Thrombosis******

Question 1

Definition of thrombosis

Answer 1

Thrombosis refers to the formation of a thrombus. A thrombis is an aggregate of coagulated blood containing platelets, fibrin and entrapped cellular elements attached to vascular endothelium, within the vascular lumen that occur during life.

Question 2

Virchow’s Triad

Answer 2

The three factors involved in the initiation of thrombosis:

• Endothelial injury
• Hypercoagulability
• _Abnormal blood flow _

_​_In normal blood vessels mild endothelial injury occurs with normal wear and tear on the vessels. Therefore the greatest risk factors are alterations in blood flow and hypercoagulability.

Question 3

Endothelial cells functions

Answer 3

• Anti-platelet function (remain intact, PGI2 and NO impede Plt adhesion and aggregation, along with adenosine diphosphatase which degrades ADP),
• anticoagulant (heparin like molecules, antithrombin III, thrombomodulin, tissue factor pathway inhibitor)
• fibrinolytic properties (tissue plasminogen activator, that produces plasmin, that cleaves fibrin) that balance pro-coagulant factors.

Question 4

Thrombophilia

Answer 4

This is a congenital or acquired predisposition to thrombosis. Suspect n young patients, FHx of thrombosis, unusual site from thrombosis or in females with recurrent miscarriage.

Question 5

Venous thrombosis

Answer 5

Usually forms as an initial platelet fibrin head, usually attached to a valve. A column of static blood forms downstream which coagulates. Turbulence as blood enters form the next tributary causes repeptition of the cycle. The thrombis can therefore extend a long distance up the vessel, yet only be attached loosly at one point.

Question 6

What factors predispose to venous thrombosis.

Answer 6

1. Statis is the most important factor in venous thrombosis. Venous statis is associated with:
   
   • Immobility - prolonged bed rest, during surgery, long distance air travel, advaced age, HF, oedema, pelvic obstruction, following AMI or trauma.
2. Hypercoagulability
   
   • _​​_Acquired hypercoagulable states
   • Genetic predisposition
3. Changes in the vessel wall: inflammation of the vessel wall.

Question 7

Acquired hypercoagulable states

Answer 7

Associated with:

• Pregnancy
• Oral contraceptive pill, hormone replacement therapy
• Malignancy (paraneoplastic syndrome)
• Antiphospholipid antibody syndrome - recurrent thrombosis, miscarriage, cardiac valve vegetations, thrombocytopenia associated with antibodies directed against plasma proteins boung to anionic phospholipids.
• Secondary antiphospholipid syndrome - seen in association with SLE.
• Associated with an increase APTT but paradoxically present with increased risk of thromosis.
• Increased platelets (thrombocythaemia) for example follofing haemorrhage or surgery. Polycythaemia.

Question 8

Congenital hypercoagulability

Answer 8

Genetic predisposition occurs with:

• *Factor V Leiden:** *variant of factor V which is resistant to inactivation by protein C; and less commonly prothrombin mutation
• *Increased factors VIII, IX, XI or fibrinogen *
• *Less commonly deficiency in: *antithrombin, protein C and protein S

Question 9

Outcomes of venous thrombosis

Answer 9

Venosu thrombi are almost always occlusive and cause congestion and oedema. The main risk from venous thrombosis is pulmonary thromboembolism.

Question 10

Arterial thrombosis contributing factors

Answer 10

• Endothelial injury: is the most important factor, usually as the result of atherosclerosis.

The initiating event may be either a direct result of impaired endothelial function, disruption of the damaged endothelium or plaque rupture.

• Turbulent flow contributes to both the formation of atheroma and of thrombosis on the surface of atheroma.

Other causes of arterial thrombi are vasculitis. This occurs in areas of high flow (ie abdominal aorta) where alternating layers of platelets, fibrin and RBC are laid down (lines of Zahn). For lamination to occur the layers must be tightly adherent and therefore laminated thrombi rarely embolise.

Question 11

What determines the presence of ischaemia with arterial thrombi?

Answer 11

The majority of arterial thrombi (except in large vessels) are occlusive. Whether ischaemia occurs depends on the presence of collateral circulation.

Question 12

Microvascular thrombi

Answer 12

Formation of thrombi in microvascular beds. Most commonly seen in association with major illness (gram negative sepsis, secondary to major haemorrhage, amniotic fluid embolism and neoplasms) and is referred to as disseminated intravascular coagulation. The clinical symptoms reflect ischaemic damage to major organs as well as a consumptive coagulopathy as fibrin and platelets are used up.

Question 13

Ebolism definition

Answer 13

Embolism refers to the blockage of vessels by material that has originated elsewhere in the body and travelled in the blood.

Question 14

Venous thromboembolism

Answer 14

Alsmot always originate from the deep veins of the lower limbs. The thrombus propagates and part or all of it may detach. They travel through the venous system until the calibre of the vessels becomes too small, almost always in the pulmonary circulation. Small emboli may be clinically silent, whereas large emboli may be fatal, causing pulmonary infarction or obstruction to right ventricular flow.

VQ mismatch may be seen with nuclear isotope scanning or blockage may be seen with CT pulmonary angiogrphy.

