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Flashcards in Thrombosis****** Deck (34):
1

Definition of thrombosis

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. 

2

Virchow's Triad

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. 

 

3

Endothelial cells functions

  • 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. 

4

Thrombophilia

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. 

5

Venous thrombosis

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. 

6

What factors predispose to venous thrombosis. 

  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. 

7

Acquired hypercoagulable states

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. 

8

Congenital hypercoagulability

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

9

Outcomes of venous thrombosis

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

10

Arterial thrombosis contributing factors

  • 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. 

11

What determines the presence of ischaemia with arterial thrombi?

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

12

Microvascular thrombi

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. 

13

Ebolism definition

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

14

Venous thromboembolism

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. 

15

Arterial thromboembolism

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). 

16

Features of ischaemic limb

Pale, painful, paralysed, pulseless and perishing cold. 

17

Other types of emboli

  • 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. 

18

Consequences of thrombo-embolic disease

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

19

Causes of infarction

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)

20

Appearance of infarcts

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. 

21

Cerebral infarction appearance

Characterised by liquefactive necrosis. 

22

Appearance of infarction of extremities and GIT

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

23

Chronic ischaemia outcome

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

24

Risk of re-occurence of pulmonary embolism

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. 

25

Factors which predispose to pulmonary embolism. 

Virchow's triangle

  • Stasis
  • Hypercoagulability
  • Endothelial damage

26

Pattern of disease for large embolus

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. 

27

Saddle embolus

A large embolus that occlues both trunks at the bifurcation. 

28

Medium sized embolus disease pattern

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

29

Small embolus disease pattern

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

30

PE risk factors

  • DVT
  • Immobility
  • Vascular damage
  • Surgery
  • Cancer

31

Investigations PE

  • 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

32

D-dimer selectivity and specificity

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). 

33

What shaped are infarcts generally?

Wedge-shaped. 

34

Healing of pulmonary infarcts

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.