Download Dr. Claudia khayat

XXIX International Congress
Buenos Aires Argentina
10-14 July 2010
Mild hemophilia A
Management of patient remain a major Challenge:
Diagnosis
in 40% of patient , discrepant factor VIII level
are measured when a one-stage clotting assay is
used as compared with a two-stage
(chromogenic) assay.
– FVIII levels are reduced by 50% when mesured by a
two stage assay, leading to missing the diagnosis when
a one stage assay is used.
– The reverse situation is less frequent
• Mutation and molecular mechanisms of
many of these discrepant cases have
been resolved
– FVIII reduced in a two stage/one stage:
Nbs of missence mutation clustered within
the A domains that lead to defective
stability of FVIIIa
– Mutation imparing FVIII activation by
thrombin result in higher activity in a two
stage
Treatment
Desmopressin
 2-6 fold increase of FVIII level over baseline
 Prior to therapeutic use the magnitude and
the half life of the FVIII response to
desmopressin should be obtained
 Predictors of the magnitude of response to
Desmopressin not well studied but the
inderlying molecular defect seems to be
important as
The response tend to be similar within families
There is reproductive pattern of response in
patient with the same mutation
Antifibrinolytic agent
Inhibitor development
Prevalence : 3-13%
Missence mutation located in the region
encoding light chain contribute to an
unexpected high incidence of inhibitors.
Arg2150 His, Arg593Cys, intensive
perioperative factor VIII
administration seems to be risk factor
Inhibitor development
 Overall success of immune tolerance seems
lower than the reported success in severe
hemophilia A
 Available data are not sufficient to offer
evidence based advice on the optimal
treatment
 Maximal use of desmopressin, avoidance of
intensive courses of treatment with FVIII
concentrate hase to be considered
Issues in the Aging person with hemophilia
Cardiovascular disease:
• Arteriosclerotic vascular disease similar to
general population
– Probably decreased risk of death from
cardiovascular disease
– Risk increased with high blood pressure, hepatitis
C, HIV, Highly Active Anti Retroviral therapy
• The hemophilia provider is challenged to
balance the bleeding and clotting risk in
individual patients when providing treatment
Issues in the Aging person with hemophilia
Cardiovascular disease:
• Concensus Guidelines:
– Avoidance of thrombolytic therapy
– Use of bare metal stents for percutanous
coronary intervention
– Use of prophylaxis during dual antiplatelets therapy
Issues in the Aging person with hemophilia
Joint disease
• Increased disability
• Pain control issues
• Osteoporosis
– Role of secondary prophylaxis
– Targeted physiotherapy
– Reducing risk of fall
Issues in the Aging person with hemophilia
Joint disease
• Joint replacement
-Optimal timming?
-Optimal factor replacement therapy?
-Role of VTE prophylaxis?
Renal disease
Cancer
Update on pathogenesis of the
bleeding joint
Recently it has been demonstrated that induced
joint bleeds in haemophilic mice lead to elevation
of pro-inflammatory cytokines (IL-1b, IL-6, KC
and MCP-1) in the synovial fluid supporting the
existence of an inflammatory synovial component
in pathogenesis of haemophilic arthropathy.
These released cytokines will have repercussions
on cartilage integrity.
Update on pathogenesis of the
bleeding joint
 The devastating effects of joint bleeding are also
evident independent of synovial inflammation.
 Exposure of cartilage tissue in vitro to whole blood (50%
volume/volume) for 4 days leads to disturbance of
cartilage matrix turnover.
 Even after a follow up period of 10 weeks matrix
synthesis is still inhibited
 However, finally repair activity prevailed and cartilage
damage vanished.
Update on pathogenesis of the
bleeding joint
 Preliminary results of recent studies demonstrated that
sufficient repeated joint bleeds finally lead to persisting
cartilage damage
 Disturbance of matrix turnover in the long-term is
considered to be caused by apoptosis of the
chondrocyte.
 Apoptosis of chondrocytes can be inhibited by addition
of IL-10.
 Most recently it appeared that IL-4 has even more
protective effects on blood induced cartilage damage
than IL-10
Middle genicular artery
embolisation in hemophilic children
and adolescents
 A new treatment option for children with recurrent
bleeding in the knee joint
 Methodology: occluding the single artery that goes
intra-articular and nourishes the synovial membrane
 Relapses after embolisation were 60% from 1 month
to 1.5 years.
 In 40% the amount of bleeding was much less and the
frequency was reduced from 1 episode after 4 years
to 2.2 episodes per year.
 Twenty percent of cases failed.