Rarer Haemostatic Disorders Treatments see UKHCDO guidelines 2004 Haemophilia 10, 593628 - PowerPoint PPT Presentation


Title: Rarer Haemostatic Disorders Treatments see UKHCDO guidelines 2004 Haemophilia 10, 593628


1
Rarer Haemostatic DisordersTreatments(see
UKHCDO guidelines 2004Haemophilia 10, 593-628)
  • Paula Bolton-Maggs
  • Consultant Haematologist
  • Manchester Royal Infirmary, UK

2
(No Transcript)
3
Bleeding disorder patients registered at CMC
Vellore, India, 1965-96
Total 1528 patients
338
4
Bleeding disorder patients registered at CMC
Vellore, India, 1965-96
154
24
38
5
Excluding FXI deficiency 1163
6
(No Transcript)
7
(No Transcript)
8
Preliminary data from the Rare Bleeding Disorders
Registry
9
Rare coagulation disorders
  • Autosomal recessive (?) inheritance
  • More common in racial groups where cousin
    marriage frequent
  • Factor XI common in Ashkenazy Jews
  • Generally, lack of clear correlation between
    bleeding and level of factor, so more difficult
    to manage

10
Severe deficiency rare disorders
(data from Peyvandi, Rare coagulation disorders,
thesis, 2000)
11
In vivo properties (1Rizza 1982, 2 Mannucci
2004)
12
What products are manufactured?
  • FV deficiency no concentrate use
    virally-treated FFP
  • Octaplas pooled from approx 1500 donations, SD
    treated, sourced from Austria, Germany and USA
  • Methylene-blue treated single donor units
  • Platelet disorders DDAVP, fibrinolytic
    inhibitors, platelet transfusions and possibly
    rVIIa

13
Fibrinogen Treatment products
  • Unlicensed virally inactivated concentrates
  • ZLB
  • SNBTS
  • LFB
  • Half life 3-5 days
  • Tranexamic acid
  • Cryo is a good source but not virally inactivated

14
Fibrinogen products
15
Treatment for FII
  • Beriplex PN (ZLB) contains II, VII, IX and X
  • DEFIX HT (SNBTS) contains II, IX and X
  • Prothromplex (Baxter) contains II, IX and X
  • Prothromplex T (Baxter) similar but also contains
    factor VII
  • Kaskadil (LFB) with VII

16
Treatment Products FVII
  • rVIIa is the treatment of choice although little
    data
  • Factor IX concentrates containing FVII
  • Factor VII concentrates (LFB and Baxter)
  • (FFP)
  • A level of 10-15 u/dl is probably sufficient for
    surgery (level of 2 u/dl shown to normalise the
    thrombin generation test but not tested in
    clinical situation)

17
Products for FVII deficiency
18
Factor X Treatment Products
  • No factor X concentrate
  • Intermediate purity Factor IX concentrates
  • Increased risk of thrombosis
  • (FFP)
  • A level of 10-25 u/dl is probably sufficient for
    surgery
  • People with levels gt10 u/dl probably require no
    replacement therapy

19
Products for FX (and FII) deficiency
20
Therapeutic options in FXI deficiency
  • Fresh frozen plasma (Virally treated)
  • Factor XI concentrates (BPL, LFB) but
    thrombogenic
  • Fibrinolytic inhibitors very effective for
    dental extractions
  • Fibrin glue main experience in Israel
  • DDAVP - unconvincing
  • rVIIa risk of thrombosis

21
Products for FXI deficiency
22
Factor XIII deficiency
  • 6 patients managed from 19-35 years
  • Prophylaxis long half life 11-14 days
  • Pasteurised plasma-derived concentrate available
    from ZLB (Fibrogammin-P)
  • Give 1000 units every 5-6 weeks which raises
    level to 30-35 u/dl (NB assay problems)
  • Platelets contain FXIII and in an emergency may
    be useful.

