Thrombosis Flashcards
What is thrombosis?
Blood clotting
What are venous thromboembolic clots rich in?
Red cells and fibrin
What is the pathophysiology of venous thrombosis?
Deterioration of venous valves causes stasis
Activation of coagulation cascade produces a fibrin clot
Are platelets involved in venous thrombosis?
No
What site do venous thromboses most commonly form in?
Deep veins of the lower legs
What are the pathophysiological causes of venous thrombosis?
Virchow’s triad:
- stasis
- hypercoagulability
- vessel wall damage
What are risk factors for venous stasis?
Previous venous thrombosis Immobility (age, obesity, pregnancy) Venous obstruction (pregnancy, tumour) Polycythaemia (excess red cell - blood is thicker and move more slowly) Varicose veins Congestive heart failure
What are risk factors for endothelial injury?
Surgery Piccs/lines Trauma Thrombophlebitis/cellulitis Hypertension Smoking
What are risk factors for hypercoagulability?
Factor V Leiden mutation Prothrombin gene mutation Protein C/S deficiency Malignancy Sepsis Trauma/major surgery Inflammatory disease Drugs - e.g. oestrogen therapy (COCP, HRT) Pregnancy and post-partum HIT - heparin-induced thrombocytopenia
What is thrombophilia?
Ant inherited or acquired tendency towards thrombosis
When should you consider a thrombophilia?
Recurrent VTE Recurrent miscarriage VTE under age 40 Strong family history of VTE VTE in unusual place - mesenteric or cerebral veins
What are examples of thrombophilias?
Inherited: - Factor V Leiden - Prothrombin 20210 mutation - Protein C/S deficiency - Anti-thrombin deficiency Acquired: - Anti-phospholipid syndrome
What is Factor V Leiden?
Inherited disorder where clotting factor V works normally in clot formation but isn’t switched off as easily by proteins C and S
What is anti-phospholipid syndrome?
Autoimmune condition affecting primary and secondary haemostasis causing recurrent arterial and venous thromboses and recurrent miscarriage
What antibodies can be detected in anti-phospholipid syndrome?
Lupus anticoagulants
What is the treatment for venous thrombosis?
Anticogulation
What are the different types of anticoagulation?
Heparin
Warfarin
DOAC
What is the mechanism of heparin?
Potentiates antithrombin by binding to the anti-thrombin and thrombin complex (undfractionated) or the anti-thrombin and factor X complex (LMWH)
What is the difference in the clotting factors that unfractionated and low molecular weight heparin inhibit?
Unfractionated - II, IX, X, XI, XII
LMWH - Xa
What are the indications for heparin?
Treatment of VTE and acute coronary syndrome
Prophylaxis in pregnancy or pre/post-surgical
What are the contraindications for heparin?
Bleeding disordes
History of peptic ulcer disease
Severe uncontrolled hypertension
Caution in renal disease - give lower dose
How is heparin monitored?
Unfractionated heparin monitored with APTT
LMWH can be monitored with anti-Xa but no need apart from complicated patients (renal failure or pregnancy)
What are the complications of heparin?
Bleeding
Heparin-induced thrombocytopenia (with thrombosis)
Osteoporosis
What is the management for bleeding caused by heparin?
Stop heparin
If severe - protamine sulphate
What is heparin-induced thrombocytopenia?
Heparin can induce antibodies that cause thrombosis
More likely in unfractioned heparin
Rare
What is the management for heparin-induced thrombocytopenia?
Switch to different anticoagulant
What is the mechanism of warfarin?
Inhibition of vit K
Vit K carboxylates clotting factors II, VII, IX, X so warfarin’s inhibition reduces the synthesis of these clotting factors
How does warfarin affect protein C and S, and how does this affect management?
Protein C and S are involved in switching off secondary haemostasis
When warfarin is introduced they will also drop, and will drop before the other clotting factors
So initially you are more likely to get a clot
For this reason heparin is always given with warfarin for the first 5-7 days to cover this period
What are contraindications for warfarin?
Pregnancy Non-compliance Non-thromboembolic strokes Severe uncontrolled hypertension Severe liver or renal disease Peptic ulcer or GI bleeds
In which stages is warfarin introduced?
- Initiation
- rapid in acute thrombosis
- slow in the community, lessening the effect on protein C and S, may be able to avoid heparin use - Stabilisation
- find dose that suits the patient - Maintenance
- take dose at same time every day
What is used to monitor warfarin?
INR
What is the range that warfarin needs to be kept in?
2-3 usually
3-4 if extra anticoagulation needed - e.g. VTE, metallic heart valve, anti-phospholipid syndrome
What are the complications of warfarin?
Bleeding
- mild: bruising, epistaxis, haematuria
- severe: GI, intracerebral, significant drop in Hb
Teratogenicity
What are examples of interactions that potentiate the action of warfarin?
Febrile illness Hyperthyroidism Cardiac failure Liver/renal disease Drugs: alcohol, omeprazole, erythromycin, ciprofloxacin, valproate Cranberry juice
What are examples of interactions that reduce the action of warfarin?
Pregnancy
Hypothyroidism
Drugs: phenytoin, carbamazepine, rifampicin
What is the management for a patient on warfarin when INR is in normal range but there is minor bleeding?
No action
What is the management for a patient on warfarin when INR is high but <6?
Stop warfarin
Restart when <5
What is the management for a patient on warfarin when INR is >8 but only minor bleeding?
Stop warfarin
Give oral vit K
Restart when <5
What is the management for a patient on warfarin when INR is >8 with severe bleeding?
Stop warfarin
Pothrombin complex concentrate or fresh frozen plasma
IV vitamin K
How long before surgery should warfarin be stopped?
5 days
What are examples of DOACs, and which clotting factor do each inhibit?
Apixaban - Xa inhibitor
Rivaroxaban - Xa inhibitor
Dabigatran - IIa inhibitor
What is arterial thrombosis?
Clots formed in arterial circulation
What is the pathophysiology of arterial thrombosis?
Damage to endothelium
Recruitment of ‘foamy’ macrophages that are rich in cholesterol
Forms plaque rich in cholesterol
When plaques rupture platelets are recruited
Platelets adhere to subendothelial collagen and aggregate
What are arterial thrombotic clots rich in?
Platelets
What are risk factors for arterial thrombosis?
Hypertension
Smoking
High cholesterol
Diabetes mellitus
What is done to reduce risk of arterial thrombosis?
Stop smoking Treat hypertension Treat diabetes Lower cholesterol Anti-platelet drugs
