THE UNIVERSITY OF
WESTERN
AUSTRALIA
DENT 3005:Introduction to
Pharmacology
**Haematology**
Dr Thuy Linh Truong
thuy.truong@uwa.edu.au
# **DENT 3005: Introduction to Pharmacology**
## **Haematology**
**Dr Thuy Linh Truong**
thuy.truong@uwa.edu.au
<img src="An abstract black and white artwork with the text 'The University of Western Australia' logo, 'Acknowledgement of country' and a statement acknowledging the Noongar land and people."> </img>
**Learning Outcomes**
**Learning objectives**
1) Understand the classes and mechanisms of
haematological drugs
2) Identify common classes of haematological
drugs: anticoagulants, antiplatelets,
fibrinolytics, haemostatic agents, drugs used
in blood disorders
3) Understand how these drugs impact
coagulation and bleeding risks
4) Recognise risks for bleeding in relation to
dental treatments and adjust management
accordingly
5) Recognise when INR monitoring is necessary
6) Understand local haemostatic measures
7) Know the implications of haematological
drugs and interactions in the dental setting
<img src="description_of_image" alt="An illustration of a doctor with a magnifying glass examining blood samples in test tubes, with red blood cells and medical symbols in the background." />
# **Learning Outcomes**
## **Learning objectives**
1) Understand the classes and mechanisms of haematological drugs
2) Identify common classes of haematological drugs: anticoagulants, antiplatelets, fibrinolytics, haemostatic agents, drugs used in blood disorders
3) Understand how these drugs impact coagulation and bleeding risks
4) Recognise risks for bleeding in relation to dental treatments and adjust management accordingly
5) Recognise when INR monitoring is necessary
6) Understand local haemostatic measures
7) Know the implications of haematological drugs and interactions in the dental setting
## Normal Coagulation
* Haemostasis: to stop bleeding
* Primary haemostasis: forms an unstable platelet plug at site of injury
* Secondary haemostasis: activation of coagulation cascade to stabilize the plug
* Intrinsic & extrinsic pathway converge at the common pathway
* Activation of factor X $\rightarrow$ Xa $\rightarrow$ fibrin clot
* Plasmin from plasminogen breaks down the clot after repair process is completed
```mermaid
flowchart TD
subgraph Intrinsic Pathway
A[Platelets cling and their surfaces provide sites for mobilisation of factors]
A --> B(XII)
A --> C(XI)
A --> D(IX)
A --> E(VIII)
B --> B1(Activated XII (XIIa))
C --> C1(Activated XI (XIa))
D --> D1(Activated IX (IXa))
E --> E1(Activated VIII (VIIIa))
F[Platelet phospholipids released]
B1 --> F
C1 --> F
D1 --> F
F --> E1
end
subgraph Extrinsic Pathway
G(VII) --> G1(Activated VII (VIIa)-TF complex)
end
subgraph Common Pathway
D1 & E1 --> H(Activated X (Xa))
G1 --> H
H --> I[Prothrombin activator]
I --> J(Thrombin)
J --> K(Fibrinogen (I))
J --> L(XIII)
K --> M(Fibrin)
L --> M1(Activated XIII (XIIIa))
M --> M2[Cross-linked fibrin polymer]
M1 --> M2
end
Plasminogen --> P(Plasmin)
P --> Q[dissolves]
Q --> M2
style B fill:#F0F0F0,stroke:#333
style C fill:#F0F0F0,stroke:#333
style D fill:#F0F0F0,stroke:#333
style E fill:#F0F0F0,stroke:#333
style G fill:#F0F0F0,stroke:#333
style L fill:#F0F0F0,stroke:#333
style B1 fill:#F0F0F0,stroke:#333
style C1 fill:#F0F0F0,stroke:#333
