HAEMOSTASIS

Mr. S. M. Sheridan
Faculty of Dentistry
Royal College of Surgeons in Ireland
 INTRODUCTION

• Routine dental procedures often cause oral soft tissue

trauma leading to local bleeding/haemorrhage.
• Fortunately in most instances the bleeding stops.
• Sometimes bleeding continues so it is important that we
understand the process so that can undertake the
necessary measures to arrest the bleeding.
• Knowledge of the process involves an understanding of
aspects of basic anatomy, physiology.
• Knowledge of basic pathology, pharmacology and
clinical dentistry is necessary to fully understand the
possible causes persistent bleeding in the dental
environment.
 DEPENDS ON THE INTERACTION
BETWEEN

• Blood vessel wall integrity and reaction to injury:

• Action of Platelets:

• Clotting cascade:
 BLOOD VESSEL REACTION

Injury
↓
automatic reflex
↓
(vascular spasm in smooth muscle in blood vessel wall)
vasoconstriction
↓
stems the flow of blood
 VASCULAR DISORDERS

• Inherited:
Marfan’s Syndrome: Connective tissue disorder with
skeletal, cardiac, ocular and dermatological
malformations
Osler-Weber-Rendu Syndrome/Hereditary Haemorrhagic
Telangiectasia (HHT/HHT1): Gene mutation
Ehlers-Danlos Syndrome: RARE (disruption of proteins
leading to fragile connective tissue)
 VASCULAR DISORDERS

Acquired:
• Trauma
• Physiological senile purpura
• Drugs: Corticosteroids
• Infections: meningococcal septicaemia
• Vitamin Deficiency: Scurvy (Vit C)
• Endocrine: Cushing’s Syndrome
 DENTAL MANAGEMENT OF INHERITED
VASCULAR DISORDERS
• Rarely cause bleeding problems
• Can be managed in Primary Care Dental environment
• Local measures to aid haemostasis:

Pressure application
Suturing
Haemostatic agents
Post-Op Instructions (verbally & in writing)
 PLATELETS (THROMBOCYTES)

Production
• Originate from the MEGAKARYOCYTE within bone
marrow.
[Thrombopoietin hormone (TPO) controls
megakaryocyte
development via myeloid stem cells →
megakaryoblasts → megakaryocte (type of giant cell)].
• Megakaryocyte undergo a process of fragmentation
releasing
1000 platelets per megakaryocyte.
 PLATELET ULTRASTRUCTURE

• Anucleate cell fragments

• Trilaminar membrane maintains integrity of cytoplasm
• Dense granules contain:
Adenosine diphosphate
Serotonin
Calcium ions
• α- granules contain:
Fibrinogen
Vitronectin
von Willebrand factor
PLATELET ULTRASTUCTURE
 PLATELET FUNCTION

• Circulate as plate-shaped cell fragments in a resting

state at the periphery of the blood vessel
(Ready to respond to vessel wall damage)
• Normal platelet level: 150-450x 109 ∕ l
• Life span: 8 days (range 5-9 days)
• Contain many structures that are critical to the arrest of
bleeding functioning by:

• Platelet Adhesion
• Platelet Aggregation
 PLATELET ADHESION

• When activated proteins on their surface allow them to

stick to breaks in the vessel wall and to stick to each
other.
• Change shape, extend filaments/tentacles
reaching out to the blood vessel wall to form a plug and
seal
• Also recruit other platelets to the site to aid in the
formation of the platelet plug
• Reliant on von Willebrand Factor (vWF) found in plasma.
 PLATELET AGGREGATION

• Platelet agonists i.e. Adenosine diphosphate

(ADP) + thrombane A2 is released.

• Fibrinogen binds to receptors on the platelet membrane,

cross-linking the platelets thus forming the primary
platelet plug thus completing Primary Haemostasis.
[Secondary Haemostasis occurs concurrently]
DISORDERS OF PLATELET NUMBERS
THROMBOCYTOPENIA

Failure of bone marrow production

Increased destruction of platelets once released:
• Immune Thrombocytopenia (ITP)
• Drug-induced Thrombocytopenia (DITP)
• Pregnancy “Gestational Thrombocytopenia”
• Thrombotic thrombocytopenia purpura (TTP)
• Thrombotic microangiopathies (TMA)
• Drug-induced TMA
• Complement-mediated TMA
• Haemolytic Uremic Syndrome (HUS)

Increased production of platelets Rare

 DISORDERS OF PLATELET FUNCTION

Hereditary:
• Glanzmann’s Disease: failure of platelet aggregation
• Bernard Soulier Syndrome: Failure of platelet adhesion
Deficiency of “glycoprotein
1b, receptor for vWF.
Acquired:
• Medication: Aspirin, Heparin, Clopidogrel, Dipyridamole
• Uraemia
• Myeloprolierative Disease
(haematopoietic stem cell mutation within bone marrow)
 ANTI-PLATELET DRUGS

