Syed (Clotting mechanisms - thromboembolism) Flashcards
Introduction- clotting mechanisms
Blood must remain as a fluid to travel to all parts of the body
However it must also have the ability to clot quickly in response to injury to prevent excess blood loss.
Clot formation and clot removal require a delicate balance to prevent both thrombosis and haemorrhage.
Favouring coagulation = thrombosis
Favouring fluidity = haemorrhage
Haemostasis
Haemostasis- the process that stops bleeding in a blood vessel. Normal haemostasis involves a complex process of extrinsic and intrinsic factors.
It is the cessation of blood loss from a damaged vessel.
Platelets first adhere to macromolecules in the sub endothelial regions of the injured blood vessel. They then aggregate to form the primary haemostatic plug.
Platelets stimulate local activation of plasma coagulation factors, leading to the generation of a fibrin clot that reinforces the platelet aggregate.
Fibrin is insoluble in blood so must be degraded during wound healing. The platelet aggregate is also degraded.
Haemostatic mechanism
Injury -> damage to vessel -> message to platelets -> platelets aggregate -> activation of coagulation phase -> activation of common pathway -> clotting factor 10 and 2 activated.
Coagulation
Coagulation cascade- as each factor is activated it acts as a catalyst that enhances the next reaction, with the net result being a large collection of fibrin that forms a plug in the vessel.
the physiological systems that control blood fluidity are both complex and elegant. Blood must remain fluid within the vasculature and yet clot quickly when exposed to non-endothelial surfaces at sites of vascular injury.
Fibrin is the insoluble protein that is essential to clot formation. Calcium, fat, macrophages, etc, add to the clot and cause it to grow.
Coagulation pathway
Intrinsic pathway
- Contact with -ve charged surface
- Coagulation factor 12 activated
- Platelets activated
- Common pathway reached (factor 10 is start)
Extrinsic pathway
- Vascular injury
- Tissue factor (not found in circulatory blood but on the outside of blood vessel and therefore an extrinsic pathway)
- Tissue factor pathway inhibitor (TFPI- an anticoagulant protein that blocks the initiation of blood coagulation)
- Common pathway
Thrombosis
Thrombosis is the formation of a clot. A thrombus may form in any vessel, artery or vein when blood flow is impeded. for example, a venous thrombus can develop as the result of venous stasis (decreased blood flow), injury to the vessel wall, or altered blood coagulation.
The thrombus may begin small, but fibrin, platelets, and red blood cells attach to the thrombus, increasing its size and shape.
When intravascular thrombi soo occur, a system of fibrinolysis is activated to restore fluidity. In a normal situation, a delicate balance prevents both thrombosis and haemorrhage and allows physiological fibrinolysis without excess pathological fibrinogenolysis.
Composition of clot in veins and arteries vary. Arterial blood has to go through vital organs whereas venous blood goes through the heart first.
What causes thrombosis?
Three primary factors influence the pathologic clot formation and are describes in Virchow’s Triad.
1. Abnormality in blood flow
- Could be bedridden
- Type of heart failure (atrial fibrillation, arrhythmia)
- Put on anti platelet therapy or warfarin to prevent stroke
2. Abnormalities of surface in contact with blood
- Injury (vascular injury, AMI, fracture, chemical irritation)
3. Abnormalities of clotting components
- Born with deficiency
- Protein C&S deficiency, thrombocytosis
Types of thrombi
Venous thrombosis- mainly found in venous circulations and is composed entirely of fibrin and erythrocytes. They most often occur in the lower extremities and are associated with venous stasis. Deep vein thrombosis (DVT) occurs in the lower extremities and is the most common type of venous thrombosis. Results in blue colour, numbness, heat and pain. Clots can be detected earlier than arterial clots through symptoms.
Arterial thrombosis- occurs mainly in regions of rapid blood flow (i.e. arteries). They can occur because of atherosclerosis or arrhythmias such as AF. They are primarily composed of platelets and small components of fibrin and leukocytes. Consequence of arterial clots occur immediately (heart attack, stroke).
Deep Vein Thrombosis (DVT)
Venous stasis resulting from prolonged bed rest, cardiac failure, or pelvic, abdominal, or hip surgery may precipitate thrombus formation in the deep veins of the leg or calf and may lead to fatal pulmonary embolism.
DVT occurs in the lower extremities and is the most common type of venous thrombosis.
The thrombus may begin small, but fibrin, platelets, and RBCs attach to the thrombus increasing its size and shape.
Risk factors for DVT
Poor blood circulation
Venous injury
Increased blood clotting
Signs and symptoms of DVT
Signs
- Patient’s superficial veins may be dilated
- Patient may experience pain in back of the knee when the examiner dorsiflexes the foot of the affected leg
Symptoms
- Leg swelling
- Pain
- Warmth
Embolism
When a thrombus detaches itself from the wall of the vessel and is carried along the blood stream, it becomes an embolus. The embolus travels until it reaches a vessel that is too small to permit its passage and it blocks the vessel.
Damage is caused when the embolus becomes trapped in a small vessel, causing occlusion and leading to ischemia (blood flow/oxygen is restricted to a part of the body) or infarction of the surrounding tissue.
An embolus is a part of a clot that breaks off and travels to another vascular system.
Pulmonary embolism (PE)
Normal clot formation maintains the integrity of the vasculature in response to injury. Pathologic clotting can occur in many clinical conditions.
Main abnormal thrombotic events include DVT and its primary complication PE.
Signs and symptoms are not very specific in PE so diagnosis is difficult. The most common symptoms are dyspnoea (sensation of running out of air), pleuritic chest pain (sharp chest pain), cough, tachycardia, fever.
Pulmonary thromboembolism is not a disease in itself but an often fatal complication of underlying venous thrombosis.
PE can arrive from DVT anywhere in the body.
Gas embolism
Gas embolism is the entry of gas int vascular structures. It is a largely iatrogenic (caused by medical exam or treatment) clinical problem that can result in serious morbidity and even death.
This can result from procedures performed in almost all clinical procedures. In most cases it is air embolism but medical gases can be a cause.
It can be of venous or arterial origin.
The entered gas can reach the lungs by pulmonary arteries causing disturbance in gas exchange, arrhythmias, pulmonary hypertension, right ventricular failure and cardiac failure.
Arterial gas embolism is caused by the entry go gas into the pulmonary veins or directly into the arteries of the systemic circulation.
Fluid embolism
Amniotic fluid embolism (AFR) is the most common type of fluid embolism.
It is mostly agreed that this condition results from amniotic fluid entering the uterine veins. In order for this to occur there are 3 pre-requisites:
- ruptured membranes
- ruptured uterine or cervical veins
- a pressure gradient from uterus to vein
AFE can occur before, during or after delivery.
