Haem - Thrombosis Flashcards
What are the complications of thrombosis
Death (mortality 5%)
Recurrent (20% in the first 2 years, 4% after)
Thrombophlebitis syndrome (recurrent pain, swelling, ulcers)
Pulmonary hypertension (if PE is not cleared properly)
What is virchow’s triad
- Blood
- Vessel wall
- Blood flow
Describe how blood contributes thrombosis risk (Virchow’s triad)
Viscosity (high haematocrit, protein/paraprotein)
Platelet count
Coagulation system - imbalance of procoagulant and anticoagulant factors
Which factors are procoagulant
F II,V, VIII, IX, X, XI
Fibrinogen
Platelets
Which factors are anticoagulant
TFPI (tissue factor pathway inhibitor)
Protein C
Protein S
Thrombomodulin
EPCR
Antithrombin
Which disorders increase risk of thrombosis
Factor V leiden
Protein S deficiency
Protein C deficiency
Antithrombin deficiency
Elevated FVIII and FXI
Describe the coagulation cascade
- Tissue Factor, exposed by vessel damage, forms a complex with FVII
Formation of an active TF-VII complex - Activation of the extrinsic pathway via FX -> FXa
- Activation of the intrinsic pathway via FIX -> FIXa
Xa leads to conversion of prothrombin -> thrombin (IIa) - Activation of FV and FVIII by thrombin and platelets
- Enhanced thrombin formation
- Thrombin then converts fibrinogen to fibrin, which is cross-linked by the XIIIa
enzyme (activated by thrombin) to form cross-linked fibrin
Describe how vessel wall contributes thrombosis risk (Virchow’s triad)
The vessel wall is usually antithrombotic as it expresses anticoagulant molecules (thrombomodulin, protein C receptor, TFPI, heparans) and does not express tissue factor
Also secretes prostacyclin and NO (antiplatelets)
Inflammation will make the wall prothrombotic
- anticoagulatns downregulated
- Adhesion molecules upregulated
- Tissue factor expressed
- vWF release → platelet and neutrophil capture, (neutrophil extracellular traps)
What stimuli will cause the vessel wall to become prothrombotic
Infection
Malignancy
Vasculitis
Trauma
Describe how blood flow contributes thrombosis risk (Virchow’s triad)
Stasis will promote thrombosis
accumulation of activated factors → platelet adhesions → promotes leukocyte adhesion (NET) and transmigration
What are the causes of blood stasis
Immobility: surgery, paraparesis, travel
Compression: tumour, pregnancy
Viscosity: polycythaemia, paraprotein
Congenital: vascular abnormalities
What is the MOA for heparin and DOACs
Heparin: Potentiates anti-thrombin activity for an immediate anticoagulant activity
DOACs:
Anti-Xa: rivaroxaban, apixaban, edoxaban
Anti-IIa (antithrombin): dabigatran
how is heparin therapy monitored
LMWH: not required
If renal failure, extremes weight or risk → Anti-Xa assay
Unfractionated heparin: APTT or anti-Xa assay
What is the MOA for warfarin
Vitamin K epoxide reductase (VKER) inhibitor
Stops synthesis of factors 2, 7, 9 , 10 → delayed anticoagulant activity (14 days full onset)
FVII and protein C reduce first
How do you reverse warfarin
Give vitamin K if high INR (12 hours)
Quickly (1 minute) – 2,7,9,10 infusion
How do you monitor for warfarin
Measure of effect is INR– international normalised ratio derived from PT
What are the following features for heparin (admin, action, onset, monitoring, half life effects, reversal, safety in pregnancy)
Admin: parenteral
Action: co-factor for antithrombin
Onset: immediate (SC 4h)
Monitor: none
Half life: 6h
Reversal: protamine
Pregnancy: safe
What are the following features for warfarin (admin, action, onset, monitoring, half life effects, reversal, safety in pregnancy)
Admin: oral
Action: vit K antagonist
Onset: delayed
Monitor: INR
Half life: 2-3 days
Reversal: factor concentrate, vit K
Pregnancy: safe
What are the following features for DOAC (admin, action, onset, monitoring, half life effects, reversal, safety in pregnancy)
Admin: oral
Action: direct enzyme inhibition
Onset: immediate, peak 4h
Monitor: none
Half life: 8-10h
Reversal: Ab to dabigatran, Xa
Pregnancy: avoid
Which patients are at an increased risk of thrombosis
Medical inpatients: infection/inflammation, immobility, age
Cancer patients: procoagulation, inflammation, flow obstruction
Surgical patients: immobility, trauma, inflammation
Previous VTE, FHX, Genetic traits
Obese
Pregnant
Elderly
What are the strategies for thromboprophylaxis
LMWH – Tinzaparin or Clexane, not monitored
TED stockings for surgery or if heparin CI
Intermittent pneumatic compression (Flowtron) – intermittent compression, increases flow
Sometimes DOAC +/- aspirin
What factors should you consider when deciding whether to put a patient on long-term coagulation
What the circumstances were when the patient had thrombosis
Gender: M>F
Proximal or distal: proximal thrombosis is more likely to have DVT
Risk of bleeding
Describe long-term anticoagulation therapy for the following features after a thrombotic event: post-surgery, COCP, flights, trauma, idiopathic
Surgery: none required
COCP: 3 months anticoagulation
Flights: 3 months anticoagulation
Trauma: 3 months anticoagulation
Idiopathic: long-term required
Which patient factors increase risk of bleeding
Haemophilia, vWD
Platelets <100
Acute CVA in previous month
BP >200/120
Severe liver or renal disease
Active bleeding
Anticoagulant therapy
What procedures increase risk of bleeding
Neuro, spinal, eye surgery
LP, spinal, epidural
