Presented by Dr.

Naema Gouda Ali

Lecturer of Oral medicine and Periodontology
HK = high molecular wt. kininogen.
PK = prekallikrein.
TF= Tissue factor (factor III)
PL = phospholipid
International nomenclature of clotting factors
 Investigations of bleeding
 Platelet count 150,000 to 500,000 platelets per ml of blood.
 < 20,000 per mL - spontaneous bleeding
 Bleeding time: Test for platelet function
Normal : 2 - 5 minutes
 Prothrombin Time: measures the clotting activity of factors
I, II, V, VII, and X Normal : 12-15 seconds
 Activated Partial Thromboplastin Time: Measures
clotting activity of factors I, II, V, VIII, IX, X, XI, and XII
Normal : 25 - 39 sec
 Factor assays: Measure the amount of specific clotting
factors.
 FDPs Fibrin degradation products in DIC
Activated partial thromboplastin time (aPTT or APTT)
 is a performance indicator measuring the efficacy of both
the "intrinsic" and the common coagulation pathways.
 Normal = 25 to 39 sec
 • Prolonged APTT may indicate:
 • heparin,
 • direct thrombin inhibitors,
 • a deficiency or inhibitor for factors in the intrinsic and
 common pathway factors II, V, VIII, IX, X, XI, XII,
 • vitamin K deficiency, or
 • severe liver disease
 Prothrombin time
 This measures the quality of the extrinsic pathway (as well as
the common pathway) of coagulation.
 The reference range for prothrombin time is usually around
12-15 seconds;
 • Prolonged PT:
 • Deficiencies of factors II, V, VII, X or fibrinogen;
 • Liver disease;
 • Vitamin K deficiency
 • Oral anticoagulants (warfarin)
 Thrombin time
 Time to clot formation after the addition of thrombin to
citrated blood.
 • Prolonged by:-
 • Heparin,
 • Direct thrombin inhibitors,
 • Fibrin degradation products (FDPs),
 • Paraproteins, and
 • Fibrinogen deficiency (both qualitative and quantitative)
FDPs
 Fragments resulting from the action of plasmin on fibrin or
fibrinogen
 Reflect high fibrinolysis states (such as DIC) when they are
elevated.
 Whole blood clotting time
 • A clot should occur in 5 to 15 minutes (inaccurate )
 • Prolonged = Severe deficiency of any of the coagulation
proteins
 Bleeding time:
 Normal values fall between 2 - 8 minutes depending on
the method used.
 provides assessment of platelet count and
function.
TOPIC CLASSIFICATION
Primary Haemophilia
(inhereited) • von Willerbrand
Disorder

Vitamin K
Secondary Deficiency
(Acquired) • Hepatic Failure
Oral anticoagulant
 Hemophilia
 Blood disease characterized by prolonged coagulation time
and hemorrhagic tendencies.
 Hereditary disease, defect being carried by x-chromosome,
 • Transmitted as a sex-linked Mendelian recessive trait.
 • Occurs only in males, transmitted through an unaffected
daughter to a grandson.
 Etiology
 • Hemophilia A- Plasma Thromboplastinogen (AHG factor
VIII) (classic haemophilia)
 • Hemophilia B- Plasma Thromboplastin component (PTC
factor IX) (Christmas disease)
 • Hemophilia C- Plasma Thromboplastin antecedent (PTA
factor XI)
 Males who inherit the defective gene will develop hemophilia.
Males with hemophilia do not pass the gene to their sons;
however, they do pass the gene to their daughters.
 Hemophilia A : 10% times more than hemophilia B and
200% more than any other type. Characterized by deficiency
of factor VIII:C and prolonged aPTT.
 Etiolog y: 70% are X-linked recessive disorder. 30%
spontaneous mutation. or acquired deficiency due to
development of factor VIII inhibitors antibody to factor
VIII:C in blood after receiving many blood transfusion
 Nature of factor VIII
 The whole factor VIII (VIII:C/vWF) is complex protein
circulate in plasma, consisting of small molecules with
coagulant activity (VIII:C) and larger part Von Willibrand
factor (VIII: vWF) associated with platelet adhesion.
 VIII: vWF appear to stabilize factor VIII:C

factor (VIII: vWF) VIII:C

Controlled by gene located on
chromosome 12.
Produced in endothelial cells.
Correct bleeding time abnormality
in Von Willibrand’s disease
Controlled by gene located on x-
chromosome.
Produced in liver cells.
Correct coagulation abnormality in
hemophilia
HAEMOPHILIA - CLASSIFICATION
APTT Clinical Manifestation Classification
prolonged Manifest in infancy. Severe
• Spontaneous bleeding – in muscles or (<1% of normal
joints (hemarthrosis)
• Excessive bleeding after minor trauma,
postoperatively, or after intramuscular
childhood vaccinations.

