Haem: Thrombosis Aetiology and Management Flashcards Preview

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Why is thrombosis important?

  • Prevalant cause of morbidity and mortality especially in hospital patients
  • Significant sequelae (death is rapid)
  • Preventable (thromboprophylaxis)
  • May be an indicator of underlying disease (cancer)


What is an important risk factor for VTE?

Age - risk of VTE doubles every decade. There is a greater risk for PE than DVT.


What are 4 main consequences of thromboembolism?

  1. Death - mortality rate is 5%
  2. Recurrence - 20% in first 2 years and 4% pa thereafter
  3. Thrombophlebitic syndrome (recurrent pain, swelling and ulcers) - Severe TPS in 23% at 2 years
  4. Pulmonary hypertension - 4% at 2 years



What is thrombophlebitic syndrome characterized by?

Thrombophlebetic syndrome:

  • Swelling
  • Painful
  • Eventual ulcers


What is a serious complication of thromboembolism?

Chronic thromboembolic pulmonary hypertension - extremely debilitating and often fatal disorder


What is Virchow's triad?

There are three contributory factors to thrombosis:


Vessel wall

Blood flow


What determines the viscosity of blood?

Haematocrit - more RBCs and less plasma means more likely to thrombose


Protein/Paraprotein content - in the plasma this increases viscosity. This may be related to multiple myeloma.


What 3 factors of the blood may effect risk of thrombosis?

  1. Viscosity - haematocrit, protein/paraprotein
  2. Platelet count
  3. Coagulation system - triggered by tissue factor, generates thrombin, thrombin converts fibrinogen to fibrin


Draw out the extrinsic and common pathway of the coagulation cascade.


Give a list of procoagulant factors.

  • V
  • VIII
  • XI
  • IX
  • X
  • II
  • Fibrinogen
  • Platelets


Draw the coagulation cascade with the addition of regulators of coagulation. 

  • TFPI
  • Protein C and S
  • Antithrombin

These are the main regulators of coagulation


Give a list of anticoagulant factors.

  • TFPI
  • Protein C
  • Protein S
  • Thrombomodulin
  • EPCR
  • Antithrombin
  • Fibrinolysis


Give examples of thrombophilic traits and their severity.

In order of severity:

  • Protein S deficiency
  • Protein C deficiency
  • Antithrombin deficiency
  • Factor V Leiden

Over 50-60 years, most people with protein C and S deficiency are getting thrombosis. Rate of thrombosis is about 1% per annum for these people. 



What percent of thrombotic events are precipitated in people with thrombophilic traits?

50% of these thrombotic events are precipitated - partly attributed to the deficiency of an anticoagulant, but this is not the whole story. There will be other factors e.g. pregnancy, cancer, broken leg, surgery etc. 


In what ways it the vessel wall normally antithrombotic?

  • Expresses anticoagulant molecules
    • Thrombomodulin
    • Endothelial protein C receptor
    • Tissue factor pathway inhibitor
    • Heparans
  • Does not express tissue factor
  • Secretes antiplatelet factors
    • Prostacyclin
    • NO


What may cause the vessel wall to become prothrombotic?


  • Infection
  • Malignancy
  • Vasculitis
  • Trauma



How does the vessel wall become prothrombotic?

  1. Anticoagulant molecules (eg TM) are down regulated
  2. Adhesion molecules upregulated
  3. TF may be expressed
  4. Prostacyclin production decreased


If you have a metastatic disease, what is the chance of thrombosis?

4% - this is much higher than the background rate in the population


How does stasis of blood flow promote thrombosis?

  • Accumulation of activated factors
  • Promotes platelet adhesion
  • Promotes leukocyte adhesion and transmigration
  • Hypoxia produces inflammatory effect on endothelium


What are causes of blood stasis?

  • Immobility
    • Surgery, Paraparesis, Travel
  • Compression
    • Tumour, pregnancy
  • Viscosity
    • Polycythaemia, Paraprotein
  • Congenital
    • Vascular abnormalities


Thrombotic risk factors often ______ to produce thrombosis. Thrombotic factors may have power _____ that are unpredictable. 

Thrombotic risk factors often combine to produce thrombosis. Thrombotic factors may have powerful interactions that are unpredictable.


Describe the combining mechanisms that increase risk of thrombosis in:

  • Pregnancy
  • Malignancy
  • Surgery

  • Pregnancy:
    • increases VIII, Fibrinogen
    • decreases Protein S
    • reduces flow
  • Malignancy:
    • increases TF expression on tumour cells
    • Inflammation
    • Obstructs blood flow
  • Surgery:
    • Trauma
    • Inflammation
    • Reduced flow


What are the 2 main uses of anticoagulation therapy?

  1. Therapeutic dose (high dose) - used on the wards for people who have had thrombosis. The whole coagulation system is very active so needs to stop. 
  2. Prophylactic (low dose) - when anticipating entering a risky period or if somebody is a high-risk patient and entering a high risk circumstance we give a low dose as prophylaxis.


Give examples of immediately acting anticoagulant drugs.

  • Heparin
    • Unfractionated heparain
    • Low molecular weight heparin
  • Direct acting anti-Xa and anti-IIa (DOACs)


Give examples of delayed acting anticoagulant drugs.

Warfarin (Vit K antagonist)


What is the mechanism of action of heparins?

Heparins include:

  • Unfractionated heparin (IV infusion)
  • Low molecular weight heparin (sub cutaneous)
  • Pentasaccharide (sub cutaneous)

They all act by potentiating antithrombin.

They provide immediate effect (e.g. for treatment of thrombosis)


What are the disadvantages of using heparin?

  • Long term disadvatnage - injections, risk of osteoporosis and thrombocytopaenia
  • Variable renal dependence - depends on pt renal function


LMWH has reliable pharmacokinetics so does not usually require constant monitoring. In what circumstances is monitoring required?

Monitoring is required in patients with renal impairment (CrCl<50) or at extreme weights. 

Can use an anti-Xa assay to monitor.


Why is it necessary to monitor unfractionated heparin?

Unfractionated heparin has:

  • Variable kinetics
  • Variable dose-response
  • Always monitor therapeutic levels with APTT and anti-Xa



When is unfractionated heparin used?

Unfractionated heparin is used in ICU but needs to monitored careful. It is given by infusion and it can be turned "off" and "on". 

It is monitored by APTT.

Unfractionated heparin is used in patients with renal failure.