style D1 fill:#F0F0F0,stroke:#333
style E1 fill:#F0F0F0,stroke:#333
style G1 fill:#F0F0F0,stroke:#333
style H fill:#F0F0F0,stroke:#333
style M1 fill:#F0F0F0,stroke:#333
style J fill:#F0F0F0,stroke:#333
style K fill:#F0F0F0,stroke:#333
style I fill:#F0F0F0,stroke:#333
subgraph Anticoagulants
Warfarin1>**Warfarin** --> D
Warfarin2>**Warfarin** --> H
Warfarin3>**Warfarin** --> J
H <-- LMWH[LMWH]
H <-- Heparin1[Heparin]
H <-- Fondaparinux[Fondaparinux]
J <-- Heparin2[Heparin]
J <-- ThrombinInhibitors[Thrombin inhibitors]
end
D --> Warfarin1
H --> Warfarin2
J --> Warfarin3
```
# **Normal Coagulation**
- Haemostasis: to stop bleeding
- Primary haemostasis: forms an unstable platelet plug at site of injury
- Secondary haemostasis: activation of coagulation cascade to stabilize the plug
- Intrinsic & extrinsic pathway converge at the common pathway
- Activation of factor X $\rightarrow$ Xa $\rightarrow$ fibrin clot
- Plasmin from plasminogen breaks down the clot after repair process is completed
```mermaid
flowchart TD
subgraph Intrinsic Pathway
A[Platelets cling and their surfaces provide sites for mobilisation of factors]
A --> B(XII)
A --> C(XI)
A --> D(IX)
A --> E(VIII)
B --> B1(Activated XII (XIIa))
C --> C1(Activated XI (XIa))
D --> D1(Activated IX (IXa))
E --> E1(Activated VIII (VIIIa))
F[Platelet phospholipids released]
B1 --> F
C1 --> F
D1 --> F
F --> E1
end
subgraph Extrinsic Pathway
G(VII) --> G1(Activated VII (VIIa)-TF complex)
end
subgraph Common Pathway
D1 & E1 --> H(Activated X (Xa))
G1 --> H
H --> I[Prothrombin activator]
I --> J(Thrombin)
J --> K(Fibrinogen (I))
J --> L(XIII)
K --> M(Fibrin)
L --> M1(Activated XIII (XIIIa))
M --> M2[Cross-linked fibrin polymer]
M1 --> M2
end
Plasminogen --> P(Plasmin)
P --> Q[dissolves]
Q --> M2
style B fill:#F0F0F0,stroke:#333
style C fill:#F0F0F0,stroke:#333
style D fill:#F0F0F0,stroke:#333
style E fill:#F0F0F0,stroke:#333
style G fill:#F0F0F0,stroke:#333
style L fill:#F0F0F0,stroke:#333
style B1 fill:#F0F0F0,stroke:#333
style C1 fill:#F0F0F0,stroke:#333
style D1 fill:#F0F0F0,stroke:#333
style E1 fill:#F0F0F0,stroke:#333
style G1 fill:#F0F0F0,stroke:#333
style H fill:#F0F0F0,stroke:#333
style M1 fill:#F0F0F0,stroke:#333
style J fill:#F0F0F0,stroke:#333
style K fill:#F0F0F0,stroke:#333
style I fill:#F0F0F0,stroke:#333
subgraph Anticoagulants
Warfarin1>**Warfarin** --> D
Warfarin2>**Warfarin** --> H
Warfarin3>**Warfarin** --> J
H <-- LMWH[LMWH]
H <-- Heparin1[Heparin]
H <-- Fondaparinux[Fondaparinux]
J <-- Heparin2[Heparin]
J <-- ThrombinInhibitors[Thrombin inhibitors]
end
D --> Warfarin1
H --> Warfarin2
J --> Warfarin3
```
| Anticoagulants | Antiplatelets |
| :--- | :--- |
| - 'Blood thinners' | - Blood platelets are inactive until injury $\rightarrow$ clump & form thrombus |
| - Delay clotting of blood | - Inhibit platelet aggregating |
| - Interfere w/ coagulation cascade | - **Indications** |
| - Reduce fibrin formation $\rightarrow$ prevent clot forming & growing | - Px & tx of ACS, ischaemic stroke & TIA |
| - **Indication** | |
| - Px & tx of venous thromboembolism | |
| - Ischaemic stroke & TIA | |
| - ACS | |
# **Overview of Antithrombotic Agents**
| Anticoagulants | Antiplatelets |
| :--- | :--- |
| - 'Blood thinners' | - Blood platelets are inactive until injury $\rightarrow$ clump & form thrombus |