23
SSC working group on Rare
Bleeding Disorders (RBDs)
  • In 2004, during the 50th SSC meeting organized by
    the ISTH and held in Venice, a SSC working group
    on "Rare Bleeding Disorders" (RBDs) was held
    within the framework of the FVIII/IX subcommittee

Flora Peyvandi Angelo Bianchi Bonomi Hemophilia
and Thrombosis Centre University of Milan-Italy
Slide provided by Flora Peyvandi
24
Database development.3
Hemophilia Treatment Centers already joined
25
Database development.3
Preliminary result of initial participation
In the period 30 June-30 July, 24 completed
joining forms came back out of 725 sent e-mails
416 Centres will be contact by ordinary mail due
to the uncorrect or unavailable e-mail
addresses
26
Database development.3
  • The largest groups of patients were communicated
    from Iran and India (327 and 264 patients
    respectively)
  • Fibrinogen and FVII deficiencies were spread
    among all responding Centres
  • FVII and FXI deficiencies are the most prevalent
    worldwide

27
Available treatments
Database development.3
28
Problems with RBDs treatments
Database development.3
  • Inability to get product and costs
  • - Central and South America, Asia and Middle
    East, Russia
  • - India sometimes products are past expiration
    date
  • No availability of product
  • - Brazil and Vietnam general lack of products
  • - FXI reported by Arizona, Brazil, Belgium,
    London-UK, Switzerland
  • centres
  • - Denmark sometimes stopped FIX-X product
  • - Iran Prothrombin complex
  • Adverse effects
  • mild urticaria, reaction to plasma, thrombosis
    with FXI in the past, fear of blood borne viral
    infections
  • Other
  • - Panama products available only for insured
    patients

29
Database development.3
Second step
  • A specific tailored questionnaire will be sent to
    all Treatment Centers, after their joining to the
    RBDD, in order to collect more detailed
    information on all enrolled patients
  • Phenotype and genotype analysis
  • Clinical manifestation
  • Type of treatment, on-demand/prophylaxis
  • Treatment-related complications
  • To each clinician will be asked patients
    informed consent and IRB approval

30
Database development.3
31
Next steps
Steering committee.4
  • Our work could represent the starting point for
    the establishment of an International Database
    under the supervision of an International Society
    such as WFH or ISTH
  • In order to create an International collaboration
    on RBDD and to decide eventual clinical trials,
    it will be necessary to build up a STEERING
    COMMITTEE composed by experts in clinic,
    treatment and genotype-phenotype characterization
    coming from all over the world

