BLEEDING TIME IN TREATED PATIENTS WITH SEVERE VON WILLEBRAND DISEASE IS NOT CORRECTED ONLY BY GIVING NORMAL MULTIMERIC PLASMA VON WILLEBRAND FACTOR

1987 ◽  
Author(s):  
P M Mannucci ◽  
M Moia ◽  
D Altieri ◽  
J Monteagudo ◽  
R Castillo
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Random Order ◽  
Von Willebrand Disease ◽  
Controlled Study ◽  
Prolonged Bleeding Time ◽  
Post Infusion ◽  
Fraction I ◽  
Von Willebrand ◽  
Willebrand Factor

Even though it is generally held that cryoprecipitate (cryo) and fraction I-0 correct the prolonged bleeding time (BT) in patients with von Willebrand disease (VWD), perusal of reported data indicates that the correction is usually short lasting and often partial. We decided to do a controlled study of the relationship between the multimeric structure of von Willebrand factor (VWF) in 5 patients with severe VWD after infusion of three plasma concentrates : "wet" cryo, lyophilized (lyo) cryo, and fraction 1-0 given in random order. The dosage of concentrates was tailored to achieve post infusion levels of RiCof above the lower normal limit (50 U/dL) for at least 3 hours. The post-infusion BT values are shown in the table.These findings indicate that the attainment of a normal BT is the exception rather than the rule after infusion of three plasma fractions used for treatment of severe VWD. In all the concentrates the proportions of large VWF multimers, calculated by scanning the electrophoretic gels, were the same as in normal standard plasmas. An intact multimeric structure was recovered in post-infusion plasma of patients treated with wet cryo, whereas there was post infusion loss of large multimers after lyo and fraction I-O. In conclusion, an intact multimeric structure in post infusion plasmas is necessary but not sufficient to sustain a normal BT in VWD patients.

scholarly journals DDAVP shortens the prolonged bleeding times of patients with severe von Willebrand disease treated with cryoprecipitate. Evidence for a mechanism of action independent of released von Willebrand factor

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 1972-1975 ◽  
Author(s):  
M Cattaneo ◽  
M Moia ◽  
P Delle Valle ◽  
P Castellana ◽  
PM Mannucci
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Von Willebrand Disease ◽  
Double Blind ◽  
Prolonged Bleeding ◽  
Primary Hemostasis ◽  
Prolonged Bleeding Time ◽  
Bleeding Episodes ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract After infusion of cryoprecipitate, the very prolonged bleeding time of patients with severe von Willebrand disease (vWD) is shortened but not always normalized in spite of normalization of plasma von Willebrand factor (vWF) levels. Therefore treatments that further improve primary hemostasis in severe vWD patients are needed. Since DDAVP shortens the bleeding time in a variety of bleeding disorders, we investigated in a double-blind, placebo-controlled crossover study the effects of the intravenous (IV) infusion of DDAVP (0.3 microgram/kg) on the bleeding times of 10 patients with severe vWD treated with cryoprecipitate. Their very prolonged bleeding times (greater than 30 minutes), partially corrected by the infusion of cryoprecipitate (14 +/- 2 minutes, mean +/- SEM), were further shortened by the administration of DDAVP (9 +/- 2 minutes, P less than .01) but not of saline (15 +/- 3 minutes, ns). Plasma vWF levels, raised from unmeasurable to normal values by cryoprecipitate, were not changed after DDAVP or saline. The defective deposition of platelets from eight patients onto human umbilical artery subendothelium was increased but not normalized by cryoprecipitate and was not significantly affected by DDAVP or saline. Therefore the infusion of DDAVP after cryoprecipitate may be of clinical benefit for management of bleeding episodes in severe vWD patients. Since severe vWD patients do not have releasable tissue stores of vWF, DDAVP must shorten their prolonged bleeding times independently of released vWF.

