Flashcards in Thrombosis and risk factors for thrombosis Deck (31):
What is usually the primary pathological abnormality in arterial thrombosis?
Atherosclerosis -> rupture of atheromatous plaques
What other pathological abnormalities may be present in arterial thrombosis?
Platelet aggregation and platelet thrombi
What are the risk factors for arterial thrombosis?
What is involved in the pathogenesis of venous thrombosis?
- Venous stasis
- Hypercoagulable states
What is the difference between arterial and venous thrombi composition?
Venous thrombi are predominantly composed of fibrin with a lesser role for platelet accumulation and aggregation.
What percentage of DVTs are clinically silent?
What percentage of patients with PE also have a DVT?
What percentage of patients with a proximal DVT have an asymptomatic PE?
What is the epidemiology of VTE?
- Incidence: 1 per 1000pa
- May present as sudden death (up to 20% of PE)
- 30% develop recurrent VTE in 10 years
- 28% develop post thrombotic syndrome
- Mortality of promptly diagnosed and adequately treated PE is 2% (direct)
What is the definition of a hospital-acquired VTE?
Includes any VTE within 90 days of discharge
What percentage of VTEs are hospital-acquired?
What are the risk factors for VTE?
- Active cancer or cancer treatment
- Age over 60 years
- Critical care admission
- Known thrombophilias
- One or more significant medical comorbidities
- Major trauma
- Hx VTE
- Oestrogen-containing contraceptive
- Varicose veins with phlebitis
- Pregnancy and postnatal period
- First degree relative with VTE
What pharmacological prophylaxis is available for inpatients?
Low dose” low molecular weight heparin
Fondaparinux (synthetic pentasaccharide)
- direct inhibitors of Factor Xa(10): rivaroxab, (apixaban)
- direct thrombin inhibitors : dabigatran
What exclusion tests can be used for the diagnosis of thrombosis?
- Validated numerical clinical probability score: Wells score
- Sensitive quantitative D-dimer with high negative predictive value
How is ultrasound used to diagnose DVT?
Duplex scanning with compression will aid to detect any thrombus.Highly sensitive and specific for diagnosing DVT.Look for loss of flow signal, intravascular defects or non collapsing vessels in the venous system
What is the treatment for VTE?
- Low molecular weight heparin
- Doses are fixed by body weight
- Usually once daily by s/c injection
- For example: enoxaparin 1.5mg/kg s/c od or tinzaparin 175u/kg s/c od
- Treat for at least 5 days
- Overlap with warfarin until INR > 2.0 for two consecutive days.
Which factor do the oral anticoagulants rivaroxaban and apixaban target?
Which factor do the parenteral anticoagulants fondaparinux and LMWH target?
Which factor does the oral anticoagulant dabigatran target?
Which factor do the parenteral anticoagulants argatroban and bivalirudin target?
How should VTE be managed long-term?
- First episode of proximal vein DVT or PE: treat for 3-6 months. For warfarin: target INR = 2.5
- Recurrent episodes of VTE: Treat with long term anticoagulation
- Proximal DVT or PE that has occurred in absence of reversible risk factor: consider long term anticoagulation
- Recurrent VTE on therapeutic anticoagulation: Increase target INR to 3.5 for warfarin
What are thrombophilias?
Familial or acquired disorders of the haemostatic mechanism which are likely to predispose to thrombosis.
What are the heritable thrombophilias?
- Antithrombin deficiciency
- Protein C deficiency
- Protein S deficiency
- Activated Protein C resistance/FV Leiden
- Prothrombin 20210A
What is the one acquired thrombophilia?
What are the clinical features of thrombophilias?
- Deep vein thrombosis
- Pulmonary embolism
- Superficial thrombophlebitis
- Thrombosis of cerebral, axillary, portal, mesenteric veins
- Arterial thrombosis (APS, only)
- Coumarin induced skin necrosis (PC deficiency)
- Obstetric complications : foetal wastage (APS)
What mutation causes the majority of Factor V Leiden cases?
- G to A(1,691)
- Arg 506 is replaced by Gln rendering FV relatively resistant to cleavage by APC
What is the most common familial thrombophilia?
Factor V Leiden
By how much does the risk of thrombosis increase in Factor V Leiden heterozygotes?
3-5 fold odds ratio
By how much does the risk of thrombosis increase in Factor V Leiden homozygotes?
30 - 50 fold odds ratio
What is prothrombin 20210A?
- Point mutation in 3’ untranslated region of prothrombin gene
- Associated with increased prothrombin levels
- 3 fold increase in venous thrombosis
- Occurs in 1-2% healthy UK population