Clinical haemostasis and Thrombosis Flashcards
What is haemostasis a balance between?
- fibrinolytic factors/anticoagulant proteins
- coagulation factors/platelets
What are the characteristics of abnormal bleeding?
Bleeding that is:
- Spontaneous
- Out of proportion to the trauma/injury
- Prolonged
- Restarts after appearing to stop
What are the main components of the primary haemostatic plug?
Platelet
Von Willebrand Factor
Collagen
Defects of Primary Haemostasis
Deficiency or Defective:
- Collagen - Vessel Wall
- Steroid therapy makes the collagen and vessel wall weak
- Ageing also weakens the vessel wall - Von Willebrand Factor
- VWF disease is a genetic deficiency in Von Willebrand Factor - Platelets
- Aspirin and other drugs can affect platelet activity
- Thrombocytopenia is a relative decrease in the number of platelets in the blood
What happens if there is no von willebrand factor?
- there is no primary haemostasis
- the platelets fly past the damaged endothelium and they can’t form a primary plug
Defects of primary haemostasis -bleeding patterns
- Immediate
- Easy Bruising
- Nosebleeds (prolonged: >20 mins)
- Prolonged gum bleeding
- Menorrhagia
- Bleeding after trauma/surgery
- Petechiae (specific for thrombocytopenia)
What is petechiae?
- Petechiae are small blood spots which occur in people who are thrombocytopenic
- These appear spontaneously and are characteristic of thromobocytopenia
What is secondary haemostasis?
Process of generating fibrin
What does a thrombogram tell us?
It allows you to visually represent thrombin production over time
Is there a burst of thrombin immediately after the tissue factor trigger?
no there is a time lag
What happens in haemophilia?
- failure to generate fibrin to stabilise the platelet plug
- plug made falls apart
- one of the coagulation factors (Factor 8) is missing causing failure of the thrombin burst
- there is a much slower increase in thrombin and not as much thrombin is produced
- this means that you do not get much of a fibrin mesh formed so the clot does not become stabilised
Defects of secondary haemostasis
Deficiency or defect of coagulation factor 1-13 e.g:
- Haemophilia: Factor 8 or Factor 9
- Liver Disease (acquired - most coagulation factors are made in the liver)
- Drugs (warfarin - inhibits synthesis of coagulation factors)
- Dilution (results from volume replacement)
- Consumption (disseminated intravascular coagulation - acquired)
Acquired Coagulation Disorders :
Disseminated Intravascular Coagulation (also called consumptive coagulopathy)
- Normally tissue factor is kept outside of the circulation
- In pathology it might be found in the blood, expressed on WBCs
- Associated with sepsis, major tissue damage, inflammation
- Consumes and depletes coagulation factors and platelets
- Activation of fibrinolysis depletes fibrinogen
What are the consequences of DIC?
- Widespread bleeding, from IV lines, bruising, internal
- Deposition of fibrin in vessels causes organ failure
Defects of secondary haemostasis: pattern of bleeding
- Often delayed (after primary haemostasis)
- Prolonged
- Deeper (joints and muscle)
- Do not tend to get excessive bleeding from small cuts (because primary haemostasis is fine)
- Small vessels are generally not badly affected
- Nosebleeds are rare
- Bleeding after trauma/surgery
- Bleeding after intramuscular injections
- Easy bruising
Haemoarthrosis and what is at a sign of?
HAEMOPHILIA
- Haemarthrosis is bleeding into joints
- They bleed into joints and the pressure builds up and the joint becomes swollen and painful
- People with haemophilia are generally fine when dealing with small cuts
Defects of Clot Stability: Excess Fibrinolysis causes
- Excess Fibrinolytic (plasma, tPA)
E.g. Therapeutic, some tumours - Deficient Antifibrinolytic (antiplasmin)
E.g. Antiplasmin Deficiency (genetic)
Unbalanced Haemostasis: Anticoagulant Excess causes
Usually due to therapeutic administration
E.g. heparin or thrombin and Xa inhibitors
What are the effects of thrombosis?
- Obstructed flow of blood
Artery = myocardial infarction, stroke, limb ischaemia
Vein = pain and swelling - Embolism
Venous Emboli –> pulmonary embolism
Arterial Emboli –> usually from heart, may cause stroke or limb ischaemia
Epidemiology of venous thrombo embolism
- 1 in 1000-10,000 per annum
- Incidence doubles with each decade
- Cause of 10% of hospital deaths
What are the consequences of thrombo embolisms?
- After the first thrombosis the valve system might be damaged thus meaning that there is more stasis
- Thrombophlebitic Syndrome = swelling and ulcers in the leg due to damage to valves leading to stasis
- Pulmonary Hypertension
What changes the risks of thrombosis?
- Above the thrombotic threshold you will get a thrombosis
- As you get older the risk of thrombosis increases
- Various genetic factors can mean that you start at different points on the risk scale
- Some things may enhance the risk e.g. inflammatory disorder, pregnancy, combined contraceptive pill
THROMBOSIS IS CAUSED BY INTERACTING GENETICS AND ENVRIONMENT
What is virchow’s triad?
Blood - dominant in venous thrombosis
Vessel Wall - dominant in arterial thrombosis
Flow - complex, contributes to both
Virchow’s triad in detail - blood
Deficiency of anticoagulant proteins - antithrombin, Protein C, Protein S
Increased coagulant proteins/activity - causes hypercoagulability e.g. Factor 8, Factor 5 Leiden
