scholarly journals Analytic Review: Von Willebrand’s Disease-Diagnostic Criteria

Blood ◽  
1968 ◽  
Vol 32 (4) ◽  
pp. 668-679 ◽  
Author(s):  
HARVEY J. WEISS
Keyword(s):  
Bleeding Time ◽  
Autosomal Dominant ◽  
Family Studies ◽  
Progressive Increase ◽  
Plasma Transfusion ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time

Abstract Our present criteria for diagnosing von Willebrand’s disease are summarized below and illustrative examples of recently studied patients are shown in Table 1. A) Prolonged bleeding time and decreased AHG: When these abnormalities, inherited as an autosomal dominant, are found in several family members, they are considered diagnostic for these patients and for their clinically affected relatives, even though the latter may now show both defects (Case 10). In the absence of family studies, the diagnosis would also be made in individual subjects if a history of bleeding in relatives was consistent with autosomal inheritance (Cases 3,13,18). When family studies are negative (sporadic cases) or no history is attainable, a diagnosis of typical von Wille-brand’s disease would also be made (Cases 1,2,4,14,15,16) unless intrinsic platelet defects were found (see below) or plasma transfusion failed to produce a progressive increase in AHG activity. B) Prolonged bleeding time, normal AHG: The diagnosis would be considered "probable" in such a patient if the following criteria were met: 1. There was no evidence of an "intrinsic" platelet abnormality, as indicated by normal values for platelet aggregation, PF-3 availability and ADP release by connective tissue and kaolin and 2. Platelet adhesiveness, by the modified Salzman test, was abnormal and/or the patient’s bleeding time was shortened by transfusion of plasma in a dosage of 13-15 ml. per Kg. body weight. C) Normal bleeding time, decreased AHG (Case 17): A diagnosis of probable von Willebrand’s disease would be made if: 1. An unequivocal pattern of autosomal dominant inheritance, by history, ruled out hemophilia. 2. The Salzman test was abnormal. 3. Transfusion of hemophiliac, as well as normal plasma resulted in a progressive increase in plasma AHG concentration. D) Normal bleeding time, normal AHG: The diagnosis would be considered as "possible" if: 1. There was no evidence of intrinsic platelet abnormality (see B 1). 2. The Salzman test was abnormal. The above criteria are tentative and, undoubtedly, will not satisfy all investigators. To confuse matters even more, some patients who appear to have the "classic" syndrome may also have abnormal platelet factor 338 or fail to "synthesize" AHG after plasma transfusion.13,38 Whether even the "classic" syndrome represents a spectrum of disorders remains to be determined.

Studies on a Variant of Factor VIII Resulting in ’von Willebrand’s Disease»

1975 ◽  
Author(s):  
F. G. H. Hill ◽  
M. C. K. Chan ◽  
R. M. Hardisty
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time

A variant of von Willebrand’s disease in a 14-year-old girl is described, characterised by a prolonged bleeding time and defective ristocetin aggregation (VIIIWF 6%), with VIIIRAg 70-110% and VIIIC 40-60%. The electrophorotic mobility of her VIIIRAg in agarose at pH 9.2 was intermediate between normal VIIIRAg and that of the patient of Kernoff et al, (1), and identical with that of Case 4 of Peake et al. (2). Further characteristics of the factor VIII molecule in this patient’s plasma and platelets will be presented, including antigenic, physicochemical and functional propeertis.1. Kernoff, P. B. A. et al. (1974). Brit. J. Haemat. 26, 435.2. Peake, I. R. et al. (1974). N. Engl. J. Med. 291, 113.

Sedimentation Behavior of Fibrinogen from Normal and Bleeder Swine

1972 ◽  
Vol 27 (01) ◽  
pp. 059-062
Author(s):  
R. G Cooper ◽  
C. N Cornell ◽  
M. E Muhrer ◽  
K Leimer
Keyword(s):  
Factor Viii ◽  
Platelet Adhesion ◽  
Bleeding Time ◽  
Sedimentation Pattern ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding ◽  
Sedimentation Behavior ◽  
Prolonged Bleeding Time ◽  
Swine Disease

SummaryThe Missouri Bleeder Swine have prolonged bleeding time, low factor VIII levels, reduced platelet adhesion, and respond to plasma and serum transfusions in a manner similar to that of patients with von Willebrand’s disease. The swine disease is thus more similar to von Willebrand’s disease than to classical hemophilia. The present work demonstrates that the sedimentation behavior of fibrinogen from these bleeder swine is like that of normal swine and does not show the anomalous sedimentation pattern of fibrinogen from classical hemophiliacs.

