1. Disroders of HemostasisDisroders of Hemostasis
•Vessel disorders
• Henoch Schonlein Purpura
•Platelet disorders
• Thrombocytopenia
•Factor disorders
• Hemophilia

2. HemophiliaHemophilia
Congenital deficiency ofCongenital deficiency of
Factor VIII (Hemophilia A)Factor VIII (Hemophilia A)
OrOr
Factor IX (Hemophilia B)Factor IX (Hemophilia B)
- CSN Vittal- CSN Vittal

3. Other Names & IncidencesOther Names & Incidences
• Hemophilia AHemophilia A 1 in 10,000 population1 in 10,000 population
• Classic hemophiliaClassic hemophilia
• Factor VIII deficiencyFactor VIII deficiency
• Hemophilia BHemophilia B 1 in 40,000 population1 in 40,000 population
• Christmas diseaseChristmas disease
• Factor IX deficiencyFactor IX deficiency
• Hemophilia CHemophilia C
• Factor XI deficiencyFactor XI deficiency

4. InheritanceInheritance
• X- Linked RecessiveX- Linked Recessive
• Gene location Xq 28 – Hemophilia AGene location Xq 28 – Hemophilia A
• Gene location Xq 27.2 – Hemophilia BGene location Xq 27.2 – Hemophilia B
• Sporadic mutation of gene 20-30%Sporadic mutation of gene 20-30%
..

7. PhysiologyPhysiology
• F VIII is a glycoprotein procofactor synthesized andF VIII is a glycoprotein procofactor synthesized and
released into the bloodstream by the vascularreleased into the bloodstream by the vascular
endothelium.endothelium.
• In the circulating blood, it is mainly bound to vonIn the circulating blood, it is mainly bound to von
Willebrand factor (vWF, also known as Factor VIII-Willebrand factor (vWF, also known as Factor VIII-
related antigen) to form a stable complex.related antigen) to form a stable complex.
• Upon activation by thrombin or factor Xa, it dissociatesUpon activation by thrombin or factor Xa, it dissociates
from the complex to interact with Factor IXa thefrom the complex to interact with Factor IXa the
coagulation cascade.coagulation cascade.
• It is a cofactor to Factor IXa in the activation of Factor X,It is a cofactor to Factor IXa in the activation of Factor X,
which, in turn, with its cofactor Factor Va, activates morewhich, in turn, with its cofactor Factor Va, activates more
thrombin.thrombin.

8. PhysiologyPhysiology
• No longer protectedNo longer protected
by vWF, activatedby vWF, activated
Factor VIII isFactor VIII is
proteolyticallyproteolytically
inactivatedinactivated
(by activated(by activated ProteinProtein
CC andand Factor IXaFactor IXa))
and quickly clearedand quickly cleared
from the bloodfrom the blood
stream.stream.
• Factor VIII isFactor VIII is
synthesizedsynthesized
predominantly in thepredominantly in the
vascularvascular
endothelium and isendothelium and is
not affected by livernot affected by liver

9. PathophysiologyPathophysiology
• Factor VIIIFactor VIII has 2 componentshas 2 components
• Factor VIII related antigen ( F VIII-Ag)Factor VIII related antigen ( F VIII-Ag)
• Factor VIII coagulant activity ( F VIII-C)Factor VIII coagulant activity ( F VIII-C)
• Normally both these are in equal proportionNormally both these are in equal proportion
• In Carriers and hemophiliacs, Factor VIII CIn Carriers and hemophiliacs, Factor VIII C
is reduced while Factor VIII Ag is normalis reduced while Factor VIII Ag is normal

10. HemophiliaHemophilia

11. HemophiliaHemophilia

12. Degrees of Severity - ClinicalDegrees of Severity - Clinical
DegreeDegree Factor VIII levelsFactor VIII levels SymptomsSymptoms
MildMild 5 - 30%5 - 30%
> 0.05 to 0.25 IU / ml> 0.05 to 0.25 IU / ml
• AsymptomaticAsymptomatic
• Prolonged bleeding while toothProlonged bleeding while tooth
extraction,extraction,
•severe trauma or following surgerysevere trauma or following surgery
ModerateModerate 1 - 4%1 - 4%
> 0.01 to 0.05 IU / ml> 0.01 to 0.05 IU / ml
•Mild to moderate traumaMild to moderate trauma
SevereSevere < 1%< 1%
< 0.01 IU / ml< 0.01 IU / ml
• Prolonged bleeding,Prolonged bleeding,
• Bleeding into joints and musclesBleeding into joints and muscles
• Severe mucosal bleedingSevere mucosal bleeding
• Excess bleeding from umbilical stumpExcess bleeding from umbilical stump
• Bleeding following circumcisionBleeding following circumcision
• Intra cranial bleedingIntra cranial bleeding

