management of bleeding due to antithrombotic - soeharsohadi, md, fiha.pdf

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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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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5/98 MedSlides.com 22

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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5/98 MedSlides.com 23

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).

management of bleeding due to antithrombotic - soeharsohadi, md, fiha.pdf

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