Download PDF
Semin Thromb Hemost 2003; 29(6): 585-594
DOI: 10.1055/s-2004-815626
Copyright © 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Advances in Care of Children with Hemophilia

Marilyn J. Manco-Johnson1,2 , Brenda  Riske2 , Carol K. Kasper3
  • 1Professor of Pediatrics, Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado Health Sciences Center and The Children's Hospital, Denver, Colorado
  • 2Director, Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado Health Sciences Center and The Children's Hospital, Denver, Colorado
  • 3Orthopedic Hospital, Los Angeles, California
Further Information

Publication History

Publication Date:
13 January 2004 (online)

    Permissions and Reprints

ABSTRACT

Care for children with severe hemophilia has moved from pediatric hospital wards and rehabilitation services to the home, school, and community. Advances in hemophilia are due largely to the development of specialized hemophilia treatment centers, which created a system of comprehensive care and focused healthcare efforts on prevention and education. Parallel advances in coagulation resulted in identification of clotting factors VIII and IX, elucidation of the protein molecular and biochemical structures and functions, sequencing of their respective genes and transfer of the human genes for production of proteins by recombinant technology, and development of gene therapy. The tragedy of the human immunodeficiency virus and hepatitis C raised awareness in patients as well as healthcare providers of the vulnerability of blood products to viral contamination and spurred progress in science leading to viral inactivation of purified proteins. Concomitantly, physicians treating bleeding episodes in the clinic investigated pharmacokinetics and pharmacoeconomics of various strategies of clotting factor replacement. The observation that trough factor levels as low as 1 to 2% were adequate to prevent most bleeding episodes led to current prophylactic regimens that allow boys to participate fully in school and community activities while factor concentrate is infused at home on a regular schedule. Currently, children with hemophilia look forward to a normal life expectancy and excellent health-related quality of life. Physician and community partnerships through research and advocacy societies have accelerated clinical advancements as well as extension of treatment to developing countries. The future of hemophilia promises a cure with gene therapy. Given the past accomplishments in hemophilia, a long-term solution to replacement of the genetically deficient protein lies on the horizon.

KEYWORDS

Hemophilia - treatment - factor concentrates - blood products - bleeding

REFERENCES

  • 1 Biggs R. Thirty years of haemophilia treatment in Oxford.  Br J Haematol . 1967;  13 452-463
    CrossrefPubMedSearch in Google Scholar
  • 2 Birch C LaF. Hemophilia, Clinical and Genetic Aspects.  Urbana, IL: University of Illinois; 1937
    Search in Google Scholar
  • 3 Macfarlane R G, Barnett B. The haemostatic possibilities of snake-venom.  Lancet . 1934;  ii 985-987
    PubMedSearch in Google Scholar
  • 4 Marfarlane R G. The normal haemostatic mechanism and its failure in the haemorrhagic states.  Thesis for the degree of M.D. London: University of London; 1938
    Search in Google Scholar
  • 5 Biggs R, Douglas A S, Macfarlane R G. The formation of thromboplastin in human blood.  J Physiol (Lond) . 1953;  119 89-101