13. Symptoms of spontaneous bleedingSymptoms of spontaneous bleeding
• Many large or deep bruisesMany large or deep bruises
• Joint pain and swelling caused by internal bleedingJoint pain and swelling caused by internal bleeding
• Unexplained bleeding or bruisingUnexplained bleeding or bruising
• Blood in your urine or stoolBlood in your urine or stool
• Prolonged bleeding from cuts or injuries, or afterProlonged bleeding from cuts or injuries, or after
surgery or tooth extractionsurgery or tooth extraction
• Nosebleeds with no obvious causeNosebleeds with no obvious cause
• Tightness in your jointsTightness in your joints

14. Emergency signs and symptoms ofEmergency signs and symptoms of
hemophiliahemophilia
• Sudden pain, swelling, and warmth of large joints,Sudden pain, swelling, and warmth of large joints,
such as knees, elbows, hips and shoulders, and of thesuch as knees, elbows, hips and shoulders, and of the
muscles of your arms and legsmuscles of your arms and legs
• Bleeding from an injuryBleeding from an injury
• Painful, lasting headachePainful, lasting headache
• Repeated vomitingRepeated vomiting
• Extreme fatigueExtreme fatigue
• Neck painNeck pain
• Double visionDouble vision

15. DiagnosisDiagnosis
• Platelet count normalPlatelet count normal
• Anemia – proportional to blood lossAnemia – proportional to blood loss
• CT, PTT – ProlongedCT, PTT – Prolonged
• Factor VIII or Factor IX decreasedFactor VIII or Factor IX decreased
• By assay orBy assay or
• By mixing study with normal plasma andBy mixing study with normal plasma and
adsorbed plasmaadsorbed plasma

16. Mixing StudiesMixing Studies
• Normal serum contains : Factor IX, X, XI, XII
• Adsorbed plasma contains : Factor V, VIII, XI, XII
Correction of aPTT withCorrection of aPTT with
normal serumnormal serum but not withbut not with
adsorbed plasmaadsorbed plasma
Factor IXFactor IX deficiencydeficiency
(Hemophelia B)(Hemophelia B)
Correction of aPTT withCorrection of aPTT with
adsorbed plasmaadsorbed plasma but notbut not
withwith normal serumnormal serum
Factor VIIIFactor VIII deficiencydeficiency
(Hemophelia A)(Hemophelia A)

17. ManagementManagement
• Principles of management:Principles of management:
• Control or prevention of bleedingControl or prevention of bleeding
episodesepisodes
• Treatment of complicationsTreatment of complications
• RehabilitationRehabilitation

18. Prevention of BleedingPrevention of Bleeding
• Toys that do not have sharp edgesToys that do not have sharp edges
• Using soft and stuffed toysUsing soft and stuffed toys
• Padding the cribPadding the crib
• Using upholsted furnitureUsing upholsted furniture
• Using helmet, pads to protect elbows and kneesUsing helmet, pads to protect elbows and knees
• Games like hockey, foot ball avoidedGames like hockey, foot ball avoided
• Using soft or sponge tipped tooth brushesUsing soft or sponge tipped tooth brushes
• Proper advise on using sharp razorsProper advise on using sharp razors
• Wear Medic Alert IDWear Medic Alert ID
• Recognizing symptoms earlyRecognizing symptoms early

19. Therapeutic OptionsTherapeutic Options
• Fresh whole bloodFresh whole blood
• Whole plasmaWhole plasma
• Fresh Frozen PlasmaFresh Frozen Plasma
• CryoprecipitateCryoprecipitate
• Factor VIII ConcentrateFactor VIII Concentrate
• Recombinant Factor VIIIRecombinant Factor VIII
• From Hamster cultureFrom Hamster culture
• Immuno affinity purifiedImmuno affinity purified

20. Replacement TherapyReplacement Therapy
• Replacing the clotting factor that’s too low orReplacing the clotting factor that’s too low or
missing.missing.
• Concentrates of clotting factor VIIIConcentrates of clotting factor VIII
oror
• Clotting factor IXClotting factor IX
are slowly dripped in or injected into a vein.are slowly dripped in or injected into a vein.

