Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease

A. B. Federici, P. M. Mannucci

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

In von Willebrand disease, the main goals of treatment are to correct the dual defect of haemostasis caused by a reduced or abnormal von Willebrand factor (vWF), i.e. the prolonged bleeding time (BT) and the deficiency of factor VIII coagulant activity (FVIII:C). The synthetic vasopressin analogue, desmopressin (DDAVP), has reduced the need for transfusions in most of the mild forms of von Willebrand disease but DDAVP is ineffective in type 3 and in other severe cases of types 1 and 2 von Willebrand disease. For many years cryoprecipitate has been the mainstay of replacement therapy but, after the introduction of virucidal methods, concentrates containing FVIII/vWF have been considered much safer than cryoprecipitate and proposed in von Willebrand disease management. FVIII/vWF concentrates have been produced and tested by many authors but there is only one report describing four virus-inactivated FVIII/vWF concentrates evaluated in a cross-over randomized trial. According to these in vitro and pharmacokinetic data, the following information can be derived: (a) no FVIII/vWF concentrate had an intact multimeric structure similar to that of normal plasma or of cryoprecipitate; (b) all FVIII/vWF concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed in the concentrate devoid of FVIII:C; (c) no FVIII/vWF concentrate consistently normalized the BT in a sustained fashion. On the other hand, clinical haemostasis can be achieved in the management of bleeding episodes and of surgery for most of von Willebrand disease cases regardless of whether the BT is corrected; in the few rare cases with mucosal bleeding not controlled by FVIII/vWF concentrates, infusion of DDAVP or platelet concentrates can be administered in addition.

Original languageEnglish
Pages (from-to)7-10
Number of pages4
JournalHaemophilia
Volume4
Issue numberSUPPL. 3
DOIs
Publication statusPublished - 1998

Fingerprint

von Willebrand Diseases
von Willebrand Factor
Deamino Arginine Vasopressin
Coagulants
Bleeding Time
Factor VIII
Therapeutics
Hemostasis
Type 1 von Willebrand Disease
Type 2 von Willebrand Disease
Hemorrhage
factor VIII, von Willebrand factor drug combination
Hemophilia A
Disease Management
Vasopressins
Cross-Over Studies
Blood Platelets
Pharmacokinetics
Viruses

Keywords

  • Desmopressin
  • Factor VIII/von Willebrand factor concentrates
  • Von Willebrand disease
  • Von Willebrand factor

ASJC Scopus subject areas

  • Hematology

Cite this

Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease. / Federici, A. B.; Mannucci, P. M.

In: Haemophilia, Vol. 4, No. SUPPL. 3, 1998, p. 7-10.

Research output: Contribution to journalArticle

@article{b466c9009a90423684723bf30af1ffcf,
title = "Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease",
abstract = "In von Willebrand disease, the main goals of treatment are to correct the dual defect of haemostasis caused by a reduced or abnormal von Willebrand factor (vWF), i.e. the prolonged bleeding time (BT) and the deficiency of factor VIII coagulant activity (FVIII:C). The synthetic vasopressin analogue, desmopressin (DDAVP), has reduced the need for transfusions in most of the mild forms of von Willebrand disease but DDAVP is ineffective in type 3 and in other severe cases of types 1 and 2 von Willebrand disease. For many years cryoprecipitate has been the mainstay of replacement therapy but, after the introduction of virucidal methods, concentrates containing FVIII/vWF have been considered much safer than cryoprecipitate and proposed in von Willebrand disease management. FVIII/vWF concentrates have been produced and tested by many authors but there is only one report describing four virus-inactivated FVIII/vWF concentrates evaluated in a cross-over randomized trial. According to these in vitro and pharmacokinetic data, the following information can be derived: (a) no FVIII/vWF concentrate had an intact multimeric structure similar to that of normal plasma or of cryoprecipitate; (b) all FVIII/vWF concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed in the concentrate devoid of FVIII:C; (c) no FVIII/vWF concentrate consistently normalized the BT in a sustained fashion. On the other hand, clinical haemostasis can be achieved in the management of bleeding episodes and of surgery for most of von Willebrand disease cases regardless of whether the BT is corrected; in the few rare cases with mucosal bleeding not controlled by FVIII/vWF concentrates, infusion of DDAVP or platelet concentrates can be administered in addition.",
keywords = "Desmopressin, Factor VIII/von Willebrand factor concentrates, Von Willebrand disease, Von Willebrand factor",
author = "Federici, {A. B.} and Mannucci, {P. M.}",
year = "1998",
doi = "10.1046/j.1365-2516.1998.0040s3007.x",
language = "English",
volume = "4",
pages = "7--10",
journal = "Haemophilia",
issn = "1351-8216",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "SUPPL. 3",

}

TY - JOUR

T1 - Optimizing therapy with factor VIII/von Willebrand factor concentrates in von Willebrand disease

AU - Federici, A. B.

