Hemostasis, thrombosis, emboli Flashcards
What is a hematoma?
Accumulation of blood in the tissues as a result of bleeding
Name 3 substances secreted by endothelial cells
Heparan sulphate
Prostacyclin
Nitric oxide
ADPase
tPA
All prevent platelet interaction and coagulation
What is the role of haemostasis?
Physiological mechanism for maintaining blood in a fluid state within the vessel. Responds to injuries in small vessels and induces a haemostatic plug.
- body is not able to control bleeding from a medium or large artery.
What are the physiological factors that normally prevent clotting?
Intact endothelial lining
Anticoagulant mechanisms
Dilution of clotting factors
Removal of activated factors
Name three counter regulatory factors of the clotting cascade (5)
Anti-thrombins inhibit thrombin and other coagulation factors
Thrombin promotes release of prostacyclin and ADPase from the endothelium (negative feedback)
Release of tPA converts the plasminogen to plasmin, which causes fibrinolysis
Blood flow removes clotting factors from the rite of injury (dilution)
Removal of activated clotting factors by the liver
What is the role of the endothelium in haemostasis?
Acts as a physical barrier which prevents platelet interaction with collagen and vWF
Secretes anticoagulant factors (prevent platelet activation, anti-thrombins)
What are the changes that take place when the endothelium becomes activated?
When endothelial cells are damaged they exhibit procoagulant functions
The vessel constricts in response to a neuogenic reflex and enothelin release from endothelial vells
Loss of barrier function exposes collagen and vWF. Platelt ECAM-1 is expressed on the cell surface. This results in platelet aggregation and adhesion
Subendothelial cells secrete tissue factor which promotes coagnulation
Fibrinolysis is inhibited by a tPA inhibitor.
Describe the vents in thrombus formation
Endothelial damge results in the exposure of collagen and vWF which mediates platelet adhesion. Platelets express surface glycoproteins receptors which bind to the ligand.
Activated platelets change shape and aggregate.
ADP is released from granules which stimulates further aggregation of platelets forming a platelet plug.
TXA2 is synthesised by platelets and causes platelet activation and vasoconstriction. Receptors on the platelt surface interact with coagulation factors to initate the clotting cascade,
Prothrombin is cleaved to thrombin, which produces fibrinogen. Fibrinogen plymerises to form a firm hemostatic plug.
Name three acquired causes of excessive bleeding
Liver disease
Excessive anticoagulation
Disseminated intravascular coagulation (septicaemia)
What is thrombosis?
Formation of a thrombus - a solid mass of blood constituents (blood clot) formed within the vascular system during life.
Composed of platelets, fibrin and blood cells
What are the three factors that predispose an indiviual to thrombosis?
Abnormalities of the vessel wall: atheroma, injury, external pressure
Abnormalites in blood flow: stasts, immobilisation, congestive heart failure (poor venous return), turbulent flow
Abnormal blood constituents: thrombocytosis, smoking, deficiency in anti-coagulants
Describe the appearance of a thrombus
Arterial thrombi are usually firmer and paler than venous thrombi
Alternate dark and pale areas corresponding to trapped platelets, fibrin and trapped RBCs (lines of Zahn)
Describe the clinical effects of arterial thrombosis
Aterial thrombosis is usually due to the rupture of a plaque or atheroma (because of a damaged vessel wall and turbulent flow)
This cuts off blood supply to part of an organ causing ischemic necrosis. (can lead to MI or stroke)
Thrombosis can also be a source of emboli.
What are the clinical effects of venous thrombosis?
Venous thrombosis usually occurs due to stasis of blood in the veins.
DVT which commonly occurs in the calf or iliofemoral vessels causes swelling, pain, tenderness, discolouration, and a raised temperature. However a patient can have DVT and be asymptomatic.
Complications of DVT include pulmonary embolism, ulcers (post phlebotic syndrome), phlelgmasia cerulae (venous gangrene)
Define emboli
A mass which travels through the vascular tree and becomes lodged to obstruct blood flow.
Most emboli come from thrombi
Thrombocytopenia
Low platelet count.
This can be caused by reduced platelet production from BM, destruction of platelets or removal by an enlarged spleen
Haemophillia
Haemophilia A: due to a lack of factor VIII
Haemophillia B: due to a lack of factor IX
Leads to abnormal bleeding due to failure of the coagulation cascade
Disseminated intravascular coagulation
Characterised by excessive activation of the coagulation cascade and may be triggered by the release of tissue thromboplastins following trauma, surgery or blood transfusion.
Can lead to uncontrolled bleeding as all the clotting factors are used up, and may result in death.
Thrombophilia
Conditions associated with excessive clotting. Can be acquired (fractures) or inherited (protein C deficiency, anticoagulant).
Disseminated intravascular coagulation
Characterised by excessive activation of the coagulation cascade and may be triggered by the release of tissue thromboplastins following trauma, surgery or blood transfusion.
Can lead to uncontrolled bleeding as all the clotting factors are used up, and may result in death.
fate of thrombus
Propagation in direction of blood flow
Fibrinolysis and removal
Organisation into scar tissue within the vessel
Recanalisation with re-established blood flow
Embolism
symptoms and signs of pulmonary thromboembolism
Symptoms : chest pain, SOB, collapse, cough, haemoptysis Signs: tachycardia, hypotension, tachypnoea, raised JVP
Diagnosis of thromboembolism
wells criteria
ECG - tachycardia, RBBB,
D-Adimer assay (breakdown product of fibrin)
Blood gases
CxR V/Q scan
CT pulmonary angiography
Treatment of DVT
Prophylactic: heparin, leg compression, mobilisation
Treatment: heparin, warfarin
Treatment for pulmonary thromboembolism
Oxygen Heparin, warfarin Thrombolysis if severe Emboli tony
Treatment of arterial thrombus
Aspirin (anti platelets) Streptokinase, TPA
sources of emboli
Air Fat Tumour cells Foreign material
Compare heparin and warfarin
Heparin: Strong, fast-acting, given IV, daily blood testing (APTT) Sides effects are bleeding, rash, headache
Warfarin: Long term treatment, pill, blood testing (prothrombin time), Side effects: bleeding, headache, rash