21. Replacement TherapyReplacement Therapy
• Complications of Replacement TherapyComplications of Replacement Therapy
• Developing antibodiesDeveloping antibodies
• 20 percent of people with severe hemophilia A and20 percent of people with severe hemophilia A and
• 1 percent of people with hemophilia B.1 percent of people with hemophilia B.
• Viral infections from human clotting factorsViral infections from human clotting factors
• Damage to joints, muscles etc. from delays inDamage to joints, muscles etc. from delays in
treatmenttreatment

22. Replacement TherapyReplacement Therapy
• Fresh Frozen Plasma (FFP)Fresh Frozen Plasma (FFP)
• Contains Factor VIII and / or Factor IXContains Factor VIII and / or Factor IX
• 1 Unit of FFP = 200 units of F-VIII or F - IX1 Unit of FFP = 200 units of F-VIII or F - IX
• CryoprecipitateCryoprecipitate from single donor containsfrom single donor contains
F- VIII, vonWillibrand Factor and fibrinogenF- VIII, vonWillibrand Factor and fibrinogen
• 1 Unit of Cryoprecipitate = 100 units of F-VIII or1 Unit of Cryoprecipitate = 100 units of F-VIII or
F – IXF – IX
Each Unit of Factor VIII or IX = activity of 1 ml of normal plasma

23. Prophylactic TherapyProphylactic Therapy
• During surgeryDuring surgery
• After traumaAfter trauma

24. Dose CalculationDose Calculation
• 20 U / kg of factors - increase the20 U / kg of factors - increase the
level by ~ 0.5 ml or 50%level by ~ 0.5 ml or 50%
Clinical Situation Factor VIII level
should be raised to
Minor bleedsMinor bleeds
(knee & elbow bleeds)(knee & elbow bleeds)
20 – 40 %20 – 40 %
In major & life threatening conditionsIn major & life threatening conditions
(hip bleeds, intracranial hemorrhages,(hip bleeds, intracranial hemorrhages,
bleeding around airways)bleeding around airways)
to be raised to 100%to be raised to 100%
(100 U/ml)(100 U/ml)

25. Treatment of HemophiliaTreatment of Hemophilia
• Half life of Factors:Half life of Factors:
Factor VIII Factor IX
1st
Dose 6-8 hrs 4-6 hrs
Subsequent
Dose
8-12 hrs 18-24 hrs

26. Drug Therapy in HemophiliaDrug Therapy in Hemophilia
• EACAEACA ((εε –amino caproic acid):–amino caproic acid):
• Inhibitor of fibrinolytic enzyme, inhibits clotInhibitor of fibrinolytic enzyme, inhibits clot
lysis and promotes hemostasis in oral bleedslysis and promotes hemostasis in oral bleeds
and other sites.and other sites.
• Contraindication : Renal bleedsContraindication : Renal bleeds

27. Drug TherapyDrug Therapy
• DesmopressinDesmopressin ::
• DDAVP stimulates the release of storedDDAVP stimulates the release of stored factor VIIIfactor VIII andand vonvon
Willebrand factorWillebrand factor
• Increases the level of these proteins in your blood.Increases the level of these proteins in your blood.
Von Willebrand factor carries and binds factor VIII, which then canVon Willebrand factor carries and binds factor VIII, which then can
stay in the bloodstream longer.stay in the bloodstream longer.
• Administration : Injection or Nasal spray.Administration : Injection or Nasal spray.
• Use:Use:
• Before dental workBefore dental work
• For treating bleeding from the mouth or noseFor treating bleeding from the mouth or nose
• For mild intestinal bleedingFor mild intestinal bleeding

28. Drug Therapy – Other DrugsDrug Therapy – Other Drugs
• Danazol :Danazol :
• Fibrin glue :Fibrin glue : Useful for controlling bleedingUseful for controlling bleeding
at surgical and orthopedic surgical sites.at surgical and orthopedic surgical sites.
• It consists of a mixture of fibrinogen, thrombin,It consists of a mixture of fibrinogen, thrombin,
and FXIII to cross-link freshly formed fibrin.and FXIII to cross-link freshly formed fibrin.
• Useful in patients with an inhibitor to FVIII.Useful in patients with an inhibitor to FVIII.

29. ComplicationsComplications
• Due to diseaseDue to disease
• ArthropathyArthropathy
• Destruction of jointsDestruction of joints
• Due to treatmentDue to treatment
• Hepatitis CHepatitis C
• Allergic reactionsAllergic reactions
• HemolysisHemolysis
• HIV transmissionHIV transmission
• ThrombosisThrombosis

30. Long Term ManagementLong Term Management
Interdisciplinary CareInterdisciplinary Care
• Families need psychological supportFamilies need psychological support
• Genetic counselingGenetic counseling
• Antenatal diagnosisAntenatal diagnosis
• Multispecialistic approachMultispecialistic approach
• Genetic CounselingGenetic Counseling
• Hemophilic associationsHemophilic associations

31. • VittalVittal
Thank YouThank You