NOVEL ANTICOAGULANTS

Dr. NADIA NOOR

 OUTLINE
➢ Introduction-Anti coagulants
➢ Types
➢ Pharmacology
➢ Indications
➢ Comparison
➢ Adverse Reaction and adverse reactions
➢ Dental implications and management
➢ Signs and symptoms of blood loss
➢ Stroke emergency and gold standard treatment
➢ References
WHAT DO YOU ASK YOUR PATIENT TAKING NON
VITAMIN K ANTAGONIST?
A SUBSTANCE THAT PREVENTS
BLOOD FROM CLOTTING BY
SUPPRESSING THE SYNTHESIS
OR FUNCTION OF CLOTTING
FACTORS. IT IS GIVEN TO
PREVENT THROMBOSIS.
TYPES




 VITAMIN K ANTAGONIST NON VITAMIN K

 ORAL / IV ANTAGONIST ORAL / IV



 ANTICOAGULANT* ANTICOAGULANT

 HEPARIN FACTOR Xa INHIBITORS







 WARFARIN THROMBIN INHIBITORS








*In combination with Antiplatelet drugs like aspirin

DRUG DENTAL
PHARMACO INDICATION compariso ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S n REACTIONS LOSS
ONS NS
DRUGS
• HEPARIN

• WARFARIN (COUMADIN)

• DABIGATRAN (PRADAXIA)

• RIVAROXABAN (XARELTO)

• APIXABAN (ELIQUIS)

• EDOXABAN (SAVAYSA)

• ENOXABAN (LOVENOX)

• FONDAPARINUX (ARIXTRA)

DRUG DENTAL
PHARMACO
pharmacolog INDICATION compariso
PROS & COMPARIS
ADVERSE REFRENCE
BLOOD
TYPES INTERACTI
OUTCOME IMPLICATIO
STUDY
LOGY
y S CONS
n REACTIONS
ON LOSS
S
ONS NS
PHARMACOLOGY
• The coagulation cascade is an intricate pathway controlled by many factors. Inhibiting one
element can turn off the entire process. The last steps of coagulation pathway involve







PROTHROMBINASE

PROTHROMBIN THROMBIN

FACTOR Xa





THROMBIN CLOT

FIBRINOGEN FIBRIN

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
 Heparin
LMWH

Fondaparinux

Weitz JI, Bates SM. New anticoagulants. J Thromb Haemost. 2005 [PubMed] [Google Scholar]
INDICATIONS
• DVTs (Deep Vein thrombosis)
• THROMBOEMBOLISM
 PREDISPOSITION
(RECURRENT ISCHEMIC STROKE) TO CLOT
• NON-VALVULAR ATRIAL FIBRILLATION FORMATION
• CARDIAC ARRYTHMIAS
• POSTSURGICAL PATIENTS

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
COMPARISON
VITAMIN K ANTAGONIST NOVAL ANTICOAGULANTS
• unpredictable pharmacokinetics • predictable pharmacokinetics
• frequent lab monitoring • no frequent monitoring

• frequent dose adjustments • no frequent dose adjustments

• affected by diet, genetics and • less affected by inter and intra

illnesses patient variables

• Idarucizumab - hemodialysis 

• reversal agents (vit-k, fresh
Aripazine, Andexanet , PCC
frozen plasma, prothrombin
can also be given
complex concentrate (PCC)

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
COMPARISON
• Half life 20-60 hrs • Rapid onset and off set
• Heparin bridging • no heparin bridging
• Cost effective • Expensive
• Many drug interactions
• Fewer drug interactions
• Long acute hospital stay
• Shorter stay
• Skin necrosis, DVTs, Rebound
• Gastrointestinal bleeding ,
hypercoagubility , Recurrence
major bleeding
(early phase), Gangrene,
major bleed, withdrawal
effects

TOOTH DRUG DENTAL

PHARMACO INDICATION COMPARIS COMPARIS
ADVERSE REFRENCE
BLOOD
TYPES PREPARATI INTERACTI
OUTCOME IMPLICATIO
STUDY
LOGY S ON REACTIONS
ON LOSS
S
ON ONS NS
 warfarin NOACs

