Haematology Coagulation 2 Flashcards
Haemophilia: Description
Defect in Factors that affect clotting factors downstream
Haemophilia A
Defect in F8 gene causing reduced FVIII
Haemophilia B
Defect in F9 causing reduced FIX
Haemophilia: Inheritance
Sex Linked – FIND OUT MORE
Haemophilia: Clinical features of Haemophilia
Mild provoked bleeding if factor level >5%
Severe spontaneous bleeding if factor level <1%
• Soft tissue and joint bleedings (leads to synovitis) – chronic inflammatory changes
• Life-threatening CNS or GI bleeds
• Chronic arthropathy
• Treatment acquired HCV and HIV
Haemophilia: Treatment
Recombinant factor concentrate – personalised prophylaxis regimes to ensure factor levels never drop to ‘severe’ levels
→ Implant venous access device for easier infusions
Venous Thrombosis: VTE disease
Formation of fibrin-rich clots in low-pressure venous system
Includes DVT, PR, or thrombosis in axillary/ subclavian/portal. Mesenteric/cerebral veins
Venous Thrombosis: Thrombophilia
Increased propensity to VTE
Acquired + genetic risk factors
Venous Thrombosis: National burden of VTE
PE
DVT – 25K deaths per year in the UK
Elective Hip and Knee surgery % risk with no prophylaxis:
• 45% Hip
• 60% knee
Venous Thrombosis:DVT presentation common
Unilateral pain
Swelling
Tenderness
Discolouration
Venous Thrombosis: DVT presentation rare
Dilated superficial veins Venous gangrene (v. rare)
Venous Thrombosis:Note
Size of clot doesn’t relate to symptoms
Venous Thrombosis: DVT diagnosis
Clinical history Physical examination Wells Score (screening) (2+) SEE MORE D Dimer blood test (screening) – low good/ Confirmatory tests
Venous Thrombosis: Confirmatory tests
Doppler ultrasound
(Venography)
CTV/MRV for VTE at unusual
Venous Thrombosis: Doppler Ultrasound
Flow (red colour is not visible in the main vein (arrows), indicating lumen filled with thrombosis (SEE image)
Pulmonary Embolism: Symptoms
SOB Cough (Pleuritic) chest pain Haemoptysis Syncope Palpitations Sweating
Pulmonary Embolism: Diagnosis and results
Wells Score ECG - Sinus tachycardia. R heart strain ABG – Low O2/Co2 CXR – Usually normal potentially with wedge infarcts V/Q scan – indeterminate in 50-70% CT pulmonary angiogram - definitive
Pulmonary Embolism: DVT and PE sequelae
PE → • Pulmonary Hypertension → Chronic PE • Death Deep Vein insufficiency • Post-thrombotic syndrome • Venous ulcers
Pulmonary Embolism: Management of VTE
Fast acting anticoagulation minimum 3 moths (LMW Heparin or rivaroxaban)
• PE with haemodynamic effect may need thrombolysis or thrombectomy
• DVT graded compression stocking for PTS (minimum 6 months post DVT)
Long term anticoagulation?
Depends on individualised risk vs. benefit
Pulmonary Embolism: Who is at risk of VTE
Genetic risk factors Acquired risk factors: • Immobility • Trauma and surgery • Pregnancy and peurperium (post natal care) • Oestrogen therapy (e.g. COCP, HRT) • Inflammatory disorder (e.g. IBD) • Myeloproliferative disorders (e.g. Essential Thrombocythaemia) • Malignancy (e.g. Adenocarcinoma) • Antiphospholipid syndrome
Factor V Leiden: Definition
Sequence change in Factor V prevents inactivation by Protein C
5-10% Caucasians
Factor V Leiden: Epi
5-10% Caucasians Found in 20% of individuals with unexplained thrombosis FVL – increased risk of VTE x 4 COCP – increased risk of VTE x4 COCP + FVL – increased risk of VTE x16
Anti-phospholipid syndrome: Clinical features
CLOTs: C: Arterial or Venous thrombosis L: Livedo reticularis O: Obstetric complications - Recurrent miscarriage T: Thrombocytopaenia
Anti-phospholipid syndrome: Caused by
Antiphospholipid antibodies – bind to membrane phopspholipid glycoprotein complexes
Anti-phospholipid syndrome: Primary or Secondary to
Connective tissue disease (SLE)
Lympjoproliferative disorders (e.g. Lymphoma, CLL)
Infection
Drug induced
Anti-phospholipid syndrome: Antiphospholipid antibodies
Anti-cardiolipin antibodies Anti-beta2 glycoprotein antibodies Lupus anticoagulants • Prolonged aPTT in the test tube • Is definitely not physiological anticoagulant – lab artefact
Antithrombotic drugs