| - Delay clotting of blood | - Inhibit platelet aggregating |
| - Interfere w/ coagulation cascade | - **Indications** |
| - Reduce fibrin formation $\rightarrow$ prevent clot forming & growing | - Px & tx of ACS, ischaemic stroke & TIA |
| - **Indication** | |
| - Px & tx of venous thromboembolism | |
| - Ischaemic stroke & TIA | |
| - ACS | |
## Anticoagulants
* **Heparins**
* Binds ATIII → inactivate clotting factors IIa (thrombin) & Xa
* **Direct Thrombin inH**
* Reversibly inhibit both free and fibrin-bound thrombin
* **Factor Xa inH**
* Selectively inhibit factor Xa, blocking thrombin production
* **Warfarin**
* Vit K antagonist
* Inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X)
| **Generic name** | **Brand Name** |
| :--- | :--- |
| **Heparins** | |
| Dalteparin | Fragmin inj |
| Danaparoid | Orgaran inj |
| Enoxaparin | Clexane inj |
| Heparin | Heparin inj |
| **Direct thrombin inhibitors** | |
| Bivalirudin | Bivalirudin inj |
| Dabigatran | Pradaxa |
| **Factor Xa inhibitor** | |
| Apixaban | Eliquis |
| Fondaparinux | Arixtra inj |
| Rivaroxaban | Xarelto |
| **Warfarin** | Coumadin |
| | Marevan |
# **Anticoagulants**
- **Heparins**
- Binds ATIII → inactivate clotting factors IIa (thrombin) & Xa
- **Direct Thrombin inH**
- Reversibly inhibit both free and fibrin-bound thrombin
- **Factor Xa inH**
- Selectively inhibit factor Xa, blocking thrombin production
- **Warfarin**
- Vit K antagonist
- Inhibits synthesis of vitamin K-dependent clotting factors (II, VII, IX, X)
| **Generic name** | **Brand Name** |
| :--- | :--- |
| **Heparins** | |
| Dalteparin | Fragmin inj |
| Danaparoid | Orgaran inj |
| Enoxaparin | Clexane inj |
| Heparin | Heparin inj |
| **Direct thrombin inhibitors** | |
| Bivalirudin | Bivalirudin inj |
| Dabigatran | Pradaxa |
| **Factor Xa inhibitor** | |
| Apixaban | Eliquis |
| Fondaparinux | Arixtra inj |
| Rivaroxaban | Xarelto |
| **Warfarin** | Coumadin |
| | Marevan |
# Warfarin
* **MOA: competitively inhibits the vitamin K epoxide reductase complex subunit 1 (VKORC1)**
* **Drug interactions (many)**
* Aspirin, azoles, dicloxacillin, flucloxacillin, macrolides, metronidazole, NSAIDs, paracetamol, tetracyclines, tramadol
* **Dental implications: invasive procedures!**
* Interruption only if advised by MGP
* CHECK INR
* Before procedure & recheck w/i 24hrs
* INR < 3.5: perform procedure
* INR >3.5: defer & refer
```mermaid
graph TD
subgraph Vitamin K Cycle
A[Inactive Clotting Factors] -->|gamma-glutamyl carboxylase| B[Active Clotting Factors];
B --> C[Vitamin KO];
C --> D[Vitamin KH2];
D --> A;
D -->|NAD+| E[Vitamin K Oxide Reductase];
E -->|NADH| C;
subgraph Warfarin Metabolism
F[Warfarin] --> G[S-warfarin];
F --> H[R-warfarin];
G -->|CYP2C9| I[7-OH-warfarin];
H -->|CYP 1A1, 1A2 and 3A4| J[6-OH, 8-OH and 10-OH warfarin];
end
end
E -.- G;
E -.- H;
```
# **Warfarin**
- **MOA:** competitively inhibits the vitamin K epoxide reductase complex subunit 1 (VKORC1)
- **Drug interactions (many)**
- Aspirin, azoles, dicloxacillin, flucloxacillin, macrolides, metronidazole, NSAIDs, paracetamol, tetracyclines, tramadol
- **Dental implications: invasive procedures!**
- Interruption only if advised by MGP
- CHECK INR
- Before procedure & recheck w/i 24hrs
- INR < 3.5: perform procedure
