10. Clinical Haemostasis Thrombosis Flashcards
What is the state of normal haemostasis?
A state of equilibrium between fibrinolytic factors, anticoagulation proteins and coagulation factors, platelets
What are the characteristics of abnormal bleeding?
1) Spontaneous
2) Out of proportion to the trauma/injury
3) Prolonged bleeding from cuts = bleeding disorder
4) Restarts after appearing to stop
5) Prolonged nose bleeds
What is primary haemostasis?
Formation of an unstable platelet plug
What is secondary haemostasis?
Process of generating fibrin from fribinogen catalysed from thrombin
What makes up the primary haemostatic plug?
Platelet + Von Willebrand Factor + Collagen
What are possible defects of the primary haemostatic plug?
Collagen - Weakening of the collagen and vessel wall due to ageing and steroid therapy
Von Willebrand Factor - Genetic deficiency in this factor
Platelets - Drugs (aspirin) can affect platelet activity
Define thrombocytopenia
A relative decrease in the number of platelets in the blood
What is exposed when the endothelial wall is damaged?
Collagen and tissue factor
What causes failure of primary haemostasis?
No Von Willebrand Factor resulting in the platelets flying past the damaged endothelium
What are the defects of primary heamostasis - Pattern of bleeding?
- Immediate
- Easy Bruising
- Nosebleeds (prolonged: >20 mins)
- Gum bleeding (prolonged)
- Menorrhagia (anaemia)
- Bleeding after trauma/surgery
- Petechiae (specific for thrombocytopenia)
What is petechiae?
Small blood spots which occur spontaneously in people who are thrombocytopenic
What can be used to measure the thrombin generation over time?
Thrombogram
In a thrombogram, after the TF trigger what happens?
There is a lag then a burst of thrombin. This lag phase is due to the cofactors and anticoagulant enzymes being generated
In haemophilia which coagulation factor is missing?
Factor VIII
How does haemophilia present itself on a thrombogram?
A slower increase in thrombin and not as much thrombin produced
What do defects of secondary haemostasis cause?
No fibrin mesh formation
What is the cause of defects of secondary haemostasis?
Deficiency or defect of coagulation factors running from 1-13
List some common examples of secondary haemostasis defects?
o Haemophilia: Factor 8 or Factor 9 (hereditary due to genetic defect) o Liver Disease (acquired - most coagulation factors are made in the liver) o Drugs (warfarin - inhibits synthesis of coagulation factors) o Dilution (results from volume replacement) o Consumption (disseminated intravascular coagulation - acquired)
What are two acquired coagulation disorders?
Disseminated Intravascular Coagulation
Consequences
What is disseminated intravascular coagulation?
Generalised activation of coagulation - Tissue Factor. This consumes and depletes coagulation factors.
What is disseminated intravascular coagulation commonly associated with?
Sepsis, major tissue damage and inflammation
What is consequences?
Widespread bleeding, from IV lines, bruising. Deposition of fibrin in vessels causes organ failure
Define haemophilia
The failure to generate fibrin to stabilise the platelet plug
In haemophilia, because there is no fibrin…
There is no fibrin mesh stabilising the plug. The plug then falls apart easily
What are the defects of secondary heamostasis - Pattern of bleeding?
- Often delayed (after primary haemostasis)
- Prolonged
- Deeper: joints and muscles
- Do not tend to get excessive bleeding from small cuts (because primary haemostasis is ok)
- Small vessels are generally ok
- Nosebleeds are rare
- Bleeding after trauma/surgery
- Bleeding after intramuscular injections
What is a hallmark sign of haemophilia?
Haemarthrosis
What is haemarthrosis?
Bleeding into joints resulting in an increase in pressure causing pain and swelling.
What can affect clot stability?
Excess fibrinolysis
Effects of thrombosis
Obstructed flow of blood
Embolism
What are the effects of obstructed blood flow in the artery?
Myocardial infarction, stroke, limb ischaemia
What are the effects of obstructed blood flow in the vein?
Pain and swelling
What are the consequences of a thromboembolism?
Valve system might be damage leading to more blood stasis.
Thrombophlebitic syndrome
Pulmonary hypertension
What is thrombophlebitic syndrome?
Swelling and ulcers in the leg due to damage to valves leading to stasis
What factors can enhance the risk of a thrombosis?
Genetic factors, inflammatory disorder, pregnancy and combined contraceptive pill
What are the three contributory factors of thrombosis?
Hypercoagulability, Stasis and Vessel wall injury
Define thrombosis?
Abnormal formation of a blood clot in the circulatory system
What will cause hypercoagulability in the blood?
Deficiency of anticoagulant proteins - Antithrombin, Protein C & S
Increased coagulant proteins/activity
Vessel wall injury causes what effects?
Down regulation of thrombomodulin in an inflammatory state
Why is there an increased risk of thrombosis in pregnancy?
There is reduced mobility and reduced flow due to the presence of the uterus and there are a number of blood coagulation changes that take place (rise in Factor 7 and Factor 8) and there is a decrease in protein S which will make the blood more procoagulant
What is the treatment for thrombosis?
To lyse the clot e.g with tPA (although this carries a risk of bleeding)
Thrombolytic therapy is only used with stroke as there is an increased risk of bleeding - Cerebral haemorrhage
How are clots prevented from happening?
Increase anticoagulant activity (heparin)
Decrease procoagulant activity
What is the increased risk of thrombosis caused by combined oral contraception associated to?
- Factor 5 Leiden
- Reduced concentration of protein S
- Reduced concentration of PAI-1
- Reduced endothelial activation
- Prolonged contact activation
