Hemophilia

Ashok RamadoraiBDS FDS RCSEd FFDRCSIre ( Oral Surg)

Hemophilia

• Defective factor VIII deficiency• Prevalence 5 in 100,000• Inherited as a sex-linked recessive trait• Affects only males, defect is carried by the

X chromosome, transmitted to an unaffected daughter to a grandson.

• All daughters of an affected male are obligate carriers , but sons are normal

• Sons of carriers have 50:50 chance of developing hemophilia while daughters of carriers have 50:50 chance of also being a carrier.

Factor VIII

• A glycoprotein which has three distinct components

• 1. Factor VIII C ( a pro coagulant that participates in the clotting cascade)

• 2. VIIIR:Ag- ( von Willebrand factor which binds to platelets and is the carrier of Factor VIIIC )

• von Williebrand factor that is synthesized by endothelial cells that will correct the platelet adherence defect in Vwd

• 3. VIII:RCo (ristocetin factor, which supports platelet aggregation)

• In hemophila only factor VIIIC is reduced.

VIII- vWF complex

• Non covalent bond, factor VIII is linked to a much larger protein called vWF

• Factor VIII- a procoagulant, which activates factor X in intrinsic pathway.

• vWF- facilitates the adhesion of platelets to subendothelial collagen, its absence leads to vWD.

• vWF- also is a carrier for factor VIII and its stability.

• vWF-endothelial cell• Factor VIII- liver• Thus VIII- vWF complex are synthesized

separately, come together and circulate in the plasma as one unit that serves to promote the clotting as well as platelet vessel wall interactions necessary to ensure hemostasis.

Clinical features

• Haemarthroses( bleeding into joints)• Joint damage cripple the patient• Abdominal haemorrhage ( acute abdomen)• Spontaneous haemorrhage• Tendency towards haemorrhage following

trauma, operative procedures• Petechiae and ecchymoses are

characteristically ABSENT!

Hemorrhage in hemophilia

• Dangerous either because of blood loss• Or because there may be damage to mucle,

joints, nerves • Pressure on vital organs• Compression on larynx and pharynx

following haematoma formation in the neck

• Dental extractions- persistent oozing for days- fatal, haemorrhage cannot be controlled by pressure.

• Characteristic feature- bleeding seems to stop immediately after the injury ( as a result of normal vascular and platelet response) but after an hour- intractable ooze- rapid blood loss and persists

SEVERE < 1 IU/dl

MODERATE 1-5

MILD 5-25

NORMAL >100 IU

DIAGNOSIS

• Prolonged activated partial thromboplastin time (APTT)

• Normal PT• Normal BT• Low factor VIIIC but normal vWF• FACTOR VIII assay!

Replacements

• 1. Fresh plasma• 2. FFP• 3. Cryoprecipitate• 4. Fractionated human factor concentrates

from pooled blood sources, risk of transmission HIV, herpes, Hep B and C

• 5. Porcine factor• 6. Genetically engineered factor VIII• Currently in practice- recombinant human

anti haemophiliac factor VIII

Dental management

• 1. History• 2. Examination• 3. Diagnostic tests• Dental- preventive dentistry, Fl, pit and

fissure sealants, diet adv, regular dental check up

LA

• Avoid blocks- IND, PSA • IDN block- haemorrhage into

parapharyngeal space- airway problems• Submucosal infiltration- sometimes

widespread haematoma• INTRALIGAMENTAY INJECTION ARE

SAFE!

GA

• ETT- bleeding from nasal trauma• LMA- may be safe

Antifibrinolytic Drugs(inhibit fibrin dissolution , tPA & fibrinolysis)

• Antifibrinolytics reduce factor VIII requirements

• Tranexamic acid is used as mouth wash 5% solution, 2 mts, qid, 7 days

• Oral dose- 25 mg/kg body wt tds• IV- I/2 to I g , tds

DDVAP

Desmopressin is a synthetic analogue of vaso pressin, induces release of factor VIIIC and vWF from endothelial cells.

Given as IV 0.3 to 0.5 micro g/kg body wtUseful in patients with factor VIII inhibitorsIt also causes release of plasminogen activator

therefore tranexamic acid should also be given.

Local measures

• 1.Protect the operative area• 2. Non resorbable sutures preferred• 3. Acrylic plates to protect the clot• 4. Wisdom teeth- buccal approach may be

safer, lingual tissue should be undisturbed.• 5. Local haemostasis may be aided with

gelfoam, surgicel, fibrin glues collagen etc.

Dental extractionDento alveolar surgeMinor OS

Minimum of 50 % factor VIII at the operation

Factor VIIITranexamic acid IVDDVAP IVAntibiotic, rest, splint, tranexamic acid MW

OMS 100 % at operation50% for 7 post op days

Factor VIII ivInpatientRestFactor VIII bd iv

Hemophilia with inhibitor

• Between 5 to 20% who have had repeated transfusion develop inhibitory antibodies which reduce the activity of factor VIII.

• For these patients- Monoclonal antibody purified factor VIII

• Recombinant factor• FEIBA- Human factor VIII inhibitor

Bypassing fractions

Other considerations

• Risk of HIV, HEP B , C • Viral hepatitis• Avoid NSAIDS• Anxiety control

Christmas disease

• Factor IX deficiency• Identical to HA• One tenth as common as HA

• Factor IX replacement• DDVAP not used

vWD

• Psedohemophilia• Deficiency of or defect in vWF• vWF• 1. Carrier of VIII• 2. Bridge between platelets and damaged

endothelium• Thus clotting and platelet defect is seen in

vWD

Diagnosis

• APTT prolonged, BT prolonged• Low vWF and factor VIII Ristocetin factor

assay• Platelet count- normal

• 125 in a million• 3% asymptomatic carriers

Clinical features

Mucocutaneos bleedEasy bruisingEpistaxisGingival bleedSevere vWD- spontaneous bleed into joints

and muscle cos of low or absent factor VIII

vWF concentrateFactor VIII concentrateDDVAPTranexamic acid