Thrombotic Disorders Flashcards
Deep Vein Thrombosis
Risk factors: cancer, pregnancy, the pill, long flights, obesity, drugs
Doppler U/S: produces 2D image of soft tissue structure, showing velocity and direction of blood flow
D-Dimer test: indicates activation of clotting cascade
Low Wells risk score and negative D-dimer = no DVT
Treatment of DVT
Therapeutic anti-coagulation using sub cut LMW heparin (no monitoring required)
Ensure adequate eGFR (if not use iv unfractionated heparin)
Switch to oral warfarin for 3-5 days when INR > 2.0+ days - target INR = 2.5
1st DVT: anticoagulation for 6 months
2nd DVT: lifelong anticoagulation
INR: PT/normal PT (11-13.5 mins or 0.8-1.1)
Pulmonary Embolus
Pleuritic pain, dyspnoea, haemoptysis
Investigations: ECG, Chest X ray, CTPA scan, CT pulmonary angiogram
Outcomes: 5% mortality rate, pulmonary hypertension,
Treatment of PE
If severe: signs of shock - thrombolysis with tPA (tissue plasminogen factor) - IV unfractionated heparin, monitor APTR.
If standard: IVC filters, DOAC as alternative - dabigatran/rivaroxaban
Anti-thrombotic Drugs
Warfarin: vit K antagonist, required for functional maturation of factor II, VII, IX, X, prolongs extrinsic pathway, inhibits natural anticoagulants
Heparin: unfractionated/low molecular weight
Newer Agents: dabigatran (thrombin FIIa inhibitor) and rivaroxaban/apixaban (direct factor Xa inhibitors)
Warfarin Interactions
Drug interaction due to cytochrome p450: enzyme inhibitros = potentiate warfarin; enzyme inducers = inhibit warfarin
Beware of interactions with alcohol: binge drinking = potentiate warfarin; chronic alcoholism = inhibits warfarin
Warfarin control affected by: binding to albumin, absorption of vit K, synthesis of vit K, hereditary
Warfarin Side Effects & reversing warfarin
tetrarogenic - use LMW heparin in pregnancy, Significant haemorrhagic risk, Skin necrosis, Alopecia
Reversing Warfarin: activated prothrombin complex, containing vit K dependent factors; dose - 25-50 units/kg or fresh frozen plasma
Heparin
Monopolysaccharide that works by potential anti-thrombin Irreversibly inactivates factor IIa and Xa Administered paranterally (injected)
Unfractionated Heparin
Given IV with 5000U bolus
Safe in renal failures
Partially reversed by protamine sulfate
complication: heparin-induced trhombocytopenia
Low Molecular Weight Heparin
Daily injections - prescribed according to weight
Patient must have creatinine clearance of at least 30ml/min, but not monitored
Tinzaparin, enoxaparin
Used for thrombophylaxis for hospital in-patients
Rivaroxaban
causes irreversible anti-coagulation
Indications: VTE prophylaxis
Used for: PE/DVT treatment, stroke prevention in AF
dosing in 15mg bd for 3 weeks, then 20mg od
Dabigatran
same uses as rivaroxaban - DVT, PE, stroke prevention
Dose: 150mg bd, 110mg when used prophylactically
confirm creatinine clearance
can be reversed by Praxbind
Thrombophilia screen
Inherited causes: factor V Leiden - deficiency of natural anti-coagulants –> anti-thrombin, protein C/S deficiency
Acquired causes: antiphospholipid syndromes - tests for lupus anti-coagulant (DRVVT) and anti-cardiolipin Abs
Direct Oral Anti-Coagulants
Developed as oral alternatives to warfarin
no monitoring required - very safe
2 classes: dabigatran and rivaroxaban
trials show clinical non-inferiority of DOACs
should not be used for cardiac valves as inferior to warfarin
Types of Anti-platelet drugs:
Aspirin: cyclo-oxygenase inhibitor Clopidogrel: ADP receptor blocker Dipyridamole: inhibits phosphodiesterase Prostacyclin: stimulates adenylate cyclase Glycoprotein IIb/IIIa inhibitors Used in angioplasty procedures