prolonged • Manifest after 2 years of life. Moderate

• Moderate trauma causes bleeding episodes (1-5% of normal)
• Occasionally spontaneous bleeding occurs

variable • Often diagnosed in teenagers and adults Mild

• Significant trauma to induce bleeding (>5% - 25% of
• No spontaneous bleeding normal)

normal Diagnosis often missed. Subclinical

Moderate bleeding from surgery or trauma. (25-50%)
 SYMPTOMS
 Excessive, uncontrollable bleeding. Bleeding may occur
even if there is no injury. Or after surgery (tonsillectomy)
 Often occurs in the joints and in the head.
 Bruising - Occur from small accidents, which can result in a
large hematoma.
 Bleeds easily - Tendency to bleed from nose, mouth, GIT .
 Bleeding into a joint - Hemarthrosis can cause pain,
immobility, joint swelling and eventually deformity if not
medically managed properly.
 Intracranial hemorrhage (brain)
 Other sources of bleeding - Blood found in the urine
(hematuria) or stool may also be a symptom of hemophilia.
Haemarthrosis
 Oral findings:
 Gingival bleeding may be massive and prolonged.
 Bleeding associated with exfoliation of teeth and eruption.
 Tooth extraction or minor surgical operation lead to severe
hemorrhage.
 Bleeding from any site of oral cavity, it may cause respiratory
obstruction if in floor of the mouth.
HAEMOPHILIA - INVESTIGATION
 Activated partial thromboplastin time (aPTT): prolonged
 Normal Prothrombin Time, Platelet Count, Bleeding Time.
 Specific factor assay : VIII (A) or IX (B) – reduced
but normal VIII: vWF.
 Joint x-ray.
 management
 Depend on severity of disease , type and site of hemorrhage
 Commercially prepared factor viii & ix
concenterate ,desmopressin acetate , cryoprecipitate.
 Chance of viral transmission (dry heat treated concentrate)
 High purity factor viii products (monoclonal antibody
purification technique) – improved viral safety.
 DDAVP (desmopressin acetate) provide transient
increase in coag factor. Absence of viral risk and lower cost
(stimulate immediate release of VIII:C and VIII: vWF from
their cell stores). But it activate plasminogen activator so
should followed by tranexamic acid (antifibrinolytic
agent) inhibit activation of plasmin.
factor VIII concentrates
 Dental management:
 Prophylactic:-
 Regular dental care.
 Fluoride application.
 Dietary advice of sugar restriction.
 Prevention of periodontal disease.
 These all reduce the need for extraction.
 Periodontal treatment: inflamed and hyperemic gingival
tissues are at increased risk of bleeding. Ultrasonic
instrumentation may result in less tissue trauma.
 For severely inflamed tissues, initial treatment with
chlorhexidine mouthwashes is recommended to reduce
tissue inflammation before deep scaling.
 Blood loss of all kinds can be controlled locally with direct
pressure or periodontal dressings with or without topical
antifibrinolytic agents.
 Restorative procedures
 Restorative treatment can be undertaken routinely providing
care is taken to protect the mucosa.
 There is a risk of bleeding with the use of matrix bands or
wooden wedges.
 can be controlled by local means or the application of topical
agents.
 Use rubber dam.
 Use saliva ejector with caution to avoid hematoma.
 Gingival retractor impregnated with epinephrine before
reduction.
 Anesthesia and pain management
 Dental pain can usually be controlled with a minor analgesic such
as paracetamol.
 Aspirin should not be used due to its inhibitory effect on platelet
aggregation.
 local anesthetic agent with vasoconstrictors may provide
additional local hemostasis. Use intrapulpal, papillar y,
interligamentary if necessary. Use nitrous oxide sedation or
diazepam.
 mandibular molar teeth are usually treated using the inferior
alveolar nerve block should only be given after raising clotting
factor levels by appropriate replacement therapy as there is a risk
of bleeding into the muscles along with potential airway
compromise due to a hematoma in the retromolar or pterygoid
space.
Management of extraction
 Ensure that the oral cavity is as healthy- remove as much
calculus and plaque as possible.
 - The regular use of an antibacterial mouthwash, for
example chlorhexidine.
 - Consider using an antifibrinolytic agent.