32
(No Transcript)
33
current databases.1
ISTH Registries
SSC Registries/Databases Clotting Factor
Concentrates www.wfh.org
Factor IX
Database www.kcl.ac.uk/ip/petergreen/haemBdatabase
.html Allergic Reactions to Factor IX
Concentrates International Registry in Acquired
von Willebrand Syndrome www.intreavws.com Protein
S Deficiency A Database of mutations First
Update Registry on Thrombosis and Thrombotic
Risk in Women Receiving Ovarian Stimulation for
Pregnancy vWF Database www.sheffield.ac.uk/vwf/
Other Registries/Databases Bernard-Soulier
Syndrome Factor VII Mutation Database
http//193.60.222.13/ Factor VIII Database
http//europium.csc.mrc.ac.uk/WebPages/Main/main.h
tml Fibrinogen Database www.geht.org/databaseang/f
ibrinogen/ Glanzmanns Thrombasthenia Database
http//sinaicentral.mssm.edu/intranet/research/gla
nzmann/menu Human Gene Mutation Database
http//archive.uwcm.ac.uk Mutation causing rare
bleeding Disorders Chapter 116 of William
Hematology 7th Edition - 2005 Protein C Database
www.xs4all.nl/7Ereitsma/Prot_C_home.htm
Slide provided by Flora Peyvandi
34
Other registries
current databases.1
  • Seitz R et al. ETRO Working Party on Factor XIII
    questionnaire on congenital factor XIII
    deficiency in Europe status and perspectives.
    Study Group. Semin Thromb Hemost. 199622415-8
  • Mariani G et al. Clinical manifestations,
    management, and molecular genetics in congenital
    factor VII deficiency the International Registry
    on Congenital Factor VII Deficiency (IRF7).
    Blood. 200096374
  • 6. Greifswalder Hämophilie-Tagung 2001
  • - Batorova A et al. Ntl registry of FVII
    deficiency in Slovakia-clinical survey of 230
    patients
  • - Astermark J et al. The Malmö registry of FVII
    deficiency
  • - Herrmann F et al. Greifswald registry of FX
    congenital deficiency
  • Dossenbach-Glaninger A and Hopmeier P.
    Coagulation factor XI a database of mutations
    and polymorphisms associated with factor XI
    deficiency. Blood Coagul Fibrinolysis.
    200516231-8
  • FranceCoag. French database collecting
    epidemiologic, clinical, treatment, and genetic
    data on patients affected by bleeding disorders
    (www.francecoag.org)
  • Acharya S et al. Rare Bleeding Disorder Registry
    deficiencies of factors II, V, VII, X, XIII,
    fibrinogen and dysfibrinogenemias. J Thromb
    Haemost 20042248-56 (NHF-MASAC)
  • AHCDC Canadian Hemophilia Registry
    (http//www.fhs.mcmaster.ca/chr/index.htm)
  • Abshire T, Sumner M. HTRS Registry - A
    collaborative effort between HTRS and
    NovoNordisk, Inc. providing a platform to collect
    a common set of data from Hemophilia Treatment
    Centers (HTCs)
  • CDC Department of Health and Human Service,
    Centres for Disease Control and Prevention
    (http//www.cdc.gov/ncbddd/hbd/hemophilia.htm)

Slide provided by Flora Peyvandi
View by Category
About This Presentation
Title:

Rarer Haemostatic Disorders Treatments see UKHCDO guidelines 2004 Haemophilia 10, 593628

Description:

Bleeding disorder patients registered at CMC Vellore, India, 1965-96 ... University of Milan-Italy. Asia/Middle East:7. North America:4. 2. 1. 1. Europe:9 ... – PowerPoint PPT presentation

Number of Views:153
Avg rating:5.0/5.0
Slides: 35
Provided by: paulabol
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Rarer Haemostatic Disorders Treatments see UKHCDO guidelines 2004 Haemophilia 10, 593628


1
Rarer Haemostatic DisordersTreatments(see
UKHCDO guidelines 2004Haemophilia 10, 593-628)
  • Paula Bolton-Maggs
  • Consultant Haematologist
  • Manchester Royal Infirmary, UK

2
(No Transcript)
3
Bleeding disorder patients registered at CMC
Vellore, India, 1965-96
Total 1528 patients
338
4
Bleeding disorder patients registered at CMC
Vellore, India, 1965-96
154
24
38
5
Excluding FXI deficiency 1163
6
(No Transcript)
7
(No Transcript)
8
Preliminary data from the Rare Bleeding Disorders
Registry
9
Rare coagulation disorders
  • Autosomal recessive (?) inheritance
  • More common in racial groups where cousin
    marriage frequent
  • Factor XI common in Ashkenazy Jews
  • Generally, lack of clear correlation between
    bleeding and level of factor, so more difficult
    to manage

10
Severe deficiency rare disorders
(data from Peyvandi, Rare coagulation disorders,
thesis, 2000)
11
In vivo properties (1Rizza 1982, 2 Mannucci
2004)
12
What products are manufactured?
  • FV deficiency no concentrate use
    virally-treated FFP
  • Octaplas pooled from approx 1500 donations, SD
    treated, sourced from Austria, Germany and USA
  • Methylene-blue treated single donor units
  • Platelet disorders DDAVP, fibrinolytic
    inhibitors, platelet transfusions and possibly
    rVIIa

