Editing Anticoagulation

== Specific drugs ==
{| class="wikitable"
|Drug
|MOA
|Washout time
|Washout time eGFR<30
|Level?
|Reversal
|-
|Apixaban
|Direct Xa inhibitor

Liver-excreted
|48 hours
|72 hours
|Anti-factor Xa
|Consider prothrombinex + FFP

* Andaxanet is not available in australia, needs RCTs. Factor Xa decoy protein

Not dialysable
|-
|Rivaroxaban
|Direct Xa inhibitor

Renally-excreted
|48 hours
|72 hours
|Anti-factor Xa

PT
|Consider prothrombinex + FFP

* Andaxanet is not available in australia, needs RCTs. Factor Xa decoy protein

Not dialysable
|-
|Dabigatran
|Direct thrombin inhibitor
|2-4 days
|5 days
|TCT - sensitive

APTT/PT
|idarucizumab (Praxbind - $3500 USD) 5mg IV

* Safe, but 5% clot risk
* Binds direct to dabigatran
* Available here since 2016
* Works within 15 minutes, 93% success rate

Could consider dialysis
|-
|Warfarin
|Vitamin K epoxide reductase inhibitor, which prevents gamma-glutamyl carboxylase from completing a vital step in synthesis of II, VII, IX, X. 

Also prevents protein C and S synthesis, which causes the paradoxical pro-thrombotic effects after commencing.
|Five days
|Five days
|INR

TCT - should be < 30 to proceed safely
|Dose depends on INR but

* Prothrombinex 25-50 units/kg + vitamin K
* If prothrombinex contraindicated, can give FFP
|-
|Clopidogrel
|Platelet P2Y(12) inhibitor - prevents platelet response to exogenous and endogenous ADP.

ADP is normally used for cross-linking of fibrin and platelet activation.
|7 days
|7 days
|No
|
|-
|Heparin
|Enhances the action of antithrombin III, an endogenous protein which normally inactivates factors IIa (thrombin) and Xa, thus inhibiting both intrinsic and extrinsic pathways
|
|
|
|
|-
|Enoxaparin
|Enhances binding of antithrombin to factor Xa, but with less anti-IIa activity than heparin
|
|
|
|
|}




== General non-reversal management of bleeding patient/patient on anticoagulants needing surgery: ==

* '''Decide how urgent surgery is!'''
* Check if anticoagulant effect is still present (level as above)
* Perform a risk assessment for coagulation risk
** Presence of stents/valves
** Previous stroke
** Chadsvasc
** Relevant haematological disorders
* Canulae, full bloods including coags, anticoagulant level, XM
** Ensure consented for blood transfusion
* Resuscitation with blood (?MTP)
* Optimise kidney function
* Consider charcoal (if ingested <2 hours)
* Symptomatic control
** PPI etc
** Tranexamic acid
* Discuss with haematology early
** Reversal options
*** Major bleeding and renal impairment
*** Major bleeding and supra-therapeutic level of blood
*** '''Urgent surgery required and therapeutic level of drug on board'''

== Low-risk factors for thromboembolism (more than one factor doesn't necessarily make the patient high-risk) ==

* AF with CHADSVASC of 2 or less
* Cardiomyopathy without previous CVA
* Mechanical aortic valve without previous CVA
* Bioprosthetic heart valves without previous CVA
* Unprovoked DVT/PE >3/12 ago
* Rheumatic heart disease without previous CVA
* Permanent IVC filter

== High-risk factors for thrombosis/thromboembolism ==

* Neurology
** Previous CVA with AF or other cardiac source
** CHADSVASC of 3 or higher
** Arterial embolism <1 month
* Cardiology
** Mechanical mitral or tricuspid heart valve
** Mechanical aortic heart valve with AF, previous thromboembolism or LV dysfunction
** Multiple mechanical heart valves
* Haematology
** Recurrent DVT/PE
** DVT/PE within 3/12
** Provoked DVT/PE >3/12 ago where the precipitant is still present
** History of DVT/PE with severe thrombophilia (protein C/S/antithrombin deficiency, or presence of antiphospholipid antibodies)
* Recent stent
** Bare metal stent 6/52 - it's possible to cease the clopidogrel sooner
** DES 12 months - should be on DAPT for all 12 months
** Ceasing of DAPT prior to this window leads to a 20-30% risk of stent occlusion