- INR >3.5: defer & refer
```mermaid
graph TD
subgraph Vitamin K Cycle
A[Inactive Clotting Factors] -->|gamma-glutamyl carboxylase| B[Active Clotting Factors];
B --> C[Vitamin KO];
C --> D[Vitamin KH2];
D --> A;
D -->|NAD+| E[Vitamin K Oxide Reductase];
E -->|NADH| C;
subgraph Warfarin Metabolism
F[Warfarin] --> G[S-warfarin];
F --> H[R-warfarin];
G -->|CYP2C9| I[7-OH-warfarin];
H -->|CYP 1A1, 1A2 and 3A4| J[6-OH, 8-OH and 10-OH warfarin];
end
end
E -.- G;
E -.- H;
```
**Antiplatalets**
* Glycoprotein IIb/IIIa inH
* Occupy glycoprotein IIb/IIIa receptor
* Prevent binding of fibrinogen to platelet
* Block platelet aggregation
* P2Y$_{12}$ antagonists
* Binds to the platelet P2Y$_{12}$ receptor
* Inhibits platelet aggregation
* Aspirin
* Irreversibly inhibiting cyclo-oxygenase
* Inhibits platelet aggregation
* Reducing the synthesis of thromboxane A$_2$
* Dipyridamole
* Inhibiting phosphodiesterase → increase platelet cAMP → inH platelet function
|Generic name|Brand Name|
|---|---|
|**Glycoprotein IIb/IIIa inhibitors**|**Only through SAS**|
|Eptifibatide|Aggrastat inj|
|Tirofiban|Aggrastat inj|
|**P2Y$_{12}$ antagonists**|**Clovix, Plavix**|
|Clopidogrel|Presugrel|
|Prasugrel|Brilinta|
|Ticagrelor|Brilinta|
|**NSAID**|**Aspirin, Solprin**|
|Aspirin|Aspirin, Solprin|
|**PDE inH**|**Persantin inj**|
|Dipyridamole|Persantin inj|
# **Antiplatelets**
- **Glycoprotein IIb/IIIa inH**
- Occupy glycoprotein IIb/IIIa receptor
- Prevent binding of fibrinogen to platelet
- Block platelet aggregation
- **P2Y$_{12}$ antagonists**
- Binds to the platelet P2Y$_{12}$ receptor
- Inhibits platelet aggregation
- **Aspirin**
- Irreversibly inhibiting cyclo-oxygenase
- Inhibits platelet aggregation
- Reducing the synthesis of thromboxane A$_2$
- **Dipyridamole**
- Inhibiting phosphodiesterase → increase platelet cAMP → inH platelet function
|Generic name|Brand Name|
|---|---|
|**Glycoprotein IIb/IIIa inhibitors**|**Only through SAS**|
|Eptifibatide|Aggrastat inj|
|Tirofiban|Aggrastat inj|
|**P2Y$_{12}$ antagonists**|**Clovix, Plavix**|
|Clopidogrel|Presugrel|
|Prasugrel|Brilinta|
|Ticagrelor|Brilinta|
|**NSAID**|**Aspirin, Solprin**|
|Aspirin|Aspirin, Solprin|
|**PDE inH**|**Persantin inj**|
|Dipyridamole|Persantin inj|
Thrombolytics
* **Alteplase & Tenecteplase**
* Converts plasminogen $\rightarrow$ plasmin
* Catalyses breakdown of fibrin
* **Indications**
* Acute STEMI
* Acute ischaemic stroke
* Acute massive VTE in patients who are hemodynamically unstable
| Generic name | Brand Name |
| :--- | :--- |
| Alteplase | Actilyse inj |
| Tenecteplase | Metalyse inj |
# **Thrombolytics**
- **Alteplase & Tenecteplase**
- Converts plasminogen $\rightarrow$ plasmin
- Catalyses breakdown of fibrin
- **Indications**
- Acute STEMI
- Acute ischaemic stroke
- Acute massive VTE in patients who are hemodynamically unstable
| Generic name | Brand Name |
| :--- | :--- |
| Alteplase | Actilyse inj |
| Tenecteplase | Metalyse inj |
# Other
* **Other drugs affecting haemostasis**
* **Tranexamic acid:** Blocks binding of plasminogen and plasmin to fibrin
* **Vitamin K:** reverses effect of vitamin K antagonists
* Essential cofactor in the synthesis of blood clotting factors II, VII, IX and X, and proteins C and S
* **Drugs for reversing anticoagulation**
* **Vitamin K**
