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Hamostaseologie 2012; 32(04): 271-275
DOI: 10.5482/HAMO-12-06-0012
Original article
Schattauer GmbH

Desmopressin testing in haemo-philia A patients and carriers

Results of a multi centre surveyDesmopressin-Testung bei Patienten mit Hämophilie A und KonduktorinnenErgebnisse einer multizentrischen Studie
R. Knöfler
1   Department of Paediatric Haematology, Oncology and Haemostaseology, University Hospital Carl Gustav Carus Dresden, Germany
,
J. Koscielny
2   Outpatient Clinic for Coagulation Disorders and Transfusion Medicine, Charité Medical University Berlin, Germany
,
J. T. Tauer
1   Department of Paediatric Haematology, Oncology and Haemostaseology, University Hospital Carl Gustav Carus Dresden, Germany
,
B. Huhn
1   Department of Paediatric Haematology, Oncology and Haemostaseology, University Hospital Carl Gustav Carus Dresden, Germany
,
A. Gneuss
1   Department of Paediatric Haematology, Oncology and Haemostaseology, University Hospital Carl Gustav Carus Dresden, Germany
,
E. Kuhlisch
3   Department of Medical Statistics, Medical Faculty of Technical University Dresden, Germany
,
A. Hofmann
4   Department of Paediatrics, Municipal Hospital Chemnitz, Germany
,
S. Petros
5   Department of Internal Medicine, University Hospital Leipzig, Germany
,
V. Aumann
6   Department of Paediatrics, University Hospital Magdeburg, Germany
,
D. Franke
7   Practice of Internal Medicine and Angiology, Magdeburg, Germany
,
K. Kentouche
8   Department of Paediatric Haematology and Oncology, University Hospital Jena, Germany
,
G. Syrbe
9   Haemophilia Centre, Asklepios Hospital Stadtroda, Germany
,
K. Seeger
10   Department of Paediatric Haematology and Oncology, Charité Medical University Berlin, Germany
,
H. Haberland
11   Department of Paediatrics, Sana Hospital Lichtenberg, Berlin, Germany
,
R. Klamroth
12   Department of Angiology and Clotting Disorders, Haemophilia Treatment Center, Vivantes Hospital Friedrichshain, Berlin, Germany
› Author AffiliationsThis study was supported by an unrestricted grant from CSL Behring.
Further Information

Publication History

received: 19 June 2012

accepted: 21 August 2012

Publication Date:
28 December 2017 (online)

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Summary

Introduction: Desmopressin (DDAVP) testing (DT) in patients (pts) with haemophilia A (HA) and carriers (CHA) is up to now not standardized. This prompted us to evaluate results of DT carried out between 1996 and 2011 in centres of the Competence Network Haemor-rhagic Diatheses East. Patients and method: An increase of the factor VIII activity (FVIII) above 50% or at least the two fold of initial values within 120 min after DDAVP was defined as complete response (CR). Data from 80 patients (31 children, 49 adults) of whom 64 suffered from HA (sub-HA: n = 48; mild: n = 14; moderate: n = 2) and 16 patients CHA were evaluated. Results: In 34 patients DDAVP was given i. v. (dose range: 0.26–0.6 μg/kg body weight, mean: 0.33), in 31 intranasally (i.n. 300–600 μg) and in 15 s. c. (15–40 μg). The maximal FVIII increase was reached 60 min after DDAVP. For i. v. application the mean FVIII increase was 3.1-fold, for i. n. 2.1-fold and for s. c. 2.4-fold. A CR was de tected in 71 patients, a non-response in 9. Mild side effects such as flush, headaches or nausea were observed in 11 patients (14%). Conclusion: For desmopressin testing in patients with haemophilia A and carriers i. v. application at 0.3 μg/kg body weight and the determination of FVIII before and 60 min after desmopressin infusion is recommended.