DDAVP shortens the prolonged bleeding times of patients with severe von Willebrand disease treated with cryoprecipitate. Evidence for a mechanism of action independent of released von Willebrand factor

Blood ◽  
1989 ◽  
Vol 74 (6) ◽  
pp. 1972-1975
Author(s):  
M Cattaneo ◽  
M Moia ◽  
P Delle Valle ◽  
P Castellana ◽  
PM Mannucci
Keyword(s):  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Von Willebrand Disease ◽  
Double Blind ◽  
Prolonged Bleeding ◽  
Primary Hemostasis ◽  
Prolonged Bleeding Time ◽  
Bleeding Episodes ◽  
Von Willebrand ◽  
Willebrand Factor

After infusion of cryoprecipitate, the very prolonged bleeding time of patients with severe von Willebrand disease (vWD) is shortened but not always normalized in spite of normalization of plasma von Willebrand factor (vWF) levels. Therefore treatments that further improve primary hemostasis in severe vWD patients are needed. Since DDAVP shortens the bleeding time in a variety of bleeding disorders, we investigated in a double-blind, placebo-controlled crossover study the effects of the intravenous (IV) infusion of DDAVP (0.3 microgram/kg) on the bleeding times of 10 patients with severe vWD treated with cryoprecipitate. Their very prolonged bleeding times (greater than 30 minutes), partially corrected by the infusion of cryoprecipitate (14 +/- 2 minutes, mean +/- SEM), were further shortened by the administration of DDAVP (9 +/- 2 minutes, P less than .01) but not of saline (15 +/- 3 minutes, ns). Plasma vWF levels, raised from unmeasurable to normal values by cryoprecipitate, were not changed after DDAVP or saline. The defective deposition of platelets from eight patients onto human umbilical artery subendothelium was increased but not normalized by cryoprecipitate and was not significantly affected by DDAVP or saline. Therefore the infusion of DDAVP after cryoprecipitate may be of clinical benefit for management of bleeding episodes in severe vWD patients. Since severe vWD patients do not have releasable tissue stores of vWF, DDAVP must shorten their prolonged bleeding times independently of released vWF.

scholarly journals Comparison of four virus-inactivated plasma concentrates for treatment of severe von Willebrand disease: a cross-over randomized trial

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3130-3137 ◽  
Author(s):  
PM Mannucci ◽  
PM Tenconi ◽  
G Castaman ◽  
F Rodeghiero
Keyword(s):  
Plasma Levels ◽  
Bleeding Time ◽  
Von Willebrand Disease ◽  
Prolonged Bleeding Time ◽  
Randomized Design ◽  
Coagulant Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

Abstract Until recently, cryoprecipitate has been the treatment of choice in patients with severe von Willebrand disease (vWD) because it can transiently correct low plasma levels of factor VIII coagulant activity (FVIII:C) and shorten or normalize the prolonged bleeding time (BT), the two laboratory hallmarks of the disease. However, cryoprecipitate may still transmit blood-borne viruses, whereas the development of virucidal methods have rendered plasma concentrates containing FVIII:C and von Willebrand factor (vWF) safer. To establish their potential usefulness in the treatment of vWD, we compared the effect of four virus-inactivated concentrates on FVII:C and vWF plasma levels and the BT (template method) in 10 patients with severe vWD using a crossover randomized design. The concentrates were an intermediate-purity, pasteurized FVIII-vWF concentrate; an intermediate-purity, dry-heated FVIII-vWF concentrate; a solvent/detergent-treated vWF concentrate, containing little FVIII; and a high-purity solvent/detergent-treated FVIII-vWF concentrate. All concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed after the vWF concentrate. The effect of concentrates on the BT, however, was less uniform and satisfactory. The pasteurized FVIII-vWF concentrate transiently corrected, completely or partially, the BT in 8 of 10 patients, the dry-heated and solvent/detergent FVIII/vWF concentrates in five, whereas in no patient did the vWF concentrate correct the BT according to the criteria used in this study. These effects on the BT were not related to the plasma levels of ristocetin cofactor activity-attained postinfusion (100 U/dL or more in the majority of patients) or to the multimeric structure of vWF in concentrates (defective in larger multimers in all cases). In conclusion, even though virus-inactivated concentrates can be used to increase FVIII:C levels in patients with severe vWD, none of the concentrates studied by us consistently normalizes the BT in a sustained fashion.

scholarly journals New variant of von Willebrand disease type II with markedly increased levels of von Willebrand factor antigen and dominant mode of inheritance: von Willebrand disease type IIC Miami