Question 15

Arterial thromboembolism

Answer 15

As with VTE, thrombi may detach and impact in downstream small vessels. Common sites of arterial thromboembolism are:

• The brain (thrombi originating from the heart associated with atrial fibrillation or post AMI and carotid artery)
• The heart (thrombi originating in the coronary circuation lodging distally)
• Aorta and it’s branches (mesenteric and renal vascular beds and the distal vessels of the lower limbs).

Question 16

Features of ischaemic limb

Answer 16

Pale, painful, paralysed, pulseless and perishing cold.

Question 17

Other types of emboli

Answer 17

• Fat embolus: associated with fractures and major trauma
• Air/gas embolus: associated with decompression accidents in divers.
• Cholesterol embolus: from rupture of an atheromatous plaque
• Foreign body embolus: most commonly seen in IV drug users
• Amniotic fluid embolism: is not technically embolism but leakage of amniotic fluid into the maternal vascular system causing activation of teh coagulation cascade fibrin formation and subsequent thrombosis.

Question 18

Consequences of thrombo-embolic disease

Answer 18

Blockage of the arterial circulation causes ischaemia and without adequate collateral circulation or removal of the blockage leads to infarction (irreversible damage).

Question 19

Causes of infarction

Answer 19

Infarction may be a consequence of thrombo-embolci disease, however, it may also be caused by:

• mechanical obstruction of teh arterial supply (e.g. compression, torsion, volvulus or vasospasm)
• hypotension
• Microvascular occlusion (e.g. the diabetic foot, DIC)

Question 20

Appearance of infarcts

Answer 20

The appearance depends on the cause, time course and organ affected

• Infarcts in tissues with a single blood supply which is acutely lost appear pale (e.g. AMI, CVA)
• Infarcts where a dual blood supply is present, where reperfusion has occurred after the tissue has died, following a venous occlusion or hypotension are clasically red.

In most tissues, infarcts appear as a region of coagulative necrosis with a rim of reactive hyperaemia which subsequently becomes a zone of inflammation and then granulation tissue.

Venous congestion occurs, usually as a secondary event.

Question 21

Cerebral infarction appearance

Answer 21

Characterised by liquefactive necrosis.

Question 22

Appearance of infarction of extremities and GIT

Answer 22

Secondary abcterial colonisation may lead to gangrene (putrefaction of tissue following colonisation with gas forming organisms).

Question 23

Chronic ischaemia outcome

Answer 23

May lead to so caled ‘dry gangrene’, especially in the distal extremities.

Question 24

Risk of re-occurence of pulmonary embolism

Answer 24

Patients with one PE have approximately a 30% lifetime risk of a second PE. Often there is an underlying coagulation abnormality or damage to the blood vessels that predisposes patients to this.

Question 25

Factors which predispose to pulmonary embolism.

Answer 25

Virchow's triangle * Stasis * Hypercoagulability * Endothelial damage

Question 26

Pattern of disease for large embolus

Answer 26

Will oclude a main pulmonary trunk (or if really large will occlude both trunks at bifurcation). Will generally have a coiled appearance. Can often cause sudden death due to ventilation/perfusion mismatcch and subsequent hypoxia.

Question 27

Saddle embolus

Answer 27

A large embolus that occlues both trunks at the bifurcation.

Question 28

Medium sized embolus disease pattern

Answer 28

Lodged in peripheral or segmental pulmonary artery. Will cause a pulmonary infarct, wedge shaped in appearance, with size depending on the level of blockage.

Question 29

Small embolus disease pattern

Answer 29

Often asymptomatic, multiple small PE can lead to pulmonary HTN and resultant problems with the heart.

Question 30

PE risk factors

Answer 30

* DVT * Immobility * Vascular damage * Surgery * Cancer

Question 31

Investigations PE

Answer 31

* _D-dimer_ is one of the breakdown products of fibrin, so therefore whenever there is elevated clotting in the blood. This tests is frequently used to assist diagnosis of PE but needs ot be used and interpreted cautiously. Diagnostic tests must supplement rather tha be used as a substitute for clinical skills. * Medical imaging (diagnosis depends on imaging) * _Nuclear medicine or VQ scan_ demonsrating ventilation/perfusion mismatch; **OR** * _Pulmonary angiography or more commonly CT pulmonary angiography_ demonstrating a blockage of the pulmonary vasculature

Question 32

D-dimer selectivity and specificity

Answer 32

It is _sensitive_ (*high true positive rate - it is positive when people have the disease, thus once diagnosed sensitive tests are good for monitoring).* It has low _specificity_ (*high false positive rate - ie positive in people hat do not have the disease - thus not a good diagnostic test). *Thus it has a high negative predictive value. This means it can be used to rule out PE if the clinical suspicion is low (with a negative result), but cannot diagnose a PE (with a positive result).

Question 33

What shaped are infarcts generally?

Answer 33

Wedge-shaped.

Question 34

Healing of pulmonary infarcts

Answer 34

Healing occurs with fibrous scarring of the area and adjacent lung tissue will expand to fill the defect, resulting in no significant chaneg in lung size but expansion of the alveoli in these adjacent areas.