HETEROGENOUS RESPONSES TO CRYOPRECIPITATE AND DDAVP IN TYPE IIA VON WILLEBRAND'S DISEASE (VWD)

1987 ◽  
Author(s):  
J Chediak ◽  
B Maxey ◽  
J Eldridge ◽  
M C Telfer
Keyword(s):  
Von Willebrand Factor ◽  
Selective Reduction ◽  
Autosomal Dominant Disorder ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Von Willebrand Factor Antigen ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen

Von Willebrand's disease is an autosomal dominant disorder characterized by excessive mucocutaneous bleeding, prolonged bleeding time (BT), and reduce amounts of ristocetin cofactor activity (RiCof). The Von Willebrand factor antigen (VWF:Ag) shows either reduced amounts or no multimers (Types I and III), or a selective reduction of high molecular weight multimers (HMW) (Type IIA and IIB). Variable responses to DDAVP have been reported in IIA VWD suggesting that IIA patients (pts) are a heterogenous group. Some IIA pts may show RiCcf activity after DDAVP infusion even though no HMW multimers are found.Von Willebrand factor antigen, RiCof and BT were analyzed in five pts (2 females and 3 males) known to have Type IIA VWD. Baseline values shov/ed marked reductions of RiCof (less than 13% of normal), BT greater than 15 minutes, faster immunoelectrophoresis of VWF:Ag and absent HMW multimers. Immunoelectrophoresis of VWF:Ag by the Laurell technique gave variable amounts ranging from 10 to 125% or normal. Three adult pts received DDAVP (Stimate) or cryoprecipitate (cryo) and the responses on abnormal parameters were assessed up to 48 hours. In two pts the BT corrected with cryo, whereas in the third patient the correction was minimal. The three pts showed a normal decay of both VWF:Ag or RiCof after cryo. However, after DDAVP the decay of VWF:Ag and RiCof was similar to that after cryo in one patient and more rapid in two patients.In these two patients, the data would be compatible with the rapid proteolysis of endogenoue VWF released by the patient's endothelial cells, whereas the exogenous VWF given as cryo showed normal survival in the patient's blood.

Von Willebrand Factor Antigen Is Less Sensitive than Ristocetin Cofactor for the Diagnosis of Type I von Willebrand Disease -Results Based on an Epidemiological Investigation

1990 ◽  
Vol 64 (03) ◽  
pp. 349-352 ◽  
Author(s):  
Francesco Rodeghiero ◽  
Giancarlo Castaman ◽  
Alberto Tosetto
Keyword(s):  
Von Willebrand Factor ◽  
Type I ◽  
Epidemiological Investigation ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Von Willebrand Factor Antigen ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor

SummaryRecently, in an epidemiological investigation involving 1,218 children aged 11-14, we demonstrated that the prevalence of von Willebrand’s disease, based on a low ristocetin cofactor activity (RiCof) in children with a personal and/or family history of hemorrhage, was at least 1% (Blood 1987; 69: 454). All the diagnosed cases had multimeric patterns typical of type I von Willebrand’s disease (vWd). Since standardization of RiCof is difficult and the test is not easily performed in a clinical laboratory, we measured von Willebrand factor antigen (vWf: Ag) in all available unthawed plasma samples of previously investigated children by ELISA, to assess the relative sensitivity of this more simple test for diagnosing vWd.Separate normal ranges were calculated by non-parametric methods for 0 and non-0 subjects, and for children and adults, since values were higher in non-0 subjects and in children.Taking into account the 90% confidence interval around the lower limit of the normal range, 7 (50%) of the 14 cases diagnosed by RiCof were detected by vWf: Ag. Furthermore, two new cases would have been diagnosed by vWf: Ag, leading to a relative Ag/ RiCof global sensitivity of 64%. A similar figure was obtained when the two tests were compared in the group of relatives of the affected children.In conclusion, measurement of vWf: Ag seems to be definitely less sensitive than the RiCof assay for detecting patients with vWd, even in type I patients, and RiCof remains the test of choice for screening for vWd in hemorrhagic patients.

scholarly journals Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 58-61 ◽  
Author(s):  
HR Gralnick ◽  
ME Rick ◽  
LP McKeown ◽  
SB Williams ◽  
RI Parker ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Time Factors ◽  
Type I ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor

