Thrombosis & Risk Factors for Thrombosis Flashcards
What are the 3 components of Virchow’s triad?
this describes the 3 broad categories of factors that are thought to contribute to thrombosis
- hypercoagulability
- haemodynamic changes (e.g. stasis, turbulence)
- endothelial injury / dysfunction
What causes arterial thrombosis?
What is the primary pathological abnormality?
atherosclerosis of the vessel wall is the primary pathological abnormality
rupture of atheromatous plaques causes endothelial injury
platelet aggregation and platelet thrombi play an important role in final vessel occlusion
What are the risk factors for arterial thrombosis?
- smoking
- hypertension
- hypercholesterolaemia
- diabetes
- family history
- obesity
- physical inactivity
- age
- male sex
What is involved in the pathogenesis of venous thrombi?
What are the thrombi composed of?
pathogenesis mainly involves venous stasis and hypercoagulable states
thrombi are predominantly composed of fibrin with a lesser role for platelet accumulation and aggregation
What % of venous thromboemobolism are unrecognised?
80% of VTEs are clinically silent
What are the 2 main consequences of venous thromboemobolism?
deep vein thrombosis:
- this is a large thrombus (usually) in the femoral vein of the leg
- 50% of patients with proximal DVT have asymptomatic PE
pulmonary embolism:
- the embolus originates in the femoral vein and travels into a pulmonary artery
- DVT is found in >80% of patients with PE
What is the incidence of VTE?
How may it present?
incidence is 1 person per 1000
it may present as sudden death (20% of PE)
30% develop recurrent VTE in 10 years
28% develop post-thrombotic syndrome
mortality of promptly diagnosed and treated PE is 2%
What is the definition of hospital-acquired VTE?
any VTE within 90 days of discharge
hospital-acquired clots account for 2/3 of all VTE
What are the strategies to prevent hospital-acquired VTE?
prophylaxis:
- involves constant risk assessment and appropriate prophylaxis
treatment:
- requires prompt diagnoses and guideline-led unified care
What are the stages involved in the care pathway for VTE?
- patient admitted to hospital
- assess VTE risk
- assess bleeding risk
- balance risks of VTE and bleeding
- reassess risks of VTE and bleeding within 24 hours of admission and whenever clinical situation changes
Why is it important to balance risks of VTE and bleeding?
offer VTE prophylaxis if appropriate
do not offer pharmacological VTE prophylaxis if patient has any risk factor for bleeding and risk of bleeding outweighs risk of VTE
What are the significant medical comorbidities that increase risk of VTE?
- heart disease
- metabolic, endocrine or respiratory pathologies
- acute infectious diseases
- inflammatory conditions
What are the 16 risk factors for VTE?
- active cancer or cancer treatment
- age over 60 years
- critical care admission
- dehydration
- known thrombophilias
- one or more significant medical comorbidities
- surgery
- major trauma
- personal history of VTE
- use of hormone replacement therapy
- use of oestrogen-containing contraceptive therapy
- varicose veins with phlebitis
- obesity
- pregnancy and postnatal period
- immobility
- first degree relative with VTE
What are the procoagulant and anticoagulant factors that need to be balanced?
procoagulant:
- platelets
- clotting factors
anti-coagulant:
- protein c
- protein s
- anti-thrombin III
- fibrinolytic system
What is general advice that is given to avoid development of VTE?
- do not allow patients to become dehydrated unless clinically indicated
- encourage patients to mobilise as soon as possible
- do not regard aspirin or other antiplatelet drugs as adequate prophylaxis for VTE
What is involved in the pharmacological prophylaxis for VTE?
“low dose” low molecular weight heparin
fondaparinux (synthetic pentasaccharide)
What are newer anticoagulants that are used as pharmacological prophylaxis for VTE?
direct inhibitors of factor Xa:
- rivaroxaban
- apixaban
direct thrombin inhibitors:
- dabigatran
How does rivaroxaban work?
it is a direct inhibitor of activated factor X (factor Xa)
this prevents FXa from cleaving prothrombin to yield active thrombin
How does dabigatran work?
it is a direct inhibitor of thrombin
How do the parenteral oral anticoagulants work?
Fondaparinux and LMWH inhibit factor Xa
Argatroban and Bivalirudin inhibit thrombin
What are the exclusion tests for diagnosing VTE?
wells score:
- this is a validated numerical clinical probability score
D-dimer:
- sensitive quantitative D-dimer with high negative predictive value
both of these tests are used in an agreed algorithm
What is D dimer?
What do high levels of D dimer in the blood suggest?
it is a fibrin degradation product
it is a small protein fragment present in the blood after a blood clot is degraded by fibrinolysis
high levels of D-dimer suggest a major clot, such as DVT
How can ultrasound be used to look for and diagnose DVT?
duplex scanning with compression will aid to detect any thrombus
it is highly sensitive and specific for diagnosing DVT
look for loss of flow signal, intravascular defects or non-collapsing vessels in the venous system
What other type of scan can be used to detect a thrombus?
spiral / multislice CT
What type of scan is used to look for pulmonary embolism?