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 169-175 ◽  
Author(s):  
MR Ledford ◽  
I Rabinowitz ◽  
JE Sadler ◽  
JW Kent ◽  
F Civantos
Keyword(s):  
Molecular Weight ◽  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Autosomal Dominant ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Dominant Inheritance ◽  
New Variant ◽  
Von Willebrand ◽  
Willebrand Factor

A variant of von Willebrand disease (vWD) was identified in six members of a kindred spanning four generations. The proband was a 46-year-old woman with a lifelong history of bleeding, a prolonged bleeding time (> 15 minutes), markedly elevated von Willebrand factor (vWF) antigen (vWF:Ag = 2.09 U/mL), slightly reduced ristocetin cofactor activity, and a plasma vWF multimer pattern similar to that of vWD type IIC. Similar findings were observed in her three children, mother, and brother. In affected family members, platelet and plasma vWF multimer patterns were discrepant with higher molecular weight multimers observed in platelet vWF. Following a 1-Des-amino-8-D-arginine vasopressin (DDAVP) challenge, the proband failed to normalize her bleeding time even though vWF: Ag rose by 70% and higher molecular weight multimers were increased slightly. Genetic studies were consistent with autosomal dominant inheritance of a mutation within the vWF gene. By sequencing of cloned genomic DNA, mutations were excluded in exons 4, 5, 14, and 15, which encode regions of the vWF propeptide proposed to be important in multimer biosynthesis. Mutations also were excluded in exons 28 to 31, which encompass the known mutations that cause vWD types IIA, IIB, and B. This new variant of vWD, characterized by autosomal dominant inheritance, a qualitative defect that resembles vWD type IIC, and increased plasma vWF:Ag, was tentatively designated vWD type IIC Miami.

Detection of Non Inhibitory Binding Antibodies to Von Willebrand Factor Affecting the Clearance of VWF:Ag in Von Willebrand Disease

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2275-2275
Author(s):  
Tobias M Suiter ◽  
Pier Mannuccio Mannucci ◽  
Christine L Kempton ◽  
Michael Laffan ◽  
Edward H Romond ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Neutralizing Antibodies ◽  
High Titer ◽  
Von Willebrand Disease ◽  
Inhibitory Antibody ◽  
Screening Assay ◽  
Post Infusion ◽  
Inhibitory Antibodies ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 2275 Von Willebrand Disease (VWD) is an inherited rare bleeding disorder caused by a deficiency of von Willebrand factor (VWF). VWF, the largest multimeric plasma glycoprotein, facilitates platelet aggregation and stabilizes FVIII in the circulation. Inhibitory antibodies to VWF have been reported in 10% – 15% of type 3 VWD patients repetitively treated with plasma-derived VWF/FVIII concentrates. The clinical impact of non-inhibitory antibodies to VWF has not been previously reported. To investigate the immunogenicity of a novel recombinant human VWF (rhVWF), both total binding anti-VWF antibodies and inhibitory anti-VWF antibodies (VWF:Ristocetin Cofactor Activity [RCo], VWF:Collagen Binding Activity [CB], VWF:FVIII Binding [FVIIIB]) were assessed in a Phase 1 multicenter clinical study. Total binding anti-VWF antibodies were determined by an enzyme-linked immunosorbent assay (ELISA) employing polyclonal anti-human IgG antibodies. Plasma samples were analyzed in two steps employing a screening assay determining the titer of the binding antibodies and in a second step, confirming the specificity of the antibody in a competition assay. Samples were considered positive, when a sample was at least two titer steps lower than the antibody titer detected in the screening assay necessitating a screening titer of at least 1:80. Neutralizing antibodies to the key functional activities of VWF, such as VWF:RCo, VWF:CB and VWF:FVIIIB, were measured by assays based on the Bethesda assay established for quantitative analysis of FVIII inhibitors (Nijmegen modification of the Bethesda assay). To exclude false positive results, the detection limit for anti-VWF inhibitors was set to 1 BU/mL for all 3 assays. Three of 39 subjects screened had a pre-existing high titer non-neutralizing binding antibody (all 1/1280) to VWF. One of these 3 subjects was excluded from the study due to the presence of an inhibitory antibody to VWF:CB (1.3 BU/mL) at screening. Two of the 3 subjects were enrolled and treated with rVWF and/or pdVWF concentrate as part of the safety, tolerability and PK assessments. The high titer binding anti-VWF antibodies were associated with a significant decreased VWF:Ag activity post infusion of either pdVWF or rVWF and consequential decreased activity of VWF:RCo, VWF:CB and FVIII:C. For example, one of the subject had a reduced VWF:Ag incremental recovery of 1.1 IU/dL/(U VWF:RCo/kg) (mean of cohort 1.6 IU/dL/[U VWF:RCo/kg]) and a reduced VWF:Ag t1/2 2.4 hours (mean of cohort t1/2 25.3 hours) post infusion of rhVWF dosed at 50 IU VWF:RCo/kg. Relevant data of all PK assessments and antibody titers will be presented. None of the study subjects developed an inhibitory antibody to either VWF or FVIII and there was no impact on the subsequent treatment of bleeding episodes with commercial pdFVIII/VWF concentrates noted by the treating physician. The clinical relevance of non-neutralizing antibodies to VWF requires additional investigation. Disclosures: Suiter: Baxter Innovations GmbH: Employment. Horling:Baxter Innovations GmbH: Employment. Reipert:Baxter Innovations GmbH: Employment. Turecek:Baxter BioScience: Employment. Varadi:Baxter Innovations GmbH: Employment. Chapman:Baxter Innovations GmbH: Employment. Engl:Baxter Innovations GmbH: Employment. Wong:Baxter Healthcare Corp: Employment. Ewenstein:Baxter Healthcare Corp: Employment.