== Avoid ceasing aspirin ==

* Increases risk of bleeding by only 1.5x
* But reduces risk of cardiac events by 80%



Heparin (info based on Austin guidelines 2022 - varies depending on local lab protocols)

== HITS ==

* IgG antibody-mediated adverse effect of heparin
* Can occur with either UFH or LMWH
* Investigate for HIT if any of the following occur between days 5 and 14 following initiation of heparin:
** Fall in platelet count >30%, even if nadir remains >150 (generally occurs 5-10 days after starting heparin in heparin-naïve patients, and can be day of starting for heparin re-exposure)
** Venous or arterial thrombosis
** Cutaneous lesions at heparin injection sites
** Acute systemic reactions
* Use 4TS score - very sensitive if score is low
*


== '''Warfarin''' ==

* Vitamin K epoxide reductase inhibitor - competitively inhibits the hepatic synthesis of the vitamin K-dependent clotting factors II, VII, IX, X
* Can be reversed by simply replacing those factors with FFP or prothrombinex, and giving supplemental vitamin K to overcome the inhibition
* FFP only leads to a median reduction of INR of 0.2. Also, it can't be administered quickly, and you need a large volume.
* Prothrombinex - generally three-factor, containing II, IX and X; but some four-complex versions are available - can be rapidly reconstituted and reversed from its stored powder form. The volume is <100mL. The main disadvantage is cost. INR <1.3 at 30 minutes from start of treatment was achieved in 62% of prothrombinex group but only 10% of FFP group.
** Three-factor prothrombinex is fine for INR <4, but it has been suggested that four-factor should be used when INR >4, or three-factor + FFP.
* Vitamin K IV results in a lower INR 4-6 hours after infusion (5-10mg diluted in 50mL N/S and given over 20 minutes)
* Prothrombinex doses

{| class="wikitable"
|Initial INR
|1.5-2.5
|2.6-3.5
|3.6-10
|>10
|-
|Target INR 0.9-1.3
|30IU/kg
|35IU/kg
|50IU/kg
|50IU/kg
|-
|Target INR 1.4-2.0
|15IU/kg
|25IU/kg
|30IU/kg
|40IU/kg
|}





== '''DOACs''' ==
'''Apixaban (from Austin guideline 12/2/2018)'''

* Half-life 12 hours
* Apixaban/dabigatran/rivaroxaban level can be done - useful in reversal or to ensure complete removal from system
** <30ng/ml are generally considered safe for surgery, while levels >400ng/mL are major rik of uncontrollable haemorrhage
* Reversal - MUST consult haem
** No specific antidote and will not be removed by dialysis
*** Andexanet is in trial stage
** Activated charcoal is useful if last oral dose was within 2/24
** Option: Prothrombinex 50 units/kg with FFP 2 units, +/- recombinant factor VIIa
**
* Elective:
**

*
* Restart 48-72 hours post-op for high bleeding risk surgery

== Dabigatran (Pradaxa) ==

* Taken from Austin guideline published 25/2/16
* Oral direct thrombin inhibitor
* Elimination half-life 12-17 hours. Eliminated at kidneys.
* Monitoring: PT and APTT are unreliable, but normal APTT suggests unlikely high levels of dabigatran. 
** Best available monitoring is thrombin clotting time (TCT) - if normal, excludes presence of dabigatran
** HEMOCLOT is a dilute thrombin clotting time assay but doesn't correlate well with risk of bleeding
* Reversal: idarucizumab - monoclonal Ab, binds to dabigatran. Achieves rapid and complete reversal. Generally safe - 5% risk of thrombosis.
** Approval required via either anaesthetist in charge or haem consultant on call
** Used in life-threatening bleeding or for urgent surgery
** Dose is 5g IV either bolus or infusion - see guideline for full order
** Perform dabigatran levels and TCT both prior to, post, and 4 hours post administration
**
* Dialysis may enhance clearance
* Elective surgery:

* Recommence 48-72 hours post high risk surgery

== Clopidogrel ==

* P2Y12 receptor blocker on platelets for ADP, which irreversibly prevents platelet activation
* No specific reversal agents

== Thrombolysis/fibrinolysis ==

* Contraindications:
** Active peptic ulcer
** Previous haemorrhagic stroke
** Recent head injury
** Prolonged traumatic CPR


[[Category:Haematology]]