Hemophilia

Galila Zaher Consultant HematologistMRCPathKAUH

PrevalenceWorld-wide occurs in all racial groups.Few decades ago, children with hemophilia had a significantly reduced life expectancy. Crippled with arthritis &joint deformity Recent studies : increased life-expectancy Now :face few limitations. Normal schools, most jobs are open with full participation in society .

Hemophilia Statistics By Country

Country-specific prevalence statisticsExtrapolations of various prevalence rates against the populations Calculation is automated and does not take into account differences across various countries May be highly inaccurate and only give a general indication to actual prevalence

CureResearch.com

Hemophilia In The Middle East (Extrapolated Statistics)

Country/Region Extrapolated Prevalence Population Estimated Used

Afghanistan 2,096 28,513,6772

Egypt 5,596 76,117,4212

Gaza strip 97 1,324,9912

Iran 4,963 67,503,2052

Iraq 1,865 25,374,6912

Israel 455 6,199,0082

Jordan 412 5,611,2022

Kuwait 165 2,257,5492

Lebanon 277 3,777,2182

Libya 414 5,631,5852

Saudi Arabia 1,896 25,795,9382

Syria 1,324 18,016,8742

West Bank 169 2,311,2042

Yemen 1,472 20,024,8672

U Arab Emirates 185 2,523,9152

Turkey 5,065 68,893,9182

Hemophilia In The Middle East (Extrapolated Statistics)Country/Region Extrapolated Incidence Population Estimated Used

Afghanistan 41 28,513,6772

Egypt 111 76,117,4212

Gaza strip 1 1,324,9912

Iran 99 67,503,2052

Iraq 37 25,374,6912

Israel 9 6,199,0082

Jordan 8 5,611,2022

Kuwait 3 2,257,5492

Lebanon 5 3,777,2182

Libya 8 5,631,5852

Saudi Arabia 37 25,795,9382

Syria 26 18,016,8742

Turkey 101 68,893,9182

United Arab Emirates 3 2,523,9152

West Bank 3 2,311,2042

Yemen 29 20,024,8672

Hemophilia Prevalence

Saudi Arabia :1,896 patients with Hemophilia

i. KFSH Riyadh >150 Patientsii. Department of Hematology Dammam :54patients

iii. KAUH :40 patients Lack of public awareness Absence of national registryUnder- diagnosis

Hereditary Coagulation Factor Deficiencies In KFSH Riyadh

Patient number >159 Hemophilia A:122 patients Hemophilia B:37 patientsPediatrics :55 ,Adults: 102

Hereditary Coagulation Factor Deficiencies In Eastern Province

In a retrospective analysis 1991-9754 patients 42 hemophiliacs, 39 hemophilia A , 2 hemophilia B 5 Saudi patients factor XIII deficiency7 patients von Willebrand disease. Hemophilia B and von Willebrand disease was lower than expected

East Mediterr Health J. 1999 Nov;5(6):1188-95.

Hereditary Coagulation Factor Deficiencies In KAUH

In a 5-year retrospective analysis (2000-2005)KAUH50 patients age 4-26 years44 inherited factor deficiency & 6 platelets defect 21 hemophilia A , 12 hemophilia B 2 patients factor V deficiency2 patients factor VII deficiencyOne FX & FXII deficiency5 patients von Willebrand disease. von Willebrand disease was lower than expected Hemophilia B was higher than expected: Referral bias

Hereditary Coagulation Factor Deficiencies In KAUH

Inherited bleeding disorders

HA

HB

VWD

FV Def

FVII Def

FX Def

FXII Def

MRN Nationality FVIII level vWF level FIX level Bethesda Virology Diagnosis Severity