    PubMedSearch in Google Scholar
  • 6 Biggs R, Douglas A S, Macfarlane R G. The initial stages of blood coagulation.  J Physiol (Lond) . 1953;  122 538-553
    PubMedSearch in Google Scholar
  • 7 Rapaport S I, Schiffman S, Patch M J. et al . A simple, specific one-stage assay for plasma thromboplastin antecedent activity.  J Lab Clin Med . 1961;  57 771-780
    PubMedSearch in Google Scholar
  • 8 Thompson A R. Structure and function of the factor VIII gene and protein.  Semin Thromb Hemost . 2003;  29 11-22
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Kurachi K, Kurachi S, Furukawa M, Yao S N. Biology of factor IX.  Blood Coagul Fibrinolysis . 1993;  4 953-973
    PubMedSearch in Google Scholar
  • 10 Gitschier J, Wood W I, Goralka T M. et al . Characterization of the human factor VIII gene.  Nature . 1984;  312 326-330
    CrossrefPubMedSearch in Google Scholar
  • 11 Anson D S, Choo K H, Rees D J. et al . The gene structure of human anti-haemophilic factor IX.  EMBO J . 1984;  3 1053-1060
    PubMedSearch in Google Scholar
  • 12 Saenko E L, Shima M, Sarafanov A G. Role of activation of the coagulation factor VIII in interaction with vWf, phospholipid, and functioning within the factor Xase complex.  Trends Cardiovasc Med . 1999;  9 185-192
    CrossrefPubMedSearch in Google Scholar
  • 13 Butenas S, van `t Veer C, Cawthern K, Brummel K E, Mann K G. Models of blood coagulation.  Blood Coagul Fibrinolysis . 2000;  11 (suppl 1S) 9-13
    PubMedSearch in Google Scholar
  • 14 Biggs R, Macfarlane R G. Haemophilia and related conditions: a survey of 187 cases.  Br J Haematol . 1958;  4 1-27
    CrossrefPubMedSearch in Google Scholar
  • 15 Biggs R, Macfarlane R G. Treatment of Haemophilia and Other Coagulation Disorders.  Oxford, UK: Blackwell Scientific; 1966
    Search in Google Scholar
  • 16 Kasper C K. A total program for the patient with hemophilia.  J Am Phys Ther Assoc . 1966;  46 1268-1285
    PubMedSearch in Google Scholar
  • 17 Praga C, Cortellaro M. Organizational aspects of comprehensive assistance to hemophiliacs.  Haematol Lat . 1969;  12 667-673
    PubMedSearch in Google Scholar
  • 18 Kerr C B. Comprehensive care for haemophilia.  J R Coll Physicians Lond . 1971;  5 263-267
    PubMedSearch in Google Scholar
  • 19 Allain J P. A boarding school for hemophiliacs: a model for the comprehensive care of hemophilic children.  Ann N Y Acad Sci . 1975;  240 226-237
    PubMedSearch in Google Scholar
  • 20 Levine P H, McVerry B A, Segelman A E, Cranford C M, Zimbler S. Comprehensive health care clinic for hemophiliacs.  Arch Intern Med . 1976;  136 792-794
    CrossrefPubMedSearch in Google Scholar
  • 21 Tann G. Recent advances in hemophilia.  Southeast Asian J Trop Med Public Health . 1979;  10 218-228
    PubMedSearch in Google Scholar
  • 22 PL 9463: The Public Health Service Act establishing the hemophilia diagnostic and treatment center program. No. 1131 of Public Law 9463.  Washington, DC: Government Printing Office; 1975
    Search in Google Scholar
  • 23 Fearns M. The management of clinical specialties: the nurse's role in the management of a haemophilia centre.  Nurs Focus . 1982;  3 8-9
    PubMedSearch in Google Scholar
  • 24 Smith P S, Keyes N C, Forman E N. Socioeconomic evaluation of a state-funded comprehensive hemophilia-care program.  N Engl J Med . 1982;  306 575-579
    PubMedSearch in Google Scholar
