Thrombotic Disorder Flashcards
The elements of homeostasis
- Primary homeostasis
- vasoconstriction
- platelet adhesion
- platelet aggregation - Blood coagulation
- insoluble fibrin formation
- fibrin cross linking - fibrinolysis
- involves urokinase and tPA interacting with factor XII to convert plasminogen -> plasmin
- plasmin then converts fibrin to fibrinogen/fibrin degradation products
What is a thrombus?
A clot arising in a wrong place
What is a thromboembolism?
Movement of a clot along a vessel
Virchows triad
- stasis
- bed rest, travel - hypercoagulability
- pregnancy, trauma - vessel damage
- atherosclerosis
Types of thrombus
Arterial
Venous
Microvascular
What is an arterial thrombosis made up of?
White clot
- platelets
- fibrin
What does an arterial thrombosis result in?
Ischaemia
Infarction
What is arterial thrombosis principally secondary to?
Atherosclerosis
Examples of arterial thrombosis
Coronary = MI, unstable angina
Cerebrovascular thromboembolism = stroke, TIA
Peripheral embolism = limb ischaemia
Risk factors for arterial thrombosis
Age smoking sedentary lifestyle HTN DM obesity Hypercholestermia
Treatment of acute presentation of arterial thrombosis
Thrombolysis
Antiplatelet/anticoagulation drugs
Prevention of arterial thrombosis
Primary
- lifestyle modification
- treatment of vascular risk factors
Secondary
What is a venous thrombosis made up of?
Red thrombus
- fibrin
- red cells
What does a venous thrombosis result in?
back pressure
What is a venous thrombosis principally due to?
Stasis
Hypercoagulability
Examples of venous thrombosis
Limb DVT PE Visceral venous thrombosis Intracranial venous thrombosis Superficial thrombophlebitis
Risk factors for venous thrombosis (stasis / hypercoagulability)
increasing age surgery obesity pregnancy hormonal therapy - COCP/HRT Immobility Systemic disease FH
Systemic diseases related to venous thrombosis
Cancer Myeloproliferative neoplasms (MPNs) Autoimmune diseases (IBD, connective tissue diseases e.g. SLE)
Diagnosis of venous thrombosis
Pretest probability score - wells score - Geneva score D-dimer Doppler-USS Ventilation/perfusion scan (V/Q) CT pulmonary angiogram
What is seen on a doppler USS in venous thrombosis?
DVT = thromboembosed vein enlarged
Non-compressible
Echogenic material seen
Treatment aims of venous thrombosis
Prevention of clot extension
Prevention of clot embolization
Prevent clot recurrent in long term treatment
Treatment of venous thrombosis
Anticoagulants - LMWH - Coumarins (warfarin) - DOACs Thrombolysis only in selected cases e.g. massive PE
What does heritable thrombophilia give you an inherited predisposition to?
Venous thrombosis
Pathology of Heritable thrombophilia
Common - factor V Leiden - Prothrombin G20210A Rare - antithrombin deficiency - protein C / S deficiency
What makes up a microvascular thrombosis?
Platelets and/or fibrin
What does microvascular thrombosis result in?
Diffuse ischaemia
What is microvascular thrombosis principally due to?
Disseminated intravascular coagulation (DIC)
When does DIC occur?
Systemic coagulation activation
DIC occurs in what conditions?
Septicaemia Malignancy Eclampsia Pancreatitis Major trauma Pregnancy
What does DIC cause?
Tissue ischaemia
- gangrene
- organ failure
Examples of vessel wall injury of virchows triad
Trauma or surgery Venepuncture Chemical irritation Heart valve disease or replacement Atherosclerosis Indwelling catheters
Causes of hypercoagulable state
Malignancy Pregnancy and post partum period Oestrogen therapy Trauma or surgery of lower extremity, hip, abdomen or pelvis IBD Nephrotic syndrome Sepsis Thrombophilia
Causes of circulatory stasis in virchows triad
AF LVD Immobility Paralysis Venous insufficiency or varicose veins Venous obstruction from tumour, obesity or pregnancy
Who should thrombophilia testing NOT be offered to?
Patients who are continuing on anticoagulation treatment
Patients who have provoked PE or DVT
Not in acute phase (within one month)
On unfractionated heparin
You cannot interpret protein C and S whilst on what? Why?
Warfarin
Vitamin K dependent
Why cant you perform thrombophilia testing on unfractionated heparin?
Interferes with antithrombin levels and other tests
Why is pregnancy a hypercoagulable state?
Resistance to activated protein C in 2nd and 3rd trimesters
Protein S activity decreases
Fibrinogen and factors II, VII, VIII and X increase
Levels and activity of fibrinolytic inhibitors increase
Why is thrombophilia testing in pregnancy less reliable?
Already protein S deficient
How does protein C work?
Activated protein C inactivates Va and VIIIa
What is a cofactor of protein C?
Protein S
Inheritance of protein C deficiency
Autosomal dominant
Causes of thrombophilia
Protein C deficiency
Protein S deficiency
Activated protein C resistance/factor V Leiden
Antithrombin deficiency
What is there a risk of in protein C deficiency?