DABIGRATAN 2HRS
Xa INHIBITOR
EFFECTIVENESS 48 - 72HRS
5 - 12 HRS

1.45 HRS

REVERSAL UPTO 72HRS 10 MIN

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
WARFARIN - COST EFFECTIVE
warfarin • xarelto
100 tabs 5mg for Rs.575 • 30 tabs Rs.7249
for 1 month Rs.172
INR test 600 to 1650 Rs
for 1 month if after every 3 days initially and
then 5 days 

for 3 day gap (9 times a month)
Rs.5400
for 5 day gap (6 times a month)
Rs.3600
loprin 75mg 30tabs 31 Rs

complete package will be around Rs.3802

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
PARADOXAL PROCOAGULANT EFFECT OF EARLY DOSES
OF WARFARIN: POSSIBLE ROLE OF NON VITAMIN K ORAL
ANTICOAGULANT IN PATIENTS WITH AF RELATED STROKE
• 71% INCREASED RISK OF STROKE IN FIRST 30 DAYS, HOWEVER DECRESE AFTER
THIS.
• IT BLOCKS TWO ENDOGENOUS ANTICOAGULANT THAT IS PROTEIN C AND S (8HRS)
AND WARFARIN DECREASES PROTEIN C LEVELS FASTER THAN COAGULATION
FACTORS. THUS IT CAN PARADOXICALLY INCREASE THE COAGULATION TENDENCY
WHEN TREATMENT HAS BEGUN.
• A case control study on female patient treating with the gold standard treatment was reported
to have thrombotic event on the other side on 7 day with skin necrosis and decrease levels of
protein C and another case on 3 day with levels as 

PROTEIN C: 13% (70-140%)

PROTEIN S: 28% (70-140%)

INR:1 PROTHROMBIN TIME:10.5SEC (9.5-12SEC)

(with no inherited or acquired prothrombin state)



JOURNAL OF STROKE 2015 MAY;17(2);216-218


DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
NOACS FAVOURS IN EMERGENCY
• Vitamin K (phytonadione), administered orally or intravenously, can be used to
accelerate warfarin reversal to some extent by counteracting its effects on
vitamin K-dependent coagulation factor synthesis. The effect of vitamin K on
reversal of VKA-based anticoagulation is not immediate but will progress over
18–24 h or more as the liver synthesises sufficient quantities of vitamin K-
dependent coagulation proteins (factors II, VII, IX and X) to re-establish effective
clotting, a process that takes even longer in the presence of liver disease or
other metabolic or nutritional problems.

• Reversal agent ciraparantag 150 mg to 300 mg


reversal happened in 10 minutes 







Thromb Haemost. 2017 Jan 26;117(2):238-245.

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
DRUG INTERACTIONS
• All four NOACs are substrate of P-glycoprotein (P-gp) transporter and Rivaroxaban
and apixaban are also substrates of cytochrome P 450 3A4 (CYP3A4)
• Inhibitors of P-gp and CYP3A4 

ketoconazole

Ritonavir

clarithromycin
• inducers of substrates like

carbamazepine

phenytoin

rifampin

St John’s Wart

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
ADVERSE REACTIONS
• INCREASE RISK OF BLEEDING WHICH CAN BE SIGNIFICANT AND EVEN FATAL

(PATIENTS SHOULD BE EDUCATED REGARDING THE SIGNS AND SYMPTOMS OF BLOOD
LOSS)
• DABIGATRAN AND RIVAROXABAN HAVE SAME RATES OF MAJOR BLEEDING SIMILAR TO
THAT OF WARFARIN. APIXABAN AND EDOXABAN HAVE REDUCED.
• GASTROINTESTINAL REACTIONS LIKE

DYSPEPSIA

GASTROESOPHAGEAL REFLUX DISEASE
• GASTROESOPHEAGEAL BLEEDING RISK HIGH IN RIVAROXABAN
• PATIENT CANNOT SKIP EVEN A SINGLE DOSE (DEMENTIA)-SHORT HALF LIFE
• RISK OF MAJOR BLEEDING IN ACUTE PHASE IF GIVEN WITHIN FIRST 3 DAYS

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
DENTAL
IMPLICATIONS
GUIDELINES
• 2015 Consensus guideline from European Heart and Rythym association (updating a 2013
guideline) suggests that interventions not necessarily requiring discontinuation of the
newer anticoagulants include 

Extraction of 1-3 teeth

Periodontal surgery

Abscess incision 

Implant positioning


• A 2015 narrative review by Elad et al


(18 randomised controlled trials)

Continue regular dose of drug

Postpone the timing of the daily dose of the anticoagulant or the dental intervention as late
as possible after the last dose.