460497 Yemeni 1% 82% 2 Negative Haemophilia A Severe

466795 Yemeni 1% ND Negative Negative Haemophilia A Severe

504823 Sudanese 5% ND ND Negative Haemophilia A Moderate

555810 Saudi 5% ND ND Negative Haemophilia A Moderate

297426 Saudi Negative Haemophilia A

506610 Saudi 10% ND Negative Haemophilia A Mild

298966 Saudi 5% ND Negative Haemophilia A Moderate

269095 Saudi 0.30% ND ND Haemophilia A Severe

465375 Yemeni 5% Negative Haemophilia A

527413 Saudi Negative Haemophilia A

527142 Saudi Haemophilia A

496784 Saudi 10% Haemophilia A Mild

318666 Saudi Haemophilia A

395720 Palestinian 3% 100% Haemophilia A Moderate

465375 Saudi Haemophilia A

564518 Saudi Haemophilia A

537778 Saudi 5% 51% 62% Negative Haemophilia A

438217 Indian 32% Haemophilia Moderate

581455 Saudi 5% 62% 100% Negative Negative Haemophilia A Moderate

Haemophilia A

472359 Indonesian 1% Acquired haemophilia Severe

Hemophilia Patient Registry In KAUH

509898 Yemeni Normal Normal Haemophilia B Mild

501241 Saudi Normal Negative Haemophilia B Moderate

492428 Afghan Haemophilia B Mild

423667 Saudi Haemophilia B

363660 Saudi 5% Negative Haemophilia B Moderate

509898 Yemeni Normal Normal 10% Haemophilia B Moderate

574140 Egyptian 52% Haemophilia B

440433 Saudi Normal Normal Reg. Negative Haemophilia B Moderate

5452394 Haemophilia Moderate

390282 Saudi Normal Von Willebrand Disease Mild

429172 Saudi Von Willebrand Disease

544348 Yemeni 10% 6% Negative VWD

561922 Saudi 5% 3% Von Willebrand Disease Severity

518075 Sudanese Normal Normal Factor VII Def.

258546 Syrian Negative Factor V Def.

232283 Syrian HCV Ab Factor V Def.

440647 Saudi Normal Normal Normal Prolonged PT

282904 Saudi Factor XI Def.

501201 Pakistani Normal Normal Normal Factor XII Def. Mild

568488 Factor X Def. Mild

Hemophilia Patient Registry In KAUH

Prevalence Of VWD

VWD commonest inherited bleeding disorderDammam 7/54 & KAUH 5/44Female patients presenting to gynecologistUnder- diagnosis : lack of lab supportVWF is an acute phase reactant

Diagnosis and Management

Base line coagulation screenMixing studies Factor AssayBethesda assay Factor ConcentrateDDAVP Tranexamic acidFFPs & CryoprecipetateFactor Concentrate

Report On The Universal DataCollection System Infectious

Disease Complications

Hemophilia (n=835)

vWD (n=94)

H B V infection

19.2% 3.2

HC V infection

48.4 10.6

Centers for Disease Control and Prevention &National Center for Infectious DiseasesAtlanta, Georgia

Prevalence Of Hepatitis B Virus Exposure and Vaccination Status

Hepatitis B Virus Infection

The rate of exposure to HBV in congenital bleeding disorders 11.1%

Trans R Soc Trop Med Hyg. 1989 Mar-Apr;83(2):256-7

26/44 not tested reflecting lack of written protocols18/44 tested and were negative reflecting the routine neonatal immunization program started 1990 in SA including HB vaccine

Hepatitis B Virus

Hepatitis B SAg negative

Hepatitis B S AgPositive

Not tested

HCV Transmission

HCV major cause of virus-induced liver diseases 1990, anti-HCV of blood donors became mandatory Incidence of post-transfusion HCV < 1% Improvements in HCV antibody assays: 1/106 Hemophilia generated new susceptible populations

Prevalence Of HCV Infection Among Persons With Hemophilia

Hepatitis C Virus Antibodies Saudi Population

HCV is endemic in the Saudi populationOverall frequency of 5.3%5 X > reported from Western Europe and USAHemophiliacs. Seropositivity rate :78.6%

Vox Sang. 1991;60(3):162-4

Hepatitis C Virus

Hepatitis C negative

Hepatitis C Positive

Not tested

Case 1

Patient name: M T Sex: Male 2 yearsDiagnosis: Hemophilia A at age of 7 m Admission date: 3-11-2002 Lethargy , vomiting & fever for 1 DTonic-clonic convulsions for 2 D

History & Examination

On/off painful joint swelling after minor injuries.Not on regular treatment Circumcision 6 m ago (FVIII).Family history of hemophilia A ,thalassemia & SCA Vitals normal Neck rigidityNeurological examination normalOther systems examination

