Haemostasis and Thrombosis Flashcards
What percentage of PEs cause hospital deaths?
5-10%
What are the consequences of thromboembolism?
o Death – mortality 5%
o Recurrence – 20% in first 2 years and 4% pa after
o Thrombophlebitis syndrome (recurrent pain, swelling, ulcers) – severe TPS in 25% at 2y (11% with stockings)
o Pulmonary hypertension (if a PE isn’t cleared properly) – 4% at 2y
State Virchow’s Triad?
- Blood
- Vessel Wall
- Blood flow
What in the blood affects the risk of thrombosis?
- Viscosity (haematocrit, protein/paraprotein)
- Platelet count
- Coagulation System (net excess pf procoagulant activity)
Describe the coagulation cascade.
What factors in the blood increase the risk of thrombosis?
Reduced prothrombin Thrombocytopenia Reduced protein C Elevated anti-thrombin Increased fibrinolysis
How is the vessel wall antithrombotic?
o Expresses anticoagulant molecules
- Thrombomodulin
- Endothelial protein C receptor
- Tissue factor pathway inhibitor
- Heparans
o Does not express tissue factor
o Secretes antiplatelet factors
- Prostacyclin (PGI2) from vessel wall
- NO
What can make the vessel wall prothrombotic?
infection
malignancy (3% thrombosis incidence)
vasculitis
trauma
What are the effects of the vessel wall becoming pro-coagulant?
- anticoagulants (i.e. TM) downregulated
- adhesion molecules upregulated
- TF expressed
- prostacyclin decreased
- von Willebrand factor is released –> platelet and neutrophil capture + neutrophil extracellular traps (NETs) form
How does blood stasis promote thrombosis?
- Accumulation of activated factors
- Promotes platelet adhesion
- Promotes leukocyte adhesion and transmigration
- Hypoxia –> inflammatory effect on endothelium - adhesion, release of vWF
What are the causes of blood stasis?
- Immobility –>surgery, paraparesis, travel
- Compression –> tumour, pregnancy
- Viscosity–>polycythaemia, paraprotein
- Congenital–>vascular abnormalities
Which factor confers the highest risk of thrombosis?
Antithrombin deficiency
How do we use anticoagulants in thrombosis?
o Low dose –> prophylactic
o High dose –> therapeutic
What are the immediate anticoagulant drugs?
Heparin –> potentiates anti-thrombin activity
• Unfractionated
• LMWH
Direct acting anti-Xa and anti-IIa (thrombin)
What are the delayed anticoagulant drugs?
Vitamin K antagonists - warfarin
What are the long-term disadvantages of heparin?
Injections
Risk of osteoporosis
Variable Renal dependance
Name Anti-Xa drugs
rivaroxaban, apixaban, edoxaban
Name Anti-IIa drugs
dabigatran
Name properties of direct acting anticoagulants
- Oral admin
- Immediate acting – peak in 3-4 hours
- Useful long-term
- Short half life
- No monitoring – advantages over Warfarin
Name properties of warfarin
- Oral
- Indirect effect on preventing recycling of Vitamin K
- Onset of action delayed (slow onset; ~14 days to onset fully)
- Procoagulants 2,7,9,10 fall (indirectly by inhibiting vitamin K) –> 2 and 1 take several days to become stable
- Levels of anticoagulant protein C and S also fall
In what order does warfarin delay the reduction in coagulation factors?
7, 9, 10 and 2
How is warfarin monitored?
International Normalised Ratio (INR) –> derived from PT
Why is warfarin therapy difficult?
- Dietary vitamin K
- Variable absorption
- Interactions with other drugs – protein binding, competition/induction of cytochromes
- Teratogenic (don’t give in pregnancy)
What patients are at increased risk of thrombosis?
- Medical in-patients –> Infection , immobility (including stroke), age
- Patients with cancer –> procoagulant molecules, inflammation, flow obstruction
- Surgical patients –> immobility, trauma, inflammation
- Previous VTE, family history, genetic traits
- Obese
- Elderly
Describe thromboprophylaxis.
-LMWH e.g. Tinzaparin 4500u/Enoxaparin 40mg od
Not monitored
- TED stockings
- Intermittent pneumatic compression (increases flow)
-Sometimes DOAC +/- aspirin (orthopaedics)
What are the 3 main goals of anticoagulant therapy?
1) Prevent thrombosis
2) Treat thrombosis
3) Prevent recurring thrombosis
Does the risk of thrombosis if untreated outweigh the risk of bleeding if treated?
- Risk of recurrence – morbidity and mortality
- Risk of therapy – bleeding – morbidity and mortality, variation of risks with different therapies
How should you give anticoagulation after first VTE?
- If very low risk after surgical precipitant –> no need for long term anticoagulation
- High risk after idiopathic VTW (10-20% in 2 yrs)–> consider long-term anticoagulation - esp with DOAC
- After minor precipitants (COCP, flight, trauma) –> usually 3 months adequate + longer duration may be dictated by presence of other thrombotic and haemorrhage risk factors