 Consider use antibiotics following a dental extraction for 10

days to prevent breakdown of clot.
 Discuss treatment requiring the administration of
coagulation factor or desmopressin (DDAVP).in dental ext.
raised to 50-70% , in major surgery raised to 100%
 Carry out the extraction out as atraumatically as possible
 Suture the socket if the gingival margins do not oppose well
 Use local hemostatic measures if indicated. This could
include the use of oxidized cellulose or fibrin glue.
Post-operative period
 No mouth rinsing for 24 hours
 No smoking for 24 hours
 Soft diet for 24 hours
 Prescribed medication must be taken as instructed
 Analgesia should be prescribed for use if required
 Salt-water mouthwashes should be used starting the day
after the extraction
 Antibacterial mouthwash may be used.
 If post-extraction hemorrhage occurs:
 Contact the hemophilia unit and consider using additional
factor concentrate
VON WILLERBRAND disease
 Most common hereditary disease transmitted as autosomal
dominant affect both males and females due to deficiency
or abnormality in von Willerbrand factor.
 Functions on both primary & secondary homestasis.
 1. To act as bridge between subendothelial collagen and
platelets
 2. Bind and protect factor VIII from rapid clearance then
delivers it to site of injury.
VWD TYPES:
 Type I (70%-80%) – Quantitative:
 Partial decrease in quantity vWF
 Mild clinical symptoms
 Type 2 (15%-20%)– Qualitative:
 Decrease affinity toward Factor VIII and platelet
 Type 3 – Quantitative: (autosomal recessive)
 Absence of von Willerbrand factor, so therefore VIII:C
 Severe clinical symptoms
 CLINICAL MENIFESTATION
 Mucous membrane bleeding
 Epistaxis
 Cutaneous bleeding (into skin) petechia
 Gingival bleeding spontaneous
or with brushing.
 Menorrhagia
 Bleeding after trauma or dental
extraction.
 Haemarthrosis is rare.
 INVESTIGATION
 Full Blood Count – platelet normal
 aPTT PROLONGED or normal
 Factor VIII LOW or normal.
 von Willerbrand Factor activity (ristocetin cofactor)
 Ristocetin, an antibiotic that causes vWF to bind to platelet
taken from plasma. In healthy people, platelet rapidly
agglutinate.
 Ristocetin induced platelet aggregation (RIPA): when
adding ristocetin to platelet rich plasma, agglutination occur,
abnormalities in vWF or in platelets receptors (Bernard-
Soulier syndrome) can make it abnormal.
TREATMENT
 Desmopressin (DDAVP) – Treatment of choice for patients
with vWD types 1 and 2 . Or fresh frozen plasma
 Concentrate of von Willerbrand Factor (Humarate P)
when high levels of vWF are needed but cannot achieved
with DDAVP (type 3)
 Contraceptive for menorrhagia cause transient amelioration.
 Clot-stabilizing medications (antifibrinolytic medications)
in dental procedure.
VITAMIN K DEFICIENCY
 3 main types of VK are:
 K-1, phylloquinone, derived from plants;
 K-2, menaquinone, produced by the intestinal flora
 K-3, menadione which is a synthetic, water-soluble form
used for treatment.
 Required for synthesis of Plasma factor II, VII, IX, and X by
the liver.
 Etiology: inadequate supply.
 Poor absorption: obstructive jaundice.
 Liver disease or anticoagulant drugs.
 Broad spectrum antibiotic lead to lack of vit.k syntesis.
General manifestation:
• Bruising. Hematuria.
• GIT bleeding. Cerebral bleeding.
• Investigation:-
• Prolonged PT, PTT (in severe deficiency of vit.k).
• ttt→ vit.k injection for several days (10 mg) preoperative
until control bleeding.
Liver diseases
 In addition to vit.k dependent factors (II, VII, IX, and X), the
liver synthetize also factor V, VIII, XI, XII, fibrinogen,
prekallikerin, high molecular weigh kininogen, plasminogen.
 Severe impairment of hepatic functions or severe necrosis of
hepatocytes in the absence of pre-existing liver disease as in
viral hepatitis, chronic hepatitis, liver cirrhosis, biliary
cirrhosis.
 History of jaundice or alcoholic consumption indicate liver
diseases.
Bleeding due to:
 1- reduced vit.k absorption.
 2- reduced synthesis of clotting factors.
 3- increased fibrinolysis.
 4- synthesis of abnormal fibrinogen molecules.
 5- thrombocytopenia.
 6- DIC may occur.
 Prolonged PT, PTT .
 Oral surgery deferred if possible until correction.
 Vit.k 10 mg given preoperatively for several days. Or fresh
frozen plasma and antifibrinolytic agent.
 anticoagulants
 These are drugs used to reduce the coagulability of blood in
case of venous thrombosis, MI, renal dialysis, cerebral
thrombosis.
 Parenteral anticoagulants
 a) Heparins • High Molecular Weight Heparin (standard)
 • Low molecular weight heparin
 B) Oral anticoagulants: Coumarin derivatives : (dicumarol),
or Warfarin.
 Oral anticoagulants
 Action: Coumarin inhibit enzyme “Vit K epoxide reductase”
that converts Vit K epoxide to its active hydroquinone
(reduced form)
 • Thus they prevent the activation of Vit K. affect clotting
factors II, VII, IX, and X production.
 Investigation:
 Prolonged PT, aPTT.
 Anticoagulant results in prolongation of PT up to 1.5-2.5
times the normal.
 Antidote of Warfarin: Vit K (Stop Warfarin)
 management
 In minor surgery, PT should be within therapeutic range up
to 1.5-2.5 times the normal.
 surgery→ atraumatic.
 Local hemostatic agent→ oxidized cellulose with suture.
 In life threating hemorrhage, vit.k 5 mg or factor concentrate
or fresh frozen plasma.
Heparin
 Prevent fibrin formation through inhibition of thrombin –
fibrinogen reaction (antithrombin)
 Inactivate factors IXa, Xa, XIa,XIIa.
 Prevention of platelet aggregation (large dose)
 Antidote: protamine sulphate.
 Prolonged PT, aPTT , TT (therapeutic range 3-4 times the
normal TT).
 In renal dialysis, surgery better carried in the next day until
effect of heparin stopped.
 dicumarol heparin