Anti-platelet agents
Anti-coagulants
Anti-platelet act to
Arterial: Inhibit arterial thrombosis (ACS, PVD, CVD)
Anti-coagulant drugs
Veins and low pressure vessels:
Inhibit coagulation pathway
Inhibit venous/low pressure thrombosis (DVT, PE, CVA in AF and mechanilca heart valves, CBP, dialysis)
UK Licensed anticoagulants
Inhibit production of thrombin: • UF Heparin • LMW heparin • Warfarin • Danaparoid • Fondaparinux • Bivalirudin • Argatoban • Apixiban • Dabigatran • Rivaroxaban
Heparin: Description
Paraentral antithrombotic
Naturally occurring glycosaminoglycan
Mixture of different wave lengths (UFH av. 50) (LMWH av. 15-20)
Heparin: MOA
Increases activity of natural anticoagulant Antithrombin
Inhibits active clotting factors esp. Factors IIa and Xa
UF Heparin Route
IV
UF Heparin bioavailability
Variable poor
UF Heparin Metabolism
Complex, renal
UF Heparin half life
1-2
UF Heparin adverse effects
Bleeding
Heparin induced thrombocytopenia
LMW Heparin route
SC
LMW Heparin bioavailability
Predictable, good
LMW Heparin metabolism
Predictable, renal
LMW Heparin half life
4-6
LMW Heparin adverse effects
Bleeding
LMWH used in
- Immediate management of VTE
- Thromboprophylaxis
- Acute coronary syndromes
- Warfarin unsuitable esp pregnancy
- Prophylaxis against venous thrombosis
UFH
- Extra-corporeal circuits
7. High risk ‘bridging’ for surgery
UHF Heparin: Absorption
Bolus Injection then IV infusion e.g. 5000 IU loading then 30,000 IU/24 hrs
UHF Heparin: Measure of heparin
- aPTT is best measure of heparin in ‘therapeutic’ activity range
- Expressed as aPTT ratio (patient aPTT/ normal aPTT)
UHF Heparin: Target aPTT range
1.5-2.5
UHF Heparin: Monitor
PLT count
LMW Heparin: Absorption
Four preparations – enoxaparin (Clexane)
LMW Heparin: Dosing
‘Prophylaxis’ 40 mg sc od
‘Treatment’ 1.5 mg/kg od or 1mg/kg bd
LMW Heparin:Monitoring
Not routine, won’t increased aPPt or PT at therapeutic levels
Anti-Xa test
LMW Heparin: Over-anticoagulation with heparin: mild or moderate bleeding
Stop Heparin
LMW Heparin: Over-anticoagulation with heparin: Severe
Stop Heparin
Protamine iv 1mg.100 IU heparin in lst hour max 40 mg)
Expect repeat treatment
Warfarin: Action
Oral anticoagulant
A coumarin derivative
Warfarin: MOA
Inhibits recycling of vit K
Vit K is needed for synthesis of clotting factors II, VII, IX and X
Warfarin: When do we use warfarin
Long term management of VTE
Stroke prevention in atrial fibrillation
Sometimes, prevention of arterial thrombosis (plus antiplatelet agent)
Warfarin: Absorption
Near 100% bio-availability
Warfarin: Half life
36 hours
Warfarin:Metabolism
Liver
Warfarin: Causes
Increased PT and increased aPTT
Warfarin: Monitoring
Longterm monitoring using INR (patient PT/ control PT)
Warfarin:Typical dose
2-8mg od
Warfarin: Interactions
Cranberry and grapefruit juice
Warfarin:INR >5 and/or mild bleeding
STOP Warfarin
Warfarin INR >8 and/or serious bleeding
STOP warfarin
Vitamin K 1-3 mg poor iv
Consider Vitamin K factor concentrate (eg Octaplex) plus Vit K1
Rivaroxaban: MOA
Oral anticoagulant
Direct inhibitor of factor Xa
Rivaroxaban: When do we use rivaroxaban
- VTE after knee/hip replacement (10 md od)
- Stroke prevention in non-valvular AF (20mg od)
- Acute treatment of DVT (15 mg bd)
- Long-term prevention of DVT and PE (20 mg od)
Rivaroxaban: Peak plasma hours
• 3 hours
Rivaroxaban:Half life
• 8 hours
Rivaroxaban: Metabolism/excretion
• 75% liver metabolised/25% renal excreted
Rivaroxaban: Interactions
Some drug interaction and unsuitable in renal impairment.
Rivaroxaban: Monitoring
None
Rivaroxaban: May cause
- Increased PT and increased aPTT but doesn’t reflect anticoagulant effect.
- Anti-Xa test
Rivaroxaban: Accidental overdose or mild bleeding
• STOP rivaroxaban
Rivaroxaban: Serious bleeding
- STOP rivaroxaban
- General measures
- Specialist agents eg APCC
Rivaroxaban:Safety of anticoagulation
Anticoagulant bleeding leads iatrogenic mortality
High bleeding risk:
• Renal impairment (heparins and RIV)
• Previous bleeding edp. CNS or GI
• Other coagulopathy eg anti-platelet drugs
• Age >75 years, frequent falls, bw <50 kg
