Week 5 - Haemostasis and Thrombosis Flashcards
Define haemostasis
The stopping of a flow of blood by the physiological properties of vasoconstriction and coagulation
What does successful haemostasis require?
- Vessel wall (blood vessels constrict to limit blood loss)
- Platelets (adhere to damaged vessel wall and each other to form a platelet plug)
- Coagulation system
- Fibrinolytic system
How is coagulation regulated?
By thrombin inhibitors
- Anti-thrombin III
- Alpha-1 anti-trypsin
- Alpha-2 macroglobulin
- Protein C and S
Why does coagulation have to be tightly regulated?
The balance between procoagulant and anticoagulant forces of various types is essential
- If the balance tips in favour of the procoagulant forces, thrombosis will occur
- If the balance tips in favour of the anticoagulant forces, there will be excessive bleeding
What is fibrinolysis?
Breakdown of fibrin
- Plasminogen is converted to plasmin by plasminogen activators
- Can be used to help break down a thrombus
What is thrombosis?
Formation of a solid mass from the constituents of the blood, within the circulatory system, during life
What is Virchow’s triad?
Predisposing factors to thrombosis
- Abnormalities of the flow of blood (stagnation, turbulence)
- Abnormalities of blood components (smokers, postpartum, post-op)
- Abnormalities of the blood vessel wall (atheroma, direct injury, inflammation)
What is the appearance of arterial thrombi?
- Pale
- Granular
- Lines of Zahn
- Low cell content
What are the effects of arterial thrombi?
- Ischaemia
- Infarction
- Depends on site (e.g. end artery) and collateral circulation
What is the appearance of venous thrombi?
- Soft
- Gelatinous
- Deep red
- Higher cell content
What are the effects of venous thrombi?
- Congestion
- Oedema
- Ischaemia
- Infarction
What are the possible outcomes of thrombosis?
- Lysis
- Propagation
- Organisation
- Recanalisation
- Embolism
What is lysis? (following thrombus)
- Complete dissolution of thrombus
- Fibrinolytic system active
- Blood flow is re-established
- Most likely when thrombi are small
What is propagation? (following thrombus)
Progressive spread of thrombosis due to disruption of flow
- Distally in arteries
- Proximally in veins
What is organisation? (following thrombus)
- Reparative process
- Ingrowth of fibroblasts and capillaries
- Lumen remains obstructed
- Converts the thrombus to fibrous tissue
What is recanalisation? (following thrombus)
- Bloodflow is reestablished but usually incompletely
- 1 or more channels are formed through organising thrombus
- These channels tend to deliver blood as well as the original vessel
- Usually occurs in arteries
What is embolism? (following thrombus)
- Parts of thrombus break off
- Travels through bloodstream
- Lodges at a distant site
What is an embolism?
Blockage of a blood vessel by solid, liquid or gas at a site distant from its origin
What are the different types of embolisms?
- Air
- Amniotic fluid
- Nitrogen (N2 bubbles form in the blood with rapid decompression)
- Medical equipment
- Tumour cells
- Thrombo-emboli
- Other: cerebral, iatrogenic, fat
Where can thrombi-emboli occur?
- Pass from systemic veins to the lungs
- Pass from the heart, via the aorta, to renal, mesenteric and other arteries
- Pass from atheromatous carotid arteries to the brain
- Pass from atheromatous abdominal aorta to arteries of the legs
What predisposing factors are there for deep vein thrombosis?
- Immobility/bed-rest
- Post-operative
- Pregnancy and post-partum
- Oral contraceptives
- Severe burns
- Cardiac failure
- Disseminated cancer
How can deep vein thrombosis be prevented?
Identify high-risk patients and offer prophylaxis
- Sub-cutaneous heparin
- Leg compression during surgery (stockings)
How can deep vein thrombosis be treated?
- Intravenous heparin (anticoagulant, cofactor for anti-thrombin III)
- Oral warfarin (interferes with synthesis of vitamin K-dependent clotting factors)
What are the different types of pulmonary embolism?
Massive PE: - >60% reduction in bloodflow - Rapidly fatal Major PE: - Medium-sized vessels are blocked - Patients are short of breath - Cough - Blood-stained sputum Minor PE: - Small peripheral pulmonary arteries are blocked - Asymptomatic, or minor shortness of breath Recurrent minor PE: - Leads to pulmonary hypertension
What is disseminated intravascular coagulation?
Pathological activation of coagulation mechanisms
- Happens in response to a variety of diseases
- Small clots form throughout body
- This disrupts normal coagulation, since they use up all the clotting factors
- Abnormal bleeding occurs from the skin
- Triggers = infection, trauma, liver disease, obstetric complications
What is thrombocytopenia?
When the platelet count is way below the reference range
What can cause thrombocytopenia?
Failure of platelet production:
- Bone marrow failure due to aplastic anaemia (may be due to chemotherapy/leukaemia/etc.)
- B12 deficiency (important for platelet production since it promotes the maturation of megakaryocytes)
Increase in platelet production:
- Idiopathic thrombocytopenia (autoimmune)
Sequestering of platelets
- By enlarged spleen
Dilution of platelets
- By large blood transfusions, without platelet transfusions
What is thrombophilia?
Blood has an increased tendency to form clots
- Sometimes associated with blood clots that are caused by genetic mutations
- Increases risk of DVT
- Often mild
What is haemophilia?
- X-linked recessive disorder
- There is a type A (defective clotting factor 8) and a type B (defective clotting factor 9)
- Can be mild, moderate or severe due to various mutations
- Due to a nonsense point mutation
- Treat with self-administered factor replacement therapy
What can haemophilia cause?
- Haemorrhage into joints, which may cause synovial hypertrophy, pain and long term damage to the joint
- Muscle bleeding, which causes pressure and necrosis of nerves (painful)
- Can haemorrhage into retroperitoneum/urinary tract
What are the signs of DVT?
- Tender swollen calf
- Warmth and redness of affected limb