* **Andexanet alfa:** Binds to apixaban or rivaroxaban $\rightarrow$ reduce their action
* **Idarucizumab:** Binds w/ dabigatran and its metabolites $\rightarrow$ stable inactive complex
* **Protamine :** Combines w/ heparin to $\rightarrow$ stable inactive complex
<table>
<thead>
<tr>
<th><p>Generic name</p></th>
<th><p>Brand Name</p></th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="2"><p><b>Drugs affecting hemostasis</b></p></td>
</tr>
<tr>
<td><p>Tranexamic acid</p></td>
<td><p>Cyklokapron</p></td>
</tr>
<tr>
<td><p>Vitamin K</p></td>
<td><p>Konakion inj</p></td>
</tr>
<tr>
<td colspan="2"><p><b>Reversing anticoagulation</b></p></td>
</tr>
<tr>
<td><p>Andexanet alfa</p></td>
<td><p>Andexxa inj</p></td>
</tr>
<tr>
<td><p>Idarucizumab</p></td>
<td><p>Praxbind inj</p></td>
</tr>
<tr>
<td><p>Protamine</p></td>
<td><p>Protamine inj</p></td>
</tr>
</tbody>
</table>
# **Other Haematological Agents**
- **Other drugs affecting haemostasis**
- **Tranexamic acid:** Blocks binding of plasminogen and plasmin to fibrin
- **Vitamin K:** reverses effect of vitamin K antagonists
- Essential cofactor in the synthesis of blood clotting factors II, VII, IX and X, and proteins C and S
- **Drugs for reversing anticoagulation**
- **Vitamin K**
- **Andexanet alfa:** Binds to apixaban or rivaroxaban $\rightarrow$ reduce their action
- **Idarucizumab:** Binds w/ dabigatran and its metabolites $\rightarrow$ stable inactive complex
- **Protamine :** Combines w/ heparin to $\rightarrow$ stable inactive complex
<table>
<thead>
<tr>
<th><p>Generic name</p></th>
<th><p>Brand Name</p></th>
</tr>
</thead>
<tbody>
<tr>
<td colspan="2"><p><b>Drugs affecting hemostasis</b></p></td>
</tr>
<tr>
<td><p>Tranexamic acid</p></td>
<td><p>Cyklokapron</p></td>
</tr>
<tr>
<td><p>Vitamin K</p></td>
<td><p>Konakion inj</p></td>
</tr>
<tr>
<td colspan="2"><p><b>Reversing anticoagulation</b></p></td>
</tr>
<tr>
<td><p>Andexanet alfa</p></td>
<td><p>Andexxa inj</p></td>
</tr>
<tr>
<td><p>Idarucizumab</p></td>
<td><p>Praxbind inj</p></td>
</tr>
<tr>
<td><p>Protamine</p></td>
<td><p>Protamine inj</p></td>
</tr>
</tbody>
</table>
# Drugs for anemia
* **Erythropoietin agonists**
* Recombinant glycoproteins that bind to erythropoietin receptors on erythroid progenitor cells
$\to$ stimulate erythropoiesis
* **Folic acid**
* Required for synthesis of purine and pyrimidine bases (DNA) and for amino acid metabolism and normal erythropoiesis
* **Iron**
* Essential element required for the formation of haemoglobin and myoglobin.
* **Vitamin B**$_{**12**}$
* Essential for nerve development, nucleic acid synthesis and normal erythropoiesis.
| Generic name | Brand Name |
| :--- | :--- |
| **Erythropoietin agonists** | |
| Darbepoetin alfa | Aranesp inj |
| Epoetin Alfa | Eprex inj |
| Epoetin beta | NeoRecormon inj |
| Methoxy pegepoetin beta | Mircera inj |
| **Other** | |
| Folic acid | |
| Iron | |
| Vitamin B12 | |
# **Drugs for Anemia**
- **Erythropoietin agonists**
- Recombinant glycoproteins that bind to erythropoietin receptors on erythroid progenitor cells $\to$ stimulate erythropoiesis
- **Folic acid**
- Required for synthesis of purine and pyrimidine bases (DNA) and for amino acid metabolism and normal erythropoiesis
- **Iron**
- Essential element required for the formation of haemoglobin and myoglobin.
