scholarly journals A Syndrome of Platelet-release Abnormality and Mild Hemophilia

Blood ◽  
1974 ◽  
Vol 43 (6) ◽  
pp. 821-830 ◽  
Author(s):  
Carolyn Chesney ◽  
Robert W. Colman ◽  
Liberto Pechet
Keyword(s):  
Factor Viii ◽  
Gel Filtration ◽  
Base Line ◽  
Clot Retraction ◽  
Presumptive Diagnosis ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Normal Platelet ◽  
Viii Level

Abstract Two families were studied because of a hemorrhagic tendency. The presumptive diagnosis of von Willebrand’s disease was suggested by low factor VIII levels (7.5%-33%), prolonged template Ivy bleeding time (9.5-17 min), low platelet adhesiveness (0%-8%), normal platelet factor 3, and normal clot retraction. Further studies, however, showed abnormal platelet aggregation with ADP, epinephrine, and collagen, and deficient release of platelet antiheparin activity and 14C serotonin. Patients’ platelets, rendered free of plasma by gel filtration, continued to show abnormal aggregation when resuspended in normal plasma. Plasma from the patients contained greater than 200% factor VIII by immunologic assay. The patients’ coagulant factor VIII level returned to base line within 24 hr after plasma or cryoprecipitate transfusions. Unlike von Willebrand’s disease, management of these patients required both platelets and cryoprecipitate to prevent bleeding.

scholarly journals Platelet-type von Willebrand's disease: characterization of a new bleeding disorder

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 790-794 ◽  
Author(s):  
JL Miller ◽  
A Castella
Keyword(s):  
Factor Viii ◽  
Single Family ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Normal Platelet ◽  
Normal Limits ◽  
Coagulant Activity ◽  
Von Willebrand ◽  
Willebrand Factor

An autosomally transmitted bleeding diathesis sharing some, but not all, features previously described in von Willebrand's disease (vWd) was studied in five patients representing three generations of a single family. Bleeding times in the upper normal range in conjunction with low-normal platelet counts, normal factor VIII coagulant activity and VIII-related antigen, decreased VIII-ristocetin cofactor activity, selective decrease of the higher molecule weight factor VIII/von Willebrand factor (VIII/vWF) multimers, and increased ristocetin- induced platelet agglutination at low ristocetin concentrations were characteristic. Binding of patient VIII/vWF to washed normal platelets was within normal limits, whereas binding of normal VIII/vWF to patient platelets was significantly increased (p less than 0.001 at 0.6 mg/ml ristocetin). This disorder accordingly appears to involve an intrinsic platelet abnormality affecting platelet-VIII/vWF interactions. It is proposed that the concept of vWD be broadened to include patients with this abnormality, which may appropriately be called “Platelet-type von Willebrand's disease.”

Study of a Caucasian Family with von Willebrand’s Disease in Association with Vascular Telangiectasia and Hemoglobinopathy

1979 ◽  
Author(s):  
W. Hanna ◽  
C. McCarroll ◽  
J. Chen ◽  
T. McDonald ◽  
D. Lin ◽  
...  
Keyword(s):  
Platelet Count ◽  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Family Members ◽  
Inherited Disorders ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Normal Platelet ◽  
Coagulant Activity

This family carries multihematological inherited disorders; namely, von Wille-brand’s, vascular telangiectasia and hemoglobinopathy. Family members were studied by quantifying the following: Factor VIII pro-coagulant activity, Factor VIII related antigen, Factor VIII inhibitors, platelet adhesion, platelet aggregation (with ristocetin, collagen and ADP), bleeding time, platelet count, partial thromboplastin time, prothrombin time, hemoglobin electrophoresis, hemoglobin finger-printing, sickling preparation and the presence of telangiectasia.The affected members of this family with von Willebrand’s express their disease in a variable tendency to bleeding from almost clinically asymptomatic cases to cases with severe bleeding tendency.One member of this family had to have a hysterectomy at the age of 20 to control the abnormal uterine bleeding after conservative treatment failed. All affected members with von Willebrand’s disease had a normal platelet count, prolonged bleeding time, decreased Factor VIII pro-coagulant activity and related antigen, negative aggregation using the ristocetin co-factor for von Willebrand’s, defective platelet adhesiveness to glass beads, and normal platelet aggregation to collagen and ADP. Some members have vascular telangiectasia in the mucous membranes. An incidental finding was the presence of an abnormal hemoglobin S in some family members.Supported in part by the Cumberland Chapter of the National Hemophilia Foundation.