• Aspirin: Affects platelet aggregation + vasoconstriction

• Dipyridamole (PERSANTIN): Affects platelet aggregation

• Clopidogrel (Plavix): Blocks adenosine diphosphate ADP

• Prasugrel: ADP inhibitor

• Ticagrelor: ADP inhibitor

VASCULAR & PLATELET DISORDERS

Post-operative problems following an extraction usually

present as prolonged bleeding immediately after the event
as part of the initial response to an injury
 DENTAL MANAGEMENT

• Patients with platelet disorders require liaison with

Haematologist for certain dental procedures.
• Important that no anti-platelet medication is stopped for
any form of dental treatment without direct consultation
with Physician in charge {risk of a thrombo-embolic
event following cessation of medication is greater than
that of a post-operative bleed}.
• Apply local haemostatic measures
• Correct timing of treatment: early morning/early in week
{allows increased time period for review post-operatively
& management of problems should they arise}
LOCAL HAEMOSTATIC MEASURES

• Apply pressure

• Use of Local Anaesthesia

• Suturing

• Haemostatic Agents: Oxidised Cellulose (Surgicel)

• Post-operative instructions: Verbal and Written

 COAGULATION CASCADE
XII→ XIIa Tissue Factor Intrinsic Pathway
↓ ↓
XI → XIa VII Extrinsic Pathway
↓ ↓
IX→ IXa VIIa Common Pathway
↓ ↓

VIII V

↓ ↓
| ____________________________ |
|
X → Xa
↓
Prothrombin → Thrombin
↓
Fibrinogen → Fibrin (monomer)

XIII → XIIIa
↓
Fibrin (polymer) → CLOT
CLOTTING FACTORS LIST

Factor I: Fibrinogen
Factor II: Prothrombin
Factor III: Thromboplastin/Tissue factor
Factor IV: Calcium
Factor V: Proaccerin/Labile factor/Ac-globulin (Ac-G)
Factor VI: Unassigned (previously Va)
Factor VII: Proconvertin/Serum prothrombin conversion accelerator
Factor VIII: Antihaemophilic factor(AHF)or globulin (AHG)
Factor IX: Christmas factor/Antihaemophilic FB
Factor X: Stuart Prower factor/Stuart factor
Factor XI: Plasma thromboplastin antecedent (PTA)/antihaemophilic FC
Factor XII: Hageman factor
Factor XIII: Fibrin stabilizing factor
 CLOT FORMATION

• Dynamic process involving a balance between the

haemostatic and the fibrinolytic systems.

• Haemostatic System:
Involves numerous cells, chemicals & plasma proteins all
of which are required for successful haemostasis.

• Fibrinolytic System:
Fibrinolysis occurs when the plasma enzyme
plasminogen activates plasmin which digests fibrin
threads in the clot.
MAJOR SOURCE OF CLOTTING FACTORS

• Liver

• FII, FVII, FIX, FX dependent on Vit K

• Vit K Deficiencies
 VITAMIN K DEFICIENCY

• Malabsorption:
Bowel pathology: Coeliac Disease

Biliary Obstruction:

• Antagonist drugs:
Coumarins: Warfarin
 CLOTTING DISORDERS

• Normal vascular and platelet response will initially mask

any problem due vasoconstriction and the formation of
the stable platelet plug.

• As the clotting response occurs last, patients will usually

complain of a delayed oozing from the socket some time
after the event.
 CLOTTING DISORDERS

Inherited Factor Deficiency:

• von Willbrand’s Disease (vWF)
• Haemophilia A (FVIII)
• Haemophilia B (FIX) / Christmas Disease
Acquired Factor Deficiency:
• Liver disease
• DIC
• Factor Inhibitors (mainly FVIII): Postpartum; Malignancy;
Autoimmune Disease: Systemic Lupus Erythematosis,
Rheumatoid arthritis
Medication: Oral anticoagulants
 VON WILLEBRAND’S DISEASE

• Most common inherited bleeding disorder.

• Caused by a deficiency of vWF or a mal-function.
• Occurs in 1% of UK population
• Symptoms:
Bruise easily
Bleeding from mucous membranes: gums, nose ,GIT,
Prolonged bleeding from cuts
Excessive bleeding after surgery
Severe menstrual bleeding
 VON WILLEBRAND’S DISEASE
CLASSIFICATION
• Type 1: mildest and commonest form ; reduced vWF

• Type 2: 4 further subtypes; mal-function vWF

• Type 3: Rarest form; no vWF present

• Pseudo or Platelet Type: platelet abnormality.