Plant origin Animal origin

Slow action (1-2 days) Rapid action (immediately)
oral Parenteral S.C or IV
Vitamin K Antidote 1% Protamine
Sulfate
Long duration (days) Short duration (hours, one
day)
 Disseminated intravascular
coagulation (DIC):
 It is widespread generation of fibrin within blood vessel. complex
thrombo-haemorrhagic disease occurring as secondary
complication of some systemic disease.
 Several clots in some vessels lead to increase consumption of the
blood clotting factors and platelets deficiency, lack or destruction
of those factors in other body parts, Several bleedings in other
areas of the body.

 MECHANISMS:
 Occurs due to simultaneous action of the following 4
mechanisms:
 1) Increased thrombin generation
 2) Suppressed physiological anticoagulant pathways
 3) Activation & subsequent impairment of fibrinolysis
 4) Activation of inflammatory pathways
 DIC
 Due to activation of blood coagulation by:
 A) endothelial damage.
 B) endotoxin (release of tissue factor).
 C) immune complex.
 Precipitating factors:
 Include incompatible blood transfusion, severe sepsis,
obstetric complication, severe trauma, burn, cancer (acute
granulocytic leukemia)
 Signs & symptoms of DIC
 Renal failure due to clotting in capillaries of kidney.
 Cough
 Confusion. (clotting in brain)
 Decreased platelets.
 Blood clots in brain, adrenal gland, kidney, liver, lung, heart.
 Drop in blood pressure. (shock due to adrenal damage)
 Sudden bruising.
 Bleeding, possibly from multiple sites in the body. due to
consumption of clotting factors, platelets, activation of
fibrinolytic system.
 Fever
Labinvestigations of DIC
 CBC
 thrombocytopenia is usually present
 Clotting times:
 Prothrombin time (PT) – prolonged
 Partial thromboplastin time (PTT) – prolonged
 Thrombin time (TT) – may be increased due to consumption
of fibrinogen.
 Plasma fibrinogen level is reduced.
 Blood film shows microangiopathic haemorrhagic
haemolytic anaemia.