  • 25 Smith P S, Levine P H. The benefits of comprehensive care of hemophilia: a five-year study of outcomes.  Am J Public Health . 1984;  74 616-617
    PubMedSearch in Google Scholar
  • 26 Levine P H, Brackmann H H, Seligsohn U. A proposed system of classification of hemophilia centers for the World Federation of Hemophilia (WFH).  Scand J Haematol . 1984;  40(suppl) 459-460
    PubMedSearch in Google Scholar
  • 27 Soucie J M, Nuss R, Evatt B, et a l, and the Hemophilia Surveillance System Project Investigators. Mortality among men with hemophilia: relations with source of medical c are. Blood .  2000;  96 437-442
    PubMedSearch in Google Scholar
  • 28 Rabiner S F, Telfer M C. Home transfusion for patients with hemophilia A.  N Engl J Med . 1970;  283 1011-1015
    PubMedSearch in Google Scholar
  • 29 Levine P H. Efficacy of self-therapy in hemophilia. A study of 72 patients with hemophilia A and B.  N Engl J Med . 1974;  291 1381-1384
    PubMedSearch in Google Scholar
  • 30 Jones P, Fearns M, Forbes C, Stuart J. Haemophilia A home therapy in the United Kingdom 1975-6.  BMJ . 1978;  1 1447-1450
    PubMedSearch in Google Scholar
  • 31 Evensen S A, Thaule R, Grøan K. Self-therapy for haemophilia in Norway.  Acta Med Scand . 1979;  205 395-399
    PubMedSearch in Google Scholar
  • 32 Allain J P, Blombäck M, Brackmann H H. et al . Recommendations on home treatment of hemophilias.  Scand J Haematol . 1977;  31(suppl) 75-77
    PubMedSearch in Google Scholar
  • 33 Soucie J M, Symons IV J, Evatt B, Brettler D, Huszti H, Linden J. The Hemophilia Surveillance System Project Investigators. Home-based factor infusion therapy and hospitalization for bleeding complications among males with haemophilia.  Haemophilia . 2001;  7 198-206
    CrossrefPubMedSearch in Google Scholar
  • 34 Miller K, Buchanan G R, Zappa S. et al . Implantable venous access devices in children with hemophilia: a report of low infection rates.  J Pediatr . 1998;  132 934-938
    PubMedSearch in Google Scholar
  • 35 Ljung R, van den Berg M, Petrini P. et al . Port-a-cath usage in children with haemophilia: experience of 53 cases.  Acta Paediatr . 1998;  87 1051-1054
    CrossrefPubMedSearch in Google Scholar
  • 36 Geraghty S, Kleinert D. Use and morbidity of venous access devices in patients with hemophilia.  J Intraven Nurs . 1998;  21 70-75
    PubMedSearch in Google Scholar
  • 37 Perkins J L, Johnson V A, Osip J M. et al . The use of implantable venous access devices (IVADs) in children with hemophilia.  J Pediatr Hematol Oncol . 1997;  19 339-344
    CrossrefPubMedSearch in Google Scholar
  • 38 Van Den Berg M H, Fischer K, Roosendaal G, Mauser-Bunschoten E P. The use of the port-a-cath in children with haemophilia-a review.  Haemophilia . 1998;  4 418-420
    CrossrefPubMedSearch in Google Scholar
  • 39 Medeiros D, Miller K L, Rollins N K, Buchanan G R. Contrast venography in young haemophiliacs with implantable central venous access devices.  Haemophilia . 1998;  4 10-15
    PubMedSearch in Google Scholar
  • 40 Hoots W K. History of plasma-product safety.  Transfus Med Rev . 2001;  15(2 suppl 1) 3-10
    CrossrefPubMedSearch in Google Scholar
  • 41 Mannucci P M, Colombo M. Revision of the protocol recommended for studies of safety from hepatitis of clotting factor concentrates.  Thromb Haemost . 1989;  61 532-534
    PubMedSearch in Google Scholar
  • 42 Pool J G, Shannon A E. Production of high-potency concentrates of antihemophilic globulin in a closed-bag system.  N Engl J Med . 1965;  273 1443-1447