- **Vitamin B**$_{**12**}$
- Essential for nerve development, nucleic acid synthesis and normal erythropoiesis.
| Generic name | Brand Name |
| :--- | :--- |
| **Erythropoietin agonists** | |
| Darbepoetin alfa | Aranesp inj |
| Epoetin Alfa | Eprex inj |
| Epoetin beta | NeoRecormon inj |
| Methoxy pegepoetin beta | Mircera inj |
| **Other** | |
| Folic acid | |
| Iron | |
| Vitamin B12 | |
**Hematology**
**Dental**
**implications**
Oral manifestations of hematopoietic disorders
* Pale oral mucosa (anaemia)
* Glossitis (inflamed, smooth tongue)
* Angular cheilitis (cracked mouth corners)
* Oral mucositis (painful sores, erythema, swelling)
Management of oral complications
* Oral mucositis: good oral hygiene, antiseptic rinses,
topical anaesthetics
* Viral outbreaks: antiviral medications, self-care
* Fungal infections (candidiasis): antifungal agents
* Bacterial infections (periodontal disease): scaling,
root planning, antibiotics
Role of dental professionals
* Early recognition of oral signs
* Multidisciplinary management approach
* Awareness of pharmacological implications
# **Dental Implications of Hematology**
## **Oral manifestations of hematopoietic disorders**
- Pale oral mucosa (anaemia)
- Glossitis (inflamed, smooth tongue)
- Angular cheilitis (cracked mouth corners)
- Oral mucositis (painful sores, erythema, swelling)
## **Management of oral complications**
- Oral mucositis: good oral hygiene, antiseptic rinses, topical anaesthetics
- Viral outbreaks: antiviral medications, self-care
- Fungal infections (candidiasis): antifungal agents
- Bacterial infections (periodontal disease): scaling, root planning, antibiotics
## **Role of dental professionals**
- Early recognition of oral signs
- Multidisciplinary management approach
- Awareness of pharmacological implications
**<span style="background-color: #5abedc; color: white; padding: 20px; display: block;">Hematology drugs-drug interactions</span>**
Direct thrombin & factor xa inhibitors
* Dabigatran, apixaban, rivaroxaban → PGP substrates
* Macrolides (clarithromycin, erythromycin), azole antifungals (ketoconazole, itraconazole) → increase bleeding risk
Warfarin interactions
* High interaction potential with:
* Antibiotics: macrolides, tetracyclines, metronidazole
* Antifungals: azoles (fluconazole)
* NSAIDs, aspirin, paracetamol, tramadol
* Monitor INR levels, consult with physician
P2Y12 antagonists & opioids
* Prasugrel, ticagrelor → metabolized by CYP3A4
* Clarithromycin, erythromycin, azole antifungals → increase bleeding risk
* Opioids: delay platelet inhibition → consider delaying if pain is manageable
Key considerations for dental practice
* Review medication history for interactions
* Be cautious with antibiotics and antifungals
* Monitor bleeding during/after procedures
* Coordinate with medical providers for safe management
# **Hematology Drugs-Drug Interactions**
## **Direct thrombin & factor xa inhibitors**
- Dabigatran, apixaban, rivaroxaban → PGP substrates
- Macrolides (clarithromycin, erythromycin), azole antifungals (ketoconazole, itraconazole) → increase bleeding risk
## **Warfarin interactions**
- High interaction potential with:
- Antibiotics: macrolides, tetracyclines, metronidazole
- Antifungals: azoles (fluconazole)
- NSAIDs, aspirin, paracetamol, tramadol
- Monitor INR levels, consult with physician
## **P2Y12 antagonists & opioids**
- Prasugrel, ticagrelor → metabolized by CYP3A4
- Clarithromycin, erythromycin, azole antifungals → increase bleeding risk
- Opioids: delay platelet inhibition → consider delaying if pain is manageable
## **Key considerations for dental practice**
- Review medication history for interactions
- Be cautious with antibiotics and antifungals
- Monitor bleeding during/after procedures
- Coordinate with medical providers for safe management
**Antithrombrotic drugs: considerations for oral & dental procedures**
* Recap
* *Antithrombotic drugs: oral anticoagulants, injectable anticoagulants, antiplatelets*
* Risk Assessment: Balance bleeding vs. thromboembolic risks
* Specialist Referral: Consider for high bleeding risk or complex procedures
* Patient Guidance: Seek help for persistent/restarting/concerned bleeding
* NSAIDs: Avoid; increase bleeding risk—use **paracetamol** instead
* Conclusion: Ensure safe management through clear communication and careful risk balancing
# **Antithrombotic drugs: considerations for oral & dental procedures**
- **Recap**
- *Antithrombotic drugs: oral anticoagulants, injectable anticoagulants, antiplatelets*
- **Risk Assessment:** Balance bleeding vs. thromboembolic risks
- **Specialist Referral:** Consider for high bleeding risk or complex procedures
- **Patient Guidance:** Seek help for persistent/restarting/concerned bleeding
- **NSAIDs:** Avoid; increase bleeding risk—use **paracetamol** instead
- **Conclusion:** Ensure safe management through clear communication and careful risk balancing
**Figure 13.30 Important patient-related factors that increase the risk of prolonged bleeding from an oral or dental procedure in patients taking antithrombotic drugs**
Patients with multiple risk factors have an additive risk of prolonged bleeding. Risk factors include:
* elevated blood pressure
* abnormal kidney or liver function
* prior stroke
* history of bleeding (particularly if this occurred with a similar procedure)
* pre-existing bleeding disorder
* poor anticoagulant control (eg labile INR)
* older age or frailty
* other drugs that predispose to bleeding [NB1], including NSAIDs (eg nonprescribed NSAIDs, low-dose aspirin)
* hazardous alcohol consumption.
