Methods and specific issues of the anticoagulant therapy

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Methods and specific issues of the anticoagulant
therapy

• Szabolcs Modok
• Dentistry, 4th year, Internal medicine

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Antithrombotic treatment

• Anticoagulants
• Heparin (UFH)
• LMWH dalteparin (Fragmin)
• nadroparin calcium (Fraxiparine/Fraxodi)
• enoxaparin sodium (Clexane) reviparin (Clivarin)
• parnaparin (Fluxum)
• certoparin (Sandoparin)
• Warfarin (Marfarin)
• Acenocoumarol (Syncumar)

• Fibrinolitics
• Streptokinase (Streptase)
• alteplase (Actilyse)
• urokinase
• Drotrecogin (Xigris)
• lepirudin (Refludan)
• desirudin (Revasc)
• bivalirudin (Angiox)

• Thrombocyteaggr. inhibitors
• ASA
• Ticlodipine
• Clopidogrel (Plavix)
• Iloprost (Ilomedin)
• Eptifibatide
• Tirofiban (Aggrastat)
• Intrifiban (Integrilin)
• Triflusal (Disgren)
• Abciximab (Reopro)

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Indications for antithrombotic treatment

• Atrial fibrillation
• Coronary heart disease
• Acute myocardial necrosis
• Coronary artery bypass grafting
• Arteficial heart valves
• Cerebral thromboses
• Peripheral arterial obstruction
• Venous thromboembolism
• DIC, TTP, HUS

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Methods of anticoagulation

• (A) parenteral
• LMWH or UFH
• (B) oral
• warfarin (Marfarin) 1, 3, 5 mg acenocumarol
  (Syncumar) 1 mg

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Heparin mechanism of action
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Parenteral anticoagulation 1st

• UFH (creatinin clearence lt 30mL/h)
• 5000 NE Na - heparin iv bolus, then either 1.
  iv Na-heparin 18 NE/bwkg/h (APTT after 6
  hours) 2. sc Ca heparin 2 x 250 NE/kg (APTT
  after 6 hours)
• target APTT 1.5 2 x starting or normal upper
  limit
• LMWH calculated per weight (bwkg) or
  according to anti-FXa levels, 4 hours after sc
  administration (gt 150 kg, renal failure,
  pregnancy)
• Antidote Protamin-sulphate
• 1 mg/100 NE UFH in the first 8 hours, then 0.5
  mg/100 NE every 8 hours (30 more for LMWH)

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Parenteral anticoagulation 2nd

• LMWH products
• - nadroparin
• Fraxiparin9500 NE/ml 2 x 85
  NE/bwkg Fraxodi19000 NE/ml 1 x 171 NE/bwkg
• - dalteparin Fragmin 2 x 200 NE/bwkg
• - enoxaparin Clexane100mg/ml 2 x 1 mg/bwkg
• Clexane Forte150mg/ml1x1.5 mg/bwkg
• - parnaparin (Fluxum 2 x 0,6 ml/day)

Therapeutic dose should be halved to
prophylactic when thrombocyte count is lt50 G/l.
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Contraindications of oral anticoagulants

• - non-compliance
• - severe liver or kidney failure
• - 1st 3rd third of pregnancy
• - active GI bleeding
• - uncontrolled hypertension
• - hereditary bleeding diathesis

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Vitamin K antagonists

• Syncumar (acenocoumarol) 1mg
• Marfarin (warfarin) 1,3,5 mg
• Start as soon as possible
• Dont have a long overlap with heparin

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Oral anticoagulation

• Dose corrections
• INR lt 2 increase weekly warfarin dose by 5 20
  
• 3 lt INR lt 5 decrease weekly warfarin dose by 5
  20
• 5 lt INR lt 9 w/o bleeding no warfarin for 1-2
  days,and/or 1 2,5 mg vitamin K (Konakion 2, 10
  mg), and reduce the weekly dose of warfarin
• 5 lt INR lt 9 w bleeding or INR gt 9 no warfarin, 5
  10 mg vitamin K, reduce weekly dose of warfarin
• Massive bleeding aPCC or FFP or recombinant
  factor VIIa (Novoseven, 90 ?g/bwkg every 2 hours)
  and 10 mg vitamin K