    CrossrefPubMedSearch in Google Scholar
  • 43 Hershgold E J, Pool J G, Pappenhagen A R. The potent antihemophilic globulin concentrate derived from a cold insoluble fraction of human plasma: characterization and further data on preparation and clinical trial.  J Lab Clin Med . 1966;  67 23-32
    PubMedSearch in Google Scholar
  • 44 Tullis J L, Melin M, Jurigian P. Clinical use of human prothrombin complexes.  N Engl J Med . 1965;  273 667-674
    PubMedSearch in Google Scholar
  • 45 Kasper C K, Kipnis S A. Hepatitis and clotting factor concentrates (letter).  JAMA . 1972;  221 510
    CrossrefPubMedSearch in Google Scholar
  • 46 Biggs R, Rizza C RC, Blackburn E K. et al . Factor VIII concentrates made in the United Kingdom and the treatment of haemophilia based on studies made 1969-72. Report of the medical research council's blood transfusion research committee working party on the cryoprecipitate method of preparing AHF concentrates.  Br J Haematol . 1974;  27 391-405
    PubMedSearch in Google Scholar
  • 47 Seeff L B, Hoofnagle J. Acute and Chronic Liver Disease in Hemophilia. Unsolved therapeutic problems in hemophilia. Proceedings of a conference sponsored by the Bureau of Biologics, FDA, Division of Blood Diseases and Resources, NHLBI, National Hemophilia Foundation. Bethesda, MD, March 1976. Fratantoni JC, Aronson DL, eds. DHEW Publication no (NIH) 77-1089. Washington, DC: U.S. Department of Health Education and Welfare, Public Health Service, NIH 1976: 61-72
    Search in Google Scholar
  • 48 Triger D R, Preston F E. Chronic liver disease in haemophiliacs.  Br J Haematol . 1990;  74 241-245
    PubMedSearch in Google Scholar
  • 49 Gerety R J, Aronson D L. Plasma derivatives and viral hepatitis.  Transfusion . 1982;  22 347-351
    CrossrefPubMedSearch in Google Scholar
  • 50 Brettler D B, Forsberg A D, Levine P H, Petillo J, Lamon K, Sullivan J L. Factor VIII: C concentrate purified from plasma using monoclonal antibodies: human studies.  Blood . 1989;  73 1859-1863
    PubMedSearch in Google Scholar
  • 51 Robertson B H, Alter M J, Bell B P. et al . Hepatitis A virus sequence detected in clotting factor concentrates associated with disease transmission.  Biologicals . 1998;  26 95-99
    CrossrefPubMedSearch in Google Scholar
  • 52 Blumel J, Schmidt I, Effenberger W. et al . Parvovirus B19 transmission by heat-treated clotting factor concentrates.  Transfusion . 2002;  42 1473-1481
    CrossrefPubMedSearch in Google Scholar
  • 53 Teitel J M. Viral safety of haemophilia treatment products.  Ann Med . 2000;  32 485-492
    PubMedSearch in Google Scholar
  • 54 Tabor E, Epstein J S. NAT screening of blood and plasma donations; evolution of technology and regulatory policy.  Transfusion . 2002;  42 1230-1237
    CrossrefPubMedSearch in Google Scholar
  • 55 Biggerstaff B J, Peterssen L R. Estimated risk of West Nile virus transmission through blood transfusion during an epidemic in Queens, New York City.  Transfusion . 2002;  42 1019-1026
    CrossrefPubMedSearch in Google Scholar
  • 56 Evatt B. Creutzfeldt-Jakob disease and haemophilia: assessment of risk.  Haemophilia . 2000;  6 (suppl 1) 94-99
    CrossrefPubMedSearch in Google Scholar
  • 57 Lusher J M. First and second generation recombinant factor VIII concentrates in previously untreated patients: recovery, safety, efficacy and inhibitor development.  Semin Thromb Hemost . 2002;  28 273-276
