management of bleeding due to antithrombotic - soeharsohadi, md, fiha.pdf
TRANSCRIPT
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8/18/2019 Management of Bleeding due to Antithrombotic - Soeharsohadi, MD, FIHA.pdf
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CARDIOVASCULAR EMERGENCIES COURSEBumi Surabaya Hotel, November 7-8th, 2015
Management of Bleeding due toAntithrombotic
RP Soeharsohadi
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CARDIOVASCULAR EMERGENCIES COURSEBumi Surabaya Hotel, November 7-8th, 2015
Hemostatis system
The major components
1. Vascular endothelium
2. Platelets
3. Coagulation and fibrinolytic
systems
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Clotting Cascade
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Anticoagulants and antiplatelets mechanisms of action
Rivaroxaban
Apixaban
dabigatran
Anticoagulants
Antiplatelets
ASA
Clopidogrel
Prasugrel
Ticagrelor
Fibrinogen
Fibrin
Clot
Platelets
Factor
Xa
GPIIb/IIIa
Thromboxane
ADP
Inflammation
Cellular proliferation
Collagen +
other
mediators
Activated
platelet
Coagulation
cascade
Mackman, 2008
Platelet
aggregation
ThrombinThrombin
LMWH
,UFHWarfarn
Bivalirudin
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General Principles Management Anticoagulant-
Associated Bleeding
• Stop the antithrombotic drug
• Antidote
• Supportif therapy
• Mechanical pressure
• Tranfusion
• Use endoscopic or surgical measures• Source of bleeding
• Specific laboratory test to measure the antithrombotic effect of the drug
• Amount of the last drug dose and presence of pre-existing renal or
hepatic impairment
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1.Vitamin K ,1-10 mg IV/PO• Infusion reactions rare; administer over 20-30 min• Takes 6 hrs (IV) to 24 hrs (PO) hours to reverse warfarin• Subcutaneous or intramuscular administration not recommended
2.Protamine sulfate 12.5-50 mg IV• Full reversal of unfractionated heparin• 60-80% reversal of LMWH
3.Platelets• Used in patients receiving antiplatelet therapy• Raise platelet count by 30 x 10 9/L
Pharmacological and blood component pro-haemostatic
therapies
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4. Prothrombin complex concentrates (PCC) 25-50 units/kg IV
• Rapid, complete INR correction in warfarin-treated patients• Small volume infusion over 10-30 minutes
• Risk of thrombosis 1.4%
• Short half-life, may need repeat dose after 6 hours
5. Recombinant factor VIIa (rFVIIa) 15-90 micrograms/kg
• Rapid infusion of small volume
• Risk of thrombosis 5-10%• Short half-life, may need repeat dose after 2 hours
6. Frozen plasma (FFP) 10-30 mL/kg (1 unit =~250 ml)• Replaces all coagulation factors• Hemostasis coagulation factor levels ~30%• Short half-life, repeat dosing after 6 hours
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7. Aminocaproic acid ,4-5 g IV, (maximum dose 30 g/24hrs)• May increase risk of thrombosis• May accumulate in patients with renal impairment,
8. Tranexamic acid• 15-25mg/kg po, 15mg/kg IV
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• Stopping an UFH infusion
• General haemostatic measures
• Protamine sulphate (1 mg per 80–100 units UFH),5 mg/min to
minimize the risk of adverse reactions.• Maximum recommended dose of protamine 50 mg
Specific management of anticoagulant associated bleeding
A. Unfractionated heparin
B. Fondaparinux
• There is no specific antidote• Management of bleeding should be through cessation of
treatment and general haemostatic measures• Recombinant FVIIa for critical bleeding
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C. Warfarin
• anticoagulation reversal in major bleeding ,25–50 U/kg PCC and 5 mgintravenous vitamin K
• rFactorVIIa is not recommended for emergency anticoagulation
reversal .
• Fresh frozen plasma should only be used if PCC is not available
• Anticoagulation reversal for non-major bleeding should be with 1–3 mg
intravenous vitamin K
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D. Low molecular weight heparin
• 8 hr,smaller doses of protamine
• rFVIIa if life-threatening bleeding
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E. Dabigatran
• There is no specific antidote
• Management of bleeding should be through cessation of treatment andgeneral haemostatic measures
• Dabigatran in the last 2 h, oral activated charcoal to prevent further
absorption
• If rapidly deployable, haemodialysis, haemofiltration and charcoal
haemoperfusion
• Life threatening bleeding PCC, APCC and rFVIIa should be considered
F. Rivaroxaban
• There is no specific antidote for rivaroxaban.
• Management of bleeding should be through cessation of treatmentand
general haemostatic measures
• In situations with ongoing life-threatening bleeding, PCC, APCC and
rFVIIa should be considered
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General consideration
1 Plasma half-life
a) clopidogrel, dipyridamole, prasugrel, ticagrelor: 7-10 hours
b) Low-dose aspirin (150 mg daily): 2 to 4.5 hours
c) An overdose of aspirin (> 4000 mg): 15-30 hours2. Reversibility antiplatelet effect
a) Aspirin, clopidogrel, and prasugrel, takes 7-10 days.
b) Ticagrelor is a reversible inhibitor
3. Circulation drug in the active metabolites form may inhibit
transfusions process
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Management bleeding• Bleeding in patient with aspirin, P2Y12 antagonists or
GPIIa/IIIb inhibitors, managed in the first instance withgeneral haemostatic measures.
• Platelet transfusion for critical bleeding or preventionbleeding before emergency surgery
• Platelet transfusion to prevent bleeding in severethrombocytopenia
Anti-platelet recovery:1. No urgent do discontinuation of treatment 5-10 days beforethe procedure.2. Urgent (no bleeding) consider platelet transfusion prior tothe procedure with a high risk of bleeding3. Urgent (bleeding): do procedure of general considerationsand platelet transfusions
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Summary
• Antitrombotic therapy is widely used as therapy in patients with
cardiovascular and cerebrovascular disease
• Side effects that occurred in the use of antithrombotic is bleeding
and can be life-threatening
• Complications from the cessation of antithrombotic, depending
on indication and the clinical condition of the patient, is
important thing to know how long the patient can stop
antithrombotic therapy, and no complications arise.
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Thank you
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Comparison of Oral Anticoagulants
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Protamine Dose for Reversal of Heparin and LMWH
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Non-urgent
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Coagulation CascadeCoagulation Cascade
XIIa
XIa
IXa
ntrinsic Pathway
surface contact)
Xa
Extrinsic Pathway
(tissue factor)
VIIa
Thrombin (IIa)
Thrombin-Fibrin
Clot
aPTT
PT
Heparin / LMWH
(AT-III dependent)
Hirudin/Hirulog(direct antithrombin)
Courtesy of VTI
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THROMBOSIS
Collagen XIa
Tissue Factor IXa
Platelet Clumping
Thrombus Formation
Thrombus Growth
HEMOSTASIS
Tissue Factor &
Collagen
Platelet Aggregation
Platelet-rich
Hemostatic Plug
Xa
Fluid
Thrombin
HEP
HEP & HIR
Heparin Inhibits HemostasisHeparin Inhibits Hemostasis
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Recommendations fibrinolitik
For major bleeding (e.g. intracerebral)within 48 h of
administration we recommend:
• Stop infusion of fibrinolytic drugs and
other antithrombotic
drugs (1C).
• Administer FFP 12 ml/kg (2C).
• Administer intravenous tranexamic acid 1
g tds (2C).
• If there is depletion of fibrinogen,
administer cryoprecipitate
or fibrinogen concentrate (2C).
• Further therapy should be guided by
results of coagulation
tests (2C).