thrombophilia

Question 1

give a general explanation of thrombophilia

Answer 1

• procoagulation is enhanced

- pathological formation of a thrombis (clot)

Question 2

where can thrombis formation occur?

Answer 2

arteries and veins

Question 3

what are the early stage effects of a thrombis? (2)

Answer 3

• ishcemia (restriction of blood flow)

- hypoxia (deprivation of cells/tissues from oxygen)

Question 4

what are the late stage effects of a thrombis? (1)

Answer 4

infarction (nercrosis/tissue death due to long term deprivaton of oxygen)

Question 5

define embolisation

Answer 5

severe complication where thrombis breaks from site of formation (now called embolus) and travels through circulation and becomes lodged in the lungs

Question 6

where do venous thrombosis’ genrally occur?

what are the two classifications of a venous thrombosis?

Answer 6

• in veins thrombi form at the valves bs high levels of turbulance
• can occur superficially or deep

Question 7

define superficial thrombophlebitis

what is the risk of embolism for these patients?

Answer 7

• characterized by localized pain along the vein with red streak-like patterns
• can usually palpate the thrombis
• risk of embolism = low

Question 8

where is deep venous thrombosis (DVT) most common?
what is the risk of embolism for these patients?
what is a life threatening posibility from this pathology?

Answer 8

-most common in leg
-proximal DVTs (above knee) are more likely to embolize
than distal DVTs
-pulmonary embolism (PE) can occur when DVT embolizes and travels through heart and lodges in pulmonary circulation

Question 9

is venous thromboembolism (VTE) more common in men or women?

Answer 9

men

Question 10

does the risk of VTE increase or decrease with age?

Answer 10

increases

Question 11

50% of the time the cause of VTE is:

other 50%?

Answer 11

• uknown (idiopathic)

- associated with other risk factors

Question 12

5-8% of the population have ______ that increase their risk of thrombophilias

Answer 12

genetic risk factors

Question 13

in addition to genetic risk factors, ______ factors can accumulate over a lifetime

Answer 13

acquired risk factors (environmental/pathological)

Question 14

in combination to genetic and/or aquired risk factos there can be ______ that lead to the development of a venous thrombosis

Answer 14

acute triggering events

Question 15

what are inherited risk factors that increase the risk of developing a venous thrombosis?

Answer 15

• increase coagulation factor activity
• decrease in anticoagulatn proteins
• abnormalities in the fibrinolytic system

Question 16

what are acquired factors that increase the risk of developing a venous thrombosis?

Answer 16

• acute/triggering risk factors (immobilization, surgery, estrogen)
• chronic or more permanent risk factors (cancer, obesity, history of blood clots)

Question 17

explain relative risk

why do we have this term?

Answer 17

• every risk factor does not contribute equally to the development of the disorder
• instead have an associated relative risk (ratio of the probability of an outcome in an exposed grp to the prob of an outcome in an unesposed grp)
• e.g. for thrombophilia - likelihood an individual w a risk factor develops a thrombis vs someone wout that risk factor

Question 18

explain 2 techniques for diagnosing DVT

Answer 18

(1) venography (GOLD STANDARD) - IV is inserted into patients foot and die is injected for x-ray imaging
(2) compression ultrasonography (MOST COMMON) - probes placed on the skin to compress veins where DVTs suspected, veins are compressible but DVT is not

Question 19

what are possible signs and symptoms of DVT?

Answer 19

• shortness of breath
• pleuritic chest pain
• cough
• leg pain
• tachycardia
• pleural rub
• syncope

Question 20

explain 2 techniques for diagnosis a PE

Answer 20

(1) pulmonary angiography (GOLD STANDARD) - contrast die injected via catheter inserted into groin and threaded up to pulmonary circulation followed by imaging (thrombus appears as filling defect or cutt off of blood flow)
(2) CT pulmonary angiography (MOST COMMON) - die delivered through IV then CT imaging

Question 21

limitations to pulmonary angiography

Answer 21

• invasive
• need well trained physician
• only offered at tertiary centrs
• cost
• risk of neurotoxicity due to die

Question 22

benefits/risk of CT pulmonary angiography

Answer 22

• increased availability bc IV not catheter to heart
• lower cost
• dont need as trained person
• risks worth it bc PE is life threatening

Question 23

explain the 3 goals of management of VTE

Answer 23

(1) to prevent thrombus extension/embolisation/recurrance
(2) prevent post-thrombic syndrome
(3) thrombolysis only in most severe cases

Question 24

are PE and DVT treated the same?