    Thieme ConnectPubMedSearch in Google Scholar
  • 58 Brinkhouse K, Sandberg H, Widlund L. et al . Preclinical pharmacology of albumin-free B-domain deleted recombinant factor VIII.  Semin Thromb Hemost . 2002;  28 269-272
    Thieme ConnectPubMedSearch in Google Scholar
  • 59 Lusher J M, Lee C A, Kessler C M, Bedrosian C L. The ReFacto Phase 3 Study Group.  Haemophilia . 2003;  9 38-49
    PubMedSearch in Google Scholar
  • 60 Mikaelsson M, Oswaldsson U, Jankowski M. Measurement of factor VIII activity of B-domain deleted recombinant factor VIII.  Semin Hematol . 2001;  38 13-23
    PubMedSearch in Google Scholar
  • 61 White II C G, Beebe A, Nielsen B. Recombinant factor IX.  Thromb Haemost . 1997;  78 261-265
    PubMedSearch in Google Scholar
  • 62 Evatt B L. Prions and haemophilia: assessment of risk.  Haemophilia . 1998;  4 628-633
    CrossrefPubMedSearch in Google Scholar
  • 63 Reid W O, Lucas O N, Francisco J, Geisler P H, Erslev A J. The use of epsilon-aminocaproic acid in the management of dental extractions in the hemophiliac.  Am J Med Sci . 1964;  248 184-188
    PubMedSearch in Google Scholar
  • 64 Bennett A E, Ingram G I, Inglish P J. Antifibrinolytic treatment in haemophilia: a controlled trial of prophylaxis with tranexamic acid.  Br J Haematol . 1973;  24 83-88
    PubMedSearch in Google Scholar
  • 65 Mannucci P M, Ruggeri Z M, Pareti F I, Capitanio A. 1-Deamino-8-d-arginine vasopressin: a new pharmacological approach to the management of haemophilia and von Willebrands' diseases.  Lancet . 1977;  1 869-872
    PubMedSearch in Google Scholar
  • 66 Smith T J, Gill J C, Ambruso D R, Hathaway W E. Hyponatremia and seizures in young children given DDAVP.  Am J Hematol . 1989;  31 199-202
    CrossrefPubMedSearch in Google Scholar
  • 67 Ingerslev J, Feldstedt M, Sindet-Pedersen D. Control of haemostasis with recombinant factor VIIa in patient with inhibitor to factor VIII.  Lancet . 1991;  338 831-832
    PubMedSearch in Google Scholar
  • 68 Hoffman M, Monroe III M D. The action of high-dose factor VIIa (FVIIa) in a cell-based model of hemostasis.  Semin Hematol . 2001;  38 (suppl 12) 6-9
    PubMedSearch in Google Scholar
  • 69 Shapiro A. Inhibitor treatment: state of the art.  Dis Mon . 2003;  49 22-38
    PubMedSearch in Google Scholar
  • 70 Rakocz M, Mazar A, Varon D, Spierer S, Blinder D, Martinowitz U. Dental extractions in patients with bleeding disorders. The use of fibrin glue.  Oral Surg Oral Med Oral Pathol . 1993;  75 280-282
    PubMedSearch in Google Scholar
  • 71 Johnson J B. The management of hemophilia with lyophile human plasma intravenously injected.  JAMA . 1942;  118 799-802
    PubMedSearch in Google Scholar
  • 72 Ahlberg A. Haemophilia in Sweden. VII. Incidence, treatment and prophylaxis of arthropathy and other musculoskeletal manifestations of haemophilia A and B.  Acta Orthop Scand . 1965;  77(suppl) 3-132
    PubMedSearch in Google Scholar
  • 73 Robinson P M, Tittley P, Smiley R K. Prophylactic therapy in classical hemophilia: a preliminary report.  Can Med Assoc J . 1967;  97 559-561
    PubMedSearch in Google Scholar
  • 74 Shanbrom E, Thelin G M. Experimental prophylaxis of severe hemophilia with a factor VIII concentrate.  JAMA . 1969;  208 1853-1856
    CrossrefPubMedSearch in Google Scholar
  • 75 Van Creveld S. Prophylaxis of joint hemorrhages in hemophilia.  Acta Haematol . 1969;  41 206-214