(7th ACCP Conference. Chest 2004126204 233)
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(No Transcript)
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Complications of anticoagulation
Thrombotic Heparin-induced thrombocytopenia
Vitamin K antagonist induced skin
necrosis Bleeding Risk factors INR gt
5 previous bleeding (GI) severe
accompanying diseases

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Heparin-induced thrombocytopenia
HIT bovine UFH gt porcine UFH gt
LMWH postoperative gt medical gt
pregnancy Thrombocyte count (UFH every other
day) Dg lt 100xG/l or 50 decrease
antibody Type 1 mild decrease heparin induced
thrombocyte aggregation Type 2 autoantibody
against the heparin PF4 complex agglutinates
thrombocytes ? thrombosis and/or severe
bleeding heparin cessation, lepirudin (0,4
mg/bwkg iv bolus, then 0,15 mg/bwkg/h iv cont.,
target APTT 2,5 x normal upper
limit) vitamin K antagonist (thrombocyte count
normal) danaparoid in pregnancy
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Heparin resistanceATIII deficiency
Drug resistance

• Vitamin K antagonist resistance
• VKORC1 deficiency

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Summary of key recommendations N1
1. The risk of significant bleeding in patients
on oral anticoagulants and with a stable INR in
the therapeutic range 2-4 (i.e. lt4) is very small
and the risk of thrombosis may be increased in
patients in whom oral anticoagulants are
temporarily discontinued. Oral anticoagulants
should not be discontinued in the majority of
patients requiring out-patient dental surgery
including dental extraction (grade A level Ib).
2. For patients stably anticoagulated on warfarin
(INR 2-4) and who are prescribed a single dose of
antibiotics as prophylaxis against endocarditis,
there is no necessity to alter their
anticoagulant regimen (grade C, level IV).
(British Society for Haematology, next review in
2011)
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4. For patients who are stably anticoagulated on
warfarin, a check INR is recommended 72 hours
prior to dental surgery (grade A, level Ib)5.
Patients taking warfarin should not be prescribed
non-selective NSAIDs and COX-2 inhibitors as
analgesia following dental surgery (grade B,
level III).
Summary of key recommendations N2

• 3. The risk of bleeding may be minimised by
• a. The use of oxidised cellulose (Surgicel) or
  collagen sponges and sutures (grade B, level
  IIb).
• b. 5 tranexamic acid mouthwashes used four
  times a day for 2 days (grade A, level Ib).

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Dental procedures

• Non-invasive
• Prosthodontics (construction of dentures)
• Scaling/polishing
• Conservation work (fillings, crowns, bridges)

• Invasive
• Endodontics (root canal treatment)
• Local anaesthesia (infiltrations, inferior
  alveolar nerve block, madibular block)
• Extractions (single and multiple)
• Minor oral surgery
• Periodontal surgery
• Biopsies
• Subgingival scaling

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Who should be referred to a centre?

• Simple procedure, but the patient on warfarin has
  severe liver, kidney disease, thrombocytopenia,
  is on antiplatelet drugs (increased risk of
  bleeding)
• Procedures not listed on the previous slide

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N1 Potential hazards

• Risk of bleeding for a patient w/o warfarin is
  appr. 1.
• Risk of bleeding for a patient on warfarin is
  appr. 10, with 2-3 of those requiring systemic
  treatment. No fatality was reported.
• Risk of thrombo-embolism is appr. 1, but 4/5
  cases were fatal.
• Importance of sutures and local
  anti-fibrinolytics (tranexamic acid, EXACYL) is
  emphasised.

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Point n2

• Frequently prescribed antibiotics
• Penicillin
• Amoxicillin
• Clindamycin
• Azithromycin