Answer 24

yes

Question 25

why do we only use thrombolysis in most severe cases?

Answer 25

serious risk of adverse bleeding bc breaks down clot formation

Question 26

when is treatment via thrombolysis appropriate?

Answer 26

(1) presence of hypotension (low bp related to PE) (2) severe hypoxemia (low o2 related to PE) (3) severe right sided heart failure (related to PE) (4) cases of extensive/severe DVT

Question 27

what is the most common thrombolytic? how is it administered? what is its mechanism of action?

Answer 27

- tissue plasminogen activator (tPA) - given intravenously when thromolysis is required - converts plasminogen to plasmin - promotes breakdown of thrombus into degredation products

Question 28

if a patient has a clearly identifiable reversible risk factor (e.g. birth control), how long would treatment with an anticoagulant last?

Answer 28

- remove the risk factor | - treatment lasts 3 months

Question 29

if a clear risk factor can not be identified, how long would treatments with anticoagulants last?

Answer 29

long-term

Question 30

what are the three classifications of anticoagulant? | do they all act on the same parts of the coagulation cascade?

Answer 30

- direct oral anticoagulants (DOACs) - heparins - other oral anticoagulants - all act on diff parts of the coagulation cascade

Question 31

explain the mechanism for direct oral anticoagulants (DOACs) | what are the benefits? limitations?

Answer 31

- either directly inhibit thrombin or FXa - benefits: oral pill, no monitoring required, rapid onset of action - limitations: antidote not available (issues for emergency surgery)

Question 32

explain the mechanism of action for unfractioned heparins (UFH) what are the benefits? limitations?

Answer 32

- acts via antithrombin to inhibit FIIa, FXa, FIXa, FXIa and FXIIa - benefits: rapid onset of action, short half life, reverse agent available - limitations: requies injection (usually IV), requires constant monitoring every 6 hours

Question 33

explain the mechanism of action for low molecular weight heparins (LMWH) what are the benefits? limitations?

Answer 33

- extracted MW fraction of UFH - acts primarily on inhibiting FXa - benefits: more predictable pharmokinetics, injection can be given by patients at home, longer 1/2 life than UFH - limitations: no direct reverisble agent available

Question 34

explain the mechanism of action for warfarin (other oral) | what are the benefits? limitations?

Answer 34

- vitamin K antagonist - interferes w carboxylation of vit. K dependent factors (VII, IX, X, II, protein C/S) - benefits: longer 1/2 life, direct reversible agent available - limitations: peek effect seen in 4-5 days - needs to be combined w faster acting drug if used acutely

Question 35

what are the adverse effects of all anticoagulants?

Answer 35

-bleeding safety

Question 36

what are the adverse effects specific to DOACs?

Answer 36

no data about pregnancy

Question 37

what are the adverse effects specific to heparins?

Answer 37

- thrombocytopenia - low platelet counts - result of adverse immune reaction - osteoporosis after long term use

Question 38

what are the adverse effects specific to warfarin?

Answer 38

- embryopathy (developmental defect in fetus') | - can cause allergic reactions (rash)

Question 39

when is genetic testing of inherited thrombophilias done?

Answer 39

in patients with a strong family history who present at a young age

Question 40

pros of genetic testing?

Answer 40

- easy - simple blood test - offers explanation for sudden occurance of a VTE without known risk factor - can find multiple defects - improves long-term treatment

Question 41

cons of genetic testing?

Answer 41

- knowing if an inherited thrombophilia is present doesn't affect initial treatment - can lead to unessecary/aggressive family testing - asymptomatic individuals - potential risk to future insurability

Question 42

is timing of thrombophilia testing critical?

Answer 42

- FVL and PGM are reliable anytime bc look for a mutation | - PC, PS and AT must be done when patient is well for an accurate result (treatment affects levels in blood)

Question 43

what are the most common thrombophilic conditions that are tested for?

Answer 43

- FVL (factor V leiden - specific gene mutation) - PGM (prothrombin gene mutation) - protein C deficiency (pheotypic assay by blood test) - protein S deficiency (pheotypic assay ") - antithrombin deficiency (pheotypic assay ")