| **INR** = international normalised ratio; **NSAIDs** = nonsteroidal anti-inflammatory drugs |
| :--- |
| **NB1:** Many other prescription, over-the-counter and complementary medicines can affect haemostasis, either directly or through drug interactions. |
# **Figure 13.30 Important patient-related factors that increase the risk of prolonged bleeding from an oral or dental procedure in patients taking antithrombotic drugs**
Patients with multiple risk factors have an additive risk of prolonged bleeding. Risk factors include:
- elevated blood pressure
- abnormal kidney or liver function
- prior stroke
- history of bleeding (particularly if this occurred with a similar procedure)
- pre-existing bleeding disorder
- poor anticoagulant control (eg labile INR)
- older age or frailty
- other drugs that predispose to bleeding [NB1], including NSAIDs (eg nonprescribed NSAIDs, low-dose aspirin)
- hazardous alcohol consumption.
| **INR** = international normalised ratio; **NSAIDs** = nonsteroidal anti-inflammatory drugs |
| :--- |
| **NB1:** Many other prescription, over-the-counter and complementary medicines can affect haemostasis, either directly or through drug interactions. |
| **Oral and dental procedures that are unlikely to cause prolonged bleeding** | |
| :--- | :--- |
| examination and diagnostic procedures (eg periodontal examination, impressions) | |
| restorative treatments (eg restorations, root canal therapy) | |
| orthodontic treatment | |
| **Oral and dental procedures that are likely to cause prolonged bleeding** | |
| **Lower risk of prolonged bleeding** | **Higher risk of prolonged bleeding [NB2]** |
| extraction of a small number of teeth (eg 1 to 3 teeth) that are not adjacent | extraction of a large number of teeth (eg 4 or more teeth) or extraction of adjacent teeth that creates a large wound|
| periodontal procedures (eg subgingival debridement) | any procedure where a mucoperiosteal flap is used (eg surgical extractions, implant placement, periapical surgery, periodontal surgery) |
| incision and drainage of swellings | extensive soft tissue biopsies |
| limited or small soft tissue biopsies | hard tissue biopsies |
NB1: The bleeding risk associated with these procedures is based on the consensus opinion of the Oral and Dental Expert Group. Risk assessment requires clinical judgment of the individual procedure, patient- and drug-related risks of bleeding, and the practitioner's competency to manage prolonged bleeding, should it occur.
NB2: Consider specialist referral for procedures with a higher risk of prolonged bleeding in patients taking antithrombotic drugs.
# **Bleeding Risk by Oral and Dental Procedure Type**
## **Oral and dental procedures that are unlikely to cause prolonged bleeding**
- examination and diagnostic procedures (eg periodontal examination, impressions)
- restorative treatments (eg restorations, root canal therapy)
- orthodontic treatment
## **Oral and dental procedures that are likely to cause prolonged bleeding**
| **Lower risk of prolonged bleeding** | **Higher risk of prolonged bleeding [NB2]** |
| :--- | :--- |
| extraction of a small number of teeth (eg 1 to 3 teeth) that are not adjacent | extraction of a large number of teeth (eg 4 or more teeth) or extraction of adjacent teeth that creates a large wound|
| periodontal procedures (eg subgingival debridement) | any procedure where a mucoperiosteal flap is used (eg surgical extractions, implant placement, periapical surgery, periodontal surgery) |
| incision and drainage of swellings | extensive soft tissue biopsies |
| limited or small soft tissue biopsies | hard tissue biopsies |
**NB1:** The bleeding risk associated with these procedures is based on the consensus opinion of the Oral and Dental Expert Group. Risk assessment requires clinical judgment of the individual procedure, patient- and drug-related risks of bleeding, and the practitioner's competency to manage prolonged bleeding, should it occur.
