Effect of Plasma and Platelet Concentrate Infusions on Factor VIII, Platelet Adhesiveness, and Bleeding Time in Bleeder Swine

1972 ◽  
Vol 28 (03) ◽  
pp. 431-439
Author(s):  
C. N Cornell ◽  
R. G Cooper ◽  
M. E Muhrer ◽  
S Garb
Keyword(s):  
Beneficial Effect ◽  
Factor Viii ◽  
Bleeding Time ◽  
Platelet Concentrate ◽  
Platelet Adhesiveness ◽  
Normal Range ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Platelet Infusion

SummaryBleeder swine are characterized by a prolonged bleeding time, decreased factor VIII levels or reduced platelet adhesiveness or both, and a factor VIII response to infusion of plasma or serum similar to that described in von Willebrand’s disease. In this study the factor VIII response of bleeder swine infused with fresh non-glass-contact pig plasma was similar to that reported in previous experiments after infusion of plasma that was frozen and stored for a variable period of time before use or was not free of glass contact. There was no beneficial effect on platelet adhesiveness. Following platelet concentrate infusion, there was no sustained normalization of platelet adhesiveness, although elevations into the normal range occurred at varying intervals after platelet infusion in two of three pigs investigated. Infusion of factor VIII-deficient plasma from a canine hemophiliac elicited a factor VIII response similar to that described in von Willebrand’s disease patients infused with plasma from factor VIII-deficient human hemophiliacs. In none of these experiments was there any apparent correction of the bleeding time.

The Spectrum of von Willebrand’s Disease

1967 ◽  
Vol 18 (01/02) ◽  
pp. 040-056 ◽  
Author(s):  
E. J Walter Bowie ◽  
P Didisheim ◽  
J. H Thompson ◽  
C. A Owen
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Severe Bleeding ◽  
Platelet Adhesiveness ◽  
Platelet Activity ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Generation Test

SummaryPatients (from 5 kindreds) with variants of von Willebrand’s disease are described. In one kindred the depression of factor VIII was moderate (20 to 40% of normal) and transfusion of 500 ml of normal plasma led to an increase higher than anticipated and to an almost normal level of factor VIII 17 to 24 hrs later. This represents the usual type of von Willebrand’s disease.In the second kindred the concentration of factor VIII was less than 2 % of normal in the son and daughter, who had severe bleeding and hemarthroses.The third kindred was characterized by reduction of factor VIII and a long bleeding time as well as by a serum defect in the thromboplastin-generation test comparable to that seen in patients with hemophilia B, yet with normal levels of factors IX, X, and VII. The severity of the serum defect, the positive result with the Rumpel-Leede test, and the reduced platelet activity in the thromboplastin-generation test are all compatible with the diagnosis of thrombopathy or ‘‘thrombopathic hemophilia.” In two other kindreds, one patient had a long bleeding time and normal levels of factor VIII and another had a normal bleeding time and decrease of factor VIII. The last patient had the type of response to transfusion usually seen in von Willebrand’s disease.In four kindreds, platelet adhesiveness in vivo was found to be strikingly abnormal (virtually absent).It would appear, therefore, that von Willebrand’s disease forms a spectrum, and whether the kindreds reported simply reflect variations of a single genetic disease state or represent separate entities will be answered only by clarification of the underlying etiology of that disease.

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.

scholarly journals The Factor VIII Molecule in Acquired Von Willebrand’s Disease

1977 ◽  
Author(s):  
F. E. Preston ◽  
R. G. Malia ◽  
B. Sampson
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Gel Filtration ◽  
Exchange Chromatography ◽  
Von Willebrand's Disease ◽  
Negative Family History ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Two Peaks ◽  
Von Willebrand

Four patients with acquired von Willebrand’s disease have been studied. The diagnosis in each case was based on acquired bleeding disorder, negative family history, prolonged bleeding time, low procoagulant factor VIII (F. VIIIC) and factor VIII related antigen (F. VIIIR. A.) activity and impaired ristocetin-induced platelet aggregation responses.Gel filtration studies were performed on plasma samples from each of the four patients and the fractions tested for F. VIIIC activity using a modified kaolin cephalin clotting time. Samples from each patient showed two peaks of procoagulant activity compared with one peak obtained on samples from controls, haemophiliacs and classical von Willebrand’s syndrome.When incubation mixtures of acquired von Willebrand plasma and a source of normal factor VIII are examined by similar gel filtration techniques, it can be shown that the normal F. VIIIC becomes dissociated into sub-units of varying size.Similar results have been obtained by incubating mixtures of the patients’ IgG obtained by ion exchange chromatography and normal sources of factor VIII.It is concluded that acquired von Willebrand’s disease is probably due to an antibody directed against the factor VIII molecule.