scholarly journals Comparison of four virus-inactivated plasma concentrates for treatment of severe von Willebrand disease: a cross-over randomized trial

Blood ◽  
1992 ◽  
Vol 79 (12) ◽  
pp. 3130-3137 ◽  
Author(s):  
PM Mannucci ◽  
PM Tenconi ◽  
G Castaman ◽  
F Rodeghiero
Keyword(s):  
Plasma Levels ◽  
Bleeding Time ◽  
Von Willebrand Disease ◽  
Prolonged Bleeding Time ◽  
Randomized Design ◽  
Coagulant Activity ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor ◽  
Ristocetin Cofactor Activity

Until recently, cryoprecipitate has been the treatment of choice in patients with severe von Willebrand disease (vWD) because it can transiently correct low plasma levels of factor VIII coagulant activity (FVIII:C) and shorten or normalize the prolonged bleeding time (BT), the two laboratory hallmarks of the disease. However, cryoprecipitate may still transmit blood-borne viruses, whereas the development of virucidal methods have rendered plasma concentrates containing FVIII:C and von Willebrand factor (vWF) safer. To establish their potential usefulness in the treatment of vWD, we compared the effect of four virus-inactivated concentrates on FVII:C and vWF plasma levels and the BT (template method) in 10 patients with severe vWD using a crossover randomized design. The concentrates were an intermediate-purity, pasteurized FVIII-vWF concentrate; an intermediate-purity, dry-heated FVIII-vWF concentrate; a solvent/detergent-treated vWF concentrate, containing little FVIII; and a high-purity solvent/detergent-treated FVIII-vWF concentrate. All concentrates were equally effective in attaining normal and sustained levels of FVIII:C postinfusion, although peak levels were more delayed after the vWF concentrate. The effect of concentrates on the BT, however, was less uniform and satisfactory. The pasteurized FVIII-vWF concentrate transiently corrected, completely or partially, the BT in 8 of 10 patients, the dry-heated and solvent/detergent FVIII/vWF concentrates in five, whereas in no patient did the vWF concentrate correct the BT according to the criteria used in this study. These effects on the BT were not related to the plasma levels of ristocetin cofactor activity-attained postinfusion (100 U/dL or more in the majority of patients) or to the multimeric structure of vWF in concentrates (defective in larger multimers in all cases). In conclusion, even though virus-inactivated concentrates can be used to increase FVIII:C levels in patients with severe vWD, none of the concentrates studied by us consistently normalizes the BT in a sustained fashion.

