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L21 Haematology 2025_formatted_text

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DENT 3005: Introduction to Pharmacology1

Haematology

Dr Thuy Linh Truong thuy.truong@uwa.edu.au

Learning Outcomes23

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 Coagulation4

  • 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 Xa fibrin clot
  • Plasmin from plasminogen breaks down the clot after repair process is completed
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

Overview of Antithrombotic Agents5

AnticoagulantsAntiplatelets
- ‘Blood thinners’- Blood platelets are inactive until injury clump & form thrombus
- Delay clotting of blood- Inhibit platelet aggregating
- Interfere w/ coagulation cascade- Indications
- Reduce fibrin formation prevent clot forming & growing- Px & tx of ACS, ischaemic stroke & TIA
- Indication
- Px & tx of venous thromboembolism
- Ischaemic stroke & TIA
- ACS

Anticoagulants6

  • 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 nameBrand Name
Heparins
DalteparinFragmin inj
DanaparoidOrgaran inj
EnoxaparinClexane inj
HeparinHeparin inj
Direct thrombin inhibitors
BivalirudinBivalirudin inj
DabigatranPradaxa
Factor Xa inhibitor
ApixabanEliquis
FondaparinuxArixtra inj
RivaroxabanXarelto
WarfarinCoumadin
Marevan

Warfarin7

  • 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
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;

Antiplatelets8

  • Glycoprotein IIb/IIIa inH
    • Occupy glycoprotein IIb/IIIa receptor
    • Prevent binding of fibrinogen to platelet
    • Block platelet aggregation
  • P2Y antagonists
    • Binds to the platelet P2Y receptor
    • Inhibits platelet aggregation
  • Aspirin
    • Irreversibly inhibiting cyclo-oxygenase
    • Inhibits platelet aggregation
    • Reducing the synthesis of thromboxane A
  • Dipyridamole
    • Inhibiting phosphodiesterase → increase platelet cAMP → inH platelet function
Generic nameBrand Name
Glycoprotein IIb/IIIa inhibitorsOnly through SAS
EptifibatideAggrastat inj
TirofibanAggrastat inj
P2Y antagonistsClovix, Plavix
ClopidogrelPresugrel
PrasugrelBrilinta
TicagrelorBrilinta
NSAIDAspirin, Solprin
AspirinAspirin, Solprin
PDE inHPersantin inj
DipyridamolePersantin inj

Thrombolytics9

  • Alteplase & Tenecteplase
    • Converts plasminogen plasmin
    • Catalyses breakdown of fibrin
  • Indications
    • Acute STEMI
    • Acute ischaemic stroke
    • Acute massive VTE in patients who are hemodynamically unstable
Generic nameBrand Name
AlteplaseActilyse inj
TenecteplaseMetalyse inj

Other Haematological Agents10

  • 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 reduce their action
    • Idarucizumab: Binds w/ dabigatran and its metabolites stable inactive complex
    • Protamine : Combines w/ heparin to stable inactive complex

Generic name

Brand Name

Drugs affecting hemostasis

Tranexamic acid

Cyklokapron

Vitamin K

Konakion inj

Reversing anticoagulation

Andexanet alfa

Andexxa inj

Idarucizumab

Praxbind inj

Protamine

Protamine inj

Drugs for Anemia11

  • Erythropoietin agonists
    • Recombinant glycoproteins that bind to erythropoietin receptors on erythroid progenitor cells 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
    • Essential for nerve development, nucleic acid synthesis and normal erythropoiesis.
Generic nameBrand Name
Erythropoietin agonists
Darbepoetin alfaAranesp inj
Epoetin AlfaEprex inj
Epoetin betaNeoRecormon inj
Methoxy pegepoetin betaMircera inj
Other
Folic acid
Iron
Vitamin B12

Dental Implications of Hematology12

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

Hematology Drugs-Drug Interactions13

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

Antithrombotic drugs: considerations for oral & dental procedures14

  • 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 drugs15

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.

Bleeding Risk by Oral and Dental Procedure Type16

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 bleedingHigher risk of prolonged bleeding [NB2]
extraction of a small number of teeth (eg 1 to 3 teeth) that are not adjacentextraction 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 swellingsextensive soft tissue biopsies
limited or small soft tissue biopsieshard 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 drugs17

  • 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.

References18

  • 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

Footnotes

  1. Original PDF page 1: L21 Haematology 2025, p.1 ↩

  2. Original PDF page 2: L21 Haematology 2025, p.2 ↩

  3. Original PDF page 3: L21 Haematology 2025, p.3 ↩

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  18. Original PDF page 18: L21 Haematology 2025, p.18 ↩

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