**NB2:** Consider specialist referral for procedures with a higher risk of prolonged bleeding in patients taking antithrombotic drugs.
**Figure 13.31 Local haemostatic measures for oral and dental procedures in patients taking antithrombotic drugs**
* Apply pressure to the wounds—pressure is the most important factor in achieving haemostasis.
* Minimise tissue trauma.
* Place cellulose and collagen, if indicated.
* Place sutures to ensure closure of the wounds, if indicated.
* Consider using tranexamic acid 4.8% mouthwash as an adjunctive measure for patients taking warfarin—tranexamic acid mouthwash can stabilise a blood clot in patients taking warfarin. There is no evidence on the use of tranexamic acid mouthwash in patients taking DOACs. Apply tranexamic acid mouthwash topically just before surgery. After the procedure, give the patient tranexamic acid 4.8% mouthwash with instructions for use (10 mL rinsed in mouth for 2 minutes then spat out, 4 times daily for 2 days) [NB1].
DOACs = direct-acting oral anticoagulants
NB1: Tranexamic acid 4.8% mouthwash can be compounded by a pharmacy. If it is not available, a suitable alternative solution can be made by crushing a 500 mg tablet and dispersing it in 10 mL of water immediately before administration.
# **Figure 13.31 Local haemostatic measures for oral and dental procedures in patients taking antithrombotic drugs**
- Apply pressure to the wounds—pressure is the most important factor in achieving haemostasis.
- Minimise tissue trauma.
- Place cellulose and collagen, if indicated.
- Place sutures to ensure closure of the wounds, if indicated.
- Consider using tranexamic acid 4.8% mouthwash as an adjunctive measure for patients taking warfarin—tranexamic acid mouthwash can stabilise a blood clot in patients taking warfarin. There is no evidence on the use of tranexamic acid mouthwash in patients taking DOACs. Apply tranexamic acid mouthwash topically just before surgery. After the procedure, give the patient tranexamic acid 4.8% mouthwash with instructions for use (10 mL rinsed in mouth for 2 minutes then spat out, 4 times daily for 2 days) [NB1].
**DOACs** = direct-acting oral anticoagulants
**NB1:** Tranexamic acid 4.8% mouthwash can be compounded by a pharmacy. If it is not available, a suitable alternative solution can be made by crushing a 500 mg tablet and dispersing it in 10 mL of water immediately before administration.
**References**
* Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. *Rang & Dale's pharmacology*. 10th ed. Edinburgh: Elsevier; 2023
* Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Blood and Electrolytes; [updated 2025; cited 2025]. Available from: UWA Onesearch
* Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
* Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
* Bullock S, Manias E. *Fundamentals of pharmacology*. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
* MIMS Australia. *eMIMSelite*: *Consumer medicine information, specific clinical monograph* [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch
![]()
A woman blowing her nose with scattered pills and flowers.
![]()
Prescription bottles with pills scattered around them.
![]()
A woman blowing her nose with scattered pills and flowers.
# **References**
- Ritter JM, Flower RJ, Henderson G, Loke YK, MacEwan D, Robinson E, editors. *Rang & Dale's pharmacology*. 10th ed. Edinburgh: Elsevier; 2023
- Australian Medicines Handbook Online [Internet]. Adelaide (AU): Australian Medicines Handbook Pty Ltd;2000. Blood and Electrolytes; [updated 2025; cited 2025]. Available from: UWA Onesearch
- Pharmaceutical Society of Australia. Australian Pharmaceutical Formulary and Handbook: A Guide to Best Practice. 25th ed. Canberra: Pharmaceutical Society of Australia; 2021
- Ali K. Clinical dental pharmacology. 1st ed. Oxford: Wiley-Blackwell; 2023
- Bullock S, Manias E. *Fundamentals of pharmacology*. 8th ed. Frenchs Forest, NSW: Pearson Australia; 2017
- MIMS Australia. *eMIMSelite*: *Consumer medicine information, specific clinical monograph* [Internet]. Sydney: MIMS Australia; [updated 2025; cited 2025 Apr 17]. Available from: UWA Onesearch
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