MANAGING VON WILLEBRAND’S DISEASE

• Dental Management:
Mandatory to seek advice of Haematologist.

• Desmopressin; nasal spray or injection

• Tranexamic Acid; mouth wash, tablet, injection

• von Willebrand factor concentrate; purified from human

plasma
HAEMOPHILIA

A rare congenital bleeding disorder occurring in people with

a limited amount of either Factor VIII (Haemophilia A) or
Factor IX (Haemophilia B or Christmas Disease).

Severity: % normal F activity

Normal 50 -100%
Mild 5 - 40%
Moderate 1 - 5%
Severe Less than 1%
 DIAGNOSIS

• Excessive bruising

• Bleeding into joints, muscles and soft tissues with pain

• Bleeding episodes: vomiting, coughing, GIT

 TREATMENT

• IV replacement: (plasma derived)

• Prophylaxis: (plasma derived or recombinant)

Small regular infusions of factor concentrate
Haem A: every 48 hours
Haem B: twice per week

{Recombinant: genetically engineered factors VIII & IX}

 COAGULATION STUDIES

• Prothrombin Time (PT).

• Activated Partial Thromboplastin Time (APTT).

• Thrombin Time (TT)

 PROTHROMBIN TIME (PT)

• Measures extrinsic system (tissue factor + FVII) &

common pathway (X, V, Prothrombin & Fibrinogen)

• Prolonged in Liver Disease & Warfarin therapy

(expressed in INR)
ACTIVATED PARTIAL THROMBOPLASTIN
TIME (APPT)
• Measures intrinsic system (XII, XI, IX & VIII) & common
pathway (X, V Prothrombin & Fibrinogen)

• Prolonged in:
Heparin therapy
Haemophilia A (FVIII)
Haemophilia B (FIX)
 THROMBIN TIME(TT)

• Measures the activity & fibrinogen in the common

pathway.

• Prolonged in:
Fibrinogen deficiency or dysfunction (Disseminated
Intravascular Clotting)

Heparin Therapy (inhibition of thrombin activity)

 CLASSIFICATION OF HAEMORRHAGE

• Primary:
At time of surgery

• Intermediate/Reactionary:
Occurs within a few hours following cessation of
vasoconstriction and failure of coagulation.

• Secondary:
Occurs 10-14 days post surgery (mainly as a result of
infection following major surgery)
LOCAL CAUSES OF HAEMORRHAGE FOLLOWING
ORAL SURGERY PROCEDURES

Trauma to
• Soft tissue:

• Vascular:
Arterial: Bright red & spurting
Venous: Dark red & steady flow
Capillary: Bright red & oozing

• Bone:
Nutrient canals in alveolar bone.
Central vessel: inferior alveolar artery
Central vascular lesion: (Haemangioma, Vascular Malformation)
 SYSTEMIC CAUSES OF HAEMORRHAGE

• Haemophilia
• von Willebrand’s Disease
• Thrombocytopenia
• Uncontrolled hypertension
• Anticoagulant therapy
 MANAGEMENT OF PRIMARY
HAEMORRHAGE INCLUDES
• Blood vessel ligation
• Pressure application
• Heat application
• Electrocautery
• Haemostatic agents
• Vasoconstrictor in L.A
MANAGEMENT OF INTERMEDIATE
HAEMORRHAGE
Identify the source of bleeding:

From Bone:
Use Haemostatic Agent: Bone Wax; Oxidised Cellulose

From Soft Tissue:

Suturing
IDENTIFICATION OF PATIENTS AT HIGH RISK OF POST
EXTRACTION HAEMORRHAGE

Clotting Factor Deficiency: Haemophilia A (FVIII) & B (FIX); vWF

Vit K Deficiency (FII,VII,IX, X)
Acquired Liver Disease: Hepatitis/Cirrhosis
Platelet Deficiency (Thrombocytopenia): Idiopathic
Drug induced
Anticoagulant therapy: Heparin; Warfarin

Vascular Anomalies: Arteriovenous malformations

Hereditary Haemorrhagic Telangiectasia
Collagen Disorders
 SUMMARY

• Knowledge of the physiology of haemostasis to

understand how haemorrhage occurs.
• Haemostasis process involves:
Vasoconstriction
Platelet Plug Formation
Coagulation Cascade Network
• Bleeding Disorders
• Classification of Haemorrhage:
Primary; Intermediary; Secondary
• Identification of those patients at risk of post extraction
haemorrhage.
• Armamentarium for post extraction haemorrhage.
 USEFUL ARTICLE TO READ

• Dental Management of Patients with Inherited Bleeding

Disorders:
Dental Update: October 2013.Vol 40 No: 8

• Dental Management of Patients with Drug-Related

Acquired Bleeding Disorders:
Dental Update: November 2013.Vol 40 No: 9