Thrombosis Flashcards by Martha Innes

What is thrombosis?

Blood clotting

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What are venous thromboembolic clots rich in?

Red cells and fibrin

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What is the pathophysiology of venous thrombosis?

Deterioration of venous valves causes stasis

Activation of coagulation cascade produces a fibrin clot

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Are platelets involved in venous thrombosis?

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What site do venous thromboses most commonly form in?

Deep veins of the lower legs

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What are the pathophysiological causes of venous thrombosis?

Virchow’s triad:

stasis
hypercoagulability
vessel wall damage

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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

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What are risk factors for endothelial injury?

Surgery
Piccs/lines
Trauma
Thrombophlebitis/cellulitis
Hypertension
Smoking

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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

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What is thrombophilia?

Ant inherited or acquired tendency towards thrombosis

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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

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What are examples of thrombophilias?

Inherited:
- Factor V Leiden
- Prothrombin 20210 mutation
- Protein C/S deficiency
- Anti-thrombin deficiency
Acquired:
- Anti-phospholipid syndrome

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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

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What is anti-phospholipid syndrome?

Autoimmune condition affecting primary and secondary haemostasis causing recurrent arterial and venous thromboses and recurrent miscarriage

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What antibodies can be detected in anti-phospholipid syndrome?

Lupus anticoagulants

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What is the treatment for venous thrombosis?

Anticogulation

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What are the different types of anticoagulation?

Heparin
Warfarin
DOAC

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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)

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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?

1. Initiation - rapid in acute thrombosis - slow in the community, lessening the effect on protein C and S, may be able to avoid heparin use 2. Stabilisation - find dose that suits the patient 3. 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 ```