L16 Thrombotic disorders Flashcards
What are the 3 components of Virchows triad that contribute to venous and arterial thrombosis and what are risk factors for this
- Flow of blood: stasis
- Immobility, Pressure: catheter/tumour, Increased viscosity: polycythaemia, EPO - Vascular injury:
- Trauma, surgery, prior thrombosis, atherosclerosis
3.Hypercoagulability of components of blood (mainly venous)
- Increase in procoagulants
-Decrease in inhibitors
or rarely impaired fibrinolysis
Other provoking risk factors:
- cancer, obesity, pregnancy, cocp, thrombophilia
Compare the two parts of Venous thrombo-embolism:
Deep Vein Thrombosis and Pulmonary embolism pathology and presentation
- Virchow triad lead to Fibrin process has been triggered in the leg.
- Leg swelling, discolouration, oedema, pain - Unstable leg clot can break off to get pulmonary embolism.
- SOB, pleuritic chest pain, Haemoptysis
- Tachycardia, tachypnoea, hypoxia
Massive PE: severe RH strain, shock/hypotension sudden death.
Treatment= thrombolysis - TPA infusion
Incidence increases with age- much more common 45+
90% occurs in the leg veins
What are the 2 tests to help diagnosis of DVT or PE and what are their shortcomings
Tests
1. Well’s score for DVT to classify high or low risk
- Low risk first have Blood D dimer to double check. If positive move on to 3.
- + is seen in 98% of DVT/ PE so good negative predictive value, however has low positive predictive value because it D dimer be high due to inflammation/surgery - Radiology (high specificity/sensitivity)
- USS for DVT - distal (below tibioperoneal trunk distal/lower risk)
-Computed tomography pulmonary angiography if PE
or V/Q- ventilation/perfusion scan which is better for pregnant women
What is Thrombophilia, and how does it manifest
4
Tendency to develop thrombosis that is mainly inherited but can be acquired or both.
- Abnormal natural inhibitor function= eg. F5 leiden
- Deficiency of natural inhibitors - PC, PS, Anti-thrombin (rarer but higher risk)
- Increased factor levels
eg. Prothrombin gene mutation 20210A or elevated factor 8. - Dysfibrinogenemia (very rare)
- Manifests as VTE but generally after a provoking risk.
What is an example of abnormal natural inhibition - The most common hereditary cause of thrombophilia in caucasians
Factor 5 Leiden:
Point mutation in factor 5 which means that activated protein C can no longer cleave f5 at arg 506.
This leads to slightly longer Factor 5a activation activity before natural degradation increasing chance of VTE
What patients is thrombophilia tested for and why
Young patients particularly spontaneous VTE, limited use in families.
This is bc the initial VTE risk is increased but recurrence and arterial risk isn’t so treatment decisions largely the same (sans antithrombin deficiency)
What is the treatment of PE and DVT (not shock) - admin, mech, time
Compare the older and the newer treatment: which is better
- Heparin either
- LMW Heparin eg. Enoxaparin given usually IM or
- unfractionated heparin given IV
immediate effect to stop the clots being worse - for at least 5 days
- Warfarin at the same time - direct oral agent. Inhibits coagulation to allow own fibrinolytic mechanisms to operate unhindered.
- Delay in start due to Vit K half life. Has to be monitored with
INR - high INR= bleeding. 2-3 is good.
- Now Warfarin may be replaced by Direct acting Oral anticoagulants that directly bind to the factor. eg.
- Rivaroxaban (Xa)
- Dabigatran (2a)
same or superior than warfarin
No monitoring is needed and less intracranial haemorrhage than warfarin.
However retained with renal impairment.
How does Heparin work and what do APTT and TCT tests look like
Heparin=(cofactor) increases anti-thrombin effect providing huge dose of cofactor to help inactivation of
- 10a and (more the LMW)
- 2a (thrombin) - more unfractionated
- Unfractionated heparin affects. APTT 1+1, TCT markedly prolonged. Reversible with protamine.
Compare the APTT, TCT or PR for Dabigatran vs Rivaroxaban
Specific assay available for both + mech
What is the antidote for both
APTT 1+1 prolonged more for D than R,
TCT extremely sensitive for D
PR prolonged to some extent for R, only if very high for D.
D. Antidote: Idarucizumab: antibody with immediate reversal but may rebound 24-48 hrs if renal impairment/high levels
R. Antidote
Andrexanet (not in NZ) which is a Xa decoy with no active site.
What two morbidities can be developed after DVT
- Post thrombotic syndrome
- venous eczema, ulceration, swelling, pain, redness.
- Helped with compression stockings - Chronic thromboembolic pulmonary hypertension (2%)
- SOB, dizziness, fatigue
