Hemophilia Galila Zaher
Sizin üçün oyun:
World-wide occurs in all racial groups.
, children with haemophilia 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 employment and marriage.
Hemophilia Statistics By Country
Country-specific prevalence statistics
Extrapolations 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
Hemophilia In The Middle East (Extrapolated Statistics)
Saudi Arabia :1,896 patients with Hemophilia
KFSH Riyadh >150 Patients
Department of Hematology Dammam :54
KAUH :40 patients
Lack of public awareness
Absence of national registry
Hereditary Coagulation Factor Deficiencies In KFSH Riyadh
Patient number >159
Hemophilia A:122 patients Hemophilia B:37 patients
Hereditary Coagulation Factor Deficiencies In Eastern Province
In a retrospective analysis 1991-97
42 hemophiliacs, 39 hemophilia A , 2 hemophilia B
5 Saudi patients
factor XIII deficiency
7 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)KAUH
47 patients age 4-26 years
40 inherited factor deficiency & 7 have platelets defect
21 hemophilia A , 9 hemophilia B
2 patients factor V deficiency, one FVII, FXI, FX &
4 patients von Willebrand disease.
von Willebrand disease was lower than expected
Haemophilia B was higher than expected
Hereditary Coagulation Factor Deficiencies In KAUH
Prevalence Of VWD
VWD commonest inherited bleeding disorder
Dammam 7/54 & KAUH 4/40
Female patients presenting to gynecologist
Under- diagnosis : lack of lab support
is an acute phase reactant
Diagnosis and Management
Base line coagulation screen
DDAVP & Tranexamic acid
FFPs & Cryoprecipetate
Report On The Universal
Data Collection System
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
22/40 not tested reflecting lack of written protocols
18/40 tested and were negative reflecting the routine neonatal immunization program started 1990 in SA including HB vaccine
Hepatitis B Virus
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 population
Overall frequency of 5.3%
5 X > reported from Western Europe and USA
Hemophiliacs. Seropositivity rate :78.6%
Vox Sang. 1991;60(3):162-4
Hepatitis C Virus
Patient name: M T
Sex: Male 2 years
Diagnosis: Hemophilia A at age of 7 m
Admission date: 3-11-2002
Lethargy , vomiting & fever for 1 D
Tonic-clonic convulsions for 2 D
On/off painful joint swelling after minor injuries.
Not on regular treatment
Circumcision 6 m ago (FVIII).
Family history of hemophilia A ,thalassemia & SCA
Neurological examination normal
Other systems examination
Hb: 9.2g/dl WBC: 16.5X109 plt:509X109
PT: 1.2 sec PTT: 69.2 sec
50/50 immediate mix PTT 40.2 sec
50/50 post- incubation mix :PTT 80 sec
Factor VIII level 2%
Inhibitor level :50 Bethesda units
CT scan brain : subdural hematoma
Patient was started on factor VIII concentrate 8 hourly
Aiming x 100% x10 D
Neurosurgery consult : observe
was improving clinically
Patient was started on Malom Protocol
Cyclophosphamide 2 mg/kg/d
Prednisolone 1 mg/kg/d
Factor VIII stat 100 IU/kg Infusion 10 IU/kg/hr x3D
Repeat CT scan : resolution of subdural hematoma
Patient was discharged on
- Tegretol 50 mg PO BID
- Cyclophosphamid 25 mg PO OD
- Prednisolone 5 mg PO BID
- F VIII conc 250
IU IV weekly
Follow-up in OPD
Inhibitor screen at Nov 2003. No evidence of inhibitors.
15 y old girl
Referred with history of PR bleeding .
History of salmonella infection.
PMH of ? 2 attacks of DVT (clinical suspicion).
CBC : Hb
g/dl PLT 159X109/L.
Isolated prolonged APTT.
Mixing studies :NC.
Factor VIII level
PRBCs TX , FFP & FVIII concentrate.
Transfer To KAUH
Fresh PR bleeding & heavy menstrual period .
Bruises on anti-cubital fossa .
Hb 7.5 g/dl & APTT 118 sec.
Mixing study :immediate & post incubation NC
Factor VIII level 2% & VWF level 80%
Bethesda assay> 500 IU.
LA screen &ACL Ab :negative .
Septic screen : negative.
Serology: HBSAg “R”,HBEAg positive
Family study FVIII level :normal
Upper GIT endoscopy “Hiatus Hernia”.