AU - Mannucci, P. M.

PY - 1998

Y1 - 1998

N2 - In von Willebrand disease, the main goals of treatment are to correct the dual defect of haemostasis caused by a reduced or abnormal von Willebrand factor (vWF), i.e. the prolonged bleeding time (BT) and the deficiency of factor VIII coagulant activity (FVIII:C). The synthetic vasopressin analogue, desmopressin (DDAVP), has reduced the need for transfusions in most of the mild forms of von Willebrand disease but DDAVP is ineffective in type 3 and in other severe cases of types 1 and 2 von Willebrand disease. For many years cryoprecipitate has been the mainstay of replacement therapy but, after the introduction of virucidal methods, concentrates containing FVIII/vWF have been considered much safer than cryoprecipitate and proposed in von Willebrand disease management. FVIII/vWF concentrates have been produced and tested by many authors but there is only one report describing four virus-inactivated FVIII/vWF concentrates evaluated in a cross-over randomized trial. According to these in vitro and pharmacokinetic data, the following information can be derived: (a) no FVIII/vWF concentrate had an intact multimeric structure similar to that of normal plasma or of cryoprecipitate; (b) all FVIII/vWF concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed in the concentrate devoid of FVIII:C; (c) no FVIII/vWF concentrate consistently normalized the BT in a sustained fashion. On the other hand, clinical haemostasis can be achieved in the management of bleeding episodes and of surgery for most of von Willebrand disease cases regardless of whether the BT is corrected; in the few rare cases with mucosal bleeding not controlled by FVIII/vWF concentrates, infusion of DDAVP or platelet concentrates can be administered in addition.

AB - In von Willebrand disease, the main goals of treatment are to correct the dual defect of haemostasis caused by a reduced or abnormal von Willebrand factor (vWF), i.e. the prolonged bleeding time (BT) and the deficiency of factor VIII coagulant activity (FVIII:C). The synthetic vasopressin analogue, desmopressin (DDAVP), has reduced the need for transfusions in most of the mild forms of von Willebrand disease but DDAVP is ineffective in type 3 and in other severe cases of types 1 and 2 von Willebrand disease. For many years cryoprecipitate has been the mainstay of replacement therapy but, after the introduction of virucidal methods, concentrates containing FVIII/vWF have been considered much safer than cryoprecipitate and proposed in von Willebrand disease management. FVIII/vWF concentrates have been produced and tested by many authors but there is only one report describing four virus-inactivated FVIII/vWF concentrates evaluated in a cross-over randomized trial. According to these in vitro and pharmacokinetic data, the following information can be derived: (a) no FVIII/vWF concentrate had an intact multimeric structure similar to that of normal plasma or of cryoprecipitate; (b) all FVIII/vWF concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed in the concentrate devoid of FVIII:C; (c) no FVIII/vWF concentrate consistently normalized the BT in a sustained fashion. On the other hand, clinical haemostasis can be achieved in the management of bleeding episodes and of surgery for most of von Willebrand disease cases regardless of whether the BT is corrected; in the few rare cases with mucosal bleeding not controlled by FVIII/vWF concentrates, infusion of DDAVP or platelet concentrates can be administered in addition.

KW - Desmopressin

KW - Factor VIII/von Willebrand factor concentrates

KW - Von Willebrand disease

KW - Von Willebrand factor

UR - http://www.scopus.com/inward/record.url?scp=0031773052&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031773052&partnerID=8YFLogxK

U2 - 10.1046/j.1365-2516.1998.0040s3007.x

DO - 10.1046/j.1365-2516.1998.0040s3007.x

M3 - Article

VL - 4

SP - 7

EP - 10

JO - Haemophilia

JF - Haemophilia

SN - 1351-8216

IS - SUPPL. 3

ER -