TY - JOUR
T1 - Patients with severe von Willebrand disease are insensitive to the releasing effect of DDAVP
T2 - Evidence that the DDAVP-induced increase in plasma factor VIII is not secondary to the increase in plasma von Willebrand factor
AU - Cattaneo, M.
AU - Simoni, L.
AU - Gringeri, A.
AU - Mannucci, P. M.
PY - 1994
Y1 - 1994
N2 - It is generally held that factor VIII (FVIII) does not increase in the plasma of severe von Willebrand disease (vWD) patients treated with DDAVP because they lack von Willebrand factor (vWF), which is the plasma carrier for FVIII. To test this hypothesis, FVIII plasma levels were monitored in severe vWD patients treated with DDAVP after normalization of vWF plasma levels with infusions of cryoprecipitate. Each of four severe vWD patients underwent four different treatments at intervals of at least 15 d: (1) cryoprecipitate plus DDAVP; (2) cryoprecipitate plus saline; (3) cryoprecipitate plus recombinant FVIII (rFVIII); (4) saline plus rFVIII. Cryoprecipitate increased the plasma levels of FVIII and vWF. The infusions of saline or DDAVP after cryoprecipitate did not further increase FVIII and vWF plasma levels and had no effect on the plasma levels of tissue plasminogen activator (tPA), which are raised by DDAVP in normal subjects and in patients with vWD of other types. The infusion of rFVIII further increased by 182 ± 32 U/dl (mean ± SEM) the plasma levels attained after cryoprecipitate, which disappeared from the circulation with a half-life of 11.95 ± 0.86 h. In contrast, the infusion of rFVIII after saline increased by only 107 ± 18 U/dl the plasma levels of FVIII, which disappeared from the circulation with a half-life of 2.68 ± 0.14 h, indicating that the vWF infused with cryoprecipitate is able to bind additional FVIII. These studies indicate that DDAVP does not increase the plasma levels of FVIII in patients with severe vWD even after normalization of plasma vWF. The possibility is discussed that severe vWD patients may be insensitive to the releasing effect of DDAVP.
AB - It is generally held that factor VIII (FVIII) does not increase in the plasma of severe von Willebrand disease (vWD) patients treated with DDAVP because they lack von Willebrand factor (vWF), which is the plasma carrier for FVIII. To test this hypothesis, FVIII plasma levels were monitored in severe vWD patients treated with DDAVP after normalization of vWF plasma levels with infusions of cryoprecipitate. Each of four severe vWD patients underwent four different treatments at intervals of at least 15 d: (1) cryoprecipitate plus DDAVP; (2) cryoprecipitate plus saline; (3) cryoprecipitate plus recombinant FVIII (rFVIII); (4) saline plus rFVIII. Cryoprecipitate increased the plasma levels of FVIII and vWF. The infusions of saline or DDAVP after cryoprecipitate did not further increase FVIII and vWF plasma levels and had no effect on the plasma levels of tissue plasminogen activator (tPA), which are raised by DDAVP in normal subjects and in patients with vWD of other types. The infusion of rFVIII further increased by 182 ± 32 U/dl (mean ± SEM) the plasma levels attained after cryoprecipitate, which disappeared from the circulation with a half-life of 11.95 ± 0.86 h. In contrast, the infusion of rFVIII after saline increased by only 107 ± 18 U/dl the plasma levels of FVIII, which disappeared from the circulation with a half-life of 2.68 ± 0.14 h, indicating that the vWF infused with cryoprecipitate is able to bind additional FVIII. These studies indicate that DDAVP does not increase the plasma levels of FVIII in patients with severe vWD even after normalization of plasma vWF. The possibility is discussed that severe vWD patients may be insensitive to the releasing effect of DDAVP.
KW - desmopressin (DDAVP)
KW - factor VIII
KW - tissue plasminogen activator
KW - von Willebrand disease
KW - von Willebrand factor
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M3 - Article
C2 - 8199023
AN - SCOPUS:0028363703
VL - 86
SP - 333
EP - 337
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 2
ER -