Temporarily interrupt drug therapy for 24 to 48 hours


DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
• 2015 Dental specific Narrative review by Thean and Alber

Balancing the risk of Post operational bleeding and risk of thrombosis

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
 PATIENT DENTIST DENTIST
DONOT SKIP THE DOSE OF DISCUSS WITH THE DELAY TREATMENT AS MUCH
NOACS UNTILL ADVISED. CONCERNED PHYSICIAN FOR POSSIBLE FROM THE LAST
THE PROCEDURE AND DOSE DOSE OF NOACS.
ADJUSTMENT
DONOT TAKE THE MEDICINE MINIMISE TISSUE TRAUMA AS PLAN MULTIPLE
3 HOURS BEFORE THE MUCH POSSIBLE. EXTRACTIONS IN A GROUP
PLANNED PROCEDURE. OF THREE

TAKE CARE OF THE POST REDUCE AREAS OF AIM AT PRIMARY CLOSURE

OPERATIVE MEASURES FOR PERIODONTAL SURGERY, OF THE WOUND
CLOT FORMING AND SCALING AND ROOT
MAINTAINING AT HOME. PLANNING- QUADRANT WISE
COMPRESS GAUZE ON THE AVOID MULTIPLE ATTEMPTS
USE COAGULATING AGENTS
SURGICAL SITE FOR 15 TO 30 DURING BLOCK ANESTHESIA
LIKE GELATIN SPONGES,
MINUTES. AND USE ASPIRABLE OXIDISED REGENERATED
SYRINGES. CELLULOSE, SYNTHETIC
COLLAGEN
BE CAUTIOUS OF ANY SIGNS USE TRANEXAMIC ACID 4.8% PROVIDE THE PATIENT WITH
AND SYMPTOMS OF AQEOUS SOLUTION ORAL AND WRITTEN
INTERNAL AND EXTERNAL MOUTHWASH BEFORE AND INSTRUCTIONS FOR POST
BLEEDING AND GO TO THE AFTER (1-2 DAYS FOUR OPERATIVE MEASURES AND
NEAREST MEDICAL FACILITY. TIMES DAILY) SURGERY. BLEEDING.
REGIONAL ANESTHESIA
“It is a type of pain management for surgery that numbs a large part of body”
• It includes spinal blocks, epidurals and nerve blocks like inferior alveolar nerve blocks.
• It does not make the patient unconscious.
• EUROPEAN GUIDELINES

Two half lives for each of the new drugs to avoid hematoma and internal bleeding

Dabigatran - 34hrs

Rivaroxaban - 22 to 26 hrs (Scandinavian suggests 18hrs)

Apixaban -26 to 30 hrs

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
PAIN CONTROL
• NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) CAN BE USED FOR SHORT
TERM USE BUT FOR LONG TERM USE ACETAMINOPHEN IS PREFERABLE AS IT
DOES NOT HAVE ANTI PLATELET EFFECT OR CAUSE PEPTIC ULCERS

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
LAB TESTS FOR NOACS


Prothrombin time PT
Partial thromboplastin time PTT
Activated thromboplastin time aPTT (dabigratan)

Diluted thrombin times test dTT

Ecarin clotting time ECT

Chromogenic FXa assay

Calibrated pt 

However, as yet, there are no specific recommendations on anticoagulant assays for use with the
oral FXa inhibitors in the clinical setting.