Abnormal Factor VIII Molecule in Mild Von Willebrand’s Disease

1979 ◽  
Author(s):  
R. Castillo ◽  
S. Maragall ◽  
F. Labal ◽  
J. Monteagudo ◽  
A. Ordinas
Keyword(s):  
Factor Viii ◽  
Concanavalin A ◽  
Gel Filtration ◽  
The Other ◽  
Agarose Gel ◽  
Immunoradiometric Assay ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Other Hand ◽  
Bleeding Episodes

In 22 cases with normal levels of the three entitles of factor VIII (VIII:C, VIIIR:AG and VIIIR:WF), FVIIIR:AG showed afaster anodal mobility and a lower concentration measured by immunoradiometric assay than that found with Laurell’s immunoelectrophoresis. Moreover, the factor VIII protein elution by agarose gel filtration of plasma and cryoprecipitate was delayed. Seven of those cases belong to a family in whom one of the member showed frequent bleeding episodes. In these individuals the FVIIIR;AG precipitation with Concanavalin A was determined and appeared decreased.On the other hand in 19 out of 20 subjects with classic moderate von willebrand’s disease (in whom the three entities of factor VIII were occasio nally reduced in parallele), FVIIIR:AG also showed a faster anodal uob{ 1-ty and the factor Vln protein elution by agarose gel filtration was delay ed.All these results suggest that patients with moderate von Willebrand’s disease show a qualitatively deficient factor VIII molecule synthesis, while the mildest cases may have normal levels of the three entities of the factor VIII.

scholarly journals Platelet-type von Willebrand's disease: characterization of a new bleeding disorder

Blood ◽  
1982 ◽  
Vol 60 (3) ◽  
pp. 790-794 ◽  
Author(s):  
JL Miller ◽  
A Castella
Keyword(s):  
Factor Viii ◽  
Single Family ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Normal Platelet ◽  
Normal Limits ◽  
Coagulant Activity ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract An autosomally transmitted bleeding diathesis sharing some, but not all, features previously described in von Willebrand's disease (vWd) was studied in five patients representing three generations of a single family. Bleeding times in the upper normal range in conjunction with low-normal platelet counts, normal factor VIII coagulant activity and VIII-related antigen, decreased VIII-ristocetin cofactor activity, selective decrease of the higher molecule weight factor VIII/von Willebrand factor (VIII/vWF) multimers, and increased ristocetin- induced platelet agglutination at low ristocetin concentrations were characteristic. Binding of patient VIII/vWF to washed normal platelets was within normal limits, whereas binding of normal VIII/vWF to patient platelets was significantly increased (p less than 0.001 at 0.6 mg/ml ristocetin). This disorder accordingly appears to involve an intrinsic platelet abnormality affecting platelet-VIII/vWF interactions. It is proposed that the concept of vWD be broadened to include patients with this abnormality, which may appropriately be called “Platelet-type von Willebrand's disease.”

Antihemophilic factor levels in bleeder swine following infusions of plasma and serum

1965 ◽  
Vol 208 (3) ◽  
pp. 508-510 ◽  
Author(s):  
Merle E. Muhrer ◽  
Eckhard Lechler ◽  
Creighton N. Cornell ◽  
John L. Kirkland
Keyword(s):  
Factor Viii ◽  
Maximum Concentration ◽  
Bleeding Time ◽  
Factor Viii Level ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Porcine Serum ◽  
Prolonged Bleeding ◽  
Viii Level ◽  
Antihemophilic Factor

Swine with a hemophilia-like disease characterized by a long bleeding time and low antihemophilic factor (AHF, factor VIII) level were infused with porcine plasma and porcine serum. Unlike the response of classical hemophiliacs, but similar to that of patients with von Willebrand's disease, the initial postinfusion levels of AHF were sustained with some fluctuation for 24 hr. Serum infusion resulted in a delayed increase in AHF which reached a maximum concentration between the 12th and 24th hr after infusion. Within 75 hr the effects of both the plasma and serum infusions had vanished. No correction of the prolonged bleeding times was observed following the infusions. The AHF levels encountered after the infusion of plasma and serum cannot be accounted for by the AHF activity contained in the infused materials; new AHF synthesis or AHF release from storage are suggested as possible mechanisms.

scholarly journals Synthesis of AHF in von Willebrand’s Disease

Blood ◽  
1964 ◽  
Vol 23 (2) ◽  
pp. 233-238 ◽  
Author(s):  
JESSICA H. LEWIS
Keyword(s):  
Factor Viii ◽  
Bleeding Time ◽  
Factor Viii Level ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Viii Level