No blood TX.
Hb level 7.5 9.5 g/dl on iron supplementation.
Males = females.
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
Titer of the inhibitor.
Associated medical condition.
Likelihood of spontaneous remission .
Risk of toxicities of therapy
Prednisolone alone without cyclophosphamide
Regular F/U in OPD
search for underlying cause
CT chest ,abdomen & pelvis every year
Autoimmune profile every 6m
3 years since diagnosis: Idiopathic Acquired Hemophilia
During F/U patient had fractured wisdom tooth for extraction
Patient was admitted prior to extraction
FVII level >1%
Bethesda assay >500IU
Trial of FVIII conc under IVIG,
no improvement in FVIII level
Recombinant FVII 90 micg ; No intra-operative nor post-operative bleed
Local fibrin glue to maintain local hemostasis
Patient name : H K
Known sever HA :bloody diarrhea Oct 2001
Post circumcision bleed
Lf knee swelling post trauma
Family history :HA brother
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
LA is a 35-y male with severe hemophilia
Left knee joint bleed.
Inhibitor titer of 35 BU
known high responder
Failed immune tolerance.
Difficult venous access.
Available treatment options
APCCs every 12 to 24 hours
APCCs is a plasma-derived product (Hep C)
An anamnestic response is not a concern since LA has already failed immune tolerance.
Low risk of thromboembolic complications
Recombinant factor VIIa
Its short half-life
Frequent dosing is needed
Difficult venous access :catheter
Higher cost than APCCs.
Porcine factor VIII may be an option.
Porcine titer to check for x-reactivity
Titer less than 10 BU, porcine factor VIII may be effective.
Mild infusion reactions in 10% of patients.
Inhibitors may develop to the porcine factor.
Porcine factor must be stored frozen.
2-year-old child with severe HA.
Spontaneous bleed in the right elbow
2X rFVIII in the last 36 hours.
However, swelling has worsened
rFVIII had been effective for past bleeds.
rFVIIa while waiting for titer results
High doses of rFVIII would be ineffective and may result in higher inhibitor levels.
X-sensitivity to porcine FVIII is unknown.
Early control of bleeding is essential to prevent permanent damage to the joint.
High inhibitor titer (BU=25).
Immune Tolerance Induction
Early initiation of ITI and a young age are two factors associated with successful ITI.
Daily factor infusions for a prolonged period of time.
rFVIIa for bleeding episodes (to avoid an anamnestic response).
Inhibitor titers monitored every 2 weeks.
ITI may be started when inhibitor titers are less than 5 BU.
Genetic Disorders &Impact
On Health Care Delivery
No agreed-upon definitive cure with acceptable risk
Chronic nature requires lifelong medical attention
Expensive supportive and symptomatic therapy
Significant burden on the health care delivery system.
East Mediterr Health J. 1999 Nov;5(6):1104-13.
Hemophilia working Group in KAUH
Blood bank specialist
Prevalence of hepatitis A virus exposure &vaccination status among persons with hemophilia.
Diagnosis & Management
Diagnosis of acquired hemophilia
Quantification of inhibitors “Bethesda assay“.
Search for an underlying disorder
No correlation between inhibitor titres and severity or the pattern of bleeding.
Treat the bleeding
Eliminate the inhibitor by Imunnosupression
Diagnose underlying conditions
Retrospective 74 bleeding episodes in 38 patients
Good efficacy in 75% of bleeds
Partial response in 17% of cases
Response usually within 8-24 hours
Hay C et al. Thromb. Haemostas. 78: 1463-1467 (1997)
The Malmo protocol
MALMÖ TREATMENT MODEL
Inhibitor titre levels > 10 Bethesda Units
Plasmapheresis with immunoadsorption initially to lower inhibitor levels as much as possible.
IV cyclophosphamide 12 -15 mg / kg x 2 days then 3 mg / kg orally x 8-10 days
D+4 IGg 0.4 g / kg x 5 days
Daily FVIII to maintain FVIII level 40 - 100 % for 2 - 3 ws
Once inhibitors are not detectable, factor VIII is 2-3x/W.
Prevalence Of HIV Infection Among Persons With Hemophilia
Dostları ilə paylaş:
Verilənlər bazası müəlliflik hüququ ilə müdafiə olunur ©muhaz.org 2017