VQ scan
How is the dose of LMWH for treatment of VTE decided?
How often is the dose taken for?
doses are fixed by body weight
they are given once daily by subcutaenous injection
patient is treated for at least 5 days
overlap with warfarin until INR > 2.0 for 2 consecutive days
What are the stages involved in treatment of uncomplicated in-patient with DVT or PE when pregnancy is excluded?
- suspected DVT / PE
- treat with a single dose of LMWH subcutaenously
- confirm diagnosis
- LMWH for 5 days
start warfarin
start patient-held anticoagulation book and inpatient warfarin chart
- overlap warfarin and heparin until two consecutive therapeutic INR results (>2.0)
When should unfractionated heparin be used instead of LMWH?
it should be given intravenously if there is a need for quick anticoagulation
What are examples of direct thrombin and direct factor Xa inhibitors?
direct thrombin inhibitors:
- dabigatran
direct anti-Xa activity:
- rivaroxaban
- apixaban
- endoxaban
What is meant by predictable dose-response?
for direct oral anticoagulants, the dose is uniform in most patients
there is no need for routine monitoring as there is a predictable effect
In which populations is a dose reduction of direct acting oral anticoagulant recommended?
- very elderly
- renal impairment
- VTE prevention
- atrial fibrillation
What is the difference in the dose of DAOC given usually and given for VTE?
rivaroxaban and apixaban have a rapid onset of action and initiation may be done directly with no need for LMWH
for VTE, the recommended dose at initiation is greater
How should a first episode of proximal vein DVT be treated compared to recurrent episodes?
first episode of proximal vein DVT or PE should be treated for 3-6 months
for warfarin, target INR is 2.5
long-term anticoagulation is used to treat recurrent episodes of VTE
What is the treatment for a proximal VTE or PE that has occurred in absence of a reversible risk factor?
consider long term anticoagulation
when someone has recurrent VTE on therapeutic anticoagulation, increase target INR to 3.5 for warfarin
What is the definition of thrombophilia?
familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis
What is the alternative definition of thrombophilia?
patients who develop VTE:
- spontaneously
- of disproportionate severity
- recurrently
- at an early age
What are the 6 heritable thrombophilias?
- antithrombin deficiency
- protein c deficiency
- protein s deficiency
- activated protein c resistance / factor V Leiden
- dysfibrinogenaemia
- prothrombin 20210A
What is an example of an acquired thrombophilia?
antiphospholipid syndrome
What are the clinical features of thrombophilia?
- deep vein thrombosis
- pulmonary embolism
- superficial thrombophlebitis
- thrombosis of cerebral, axillary, portal & mesenteric veins
- arterial thrombosis
- coumarin induced skin necrosis
- obstetric complications
What is thrombophlebitis?
an inflammatory process that causes a blood clot to form and block one or more veins
What happens in protein c and s deficiency?
there is increased risk of developing abnormal blood clots
protein c and s are vitamin-K-dependent plasma proteins that work as a natural anticoagulant system
How does factor V Leiden work?
there is a gene mutation which leads to an abnormal Factor V
the mutation means that Protein C cannot bind to and inhibit the pro-clotting activity of Factor V
this leads to a hypercoagulable state
What is the role of antithrombin?
it is a small protein that inactivates several clotting factors
What mutation is usually responsible for Factor V Leiden?
APC resistance is associated with a single point mutation in the factor V gene
Arg506 is replaced by GIn rendering FV relatively resistant to cleavage by APC
What is the increased risk of VTE in factor V Leiden?
heterozygotes:
- 3-5 fold increased risk for venous thrombosis
homozygotes:
- 30-50 fold increased risk for venous thrombosis
- risk of recurrent VTE is not increased
What causes prothrombin 20210A?
What is it associated with?
point mutation in 3’ untranslated region of the prothrombin gene
associated with increased prothrombin levels
3 fold increase in venous thrombosis risk
How is antiphospholipid syndrome diagnosed?
antiphospholipid antibodies (lupus anticoagulant or anticardiolipin antibody) on at least 2 occasions 8 weeks apart in association with:
venous thrombosis
arterial thrombosis
or recurrent foetal loss
What are the confounding factors in thrombophilia testing?
- acute phase of thrombosis
- anticoagulation
- warfarin
- heparin
- liver disease
- acute major illness (e.g. sepsis)
- pregnancy
- COCP/oestrogen use
How does a diagnosis of heritable thrombophilia affect management of VTE?
a diagnosis of heritable thrombophilia rarely changes acute management of VTE
When are people screened for thrombophilia?
Who?
- not indicated in unselected patients with VTE
- younger patients
- positive family history
- if management will change
When?
- avoid confounding factors
- e.g. acute VTE, anticoagulants, pregnancy, COCP
Which tests?
- for selected patients with arterial events or recurrent miscarriage, antiphospholipid antibody screen only