    CrossrefPubMedSearch in Google Scholar
  • 76 Hirschman R J, Itscoitz S B, Shulman N R. Prophylactic treatment of factor VIII deficiency.  Blood . 1970;  35 189-194
    PubMedSearch in Google Scholar
  • 77 Kasper C K, Dietrich S L, Rapaport S I. Hemophilia prophylaxis with factor VIII concentrate.  Arch Intern Med . 1970;  125 1004-1009
    CrossrefPubMedSearch in Google Scholar
  • 78 Aronstam A, Arblaster P G, Rainsford S G. et al . Prophylaxis in haemophilia: a double-blind controlled trial.  Br J Haematol . 1976;  33 81-90
    PubMedSearch in Google Scholar
  • 79 Aronstam A, Kirk P J, McHardy J W. et al . Twice weekly prophylactic therapy in haemophilia A.  J Clin Pathol . 1977;  30 65-67
    PubMedSearch in Google Scholar
  • 80 Nilsson I M, Blombäck M, Ahlberg Ä. Our experience in Sweden with prophylaxis on haemophilia. The hemophiliac and his world.  Bibl Haematol . 1970;  34 111-124
    PubMedSearch in Google Scholar
  • 81 Nilsson I M, Berntorp E, Lofqvist T, Pettersson H. Twenty-five years' experience of prophylactic treatment in severe haemophilia A and B.  J Intern Med . 1992;  232 25-32
    CrossrefPubMedSearch in Google Scholar
  • 82 Manco-Johnson M J, Nuss R, Geraghty S, Funk S, Kilcoyne R. Results of secondary prophylaxis in children with severe hemophilia.  Am J Hematol . 1994;  47 113-117
    CrossrefPubMedSearch in Google Scholar
  • 83 Hacker M R, Geraghty S, Manco-Johnson M. Barriers to compliance with prophylaxis therapy in haemophilia.  Haemophilia . 2001;  7 392-396
    CrossrefPubMedSearch in Google Scholar
  • 84 Manco-Johnson M J, Blanchette V. North American prophylaxis studies for persons with severe hemophilia: background, rationale and design.  Haemophilia . 2003;  9 (suppl 1) 44-49
    CrossrefPubMedSearch in Google Scholar
  • 85 DiMichele D M. Inhibitors in haemophilia: a primer.  Haemophilia . 2000;  6 (suppl 1) 38-40
    CrossrefPubMedSearch in Google Scholar
  • 86 Lollar P, Healey J F, Barrow R T, Parker E T. Factor VIII inhibitors.  Adv Exp Med Biol . 2001;  489 65-73
    PubMedSearch in Google Scholar
  • 87 Scandella D H. Properties of anti-factor VIII inihibitor antibodies in hemophilia patients.  Semin Thromb Hemost . 2000;  26 137-142
    Thieme ConnectPubMedSearch in Google Scholar
  • 88 Kasper C K, Aledort L M, Aronson D. et al . Proceedings: a more uniform measurement of factor VIII inhibitors.  Thromb Diath Haemorrhag (Stuttg) . 1975;  34 619-872
    PubMedSearch in Google Scholar
  • 89 Fakharzadeh S S, Kazazian Jr H H. Correlation between factor VIII genotype and inhibitor development in hemophilia A.  Semin Thromb Hemost . 2000;  26 167-171
    Thieme ConnectPubMedSearch in Google Scholar
  • 90 Oldenburg J, Brackmann H H, Schwaab R. Risk factors for inhibitor development in hemophilia A.  Haematologica . 2000;  85(10 suppl) 7-13
    PubMedSearch in Google Scholar
  • 91 Goodeve A C, Peake I R. The molecular basis of hemophilia A: genotype-phenotype relationships and inhibitor development.  Semin Thromb Hemost . 2003;  29 23-30
    PubMedSearch in Google Scholar
  • 92 Gill J. The role of genetics in inhibitor formation.  Thromb Haemost . 1999;  82 500-504
    PubMedSearch in Google Scholar
  • 93 Fijnvandraat K, Bril W S, Voorberg J. Immunobiology of inhibitor development in hemophilia A.  Semin Thromb Hemost . 2003;  29 61-68
    Thieme ConnectPubMedSearch in Google Scholar
  • 94 Aledort L M, Miners A, Bohn R. et al . Economic aspects of haemophilia care.  Haemophilia . 1999;  5 216-219