Investigations 

 Hb: 9.2g/dl WBC: 16.5X109 plt:509X109

PT: 1.2 sec PTT: 69.2 sec50/50 immediate mix PTT 40.2 sec50/50 post- incubation mix :PTT 80 secFactor VIII level 2%Inhibitor level :50 Bethesda units CT scan brain : subdural hematoma

Management

Patient was started on factor VIII concentrate 8 hourly Aiming x 100% x10 D Neurosurgery consult : observePatient was improving clinically 

Management

Patient was started on Malom ProtocolCyclophosphamide 2 mg/kg/dPrednisolone 1 mg/kg/dFactor VIII stat 100 IU/kg

Infusion 10 IU/kg/hr x3D

Hospital Course

Repeat  CT scan : resolution of subdural hematoma  Patient was discharged onTegretol 50 mg PO BIDCyclophosphamid 25 mg PO ODPrednisolone 5 mg PO BIDF VIII conc 250 IU IV weekly

 Follow-Up

 Follow-up in OPD Inhibitor screen at Nov 2003: Negative

Case 2

15 y old girl Referred with history of PR bleeding .History of salmonella infection.PMH of ? 2 attacks of DVT (clinical suspicion).

Case History cont

CBC : Hb 3.5 g/dl PLT 159X109/L.Isolated prolonged APTT.Mixing studies :NC.LA screen :negativeFactor VIII level 2%.PRBCs TX , FFP & FVIII concentrate.

Transfer To KAUH

Fresh PR bleeding & heavy menstrual period .Febrile .Bruises on anti-cubital fossa .

Investigations

Hb 7.5 g/dl & APTT 118 sec. Mixing study :immediate & post incubation NCFactor VIII level 2% & VWF level 80%Bethesda assay> 500 IU.LA screen &ACL Ab :negative . Septic screen : negative.Serology: HBSAg “R”,HBEAg positiveFamily study FVIII level :normal

Admission Course

Upper GIT endoscopy “Hiatus Hernia”.No blood TX.Hb level 7.5 9.5 g/dl on iron supplementation.

Incidence

1/1,000,000 annually.Males = females.5th decade. IgG 1-4 K or mixed .Against A2 domain in 48%.Or C2 domain : FVIII binding to VWF.

Haemophilia 1998 Jul;4(4):558-63

idiopathic

pregnancy

malignancy

drugs

autoimmune

Green D & Lechner K: Thrombosis and Haemostasis 45: 200-203 (1981)

Management

Clinical presentation.Titer of the inhibitor.Associated medical condition.Likelihood of spontaneous remission .Risk of toxicities of therapy .Cost .

Management

Prednisolone 6 weeksRegular F/U in OPDContinuous search for underlying cause CT chest ,abdomen & pelvis every yearAutoimmune profile every 6m3 years since diagnosis: Idiopathic Acquired Hemophilia

Dental Extraction

During F/U fracture wisdom tooth for extractionPatient was admitted prior to extractionFVII level >1%Bethesda assay >500IUTrial of FVIII conc under IVIG, no improvement Recombinant FVII 90 micg ; No intra-operative nor post-operative bleedLocal fibrin glue to maintain local hemostasis

Case 3

Patient name : H K Known sever HA :bloody diarrhea Oct 2001Post circumcision bleedLf knee swelling post trauma Family history :HA brother

Follow Up

Intra-muscular hematoma Wasting of the Rt hand muscles post wrist bleed Age :3 years :Inhibitor : 50 B IU Rt knee hemarthrosis limited extension & flexion Sever tongue bleed which required ICU admission Inhibitor assay 2BU Low responder

Genetic Disorders &Impact On Health Care Delivery

No agreed-upon definitive cure with acceptable riskChronic nature requires lifelong medical attentionExpensive supportive and symptomatic therapy Significant burden on the health care delivery system.

el-Hazmi MA East Mediterr Health J. 1999 Nov;5(6):1104-13.

Hemophilia working Group in KAUH

Blood bank specialistPediatricianInfectious disease specialistOrthopedic surgeonDentistPharmacistHemophilia nurseSocial workerHematologist

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