Zusammenfassung

Einleitung: Der Desmopressin(DDAVP)-Test (DT) bei Patienten mit Hämophilie A (HA) und Konduktorinnen (KHA) ist nicht standardisiert. Das veranlasste uns, die Desmopressin-tests der Zentren des Kompetenznetzwerks Hämorrhagische Diathesen Ost von 1996 bis 2011 zu analysieren. Patienten, Methode: Ein Faktor-VIII-Aktivitätsanstieg (FVIII) auf über 50% oder um mindestens das Doppelte der Initialwerte innerhalb von 120 min nach DDAVP wurde als komplette Response (KR) gewertet. Daten von 80 Patienten (31 Kinder, 49 Erwachsene), davon 64 mit HA (Sub: n = 48; leicht: n = 14; mittelschwer: n = 2) und 16 KHA wurden evaluiert. Ergebnisse: Bei 34 Patienten wurde DDAVP i. v. gegeben (Bereich: 0,26–0,6 μg/kg Körpergewicht, Mittel: 0,33), bei 31 intranasal (i. n.; 300–600 μg) und bei 15 s. c. (15–40 μg). Der maximale FVIII-Anstieg wurde 60 min nach DDAVP erreicht. Nach i.v.-Gabe war der mittlere FVIII-Anstieg 3,1-fach, nach i. n.-Applikation 2,1-fach und nach s.c.-Gabe 2,4-fach. Ein KR lag bei 71 Patienten und ein Non-Response bei 9 vor. Leichte unerwünschte Arzneimittelwirkungen wie Flush, Kopfschmerzen oder Übelkeit traten bei 11 Patienten (14%) auf. Schlussfolgerung: Bei Patienten mit Hämophilie A und Konduktorinnen wird zur Testung i.v. DDAVP 0.3 μg/kg Körpergewicht mit FVIII- Bestimmung vor und 60 min nach Infusion empfohlen.

