ILA 4 - thrombosis Flashcards
describe the whole coagulation cascade
extrinsic:
- tissue damage deads to
- F7 - F7a
- F3 - F3a
- F7a + F3a - X - Xa
intrinsic:
- F 12 - 11 - 9 - 8 - 10
- F10 - 10a
common pathway:
- F10a + F5a + Ca bind forming prothrombin
- complex is now prothrombin - thrombin
- thrombin converts fibrinogen to fibrin
- factor 13a + fibrin forms a stable clot
Describe the difference between arterial and venous thrombosis
Arterial thrombosis:
- Caused by atherosclerotic plaques
- These become unstable and a thrombus forms
- This can either occlude the artery at site of formation or break off and form an embolism, obstructing a different arterial in which it has travelled to.
Venous thrombosis:
- Caused by factors of Virchow’s triad: endothelial damage, statant flow, hypercoagulation
- An increase in any of these factors increases ones likelihood of developing a venous thrombosis
- Examples of each:
- Endothelial damage – smoking
- Statant flow – pregnancy + long-haul flights
- Hypercoagulation – thrombophilia
describe composition of clots - important for identifying medication
Arterial (platelet rich - white clots) - Antiplatelets (Aspirin, Clopidogrel), thrombolysis, stents
Venous (fibrin + RBC rich - red clots) - Anticoagulants (Heparin, DOACs), compression stockings
outline arterial + venous thrombosis in general
contrast the different treatment types for arterial vs venous thrombosis
arterial - platelet clot
- antiplatelets
eg:
- aspirin
- clopidogrel - P2y12 inhib
venous - fibrin clot
- anticoagulants
eg:
- DOACS - apixiban
- LMWH
- warfarin
first line drug for dvt
ANY DOAC - N - apixaban
Describe the therapeutic agents used to treat venous thrombosis
- First line – DOAC – apixaban or rivaroxaban
- LMWH – factor Xa + thrombin antagonist
- Thrombolysis in some cases when haemodynamically unstable – streptokinase
how long should you be on apixaban for
Provoked DVT – 3 months apixaban
Unprovoked + cancer DVT – 6 months apixaban
if apixaban / rivoxiban unsuitable
- Apixaban / rivoxiban 1st line
- If unsuitable – LMWH 5+ days followed by dabigatran/edoxaban /LMWH + vitK antagonist
- until the INR is at least 2.0 for 2 consecutive readings, followed by a vitamin K antagonist on its own
Describe the preventative measures that can be taken to reduce the risk of developing venous thrombosim
Chemical:
Provoked DVT – 3 months apixaban
Unprovoked + cancer DVT – 6 months apixaban
Mechanical:
- Compression stockings
- Intermittent pneumatic compression - device applying intermittednt compression to the legs
- Special groups – eg stroke patients
- IVC filter – used in recurrent clots
name a couple of hypercoagulation conditions
- factor V Leiden
- protein C + S deficiency
outline the process of the primary haemostasis
- endothelium disrupted when vessel injured - exposure of collagen fibres
- platelets adhere to collagen fibres via VWF
- the VWF is adhered to collagen already via GP1b
- binding of platelets triggers the release of alpha and dense protein granules via exocytosis
- platelets are amplified by the activation of P2Y12 activation
- thrombin binds to PAR1 + PAR4 receptors inducing platelet activation
- activation changes the smooth discoid shape to a spikey shape to inc SA
- expression of glycoprotein IIb/IIIa receptors which bind to fibrinogen, enabling new platelets to adhere
- platelet plug forms and release thromboxane A2 causes vasoconstriction
Describe the difference in presentation (signs and symptoms) between an arterial thrombosis and venous thrombosis
arterial thrombosis:
- Diminished or absent pulse
- Pain → intermittent claudication, constant
- Cool to cold temperature
- Nails thickened and rigid
- Skin-dependent rubor (redness of skin)
V IMPORTANT - 6 P’s: pulselessness, perishingly cold, paraesthesia, paralysis, pain and pallor
venous thrombosis:
- Pulse present
- Pain → aching + cramping
- Skin → pigmentation in the gaiter area , may be thickened and tough, have reddish/blue colour (associated with dermatitis), hot to touch
- Deep venous thrombosis associated with increased calf size (measured with tape measure in cm the difference between normal and affected leg).
What blood test might you do to help confirm a diagnosis of a DVT? Why does the blood level of this ‘substance’ increase with the presence of DVT?
D-dimer test:
- fibrin detection product
- fibrin is elevated in presence of DVT
- so, so is d-dimer
what pathway does heparin + LMWH act on
intrinsic
what pathway does warfarin act on
extrinsic pathway
indirect thrombin inhibitor
heparin
- binds to antithrombin - promotes it
what factors does heparin inhibit
ALL THE FACTORS OF THE INTRINSIC PATHWAY APART FROM FACTOR 8
Xa
2a (thrombin)
9
11
12
What potentially fatal complication of a DVT should they be made aware of and what signs and symptoms should they look out for?
Pulmonary Embolism (PE)
SYMPTOMS:
Shortness of breath Pleuritic/typical chest pain Calf/thigh pain Calf/thigh swelling Cough Asymptomatic Orthopnea Wheezing Haemoptysis Syncope
SIGNS:
Tachypnoea
Signs of DVT (oedema, tenderness, erythema, palpable cord) Hypoxia (ABG) Tachycardia
Rales
Reduced breath sounds
JVD
Fever
Hypotension
What advice would you give to students who need to take long haul flights in order to reduce their risk of developing a DVT?
● Move around as much as possible
● Choose an aisle seat when feasible
● Carry out calf muscle exercises (flex and extend the ankles to encourage blood flow)
● Try to avoid placing cabin bag where it can restrict leg movement
● Avoid excessive alcohol consumption and the use of tranquilizers or sleeping tablets as
this may discourage moving
● Keep well hydrated as this encourages moving to toilet
● Seek urgent medical attention if develop swollen, painful legs (especially if one is more
so than the other) or have breathing difficulties
● Wear loose, comfortable clothing
● Use anti-embolism stockings (if at increased risk of DVT or PE)
what factors + pathway does warfarin inhibit
intrinsic bc inhibits factor 7