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.

scholarly journals DDAVP in type IIa von Willebrand's disease

Blood ◽  
1986 ◽  
Vol 67 (2) ◽  
pp. 465-468 ◽  
Author(s):  
HR Gralnick ◽  
SB Williams ◽  
LP McKeown ◽  
ME Rick ◽  
P Maisonneuve ◽  
...  
Keyword(s):  
Factor Viii ◽  
Protease Inhibitors ◽  
Von Willebrand Factor ◽  
Bleeding Time ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Time Period ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

Abstract 1-D-Amino(8-D-arginine)-vasopressin (DDAVP) infusion in three patients with type IIa von Willebrand's disease (vWD) resulted in a normalization of the factor VIII coagulant, factor VIII-related antigen, and von Willebrand factor (vWF) (ristocetin cofactor) activities and the bleeding time. The normalization of these hemostatic parameters persisted for four hours. Over the same time period there was a marked increase in the quantity of the vWF multimers when blood was collected in the presence of protease inhibitors. The vWF multimers present were even larger than the normal. When blood was collected in the absence of protease inhibitors, a smaller increase in the plasma vWF multimers was observed and fewer of the intermediate and larger vWF multimers were seen; multimers larger than those present in normal plasma were not visualized. The platelet vWF multimers and activities did not change with or without inhibitors. These studies suggest that there is a subgroup of patients with type IIa vWD who respond to DDAVP with complete normalization of their hemostatic abnormalities and whose vWF is sensitive to proteolysis.

scholarly journals Multimeric composition of factor VIII/von Willebrand factor following administration of DDAVP: implications for pathophysiology and therapy of von Willebrand's disease subtypes

Blood ◽  
1982 ◽  
Vol 59 (6) ◽  
pp. 1272-1278 ◽  
Author(s):  
ZM Ruggeri ◽  
PM Mannucci ◽  
R Lombardi ◽  
AB Federici ◽  
TS Zimmerman
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Resting State ◽  
Bleeding Time ◽  
Type I ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Plasma Factor ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract We have studied the modifications in the multimeric composition of plasma factor VIII/von Willebrand factor and the bleeding time response following administration of 1-Deamino-[8-D-arginine]-Vasopressin (DDAVP) to patients with different subtypes of von Willebrand's disease. In type I, all multimers were present in plasma in the resting state, though they were decreased in concentration. Administration of DDAVP resulted in an increased concentration of these forms as well as the appearance of larger forms than were previously present. There was concomitant correction of the bleeding time. In type IIA, large multimers were absent in the resting state, and although DDAVP induced an average threefold increase in the plasma concentration of factor VIII/von Willebrand factor, the larger multimers did not appear and the bleeding time, although shortened, was not corrected. In contrast, the larger multimers that were also absent from type IIB plasma in the resting state rapidly appeared following DDAVP administration. However, their appearance was transitory and the bleeding time, as in IIA patients, was shortened but not corrected. The characteristic multimeric composition of platelet factor VIII/von Willebrand factor in given subtypes predicted the alteration in plasma factor VIII/von Willebrand factor induced by DDAVP. These studies provide evidence that the different subtypes of von Willebrand's disease represent distinct abnormalities of factor VIII/von Willebrand factor. They also suggest that complete hemostatic correction following DDAVP can be routinely expected only in type I von Willebrand's disease, and only if factor VIII/von Willebrand factor can be raised to normal levels.

Variant von Willebrand’s Disease

1980 ◽  
Vol 43 (01) ◽  
pp. 002-005 ◽  
Author(s):  
David Green ◽  
K J Philip
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Excessive Bleeding ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Crossed Immunoelectrophoresis ◽  
The Family ◽  
History Of ◽  
Autosomal Dominance ◽  
Ristocetin Cofactor

Summary30 members of an Illinois kindred were studied with a battery of haemostatic tests including the template bleeding time, platelet retention by glass beads (PRGB), measurement of activities related to factor VIII, and crossed-immunoelectrophoresis (CIEP). 9 family members had a history of excessive bleeding, and all 9 had prolonged bleeding times and increased migration of their factor VIII-related antigen (VIIIR:Ag) on CIEP. Of the other tests performed, the VIII: Ristocetin Cofactor and the PRGB showed the best correlation with the bleeding time. 3 subjects who were not bleeders, but who came from a branch of the family where there were several affected members, also had an abnormal VIIIR: Ag. The pattern of inheritance of the altered VIIIR: Ag in this family was one of autosomal dominance with full penetrance. The CIEP is a valuable screening test for the detection of variant von Willebrand’s disease and the recognition of silent heterozygotes.

Increased Activity of “Anti-Willebrand Factor” in Diabetic Plasma

1964 ◽  
Vol 11 (01) ◽  
pp. 027-037 ◽  
Author(s):  
A. E Ödegaard ◽  
B. A Skalhegg ◽  
A. J Hellem
Keyword(s):  
Platelet Adhesiveness ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Prolonged Bleeding Time ◽  
Platelet Reaction ◽  
Willebrand Factor ◽  
Increased Activity

SummaryIn a group of 25 patients with insulin-treated diabetes mellitus a marked increase in the ADP-induced platelet adhesiveness was demonstrated. This phenomenon was due to a plasmatic factor. In vitro-plasma from these patients restored the decreased ADP-induced platelet adhesiveness in von Willebrand’s disease.The factor was also effective in vivo, since transfusion of 450 ml diabetic plasma to a patient with von Willebrand’s disease normalized the decreased platelet adhesiveness and shortened the prolonged bleeding time. The role of this factor in the ADP platelet reaction as a cofactor together with calcium is stressed.

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.

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