HAEM: Coagulation II - Thrombotic Disorders Flashcards
Why do thromboses develop?
Virchow’s triad:
- changes in the vessel wall (e.g. atheromatous plaques)
- changes in blood flow (e.g. atrial fibrillation)
- changes in the blood consistuents (hypercoagulability)
What are the clinical features of pulmonary embolism?
- Pleuritic chest pain
- Shortness ofbreath
- Cough/haemoptysis
- Palpitations
- Syncope
What are the DDs of pulmonary embolism?
- Chest infection (pneumonia)
- Cardiac failure
- Malignancy
- Other (???)
List the inherited thrombophilic syndromes and their multiplicative thrombotic effect
- Antithrombin deficiency (x10)
- Protein C deficiency (x10)
- Protein S deficiency (x10)
- Factor V leiden (x3-7, although if homozygous x50-80)
- Prothrombine gene mutation (x3)
What are the natural inhibitors of coagulation and their inherited deficiencies?
-
Antithrombin
- major inhibitor of thrombin, Xa and other serine proteases in extrinsic pathway
deficiency = autosomal dominant; variable clinical penetrance
-
Protein C
- vitamin K dependent protein
- synthesised in liver
- anticoagulation after being activated (become aPC)
- inactivates Va and VIIIa
deficiency = autosomal dominant
-
Protein S
- vitamin K dependent
- co-factor for protein C system
deficiency = autosomal dominant; acquired deficiency in pregnancy
- Factor V Leiden
deficiency = point mutation, argining to glutamine at position 506
- protein C unable to inactive factor V
- Prothrombin Gene Mutation
deficiency = look it up lol it’s complicated (G20210A transition in 3’ untranslated region)
- heterozygous carriers have 30% higher palsma prothrombin levels
What are the clinical features and differential diagnoses of DVT?
How is DVT diagnosed?
Can’t be safely diagnosed/excluded on history/exam alone.
Diagnosis involves:
- assessment pre-test probability with clinical prediction guide (e.g. Wells’ DVT Clinical Prediction guide)
-
D-dimer
- used with clinical prediction guide to exclude DVT (-ve redictive value = ~100%)
- ultrasonography (imaging)
How are pulmonary embolisms diagnosed?
- Clinical assessment
- history/exam
- CXR/ECG/FBP
- pulse oxymetry
- Calculate pre-test probability of PE
- D-dimer
- Imagine
- Ventilation/perfusion lung scane (V/Q)
- CT pulmonary angiogram (CTPA)
What are the aims of VTE treatment?
- Relieve symtoms
- Prevent pulmonary embolism (DVT patients)
- Prevent death (PE patients)
- Prevent recurrence
- Prevent complications
Anticoagulation is the mainstay of treatment
What is the treatment of a DVT/PE?
- Parenteral anticoagulants
-
Unfractionated heparin (IV, mix of heparin with different molecular weights)
- inhibits thrombin and factor Xa in complex with antithrombin
- in-patient treatment, monitor by APTT
-
Low Molecular Weight Heparin (LMWH)
- binds antithrombin and inhibits factor Xa
- increasingly out-patient, predictable pharmacokinetics
-
Unfractionated heparin (IV, mix of heparin with different molecular weights)
- Oral anticoagulants (Vitamin K antagonists)
-
Warfarin
- blocks vitamin K epoxide reductase
- monitored with the INR
-
Warfarin
- New oral anticoagulants
- Dabigatran - direct thrombin inhibitor
- Ribaroxaban - direct factor Xa inhibitor
- Apixaban - direct factor Xa inhibitor
What are the limitations of warfarin?
What are the MoA and the advantages of new oral agents?
Direct inhibitors of factor Xa:
- Apixaban
- Betrixaban
- Edoxaban
- Rivaroxaban
Is prevention of VTE important?
- 7% of deaths in Australian hospitals due to VTE (more than cancer)
- Only half of hospital patients at risk receive VTE prophylaxis
- All patients admitted to hospital required VTE risk assessment (but compliance is bad)
What is some approrpaite thromboprophylaxis?
- Graduated compression stockings
- Intermittent pneumatic compression (IPC)
- Low dose clexane
- Low dose unfractionated heparin
