Haemostasis and Thrombosis Flashcards
What is the case mortality of VTE?
5%
What is thrombophlebitic syndrome?
Post-thrombotic syndrome resulting in recurrent pain, swelling, ulcers etc.
23% recurrence at 2-years (11% with TED stockings)
What can be a complication of PE?
Pulmonary hypertension (heart failure with high mortality)
4% recurrence at 2 years
Why is thrombosis important?
Significant sequelae (death is rapid) but is preventable thorugh thromboprophylaxis
Can also be indicator of underlying disease (cancer)
What is Virchow’s Triad?
Three contributory factors to thrombosis
- Viscocity
- Blood flow
- Vessel wall damage
What can cause high viscocity of blood?
Increased haematocrits and protein paraprotein or high platelet count
More active blood coagulation pathway
How do heparans work?
They are a protein C coreceptor
How do endothelial protein C receptors (EPCR) contribute?
Decreases protein C
What are some stimuli for increased haemostasis?
Infection, malignancy, vasculitis, trauma
How do the stimuli result in increased haemostasis?
Thrombomodulin (TM) regulated
TF expressed
Prostacyclin production decreased
Adhesion molecules upregulated
vWB fragment expressed
What is netosis?
Neutrophils releasing DNA, vWF and histones
Activates XII to XIIIa
Why is netosis important?
Key to immunothrombosis
Inflamation is important drive of thrombosis
How does a change in blood flow affect thrombosis?
Can result in accumulation of activated factors
Promotion of platelet adhesion and leukocyte adhesion and transmigration
Hypoxia produces inflammatory effect on endothelium
What are some causes of stasis?
Immobility - long haul flights
Compression - tumours or pregnancy
Viscosity - polycythaemia, paraprotein
Congenital - vascular abnormalities
What is the difference in high dose and low dose anticoagulation?
High dose anticoagulation - therapeutic
Low dose anticoagulation - prophylactic
What are some immediate anticoagulation treatments?
- Heparin, unfractionated and LMWH
- Direct acting anti-Xa and anti-IIa
What are some delayed anticoagulation treatments?
VitK antagonist (warfarin)
How are heparins given?
They are immediate acting
Unfractionated - IV infusion
LMWH - subcut
pentasaccharide - subcut
What is the long term disadvantage to heparins?
Osteoporosis
How do DOACs work?
Bind directly to enzyme
Anti-Xa - rivaroxaban, apixaban
Anti-IIa - Dabigatran
What are the pharmacodynamics and pharmacokinetics of DOACs?
Oral administration
Peak in approx 3-4 hours
Useful in long term
Short half life, no monitoring required
What are the pharmacodynamics and pharmacokinetics of warfarin?
Orally, indirect effect
Onset of action is delayed
Levels of II, VII, IX, X fall
Protein C and protein S also fall
Can you give warfarin in an emergency?
No
Also no point in giving larger dose since it’s delayed no matter what
What is always important to consider when giving warfarin?
Need to measure INR (derived from prothombin time)
What are some of the complications of warfarin?
- Dietry VitK
- Variable absorption
- Interaction with other drugs - protein binding, competition induction of cytochromes
- Teratogenic, so can’t be used through pregnancy, must stop within 6 weeks or risk of fetal malformation
What are some things which can be given for prophylaxis?
Tinz or Enox
TED stockings
DOAC +/- aspirin (orthopaedics)
Why are DOACs preferred over other methods of anticoagulation?
They reduce the risk of bleeding by half compared to other drugs