Warfarin induced skin necrosis
Acquired causes of protein C deficiency
Liver disease
Severe infection / septic shock / DIC
Post op state
Where is protein C synthesised?
Vitamin K dependent synthesis in the liver
Inheritance of protein S deficiency
Autosomal dominant
How does protein S work?
Vitamin K dependent cofactor protein S which inactivates factor Va and VIIIa
Causes of acquired protein S deficiency
Pregnancy / oral contraceptives DIC Acute thromboembolic disease Nephrotic syndrome Liver disease
Penetrance of protein S deficiency
Variable
Risk increased by factor V leiden
What is factor V leiden and how does it work?
Mutation on cleavage site of factor V
Do not have appropriate anticoagulant response to activated protein C
Inheritance of factor V leiden
Autosomal dominant
What causes increased risk of clots when have factor V leiden?
OCP
How does antithrombin work?
Inhibits the coagulatiton proteases including IIa, Xa, IXa and XIa
What augments antithrombins activity?
Heparin
Inheritance of antithrombin deficiency?
Autosomal dominant
Causes of acquired antithrombin deficiency
Nephrotic syndrome
Liver disease
DIC
How would you treat antithrombin deficiency during pregnancy?
LMWH
Stop when labour begins
Continue 6/52 post
Can switch to warfarin
What is antiphospholipid syndrome characterised by?
Venous thrombosis
Arterial thrombosis
Miscarriage
Lab evidence of antiphospholipid antibodies (aPL)
Anticardiolipin antibodies
Lupus anticoagulant
What can antiphospholipid syndrome be assosiated with?
SLE
When does HIT usually appear?
Within 10 days of initiation
What does HIT stand for?
Heparin induced thrombocytopenia
What commonly drops on initiation of heparin (non immune)?
Platelets
What types of heparin is there an increased incidence of HIT with?
Longer duration heparin
Unfractionated heparin
Even though there is low platelets in HIT, what is there a high risk of?
Thrombosis 50-75%
Treatment of PE
Immediate start of dalteparin
Start warfarin for 3 MONTHS
Continue dalteparin until INR in target range
Typical blood picture of DIC
Low platelets
Prolonged APTT, prothrombin and bleeding time
Fibrin degradation products often raised
Schistocytes due to microangiopathic haemolytic anaemia
Typical blood picture of warfarin administration
Prothrombin time prolonged
APTT normal
Bleeding time normal
Platelet count normal
Typical blood picture of aspirin administration
Prothrombin time normal
APTT normal
Bleeding time prolonged
Platelet count normal
Typical blood picture of heparin
Prothrombin time normal or prolonged
APTT prolonged
Bleeding time normal
Platelets normal
What NOAC is preferred for patients with renal impairment due to minimal renal drug clearance?
Apixaban
How long is warfarin treatment carried on for in a provoked DVT (e.g. recent surgery)?
3 months
How long is warfarin treatment carried on for in an unprovoked DVT?
6 months
What is factor V Leiden?
Activated protein C resistance
If a patient presents with symptoms of a DVT of the calf, but the wells score is 1, what must be done next?
- D dimer. If +ve, order…..
2. Doppler USS of leg
What are oral contraceptives a known risk factor for?
Thrombosis
If a patient is on OCP and needs to undergo surgery, how long before the surgery should the pill be stopped and why is this done?
4 weeks before surgery
To prevent a pulmonary embolism
If a patient is suspected of having a DVT, what should be performed?
two level DVT-wells score
Features of the two level DVT wells score that count for 1 point each
Active cancer (ongoing, within 6 months or palliative)
Paralysis, paresis or recent plaster immobilisation of lower extremities
Recently bedridden for 3 days or more, or major surgery within 12 weeks requiring general or regional anaesthesia
Localised tenderness along the distribution of the deep venous system
Entire leg swollen
Calf swelling at least 3cm larger than asymptomatic side
Pitting oedema confined to symptomatic leg
Collateral superficial veins (non varicose)
Previously documented DVT
What two level DVT wells score feature gives a score of -2?
An alternative diagnosis is at least as likely as DVT
Clinical probability simplified score of the wells score
DVT likely - 2 points of more
DVT unlikely - 1 point or less
What should be done if a DVT is likely (i.e. 2 or more points)?
Proximal leg vein USS within 4 hours
If -ve - D dimer
If cannot perform USS within 4 hours, D dimer should be performed and a LWMH administered (USS should be done within 24 hours)
What should be done if a DVT is unlikely (I.e. 1 point or less)?
D dimer.
If +ve, arrange proximal leg USS within 4 hours
If USS cannot be performed under 4 hours, LWMH should be given (USS must be carried out within 24 hours)
Treatment of DVT
Initially after diagnosis - LWMH or fondaparinux (at least 5 days or INR sorted. If active cancer - 6 months)
Warfarin within 24 hours diagnosis (for 3 months provoked, 6 months unprovoked)
Should compression stockings be offered routinely to all patients with DVT?
NO