Abstract We studied 17 patients with moderate to mild type I von Willebrand's disease (vWd) and correlated the bleeding time with the plasma von Willebrand factor antigen (vWf Ag), the plasma vWf activity (ristocetin cofactor), the platelet vWf Ag, and the platelet vWf activity. We found an excellent correlation between the bleeding time and the platelet vWf activity and, to a lesser extent, between the bleeding time and the platelet vWf Ag. The length of the bleeding time was inversely proportional to the level of the platelet vWf (P less than .001) or, to a lesser extent, the platelet vWf Ag (P less than .05). The plasma vWf Ag and activity did not correlate significantly with the bleeding time. These studies indicate that the platelet vWf is one of the important bleeding time factors in type I vWd and that the platelet vWf plays an important role in the early steps of hemostasis.

scholarly journals Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1213-1217 ◽  
Author(s):  
U Budde ◽  
JA Dent ◽  
SD Berkowitz ◽  
ZM Ruggeri ◽  
TS Zimmerman
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Polyacrylamide Gel Electrophoresis ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Myeloproliferative Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract In order to evaluate the role of proteolysis in acquired von Willebrand's disease (vWD) associated with the myeloproliferative syndrome, we have determined the relative quantity of von Willebrand factor (vWF) fragments as compared with the intact 225 kDa subunit in four patients. The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated. Plasma was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF was isolated from plasma by immunoadsorbent chromatography, reduced, subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased in proportion to the intact 225 kDa subunit indicating increased proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count. This was associated with a correction of the bleeding time, a partial correction of the multimeric abnormality, and a lessening of vWF cleavage. In a patient with polycythemia rubra vera (PRV) the proportion of the 176 kDa fragment was increased to the upper limit of normal but there was no definite evidence of increased proteolysis. These studies provide evidence that proteolysis plays a role in the acquired von Willebrand's disease associated with the myeloproliferative syndrome. However, other mechanisms must also be considered.

scholarly journals Subunit composition of plasma von Willebrand factor in patients with the myeloproliferative syndrome

Blood ◽  
1986 ◽  
Vol 68 (6) ◽  
pp. 1213-1217 ◽  
Author(s):  
U Budde ◽  
JA Dent ◽  
SD Berkowitz ◽  
ZM Ruggeri ◽  
TS Zimmerman
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Polyacrylamide Gel Electrophoresis ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Myeloproliferative Syndrome ◽  
Von Willebrand ◽  
Willebrand Factor

In order to evaluate the role of proteolysis in acquired von Willebrand's disease (vWD) associated with the myeloproliferative syndrome, we have determined the relative quantity of von Willebrand factor (vWF) fragments as compared with the intact 225 kDa subunit in four patients. The plasma vWF of each individual lacked large multimers; each had a prolonged bleeding time; and both platelet and leukocyte counts were elevated. Plasma was obtained from blood drawn into 1 mmol/L leupeptin, 6 mmol/L N-ethylmaleimide, and 5 mmol/L EDTA to prevent in vitro proteolysis. vWF was isolated from plasma by immunoadsorbent chromatography, reduced, subjected to SDS-5% polyacrylamide gel electrophoresis, and immunoblotted with a mixture of 55 anti-vWF monoclonal antibodies. In three patients with essential thrombocytosis (ET) the 176 and 140 kDa fragments were increased in proportion to the intact 225 kDa subunit indicating increased proteolysis. Treatment of one ET patient with CCNU (Lomustine) decreased the platelet count and, to a lesser extent, the white blood cell count. This was associated with a correction of the bleeding time, a partial correction of the multimeric abnormality, and a lessening of vWF cleavage. In a patient with polycythemia rubra vera (PRV) the proportion of the 176 kDa fragment was increased to the upper limit of normal but there was no definite evidence of increased proteolysis. These studies provide evidence that proteolysis plays a role in the acquired von Willebrand's disease associated with the myeloproliferative syndrome. However, other mechanisms must also be considered.

scholarly journals Platelet von Willebrand factor: an important determinant of the bleeding time in type I von Willebrand's disease

