Hemostasis, thrombosis, emboli

Question 1

What is a hematoma?

Answer 1

Accumulation of blood in the tissues as a result of bleeding

Question 2

Name 3 substances secreted by endothelial cells

Answer 2

Heparan sulphate

Prostacyclin

Nitric oxide

ADPase

tPA

All prevent platelet interaction and coagulation

Question 3

What is the role of haemostasis?

Answer 3

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.

Question 4

What are the physiological factors that normally prevent clotting?

Answer 4

Intact endothelial lining

Anticoagulant mechanisms

Dilution of clotting factors

Removal of activated factors

Question 5

Name three counter regulatory factors of the clotting cascade (5)

Answer 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

Question 6

What is the role of the endothelium in haemostasis?

Answer 6

Acts as a physical barrier which prevents platelet interaction with collagen and vWF

Secretes anticoagulant factors (prevent platelet activation, anti-thrombins)

Question 7

What are the changes that take place when the endothelium becomes activated?

Answer 7

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.

Question 8

Describe the vents in thrombus formation

Answer 8

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.

Question 9

Name three acquired causes of excessive bleeding

Answer 9

Liver disease

Excessive anticoagulation

Disseminated intravascular coagulation (septicaemia)

Question 10

What is thrombosis?

Answer 10

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

Question 11

What are the three factors that predispose an indiviual to thrombosis?

Answer 11

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

Question 12

Describe the appearance of a thrombus

Answer 12

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)

Question 13

Describe the clinical effects of arterial thrombosis

Answer 13

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.

Question 14

What are the clinical effects of venous thrombosis?

Answer 14

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)

Question 15

Define emboli

Answer 15

A mass which travels through the vascular tree and becomes lodged to obstruct blood flow.

Most emboli come from thrombi

Question 16

Thrombocytopenia

Answer 16

Low platelet count.

This can be caused by reduced platelet production from BM, destruction of platelets or removal by an enlarged spleen

Question 17

Haemophillia

Answer 17

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

Question 18

Disseminated intravascular coagulation

Answer 18

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.

Question 19

Thrombophilia

Answer 19

Conditions associated with excessive clotting. Can be acquired (fractures) or inherited (protein C deficiency, anticoagulant).

Question 20

Disseminated intravascular coagulation

Answer 20

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.

Question 21

fate of thrombus

Answer 21

Propagation in direction of blood flow

Fibrinolysis and removal

Organisation into scar tissue within the vessel

Recanalisation with re-established blood flow

Embolism

Question 22

symptoms and signs of pulmonary thromboembolism

Answer 22

Symptoms : chest pain, SOB, collapse, cough, haemoptysis Signs: tachycardia, hypotension, tachypnoea, raised JVP

Question 23

Diagnosis of thromboembolism

Answer 23

wells criteria

ECG - tachycardia, RBBB,

D-Adimer assay (breakdown product of fibrin)

Blood gases

CxR V/Q scan

CT pulmonary angiography

Question 24

Treatment of DVT

Answer 24

Prophylactic: heparin, leg compression, mobilisation

Treatment: heparin, warfarin

Question 25

Treatment for pulmonary thromboembolism

Answer 25

Oxygen Heparin, warfarin Thrombolysis if severe Emboli tony

Question 26

Treatment of arterial thrombus

Answer 26

Aspirin (anti platelets) Streptokinase, TPA

Question 27

sources of emboli

Answer 27

Air Fat Tumour cells Foreign material

Question 28

Compare heparin and warfarin

Answer 28

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