Thrombosis Flashcards
components of a thrombus
- fibrin
- platelets
definition of a thrombus
a solid mass, formed in the circulation from the constituents of the blood during life
where do atheromas tend to develop?
areas of turbulent blood flow
how are white thrombi formed?
Platelets adhere to the damaged vascular
endothelium and aggregate in response to ADP and TXA2
what limits the growth of thrombi?
- PGI2
- NO
how does plaque rupture lead to thrombus formation?
Plaque rupture leads to the exposure of blood containing factor VIIa to tissue factor within
the plaque, which may trigger blood coagulation and lead to thrombus formation.
main component of a white thrombus
platelet
what are red thrombi?
these are also known as venous thrombi and contains more fibrin
management of venous thrombi
antifibrin like heparin or warfarin
management of arterial thrombi
antiplatelet like aspirin
major causes of venous thrombi
- stasis
- hypercoagulability
what is postphlebetic syndrome?
Chronic venous
obstruction following thrombosis in the deep veins of the leg frequently results in a
permanently swollen limb and may lead to ulceration
patient factors that are risk factors for VTE
- age
- high BMI
- varicose veins
- frequent/recent continuous travel
- immobility
- pregnancy and puerperium
- thrombophilia
- oestrogen therapy
- dysfibrinogenaemia
- plasminogen deficiency
diseased stated that are risk factors for VTE
- trauma/surgery
- cardiac/resp failure
- malignancy
- recent MI/CVA
- acute medical illness/severe infection
- inflammatory bowel disease
- behcet’s disease
- nephrotic syndrome
- myeloproliferative disorders
- paroxysmal noctural haemoglobinuria
- paraproteinaemia
- sickle cell anaemia
- central venous catheter
who has problems with blood stagnation?
- long distance flights
- bedridden patients
- sedentary occupations
problems with coagulability
- clotting factors and natural anticoagulants
- pregnancy
- oestrogen therapy/hormone
- post-inflammation/surgery
what causes endothelial damage?
- trauma
- fractures
- cannulation
what’s Virchow’s triad?
- circulatory stasis
- vascular wall injury
- hypercoaguable state
risk factors for arterial thrombosis
- HTN
- DM
- hypercholesterolaemia
- smoking
- hyperlipidaemia
what are the 3 systems involved in clot formation?
- platelets
- clotting factors
- endothelium
what are steps does the platelet go through in clotting?
- platelet activation
- platelet adhesion
- platelet aggregation
what substances mediate platelet adhesion?
- vWF
- GPIb
what substances change the shape of the platelet?
- ADP
- Ca
- serotonin
which substances mediate platelet aggregation?
- GPIIb/IIIa
- fibrinogen
- prostacyclin
how many pathways does the clotting cascade have?
2; intrinsic and extrinsic
what is the result of the clotting cascade?
conversion of fibrinogen into fibrin
what is PT?
prothrombin time
another name for PT
INR
which pathways does the INR monitor?
- extrinsic
- common
which clotting factors are monitored through the INR?
- 5
- 7
- 10
- prothrombin
- fibrinogen
normal INR
1.0
INR for people on warfarin
2.0-3.0
what does a high INR indicate?
bleeding risk
what dose a low INR indicate?
thrombosis risk
which medication can be monitored using APTT?
heparin
what is APTT?
activated prothrombin clotting time
which pathways are monitored through APTT?
- intrinsic
- common
which factors are monitored through the APTT?
- 5
- 8
- 9
- 10
- 11
- 12
- prothrombin
- fibrinogen
causes of a prolonged APTT
- heparin use
- antiphospholipid antibody
- coagulation factor deficiency
- sepsis
- presence of antibodies against coagulation factors
what is the principle enzyme for haemostasis?
thrombin
what does thrombin do?
- fibrinogen to fibrin
- activates V, VIII, XI and XIII
- activates Protein C, when bound to thrombomodulin
- activates platelets
- plasminogen to plasmin (this breaks the clot)
what do we use to break down clots?
thrombolytics
what do protein C and S collectively inhibit?
factor V
what are people deficient in protein C or S prone to?
thrombosis
prevention and treatment of arterial thrombosis
- minimise risk factors for thrombosis
- antiplatelet drugs
- thrombolytic therapy
what are the main antiplatelet drugs?
- aspirin
- clopidogrel
what does aspirin bind to?
cyclooxygenase, which reduces the platelet production of TXA2
what does clopidogrel inhibit?
ADP receptor on platelet cell membranes
types of thrombolytics
- streptokinase
- plasminogen activators
what does streptokinase do?
- binds to plasminogen, activating it to produce more plasmin
- risk of haemorrhage as indiscriminate of the clots it breaks down
example of a plasminogen activator
alteplase i.e. TPA
which of the thrombolytic drugs are antigenic and thus, can cause allergic reasons?
streptokinase
what are the 2 types of oral anticoagulants?
- coumarins
- indanediones
the most common coumarin used
warfarin
what does warfarin inhibit?
the reductase enzyme which activates Vitamin K, making it impossible to produce factors 2, 7, 9, 10
what will be prolonged as warfarin is used?
- PTT (factor 7, 10)
- APTT (factor 9, 10)
in which situation should the INR be between 3 and 4?
- recurrent VTE
- antiphospholipid syndrome
- mechanical prosthetic heart valve
- coronary artery graft thrombosis
- stroke prevention
in which situations should the INR be between 2 and 3?
- PE
- proximal and calf DVT
- recurrent VTE wo warfarin therapy
- symptomatic inherited thrombophilia
- atrial fibrillation
- cardioversion
- mural thrombus
- cardiomyopathy
how long should you give warfarin in situations of VTE?
- at least 6w-3m if the cause goes away
- at least 6m if no cause is found
- indefinite if no cause is found or if this is persistent
contraindications to anticoagulants
- severe uncontrolled hypertension
- non-thromboembolic strokes
- peptic ulceration
- severe liver and renal disease
- pre-existing haemostatic defects
- non-compliance
- pregnancy
what happens if the INR is too high?
- depending on the INR level, reduce or stop the warfarin, until the INR is lower than 5
- if above 8 and the patient is not bleeding, administer Vitamin K
- if there is a major bleed, stop the warfarin and give a prothrombin complex concentrate
what enhances warfarin action?
- alcohol
- aspirin
- NSAIDs
what decreases warfarin action?
- contraceptive steroids
- vitamin K
example of an anti-Xa inhibitor
- rivaroxaban (xarelto) (you do not need monitoring with this)
example of an active direct thrombin
dabigatran
what does heparin bind to?
anti-thrombin
actions of heparin
- activates anti-thrombin
- inhibits factor 10
- mild inhibitor of all factor except 7
which clotting screen tests are altered due to heparin?
- PT (prolonged)
- APTT (more prolonged)
what is the target ratio for heparin patients?
1.5-2.0
which drug can be used as an antidote in high dose heparin situations?
protamine sulfate
why are LMWH heparins used instead of UFH?
- higher bioavailability
- more potent against factor Xa than IIa (lower risk of bleeding)
- longer half-life than normal heparin
- have little effect on the clotting screen
- less likely to cause HIT
what eliminates the LMWH?
kidneys
administration method of LMWH
subcutaneous
administration method of UFH
IV
what complication can happen with heparin?
- bleeding
- heparin-induced thrombocytopenia
- osteoporosis
- hyperkalaemia
when does heparin-induced thrombocytopenia happen?
5-14 days
contraindications of heparin
- bleeding disorders
- low platelet count
- HIT
- peptic ulcer
- cerebral haemorrhage
- severe hypertension
- neurosurgery