Von Willebrand Disease (vWd) Characterized by Increased Ristocetin Aggregation: A Study of Eleven Cases

1975 ◽  
Author(s):  
N. Ciavarella ◽  
F. I. Pareti ◽  
Z. M. Ruggeri ◽  
P. M. Mannucci
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Autosomal Dominant ◽  
Von Willebrand Disease ◽  
Bleeding Tendency ◽  
Laboratory Findings ◽  
Prolonged Bleeding Time ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Antihemophilic Factor

The defective ristocetin aggregation occurring in patients with vWd is thought to depend on the decrease of a plasmatic factor related to factor VIII (Willebrand factor, VIIIVWF) 10 patients from 3 families had a mild to moderate bleeding tendency with autosomal dominant pattern of inheritance and laboratory findings suggestive for vWd (decreased levels of antihemophilic factor, and factor- VIII related antigen reduced platelet retention to glass beads columns and prolonged bleeding time). However, ristocetin aggregation in PRP was markedly increased, although VIIIVWF plasma levels were decreased. Aggregation induced in PRP by other agents (such as ADP, adrenaline and collagen), and the release of 14C serotonin was normal; the addition of purified bovine factor VIII was followed by normal aggregation in patients’ PRP and washed platelets. Patients’ washed platelets added to normal plasma aggregated to ristocetin more than normal washed platelets with patients’ plasma; the most marked aggregation response, however, was obtained when patients’ washed platelets were mixed with their own plasma. These findings suggest that a, platelet component is involved in the hyperaggregation response to ristocetin of these patients; however, the interaction of platelets with patients’ plasma is needed to produce the maximum response.Supported by a grant of the Fondazione Angelo Bianchi Bonomi.

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.

Recombinant Human Von Willebrand Factor (rhVWF): First-In-Human Study Evaluating Pharmacokinetics, Demonstrating Safety and Tolerability In Type 3 Von Willebrand Disease

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 237-237 ◽  
Author(s):  
Tobias Suiter ◽  
Michael Laffan ◽  
Pier M. Mannucci ◽  
Christine L. Kempton ◽  
Edward H Romond ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Von Willebrand Factor ◽  
Phase 1 ◽  
Von Willebrand Disease ◽  
Fviii Activity ◽  
Post Infusion ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 237 Von Willebrand Disease (VWD) is an inherited rare bleeding disorder caused by a deficiency of von Willebrand factor (VWF). VWF is the largest soluble multimeric plasma glycoprotein, which facilitates platelet aggregation and stabilizes FVIII in the circulation. Patients with type 3 disease display severe hemorrhagic symptoms, mainly in mucosal tissues, muscle and joints. Replacement of VWF stabilizes endogenous FVIII to hemostatic levels within hours. Commercially available VWF/FVIII concentrates are plasma-derived (pd) and subject to limitations such as donor dependency, risk of blood-borne pathogen transmission, lack of high molecular weight VWF multimers, and variation in multimer composition. A novel recombinant human VWF (rhVWF) has been developed using a plasma-free method, which represents the largest protein ever produced using recombinant technology. Safety, tolerability and pharmacokinetics of the rhVWF combined at a fixed ratio with rFVIII were investigated in a Phase 1 multicenter, international clinical study in 31 patients with type 3 VWD and severe type 1 VWD. Four concentrations of rhVWF (2, 7.5, 20 and 50 IU VWF:RCo/kg) were administered in a dose-escalating manner in separate cohorts. rhVWF was well tolerated, and no thrombotic events, VWF inhibitors or other serious adverse reactions were observed. Pharmacokinetics of rhVWF/rhFVIII (50 IU VWF:RCo/kg and 38.5 IU FVIII/kg) compared with pdVWF/pdFVIII (50 IU VWF:RCo/kg and 21 IU/kg FVIII/kg) were evaluated in a sub-group of 8/31 patients using a randomized, crossover design (8-day minimum washout period). Interim data in 8 subjects show a higher degree of secondary FVIII activity with rhVWF/rhFVIII compared to pdVWF/pdFVIII (see Figure 1) that is not solely due the difference in the rhVVF:FVIII infusion ratio (1.3:1 rhVWF/rhFVIII vs. approximately 2:1 pdVWF/pdFVIII). The pharmacokinetics of the rhVWF:RCo and pdVWF:RCo were comparable and were also reflected in the VWF:Ag and collagen binding activity. Evidence is also provided for the in vivo cleavage of the ultra-high molecular weight multimers of rhVWF by endogenous ADAMTS13. In summary, interim data from the ongoing Phase 1 study, demonstrate that rhVWF is safe and well tolerated, has VWF:RCo pharmacokinetics that are comparable to pdVWF and enhances stabilization of endogenous FVIII. Multiple doses of rhVWF/rhFVIII would be expected to have beneficial effects in major surgery and severe mucosal bleeding events. These data would also support the treatment concept to administer rhVWF alone once a therapeutic baseline level of endogenous FVIII is achieved (after 1–2 doses).Figure 1:Preliminary PK data from 8 subjects post-infusion of either rhVWF/rhFVIII or pdVWF/pdFVIII. Endogenous FVIII activity reached a plateau after 6 hours and remained stable for at least 30 hours. FVIII was still elevated well above baseline at 96 hoursFigure 1:. Preliminary PK data from 8 subjects post-infusion of either rhVWF/rhFVIII or pdVWF/pdFVIII. Endogenous FVIII activity reached a plateau after 6 hours and remained stable for at least 30 hours. FVIII was still elevated well above baseline at 96 hours Disclosures: Suiter: Baxter BioScience: Employment. Laffan:Baxter BioScience: Consultancy. Mannucci:Baxter BioScience: Consultancy. Kempton:Baxter BioScience: Consultancy. Romond:Baxter BioScience: Consultancy. Shapiro: Baxter BioSci- ence: Consultancy. Birschmann:Baxter BioScience: Consultancy. Gill:Baxter BioScience: Consultancy. Ragni:Baxter BioScience: Consultancy. Turecek:Baxter BioScience: Employment. Ewenstein:Baxter Bioscience: Employment. Baxter BioScience:Baxter BioScience: Employment.

