W1 - Haemostasis & Thrombosis Flashcards
4 long-term consequences of thromboembolism?
- pulmonary hypertension (4% at 2yrs)
- Thrombophlebitic syndrome TPS (23% at 2 years, 11% with stockings)
- Recurrence (20% in 1st 2 years)
- Death (mortality 5%)
What is TPS?
Thrombophlebitic syndrome - recurrent pain, swelling, and ulcers
What makes thrombosis likely?
Virchow’s triad:
- Blood
- Vessel wall
- Blood flow
Name 3 blood parameters that contribute to likeliness of thrombotic event
- viscosity
- haematocrit
- protein/paraprotein - platelet count
- coagulation system
- net excess of procoagulant activity
Name procoagulant factors in the blood
V, VIII, XI, IX, X, II, fibrinogen, platelets
Name anticoagulant factors in the blood
TFPI, Protein C, Protein S, thrombomodulin, EPCR, antithrombin, fibrinolysis
Is the vessel wall pro or antithrombic under normal conditions? and why?
Antithrombic
- Expresses anticoagulant molecules
- Thrombomodulin
- Endothelial Protein C receptor
- TFPI
- Heparans - Does NOT express TF
- Secretes antiplatelet factors
- Prostacyclin
- NO
Name 4 stimuli that can make the vessel wall prothrombotic
Infection – including COVID-19
Malignancy
Vasculitis
Trauma
How does the vessel wall become prothrombotic
- Anticoagulant molecules (eg TM) are down regulated
- TF may be expressed
- Prostacyclin production decreased
- Adhesion molecules upregulated
- Von Willebrand factor release
- Platelet and neutrophil capture
- Neutrophil extracellular traps (NETS) form
Inflammation is an important driver of thrombosis by activating ______ cells and ________ immune cells
endothelial, neutrophil
What sort of blood flow promotes thrombosis?
Stasis
How does blood stasis promote thrombosis?
- Accumulation of activated factors
- Promotes platelet adhesion
- Promotes leukocyte adhesion and transmigration
- Hypoxia produces inflammatory effect on endothelium
- Adhesion, release of VWF
Name 4 common causes of stasis and provide an example of each
- Immobility (Surgery, Paraparesis, Travel)
- Compression (Tumour, pregnancy)
- Viscosity (Polycythaemia, Paraprotein)
- Congenital (Vascular abnormalities)
What is the relationship between risk of PE and distance/duration of air travel
Increase together
flight duration >12 hours, 4.77/10^6 risk of PE
flight duration 9-12 hours, 2.66/10^6 risk of PE
Name 4 thrombophilic genetic diseases
Factor V Leiden
Protein S deficiency
Protein C deficiency
Antithrombin deficiency
Explain the interaction between OCP and FVL
Synergistic
OCP alone - 5-6 fold increased risk of VTE
FVL alone - 7 fold increased risk of VTE
OCP + FVL = 30 fold increased risk of VTE
Describe immediate and delayed anticoagulant drugs
Immediate:
Heparin
- Unfractionated heparin
- LMWH
Direct acting anti-Xa and anti-IIa
Delayed:
Vitamin K antagonists
- Warfarin
MOA of immediate anticoagulant therapy
act by activating antithrombin in the circulation
Describe the administration of different types of heparins
- Unfractionated heparin - iv infusion (Monitored)
- LMWH - sub cut (No monitoring)
- Pentasaccharide - sub cut (No monitoring)
Describe the properties (administration, peak [] time, short term/long term use, half life) of direct acting anticoagulants
- Oral administration
- Immediate acting –peak in approx. 3-4 hours
- Also useful in long term
- Short half-life
- No monitoring
Name of direct acting anticoagulants
- Anti-Xa (Rivaroxaban, apixaban, edoxaban)
- Anti-IIa (Dabigatran)
Describe the administration of delayed anticoagulation (warfarin)
- Given orally and has delayed effect
Describe the MOA of warfarin
- Indirect effect by preventing recycling of Vit K
- onset of action is delayed
- Levels of procoagulant factors II, VII, IX & X fall
- Levels of anticoagulant protein C and protein S fall
Which anticoagulants require monitoring?
warfarin
- monitor INR (derived from PT time)
What are the caveats of warfarin use?
- Dietary Vitamin K
- Variable absorption
- Interactions with other drugs
- Protein binding, competition/induction of cytochromes
- Teratogenic
which anticoagulant is safe to use in pregnancy?
Heparin
What do we use to anticoagulate patients with prosthetic valves?
Warfarin - target INR 2.5-3.5
List 6 patient categories at increased risk of thrombosis
- Medical in patients
- Patients with cancer
- Surgical patients
- Previous VTE, Family history, genetic traits
- Obese
- Elderly
Describe a generic thromboprophylaxis treatment
- Low molecular weight heparin (LMWH)
- Eg: Tinzaparin 4500u/ Enoxaparin 40mg od
- Not monitored - TED Stockings (for surgery or if heparin C/I)
- Intermittent pneumatic compression (increases flow)
- Sometimes DOAC +/- aspirin (orthopaedics)
When comparing risk of bleeding between DOACs and VKA, which produces less bleeding?
DOACs - half the risk of intracranial bleeding which is often what kills people on warfarin
Who has the highest risk of VTE recurrence - idiopathic, surgery, non-surgical (COCP, flight)?
Idiopathic > non-surgical > surgery
*idiopathic (10-20% in 2 years)
who has the highest risk of VTE recurrence - men or women?
men (RR 3.6)
who has the highest risk of VTE recurrence - distal, proximal, or PE event?
PE = proximal > distal
What is the anticoagulation regimen for 1st time VTE:
- surgical precipitant
- idiopathic
- COCP, flight, trauma
- No need for long-term anticoagulation
- Consider long-term with DOAC
- Usually 3 months is adequate
Which patient is most likely to benefit from long-term anticoagulation after a DVT?
- 57 year old man after flying from Kuala Lumpur
- 27 year old woman during pregnancy
- 33 year old woman on COCP
- 77 year old man after hip replacement
- 30 year old man after a long walk
5
a 33 yr old man collapses at work and is found to have a PE. What is the most appropriate first line of treatment?
Therapeutic dose LMWH
A 67 year old presents with DVT. He is anticoagulated with apixaban but also has a week history of weight loss. What is the most appropriate next step?
A) switch to parenteral anticoagulation
B) Reverse anticoagulation
C) Perform CT-AP
D) Supplement the diet with vitamin K
E) Switch to warfarin
C - likely a malignancy