Keywords

Haemophilia A - desmopressin testing - DDAVP

Schlüsselwörter

Hämophilie A - Desmopressintest - DDAVP
 

  • References

  • 1 Lethagen S. Desmopressin in mild hemophilia A: indications, limitations, efficacy, and safety. Semin Thromb Hemost 2003; 29: 101-106.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Castaman G. Desmopressin for the treatment of haemophilia. Haemophilia 2008; 14 (Suppl. 01) 15-20.
    PubMedGoogle Scholar
  • 3 Miesbach W, Krekeler S, Dück O. et al. Clinical assessment of efficacy and safety of DDAVP. Hämostaseologie 2010; 30 (Suppl. 01) S172-S175.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Sanchez-Luceros A, Meschengieser SS, Woods AI. et al. Biological and clinical response to desmopressin (DDAVP) in a retrospective cohort study of children with low von Willebrand factor levels and bleeding history. Thromb Haemost 2010; 104: 984-989.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Hanebutt FL, Rolf N, Loesel A. et al. Evaluation of desmopressin effects on haemostasis in children with congenital bleeding disorders. Haemophilia 2008; 14: 524-530.
    CrossrefPubMedGoogle Scholar
  • 6 Revel-Vilk S, Blanchette VS, Sparling C. et al. DDAVP challenge tests in boys with mild/moderate haemophilia A. Br J Haematol 2002; 117: 947-951.
    CrossrefPubMedGoogle Scholar
  • 7 Nolan B, White B, Smith J. et al. Desmopressin: therapeutic limitations in children and adults with inherited coagulation disorders. Br J Haematol 2000; 109: 865-869.
    CrossrefPubMedGoogle Scholar
  • 8 Lethagen S, Harris AS, Sjorin E, Nilsson IM. Intranasal and intravenous administration of desmopressin: effect on FVIII/VWF, pharmacokinetics and reproducibility. Thromb Haemost 1987; 58: 1033-1036.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Lethagen S, Harris AS, Nilsson IM. Intranasal desmopressin (DDAVP) by spray in mild hemophilia A and von Willebrand’s disease type I. Blut 1990; 60: 187-191.
    CrossrefPubMedGoogle Scholar
  • 10 Mannucci PM, Vicente V, Alberca I. et al. Intravenous and subcutaneous administration of desmopressin (DDAVP) to hemophiliacs: pharmacokinetics and factor VIII responses. Thromb Haemost 1987; 58: 1037-1039.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 11 Seary ME, Feldman D, Carcao MD. DDAVP responsiveness in children with mild or moderate haemophilia A correlates with age, endogenous FVIII:C level and with haemophilic genotype. Haemophilia 2012; 18: 50-55.
    CrossrefPubMedGoogle Scholar
  • 12 Castaman G, Mancuso ME, Giacomelli SH. et al. Molecular and phenotypic determinants of the response to desmopressin in adult patients with mild hemophilia A. J Thromb Haemost 2009; 07: 1824-1831.
    CrossrefPubMedGoogle Scholar
  • 13 De la Fuente B, Kasper CK, Rickles FR, Hoyer LW. Response of patients with mild and moderate hemophilia A and von Willebrand’s disease to treatment with desmopressin. Ann Intern Med 1985; 103: 6-14.
    CrossrefPubMedGoogle Scholar
  • 14 Rodeghiero F, Castaman G, Di Bona E, Ruggeri M. Consistency of responses to repeated DDAVP infusions in patients with von Willebrand’s disease and hemophilia A. Blood 1989; 74: 1997-2000.
    PubMedGoogle Scholar
  • 15 Tagliaferri A, Di Perna C, Riccardi F. et al. The natural history of mild haemophilia: a 30-year single centre experience. Haemophilia 2012; 18: 166-174.
    CrossrefPubMedGoogle Scholar
  • 16 Castaman G, Giacomelli SH, Mancuso ME. et al. Deep intronic variations may cause mild hemophilia A. J Thromb Haemost 2011; 09: 1541-1548.
    CrossrefPubMedGoogle Scholar
  • 17 Mannucci PM. Desmopressin (DDAVP) for treatment of disorders of hemostasis. Prog Hemost Thromb 1986; 08: 19-45.
    PubMedGoogle Scholar
  • 18 Gillam PMS. Desmopressin and arterial thrombosis. Lancet 1989; 01: 938-939.
    PubMedGoogle Scholar
  • 19 Cattaneo M, Mannucci PM. Desmopressin and blood loss after cardiac surgery. Lancet 1993; 342: 812.
    CrossrefPubMedGoogle Scholar
  • 20 Mannucci PM, Lusher JM. Desmopressin and thrombosis. Lancet 1989; 02: 675-676.
    PubMedGoogle Scholar
  • 21 O’Brien JR, Green PJ, Salmon G. et al. Desmopressin and myocardial infarction. Lancet 1989; 01: 664-665.
    PubMedGoogle Scholar
  • 22 Bond L, Bevan D. Myocardial infarction in a patient with hemophilia treated with DDAVP. N Engl J Med 1988; 318: 121.
    PubMedGoogle Scholar
  • 23 Lowe G, Pettigrew A, Middleton S. et al. DDAVP in haemophilia. Lancet 1977; 02: 614-615.
    PubMedGoogle Scholar
  • 24 Shepherd LL, Hutchinson RJ, Worden EK. et al. Hyponatremia and seizures after intravenous administration of desmopressin acetate for surgical hemostasis. J Pediatr 1989; 114: 470-472.
    CrossrefPubMedGoogle Scholar
  • 25 Salvatoni A, Maghnie M, Lorini R, Marni E. Hyponatremia and seizures during desmopressin acetate treatment in hypothyroidism. J Pediatr 1990; 116: 835-836.
    PubMedGoogle Scholar
  • 26 Weinstein RE, Bona RD, Altman AJ. et al. Severe hyponatremia after repeated intravenous administration of desmopressin. Am J Hematol 1989; 32: 258-261.
    CrossrefPubMedGoogle Scholar
  • 27 Smith TJ, Gill JC, Ambruso DR, Hathaway WE. Hyponatremia and seizures in young children given DDAVP. Am J Hematol 1989; 31: 199-202.
    CrossrefPubMedGoogle Scholar
  • 28 Huhn B, Hofmann A, Hofmann K. et al. Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia. Hämostaseologie 2009; 29 (Suppl. 01) S98-S102.
    Article in Thieme ConnectPubMedGoogle Scholar