Results expression for tests used to measure the anticoagulant effect of new oral
anticoagulants;thrombosis journal;june2013

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
 DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
SIGNS AND SYMPTOMS OF BLOOD LOSS
MILD SYMPTOMS

Headache

Nausea 

Profuse sweating

Dizziness

fatigue
SEVERE SYMPTOMS

Pale skin 
 Blue lips and finger nails

Cold clammy skin 
 Lightheadedness

Rapid shallow breathing
 Loss of consciousness

Rapid heart rate
 Blood in urine

Little or no urine
 Blood in stool

Confusion
 Vomiting blood

Weakness

Weak pulse

DRUG DENTAL
PHARMACO INDICATION COMPARIS ADVERSE BLOOD
TYPES INTERACTI IMPLICATIO
LOGY S ON REACTIONS LOSS
ONS NS
Ambulance
115
 ▪ Sudden confusion, trouble
speaking or understanding
speech.
▪ Sudden numbness or
weakness of face, arm or leg.
Especially on one side of the
body.
▪ Sudden trouble seeing in
one or both eyes.
▪ Sudden trouble walking,
dizziness, loss of balance or
coordination.
▪ Sudden severe headache
with no known cause.

DRUG DENTAL SIGNS AND GOLD

COMPARIS ADVERSE BLOOD REFERENC
INTERACTI IMPLICATIO SYMPTOMS STANDARD
ON REACTIONS LOSS E
ONS NS OF STROKE REGIME
 ISCHEMIC STROKE

1. 1.
ALTEPLASE INTRA-ARTERIAL IV LMWH / LOVENOX
tPA (trans THROMBOLYSIS >6HRs(a (IV enoxaparan)

catheter through groin in the if the window closes this
plasminogen activator
 becomes the first line and then
affected vessel

3 - 4.5HRS oral regime

MERCI

>8HRS
Mechanical embolectomy
then oral regime
ORAL REGIME

warfarin
 NOACs

After 24-48hrs
 2-5days but with respect to major
INR 2-3
 bleeding 5day is more safe

Triple Axel clinical trials 

reaches safe levels 3-5 days
 5 days



AHA/ASA-GUIDELINES;2018
1. first line drug options plus with them no anticoagulant before 24hrs and then heparin or MERCI and then
oral regime.
• JOURNAL OF CLINICAL AND EXPERIMENTAL DENTISTRY 

NOV 2017
• CONSENSUS GUIDELINE FROM EUROPEAN HEART AND
RYTHYM ASSOCIATION 

2015
• NARRATIVE REVIEW OF ELAD ET AL

2015
• DENTAL SPECIFIC NARRATIVE REVIEW BY THEAN AND
ALBER

2015
• INTERNATIONAL MED CASE REP J.2014- WARFARIN
INDUCED DVTs
• PARADOXICAL PROCOAGULANT EFFECT OF EARLY DOSES
OF WARFARIN: POSSIBLE ROLE OF NON VIT-K ORAL
ANTICOAGULANT IN PATIENTS WITH AF RELATED STROKE
JOURNAL OF STROKE.2015 MAY: 17(2):216-218
• AMERICAN HEART ASSOCIATION (AHA) / AMERICAN STROKE
ASSOCIATION (ASA) GUIDELINES 2018

REFERENCE
TOOTH
DRUG DENTAL SIGNS AND GOLD
COMPARIS INDICATION
ADVERSE PROS & BLOOD REFRENCE
REFERENC
TYPES PREPARATI
INTERACTI IMPLICATIO OUTCOME SYMPTOMS STANDARD
STUDY
ON REACTIONS
S CONS LOSS SE
ONS
ON NS OF STROKE REGIME
• PREVENTING STROKE AND MANAGING ATRIAL FIBRILLATION
BY ICI-2015
• NEW ORAL ANTICOAGULANTS AND REGIONAL ANESTHESIA.
BRITISH JOURNAL OF ANESTHESIA, VOLUME 111, ISSUE
SUPPL_1, DECEMBER 2013
• A REVIEW OF THE ROLE OF NON VITAMIN K ANTAGONIST IN
SHORT AND LONG TERM TREATMENT OF VENOUS
THROMBOEMBOLISM-CARDOIL THER- JUNE 2018
• COAGULATION ASSESSMENT WITH NEW GENERATION OF
ORAL ANTICOAGULANTS- EMERGENCY MEDICAL JOURNAL
• www.googlescholar.com

REFRENCES
DRUG DENTAL SIGNS AND GOLD
COMPARIS ADVERSE BLOOD REFRENCE
REFERENC
INTERACTI IMPLICATIO SYMPTOMS STANDARD
ON REACTIONS LOSS SE
ONS NS OF STROKE REGIME