Blood ◽  
1986 ◽  
Vol 68 (1) ◽  
pp. 58-61 ◽  
Author(s):  
HR Gralnick ◽  
ME Rick ◽  
LP McKeown ◽  
SB Williams ◽  
RI Parker ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Time Factors ◽  
Type I ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor

We studied 17 patients with moderate to mild type I von Willebrand's disease (vWd) and correlated the bleeding time with the plasma von Willebrand factor antigen (vWf Ag), the plasma vWf activity (ristocetin cofactor), the platelet vWf Ag, and the platelet vWf activity. We found an excellent correlation between the bleeding time and the platelet vWf activity and, to a lesser extent, between the bleeding time and the platelet vWf Ag. The length of the bleeding time was inversely proportional to the level of the platelet vWf (P less than .001) or, to a lesser extent, the platelet vWf Ag (P less than .05). The plasma vWf Ag and activity did not correlate significantly with the bleeding time. These studies indicate that the platelet vWf is one of the important bleeding time factors in type I vWd and that the platelet vWf plays an important role in the early steps of hemostasis.

Further Studies on Aggregation of Platelet-Type von Willebrand’s Disease Platelets by Human von Willebrand Factor

1986 ◽  
Vol 55 (03) ◽  
pp. 338-341 ◽  
Author(s):  
H Takahashi ◽  
W Tatewaki ◽  
M Hanano ◽  
R Nagayama ◽  
A Shibata
Keyword(s):  
Von Willebrand Factor ◽  
Ricinus Communis ◽  
Divalent Cations ◽  
Peanut Agglutinin ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Ricinus Communis Agglutinin ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor

SummaryPlatelet-type von Willebrand’s disease (vWD) is a bleeding disorder characterized by a heightened interaction between platelets and von Willebrand factor (vWF) as the result of an intrinsic platelet abnormality (probably in GPIb). Platelet aggregability was nearly normal in response to thrombin, wheat germ agglutinin and Ricinus communis agglutinin in this disorder. Unmodified platelets showed no aggregation upon the addition of peanut agglutinin. Partially purified human vWF induced little aggregation of washed patient platelets, but the aggregation was greatly enhanced in the presence of plasma devoid of vWF. Monoclonal antibodies directed against GPIb and GPIIb/IIIa as well as EDTA completely inhibited vWF-induced aggregation. These results indicate that human vWF induces aggregation of platelet-type vWD platelets in the presence of divalent cations and some plasma cofactor(s), and that both GPIb and GPIIb/IIIa are involved in this aggregation.

scholarly journals Studies of the pathophysiology of acquired von Willebrand's disease in seven patients with lymphoproliferative disorders or benign monoclonal gammopathies

Blood ◽  
1984 ◽  
Vol 64 (3) ◽  
pp. 614-621 ◽  
Author(s):  
PM Mannucci ◽  
R Lombardi ◽  
R Bader ◽  
MH Horellou ◽  
G Finazzi ◽  
...  
Keyword(s):  
Lymphoproliferative Disorders ◽  
Type I ◽  
Agarose Gel Electrophoresis ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Monoclonal Gammopathies ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Factor Antigen ◽  
Ristocetin Cofactor

Abstract In seven patients with acquired von Willebrand's disease (AvWD) associated with lymphoproliferative disorders or benign monoclonal gammopathies, the platelet contents of von Willebrand factor antigen and ristocetin cofactor (vWF:Ag and vWF:RiCof, respectively) were normal. All the multimers of vWF:Ag could be seen in the 1.6% SDS- agarose gel electrophoresis patterns of plasma and platelet lysates. Infusion of 1-deamino-8-D-arginine vasopressin (DDAVP) augmented plasma levels of vWF:Ag and vWF:RiCof of all patients and corrected prolonged bleeding times (BT). However, compared with patients with congenital vWD type I and comparable degrees of baseline abnormalities treated in the same way, vWF:Ag and vWF:RiCof were increased less and cleared more rapidly from plasma and the BT remained normal for a shorter period of time. These studies provide evidence that these AvWD patients have qualitatively normal vWF in plasma, but at lower concentrations, that vWF in platelets is normal both qualitatively and quantitatively, and that cellular vWF can be rapidly released into plasma by DDAVP to correct the hemostatic abnormalities. However, vWF is removed rapidly from plasma, making the correction more transient than in congenital vWD type I.

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