Comparison of PFA-100 testing and bleeding time for detecting platelet hypofunction and von Willebrand disease in clinical practice

2003 ◽  
Vol 90 (09) ◽  
pp. 483-490 ◽  
Author(s):  
Emoke Posan ◽  
Robert McBane ◽  
Diane Grill ◽  
Cheri Motsko ◽  
William Nichols
Keyword(s):  
Clinical Practice ◽  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Von Willebrand Disease ◽  
Hemorrhagic Diathesis ◽  
Primary Hemostasis ◽  
Platelet Aggregometry ◽  
Function Analyzer ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe PFA-100 instrument (Platelet Function Analyzer, Dade Behring) has been reported to be superior to the bleeding time (BT) as a screening test of primary hemostasis. However evaluation of this device has been principally limited to selected populations.The study’s aim was to determine testing performance in clinical practice, by comparing the PFA-100 to the BT for the identification of von Willebrand disease (VWD) and intrinsic platelet hypofunction.From 1998-2000, PFA-100 closure time (CT) for epinephrine-collagen (EPI) and ADP-collagen (ADP) cartridges and modified Ivy BTs were performed on outpatients referred for testing for suspected or known hemorrhagic diathesis (n=346). Evaluation included assays of von Willebrand factor and platelet aggregometry in addition to platelet flow cytometry and electron microscopy when indicated. The normal distribution of PFA-100 CTs was determined using blood samples from 61 normal donors studied on 155 occasions.Results show that thirty-four patients met the diagnostic criteria for VWD and 31 patients were diagnosed with congenital or acquired intrinsic platelet hypofunction. The sensitivity of the PFA-100 for identification of VWD was significantly better (p<0.01) than the BT with similar specificity. In contrast, the PFA-100 was comparable, but not superior to the BT for detecting platelet hypofunction.We conclude that the PFA-100 performance compares favor-ably to the BT for the identification of intrinsic platelet hypofunction in clinical practice with superior sensitivity for detecting VWD.Therefore, the PFA-100 could replace the BT for purposes of screening for VWD and intrinsic platelet hypofunction. When clinical suspicion is strong, testing should be supplemented with assays of von Willebrand factor and platelet aggregometry.

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