    CrossrefPubMedSearch in Google Scholar
  • 95 Nilsson I M, Hedner U, Bjorlin G. Suppression of factor IX antibody in hemophilia B by factor IX and cyclophosphamide.  Ann Intern Med . 1973;  78 91-95
    PubMedSearch in Google Scholar
  • 96 Nilsson I M, Hedner U, Holmberg L. Suppression of factor VIII antibody by combined factor VIII and cyclophosphamide.  Acta Med Scand . 1974;  1-2 64-72
    PubMedSearch in Google Scholar
  • 97 Nilsson I M, Berntorp E, Zettervall O. Induction of immune tolerance in patients with hemophilia and antibodies to factor VIII by combined treatment with intravenous IgG, cyclophosphamide, and factor VIII.  N Engl J Med . 1988;  318 947-950
    CrossrefPubMedSearch in Google Scholar
  • 98 Brackmann H H, Gormsen J. Massive factor VIII infusion in hemophiliacs with factor VIII inhibitor, high responder.  Lancet . 1977;  2 933
    PubMedSearch in Google Scholar
  • 99 Mauser-Bunschoten E P, Nieuwerhuis H K, Rosendaal G, van den Berg M H. Low dose immune tolerance induction in hemophilia A patients with inhibitors.  Blood . 1995;  86 983-988
    PubMedSearch in Google Scholar
  • 100 DiMichele D, Kroner B. The North American Immune Tolerance Registry: practices, outcomes, outcome predictors.  Thromb Haemost . 2002;  87 52-57
    PubMedSearch in Google Scholar
  • 101 Hay C RM. Immune tolerance induction: prospective clinical trials.  Haematologica . 2000;  85 52-56
    PubMedSearch in Google Scholar
  • 102 Hilgartner M W. Current treatment of hemophilic arthropathy.  Curr Opin Pediatr . 2002;  14 46-49
    CrossrefPubMedSearch in Google Scholar
  • 103 Fischer M, Modder G. Radionuclide therapy of inflammatory joint diseases.  Nucl Med Commun . 2002;  23 829-831
    CrossrefPubMedSearch in Google Scholar
  • 104 Manco-Johnson M J, Nuss R, Lear J. et al . 32P Radiosynoviorthesis in children with hemophilia.  J Pediatr Hematol Oncol . 2002;  24 534-539
    CrossrefPubMedSearch in Google Scholar
  • 105 Siegel H J, Luck J V, Siegel M E, Quinones C. Phosphate-32 colloid radiosynovectomy in hemophilia: outcome of 125 procedures.  Clin Orthop . 2001;  392 409-417
    PubMedSearch in Google Scholar
  • 106 Gilbert M S, Radomisli T E. Therapeutic options in the management of hemophilic synovitis.  Clin Orthop . 1997;  343 88-92
    PubMedSearch in Google Scholar
  • 107 Wiedel J D. Arthroscopic synovectomy of the knee in hemophilia: 10-to-15 year followup.  Clin Orthop . 1996;  328 46-53
    PubMedSearch in Google Scholar
  • 108 Carman C J. Developing and maintaining of hemophilia programs in developing countries.  Southeast Asian J Trop Med Public Health . 1993;  24 (suppl 1) 46
    PubMedSearch in Google Scholar
  • 109 Srivastava A, Chuansumrit A, Chandy M, Duraiswamy G, Karagus C. Management of haemophilia in the developing world.  Haemophilia . 1998;  4 474-480
    CrossrefPubMedSearch in Google Scholar
  • 110 Evatt B L, Robillard L. Establishing haemophilia care in developing countries: using data to overcome the barrier of pessimism.  Haemophilia . 2000;  6 131-134
    CrossrefPubMedSearch in Google Scholar
  • 111 Isarangkura P. Haemophilia care in the developing world: benchmarking for excellence.  Haemophilia . 2002;  8 205-210
    CrossrefPubMedSearch in Google Scholar
  • 112 High K A. Gene transfer as an approach to treating hemophilia.  Semin Thromb Hemost . 2003;  29 107-119
    PubMedSearch in Google Scholar