13
Fibrinogen Treatment products
  • Unlicensed virally inactivated concentrates
  • ZLB
  • SNBTS
  • LFB
  • Half life 3-5 days
  • Tranexamic acid
  • Cryo is a good source but not virally inactivated

14
Fibrinogen products
15
Treatment for FII
  • Beriplex PN (ZLB) contains II, VII, IX and X
  • DEFIX HT (SNBTS) contains II, IX and X
  • Prothromplex (Baxter) contains II, IX and X
  • Prothromplex T (Baxter) similar but also contains
    factor VII
  • Kaskadil (LFB) with VII

16
Treatment Products FVII
  • rVIIa is the treatment of choice although little
    data
  • Factor IX concentrates containing FVII
  • Factor VII concentrates (LFB and Baxter)
  • (FFP)
  • A level of 10-15 u/dl is probably sufficient for
    surgery (level of 2 u/dl shown to normalise the
    thrombin generation test but not tested in
    clinical situation)

17
Products for FVII deficiency
18
Factor X Treatment Products
  • No factor X concentrate
  • Intermediate purity Factor IX concentrates
  • Increased risk of thrombosis
  • (FFP)
  • A level of 10-25 u/dl is probably sufficient for
    surgery
  • People with levels gt10 u/dl probably require no
    replacement therapy

19
Products for FX (and FII) deficiency
20
Therapeutic options in FXI deficiency
  • Fresh frozen plasma (Virally treated)
  • Factor XI concentrates (BPL, LFB) but
    thrombogenic
  • Fibrinolytic inhibitors very effective for
    dental extractions
  • Fibrin glue main experience in Israel
  • DDAVP - unconvincing
  • rVIIa risk of thrombosis

21
Products for FXI deficiency
22
Factor XIII deficiency
  • 6 patients managed from 19-35 years
  • Prophylaxis long half life 11-14 days
  • Pasteurised plasma-derived concentrate available
    from ZLB (Fibrogammin-P)
  • Give 1000 units every 5-6 weeks which raises
    level to 30-35 u/dl (NB assay problems)
  • Platelets contain FXIII and in an emergency may
    be useful.

23
SSC working group on Rare
Bleeding Disorders (RBDs)
  • In 2004, during the 50th SSC meeting organized by
    the ISTH and held in Venice, a SSC working group
    on "Rare Bleeding Disorders" (RBDs) was held
    within the framework of the FVIII/IX subcommittee

Flora Peyvandi Angelo Bianchi Bonomi Hemophilia
and Thrombosis Centre University of Milan-Italy
Slide provided by Flora Peyvandi
24
Database development.3
Hemophilia Treatment Centers already joined
25
Database development.3
Preliminary result of initial participation
In the period 30 June-30 July, 24 completed
joining forms came back out of 725 sent e-mails
416 Centres will be contact by ordinary mail due
to the uncorrect or unavailable e-mail
addresses
26
Database development.3
  • The largest groups of patients were communicated
    from Iran and India (327 and 264 patients
    respectively)
  • Fibrinogen and FVII deficiencies were spread
    among all responding Centres
  • FVII and FXI deficiencies are the most prevalent
    worldwide

27
Available treatments
Database development.3
28
Problems with RBDs treatments
Database development.3
  • Inability to get product and costs
  • - Central and South America, Asia and Middle
    East, Russia
  • - India sometimes products are past expiration
    date
  • No availability of product
  • - Brazil and Vietnam general lack of products
  • - FXI reported by Arizona, Brazil, Belgium,
    London-UK, Switzerland
  • centres
  • - Denmark sometimes stopped FIX-X product
  • - Iran Prothrombin complex
  • Adverse effects
  • mild urticaria, reaction to plasma, thrombosis
    with FXI in the past, fear of blood borne viral
    infections
  • Other
  • - Panama products available only for insured
    patients