Effect Of Prednisone On Platelet Function In Patients With Bleeding Disorders

1981 ◽  
Author(s):  
R McKenna ◽  
F Bachmann ◽  
O Pichairut ◽  
B Whittaker
Keyword(s):  
Platelet Count ◽  
Platelet Function ◽  
Bleeding Time ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Before And After ◽  
History Of ◽  
The Mean ◽  
One Year

There is considerable controversy regarding the effect of Prednisone on the hemostatic mechanism of normal people versus patients with bleeding diatheses. We administered Prednisone 15 mg TID to patients with a positive history of a bleeding disorder, and evaluated the bleeding time and other in-vitrc tests of platelet function prior to and between the 5th and 7th day after Prednisone.Eleven patients were admitted into this study over a one year period. All patients had a history of excessive bruising, epistaxis, bleeding after dental extractions, and gastrointestinal or other bleeding in various combinations. Two out of the eleven had template bleeding times of greater than 15 minutes both before and after the Prednisone. These two patients were subsequently proven to have von Willebrand’s disease by the washed platelet ristocetin assay. In the remaining 9 patients, the pre-Prednisone bleeding time was 9.3 ±3.7 minutes (x ± 1 S.D.) whereas the post-Prednisone bleeding time was 5.8 ±3.6 minutes (x ±1 S.D.). These results were significant(td=3.83;df:7;p=0.007).Platelet aggregation in response to exogenous ADP (1 μM, 3 μM) Sigma bovine tendon collagen (1.8 mg/ml F) and epinephrine (5.5 × 104M), platelet retention in a glass bead column or platelet factor 3 availability did not improve or worsen after Prednisone therapy. The mean platelet count of 328,000±94,000 (x ±1 S.D.) was significantly (p=0.05) higher than the mean pre-Prednisone platelet count of 268,000±77,000 (x ±1 S.D.).In conclusion, we have shown that large doses of Prednisone appear to shorten the bleeding time in patients with significant defects in the primary hemostatic mechanism. However the bleeding time improvement is not evident in patients with von Willebrand’s disease.

scholarly journals Patients with a prolonged bleeding time and normal aggregation tests may have storage pool deficiency: studies on one hundred six patients

Blood ◽  
1987 ◽  
Vol 70 (3) ◽  
pp. 620-623 ◽  
Author(s):  
HK Nieuwenhuis ◽  
JW Akkerman ◽  
JJ Sixma
Keyword(s):  
Platelet Count ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Von Willebrand's Disease ◽  
Common Disorder ◽  
Storage Pool ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Platelet Serotonin

Abstract One hundred six patients with storage pool deficiency (SPD) were studied with respect to platelet count, bleeding time, total platelet ATP and ADP, platelet serotonin, and in vitro aggregation. The diagnosis of SPD was made on basis of a prolonged bleeding time, a decreased total platelet ADP, and a diminished level of serotonin. Fifty-one patients from 34 unrelated families had congenital SPD, and 55 patients had acquired SPD. Congenital SPD was a common disorder in patients with a lifelong bleeding tendency and a prolonged bleeding time. The frequency in this group of patients was 18%, about one-half the frequency of von Willebrand's disease (vWd). Twenty-three percent of all patients had normal aggregation responses to ADP, epinephrine, and collagen; 33% had aggregation tracings typical for a secretion defect; and 44% had miscellaneous aggregation abnormalities. These findings indicate that SPD is common, heterogeneous, and not necessarily associated with in vitro aggregation abnormalities.

Ristocetin Induced Platelet Factor 3 Availability, A Possible New Tool In The Diagnosis Of Von Willebrand’S Disease

1981 ◽  
Author(s):  
L Muszbek ◽  
H Losonczy ◽  
B Hársfalvi ◽  
I Nagy
Keyword(s):  
Bleeding Time ◽  
Laboratory Diagnosis ◽  
Von Willebrand Disease ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Total Inhibition ◽  
Plasma Factor ◽  
Von Willebrand ◽  
Normal Controls

Ristocetin induced platelet aggregation (RIPA) is a highly valuable technique in the laboratory diagnosis of von Willebrand’s disease (vWD) and together with the estimation of bleeding time, F VIII procoagulant activity and F VIII related antigen in most cases it makes also division of vWD into phenotypic subgroups possible. We have shown that ristocetin makes platelet factor 3 available and ristocetin induced platelet factor 3 availability (RIPF3) similarly to RIPA also depends on a plasma factor. In the present paper it was examined if RIPF3 can be applied as a laboratory test in the diagnosis of vWD. PRP from normal controls, patients with various release defects and von Willebrand patients was incubated and continuously stirred with ristocetin or phys. saline and after 20 min the RW clotting times were determined. RIPF3 activity was expressed as the ratio of the clotting times obtained following incubation with phys. saline and ristocetin.In healthy controls and patients with release defect (n=21) this ratio was higher than 1.5, and in most cases between 1.8-2.5. In patients with vWD (n=10) the ratio was well below 1.5 (with one exception it ranged between 0.95-1.2). In 9 of the lO patients the absence or strong diminution of RIPA and RIPF3 showed close paralellism. In one patient only the slope of first vawe of ristocetin aggregation was decreased while at the same time an almost total inhibition of RIPF3 could be observed. The results indicate that RIPF3 is a valuable quantitative diagnostic test in von Willebrand disease. It can be used if expensive aggregometer is not available and it may also have an importance as additional test to RIPA in the division of vWD into subgroups. An attempt was made to develop this test further by using chromogenic substrate for the measurement of RIPF3.

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.

Sign in / Sign up

Export Citation Format

Share Document