Abstract A 5 year old girl suffering from a severe hemorrhagic disorder which appears identical to von Willebrand’s disease is presented. Transfusion of either normal or hemophilic plasma resulted in brief shortening of the bleeding time and gradual and sustained elevation of the AHF (factor VIII) level. The latter observation suggested that this patient was able to synthesize her own AHF when infused with a material present in normal or hemophilic plasma.

scholarly journals Immunologic Studies of Antihemophilic Factor (AHF, Factor VIII). III. Comparative Binding Properties of Human and Rabbit Anti-AHF

Blood ◽  
1972 ◽  
Vol 39 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Leon W. Hoyer
Keyword(s):  
Factor Viii ◽  
Gel Filtration ◽  
Agarose Gel ◽  
Sensitive Assay ◽  
Binding Properties ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Comparative Binding ◽  
Antihemophilic Factor

Abstract The binding properties of human and rabbit antibodies to antihemophilic factor (AHF, factor VIII) have been compared in experiments that sought the basis for their different specificities and secondary properties. Agarose gel filtration demonstrated the formation of stable complexes of AHF with rabbit anti-AHF but not with human anti-AHF. Measurement of bound radiolabeled rabbit anti-AHF provides a very sensitive assay for the AHF antigen that is present in normal and hemophilic plasmas but that is markedly reduced in plasmas from patients with von Willebrand’s disease.

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.

Gel Filtration Patterns of Factor VIII Coagulant Antigen and Factor VIII Related Antigen in Normal and von Willebrand’s Disease

1983 ◽  
Vol 50 (02) ◽  
pp. 509-512
Author(s):  
Juan Chediak ◽  
Ian Peake ◽  
Arthur Bloom
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Gel Filtration ◽  
Low Molecular Weight ◽  
Type I ◽  
Type Ii ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Coagulant Activity

SummaryGel filtration (sepharose 2B CL) patterns of factor VIII coagulant antigen (VIIIC :Ag) and factor VIII related antigen (VIIIR: Ag) were obtained using normal plasma and plasma from patients with von Willebrand’s disease. The latter group consisted of five individuals with normal mobility of factor VIIIR :Ag on cross-immunoelectrophoresis (Type I) and five others with abnormal (increased) mobility (Type II). Results showed that the elution of VIIIC: Ag was delayed in those subjects whose ratio of VIIIR :Ag to VIIIC :Ag was reduced. It has previously been reported that VIIIR :Ag exerts a stabilizing influence on the coagulant activity of factor VIII (VIII: C); our data suggests that when VIIIR :Ag is deficient, abnormal (low molecular weight) forms of VIIIC: Ag circulate.

scholarly journals von Willebrand Activity and Electrophoretic Mobility of Platelet Factor VIII Related Antigen in Patients with von Willebrand’s Disease

1977 ◽  
Author(s):  
Y. Sultan ◽  
J. Lamazière ◽  
P. Maisonneuve
Keyword(s):  
Factor Viii ◽  
Electrophoretic Mobility ◽  
Secondary Process ◽  
Functional Protein ◽  
Platelet Factor ◽  
Von Willebrand's Disease ◽  
Factor Viii Related Antigen ◽  
Von Willebrand’S Disease ◽  
Number Of Patients ◽  
Von Willebrand

We have previously shown that patients with severe Von Willebrand’s disease (VWd), mainly homozygotes had no factor VIII related antigen (F VIIIRA) in their platelets as well as no Von Willebrand activity (F VIIIVW) as measured by the ristocetin cofactor assay. In all other patients with less severe form of the disease platelet F VIIIRA was detectable. In normal controls electrophoretic mobility of platelet F VIIIRA was found to be identical to the mobility of plasma VIII-RA either on the total platelet lysate or after isolation on sepharose 4B columns.In the present study F VIIIVW and the electrophoretic mobility of F VIIIRA were compared in platelet extracts and the plasma of a number of patients. Seven of the ten patients tested were genetic variants of vwd with very low ratio of F VIIIVW/F VIIIRA suggesting a non functional protein with an increased electrophoretic mobility : one group of patients showed abnormalities of plateletF VIIIRA identical to those found in the plasma. However another group showed a high ratio of F VIIIVW/F VIIIRA suggesting a more active protein than the one in patient’s plasma although the platelet F VIIIRA had an increased electrophoretic mobility. These results are the first example of a F VIIIRA with abnormal electrophoretic mobility associated to high F VIIIVW activity. The loss of F VIIIVW in the patient’s plasma would be a secondary process occuring after F VIIIRA is released in the circulation.

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