29
Database development.3
Second step
  • A specific tailored questionnaire will be sent to
    all Treatment Centers, after their joining to the
    RBDD, in order to collect more detailed
    information on all enrolled patients
  • Phenotype and genotype analysis
  • Clinical manifestation
  • Type of treatment, on-demand/prophylaxis
  • Treatment-related complications
  • To each clinician will be asked patients
    informed consent and IRB approval

30
Database development.3
31
Next steps
Steering committee.4
  • Our work could represent the starting point for
    the establishment of an International Database
    under the supervision of an International Society
    such as WFH or ISTH
  • In order to create an International collaboration
    on RBDD and to decide eventual clinical trials,
    it will be necessary to build up a STEERING
    COMMITTEE composed by experts in clinic,
    treatment and genotype-phenotype characterization
    coming from all over the world

32
(No Transcript)
33
current databases.1
ISTH Registries
SSC Registries/Databases Clotting Factor
Concentrates www.wfh.org
Factor IX
Database www.kcl.ac.uk/ip/petergreen/haemBdatabase
.html Allergic Reactions to Factor IX
Concentrates International Registry in Acquired
von Willebrand Syndrome www.intreavws.com Protein
S Deficiency A Database of mutations First
Update Registry on Thrombosis and Thrombotic
Risk in Women Receiving Ovarian Stimulation for
Pregnancy vWF Database www.sheffield.ac.uk/vwf/
Other Registries/Databases Bernard-Soulier
Syndrome Factor VII Mutation Database
http//193.60.222.13/ Factor VIII Database
http//europium.csc.mrc.ac.uk/WebPages/Main/main.h
tml Fibrinogen Database www.geht.org/databaseang/f
ibrinogen/ Glanzmanns Thrombasthenia Database
http//sinaicentral.mssm.edu/intranet/research/gla
nzmann/menu Human Gene Mutation Database
http//archive.uwcm.ac.uk Mutation causing rare
bleeding Disorders Chapter 116 of William
Hematology 7th Edition - 2005 Protein C Database
www.xs4all.nl/7Ereitsma/Prot_C_home.htm
Slide provided by Flora Peyvandi
34
Other registries
current databases.1
  • Seitz R et al. ETRO Working Party on Factor XIII
    questionnaire on congenital factor XIII
    deficiency in Europe status and perspectives.
    Study Group. Semin Thromb Hemost. 199622415-8
  • Mariani G et al. Clinical manifestations,
    management, and molecular genetics in congenital
    factor VII deficiency the International Registry
    on Congenital Factor VII Deficiency (IRF7).
    Blood. 200096374
  • 6. Greifswalder Hämophilie-Tagung 2001
  • - Batorova A et al. Ntl registry of FVII
    deficiency in Slovakia-clinical survey of 230
    patients
  • - Astermark J et al. The Malmö registry of FVII
    deficiency
  • - Herrmann F et al. Greifswald registry of FX
    congenital deficiency
  • Dossenbach-Glaninger A and Hopmeier P.
    Coagulation factor XI a database of mutations
    and polymorphisms associated with factor XI
    deficiency. Blood Coagul Fibrinolysis.
    200516231-8
  • FranceCoag. French database collecting
    epidemiologic, clinical, treatment, and genetic
    data on patients affected by bleeding disorders
    (www.francecoag.org)
  • Acharya S et al. Rare Bleeding Disorder Registry
    deficiencies of factors II, V, VII, X, XIII,
    fibrinogen and dysfibrinogenemias. J Thromb
    Haemost 20042248-56 (NHF-MASAC)
  • AHCDC Canadian Hemophilia Registry
    (http//www.fhs.mcmaster.ca/chr/index.htm)
  • Abshire T, Sumner M. HTRS Registry - A
    collaborative effort between HTRS and
    NovoNordisk, Inc. providing a platform to collect
    a common set of data from Hemophilia Treatment
    Centers (HTCs)
  • CDC Department of Health and Human Service,
    Centres for Disease Control and Prevention
    (http//www.cdc.gov/ncbddd/hbd/hemophilia.htm)

Slide provided by Flora Peyvandi
About PowerShow.com