged
- Deeper: joints and muscles
- Don’t tend to bleed excessively from small cuts (primary haemostasis is usually enough)
- Nosebleeds are rare
- Bleeding after trauma/surgery
- Bleeding after intramuscular injections
- Easy brusing
What is the hallmark of haemophilia?
- Haemarthrosis - bleeding into joints
- Pressure builds up and joints become swollen and painful
- Characteristic of severe haemophilia A and B
What are 2 types of excess fibrinolysis?
- Excess fibrinolytic (plasma, tPA) e.g. therapeutic administration, some tumours
- Deficient antifibrinolytic (antiplasmin) e.g. antiplasmin deficiency (genetic)
Give examples of anticoagulant excess
• Usually due to therapeutic administration:
- Heparin
- Thrombin inhibitor
- Xa inhibitor
What can a thrombosis in the artery and vein cause?
Artery
• Myocardial infarction
• Stroke
• Limb ischaemia
Vein
• Pain and swelling
What can a venous and arterial embolism lead to?
- Venous - pulmonary embolism
- Arterial - usually from heart, may cause stroke or limb ischaemia
(right side of the heart goes to the lungs, left side of the heart goes to the brain)
What is the prevalence of venous thromboemboli?
- 1 in 1000-10,000 per annum
- Incidence doubles with each decade
- Pulmonary embolism is the cause of 10% of hospital deaths
- Estimated 25,000 preventable deaths per annum
What is the case mortality and recurrence of thrombo-embolism?
- Mortality - 5%
* Reccurence - 20% in first 2 years, 4% per annum after
Why is the recurrence high after an initial thrombosis?
- Valve system might be damaged
- More stasis
- More likely to have another thrombosis
