Flashcards in Haemostasis, Thrombosis and Embolisms Deck (18):
What is the first most important part of haemostasis?
The first part of haemostasis involves the constriction of all blood vessels that are involved to limit blood loss.
What are plaetlets and how are they involved in Haemostasis?
Platelets are formed from megakaryocytes and are effectively cell fragments that adhere to vessels walls, each other and form a platelet plug. Once activated they are involved in a mechanism called platelet release reaction which involves formation of the platelet plug and stimulating the coagulation system. This reaction uses up energy and the ADP along with thromboxane A2 causes platelet aggregation. 5HT (5 hydroxytryptamine) and platelet release factor 3 are also released and these are involved in the coagulation cascade. These platelets come together to form one large mass and with the activation of fibrinogen (from thrombin (itself from prothrombin)) forming the fibrin plug, the clot is complete.
How is the clotting cascade controlled? How can this go wrong?
Inactive factors and procoagulants and anticoagulants. For example: anti thrombin III, alpha 1 anti-trypsin, alpha 2 macroglobulin and protein C and S, which are all thrombin inhibitors.
There are deficiencies associated with anti-thrombin III and protein C and S that cause people to develop a large amount of thromboses.
Describe how fibrinolysis occurs
This is achieved by the conversion of plasminogen into plasmin which then goes on to cause fibrinolysis. We’ve learnt from this to use it in certain therapies such as Streptokinase and tPA to enhance fibrinolysis. On top of this the endothelium produces anti thrombotic substances such as plasminogen activators, prostacyclin, nitric oxide and thrombomodulin.
What is thrombosis?
Thrombosis – this is the formation of a solid mass of blood within uninterrupted blood vessel (i.e. no haemorrhage) during life.
What are the 3 overall reasons for thrombus formation?
1. Abnormalities of the vessel wall such as atheroma, direct injury or inflammation
2. Abnormalities of the blood flow such as stagnation or turbulence
3. Abnormalities of blood components such as people who smoke, post-partum and during pregnancy (hypercoagulative) and finally post operative.
How do thrombi differ between arteries and veins?
• In arteries they are pale, granular, layers (lines of Zahn) and have a lower cell count
• In veins there are soft, gelatinous, deep red and have a higher cell count.
What are the possible outcomes of thrombus formation?
• Lysis – complete dissolution of the thrombus by the fibrinolytic system, blood flow is re-established and is most common, especially when thrombi are small
• Propagation – the thrombus gets bigger and causes the formation of more thrombi in the direction of the flow of blood due to the stagnation and turbulence created when a new vessels anastomoses
• Organisation – reparative process where there is an ingrowth of fibroblasts and capillaries sort of similar to granulation tissue however the lumen remains obstructed
• Recanalisation – blood flow re-established but potentially by multiple smaller tubes so blood flow is still restricted
• Embolism – thrombus breaks off and gets stuck in the next set of smaller vessels
What does thrombus formation cause in veins vs arteries?
1. In Veins it will cause congestion, oedema, ischaemia and infarction but only if it increases tissue pressure above that of arterial pressure
2. In arteries it will cause ischaemia and infarction but this depends upon the site and the collateral circulation
What is an embolism?
An embolism is the blockage of a blood vessel by a solid, liquid or gas at a site distant from its origin. 90% are from thrombi but other causes of them include air, nitrogen, amniotic fluid, medical equipment and tumour cells.
What are pre disposing factors to DVT?
• Pregnancy and post-partum
• Oral contraceptives
• Severe burns
• Cardiac failure
• Disseminated cancer
• Fat and cholesterol (tend to be after a fracture – bone marrow and fat escapes)
How do we prevent high risk patients of getting PE
Offered prophylaxis such as sub-cutaneous supply of heparin and leg compression during surgery (also special socks). Can be treated with intravenous heparin and oral warfarin.
How does PE embolism differ in its outcome depending on its size?
• Massive PE > 60% reduction in blood flow is rapidly fatal due to reflex cardiac failure and hypoxia
• Major PE such as a medium sized vessel blocked leads to shortness of breath and coughing up blood stained sputum.
• Minor PE small peripheral pulmonary arteries blocked – asymptomatic or minor shortness of breath (although repetitive minor PE can cause dangerous vascular changes in the pulmonary circulation causing pulmonary hypertension)
What does a fat embolism in the brain cause?
Fat embolism in the brain can cause people to get very confused.
What is haemophilia?
X linked recessive and two different types. Haemophilia A results in deficiencies of factor VIII and B results in deficiencies of factor IX. There are different mutations for it and so has different effects depending upon the mutation. Results in haemorrhage that won’t stop, bleeding into muscles causes pressure and necrosis causing pain. Treated with self-administered replacement therapy.
What is DIC?
Disseminated Intravascular Coagulation (DIC) is a pathological activation of the coagulation system in response to a range of diseases. This causes small clots to form all over the body which disrupting normal coagulations by using up all the clotting factors. This results in abnormal bleeding all over the skin and can be triggered by infection, trauma, liver disease and obstetric complications.
What is thrombocytopenia?
Low platelet count due to failure of production, increase in destruction or hiding of platelets. This is usually accompanied by some sort of bone marrow dysfunction.