Theme 7 Haematology: Thrombosis Flashcards
What is Virchow’s triad?
- stasis
- vessel wall injury
- hypercoagubility
What is thrombosis and why does it arise?
-abnormal clotting inside a blood vessel
occurs either because:
- vascular endothelium damage (because blood is too sticky)
- or because blood flow has been altered
- this produces stasis which results in hypercoagulability
What is the usual primary abnormality that leads to arterial thrombosis?
atherosclerosis
What are the risk factors for arterial thrombosis?
smoking hypertension hypercholesterolaemia diabetes family history obesity physical inactivity age male sex
What are thrombi predominantely composed of?
fibrin
What is the most common clinical manifestation of venous thrombosis?
DVT
what is VTE and what are the long term complications of VTE?
- Venous thromboembolism
- can develop chronic VTE
- can develop post thrombotic syndrome (damage to the vein leads to reduction in flow, chronic swelling, chronic pain and leg ulceration
Why is hospital admission a risk factor for VTE?
- because of the underlying condition
- because of the fact they are immobile when they are in the hospital bed
- definition includes any VTE within 90 days of discharge
What is NICE guidelines ‘care pathway’ for VTE?
- consistent risk assessment
- assess VTE risk and assess bleeding risk and balance
- offer VTE prophylaxis if appropriate but not if there is risk of bleeding
What are the risk factors for VTE?
- active cancer or cancer treatment
- age > 60
- critical care admission
- dehydration
- personal history of VTE
- use of hormone replacement therapy
- use of oestrogen containing contraceptive therapy
- varicose veins with phlebitis
- known thrombophilias
- obesity
- immobility
- surgery
- co morbidities
- major trauma
- pregnancy
Why does a heritable thrombophillia leave you at increased risk of VTE?
-deficiencies in factors in blood that protect us from having thrombus
Why do we use white stockings to prevent VTE?
They exert graduated pressure on the veins up the leg to keep the blood flowing in the right direction when they are immobile
What are the the options for prophylaxis against VTE?
- low dose low molecular weight heparin
- fondaparinux (an alternative to heparin as it comes from pigs lungs or patients could be allergic)
What is rivaroxaban?
- new anticoagulant
- direct inhibitor of FXa
How do heparins work?
- by binding to the natural anti coagulant called antithrombin
- antithrombin is an inhibitor of thrombin and FIIa and FXa
- so this prevents blood clots
What is dabigatran?
- new anticoagulant
- direct thrombin inhibitor
How do we assess the clinical probability of VTE?
Wells score
How can D-dimer levels diagnose VTE?
D dimers are break down products of fibrin which is with what that clots are made
so D dimers would be high in a patient with VTE
How is the dose of LMWH decided for treatment of VTE?
- doses are fixed by body weight
- usually once daily by s/c injection
Explain the treatment pathway of an uncomplicated patient with DVT or PE
- treat with single dose LMWH
- Confirm diagnosis
- LMWH for 5 days
- Start warfarin
- Overlap warfarin and heparin until two consecutive therapeutic INR results
what is a thrombophillia?
familial or acquired disorders of the haemostatic mechanism which are likely to pre dispose to thrombosis
What are some examples of heritable thrombophilias?
- antithrombin deficiency
- protein C deficiency
- protein S deficiciency
- activated protein C resistance/ FV Leiden
- dysfibrinogenaemia –> fibrin is not working properly
- prothrombin 20210A
What is anti phospholipid syndrome?
- acquired thrombophilia
- autoimmune disorder where patients develop autoantibodies against negatively charged phospholipids
- this tips the balance towards the pro coagulant state
What are the clinical features of thrombophilia?
- DVT
- PE
- superficial thrombophlebitis –> thrombus forms in superficial veins often associated with inflammation
- thrombosis of cerebral, axillary, portal, mesenteric veins
- arterial thrombosis
- obstetric complications
What is the role of protein C and protein S?
- Protein C is a natural anticoagulant that cleaves and breaks down activated factor V and VIII factor V is a co factor in the common pathway and factor VIII is a cofactor in the intrinsic pathway
- Protein S is a co factor for protein C
- Protein C can also bind to thrombin so it can no longer act
What is Factor V leiden?
- a point mutation in the FV that codes for the pro-coagulation protein
- at the point where protein C cleaves FV
- so FV stays for longer as it cannot be activated by protein C
- increases your chance of thrombosis
What is the most common familial thrombophilia?
factor V leiden
What is prothrombin 20210A?
- point mutation in 3’ untranslated region of prothrombin gene
- associated with increased prothrombin levels
- 3 fold increase in venous thrombosis
Thrombophilia screening:
- Who?
- When?
- Which tests?
- 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, on anticoagulants. Pregnancy and OCP also affect results
- do not test unselected patients
- do not test asymptoatic relatives - Which tests: For selected patients with arterial events for recurrent miscarriage: antiphospholipid antibody screen only
