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.

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.”

Abnormal Ristocetin-Aggregation of Platelets in Uraemia and on Haemodialysis Therapy

1979 ◽  
Author(s):  
H. F. Woods ◽  
J. Turney ◽  
M. J. Weston
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Dialysis Patients ◽  
Normal Platelet ◽  
Crossover Studies ◽  
Coagulant Activity ◽  
Aggregation Of Platelets ◽  
Ristocetin Cofactor ◽  
Membrane Defect

Impaired platelet aggregation to ADP and collagen is recognised in uraemia and the loss of normal platelet function contributes to the prolonged capillary bleeding time observed in uraemia. in von Willebrand’s disease prolongation of capillary bleeding time is associated with impaired platelet aggregation to ristocetin because of a relative or absolute deficiency of the Factor VIII-Ristocetin Cofactor. We have studied platelet aggregation to ristocetin and Factor VIII coagulant activity (CA) and related antigen (RA) in 14 uraemic and 28 dialysed patients. Ristocetin aggregation (delta-0.D/min) was significantly less in uraemia (50 ± 21: m ± S.D) and in dialysis patients (38 ± 18) than in controls (78 ± 20). Factor VIII CA and RA were significantly higher in uraemic and dialysed patients than in controls.In crossover studies plasma from uraemic patients either enhanced or did not change ristocetin aggregation of normal platelets but plasma from dialysed patients impaired ristocetin aggregation of normal platelets. Plasma from dialysed patients was not contaminated by heparin. Thus in uraemia impaired platelet aggregation to ristocetin is unlikely to be due to a Factor VIII deficiency and may be due to a membrane defect as in Bernard-Soulier disease. in dialysed patients’ plasma there appears to be an additional circulating inhibitor of platelet-ristocetin interaction.

Abnormal Ristocetin-Aggregation of Platelets in Uraemia and on Haemodialysis Therapy

1979 ◽  
Author(s):  
H.F. Woods ◽  
J. Turney ◽  
M.J. Weston
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Dialysis Patients ◽  
Normal Platelet ◽  
Crossover Studies ◽  
Coagulant Activity ◽  
Aggregation Of Platelets ◽  
Ristocetin Cofactor ◽  
Membrane Defect

Impaired platelet aggregation to ADP and collagen is recognised in uraemia and the loss of normal platelet function contributes to the prolonged capillary bleeding time observed in uraemia. In von Willebrand’s disease prolongation of capillary bleeding time is associated with impaired platelet aggregation to ristocetin because of a relative or absolute deficiency of the Factor VIII-Ristocetin Cofactor. We have studied platelet aggregation to ristocetin and Factor VIII coagulant activity (CA) and related antigen (RA) in 14 uraemic and 28 dialysed patients. Ristocetin aggregation (delta-0.D/min) was significantly less in uraemia (50 ± 21: m ± S.D) and in dialysis patients (38 ± 18) than in controls (78 + 20). Factor VIII CA and RA were significantly higher in uraemic and dialysed patients than in controls.In crossover studies plasma from uraemic patients either enhanced or did not change ristocetin aggregation of normal platelets but plasma from dialysed patients impaired ristocetin aggregation of normal platelets. Plasma from dialysed patients was not contaminated by heparin. Thus in uraemia impaired platelet aggregation to ristocetin is unlikely to be due to a Factor VIII deficiency and may be due to a membrane defect as in Bernard-Soulier disease. In dialysed patients’ plasma there appears to be an additional circulating inhibitor of platelet-ristocetin interaction.

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.”

The Presence and Significance of Electrophoreticaily Normal and Abnormal Factor VIII Related Protein in von Willebrand’s Disease

1975 ◽  
Author(s):  
I. R. Peake ◽  
A. L. Bloom ◽  
J. C. Giddings
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Electrophoretic Mobility ◽  
Bleeding Time ◽  
Factor Vii ◽  
Two Dimensional ◽  
Related Protein ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Crossed Immunoelectrophoresis

The presence of normal amounts of a factor-VII related protein (FVIIIRP) which has abnormal electrophoretic mobility at pH 9.2 has been demonstrated on two dimensional crossed immunoelectrophoresis in some patiente with von Willebrand’s disease (vWd) and these investigations have now been extended to a study of over 14 patients. In those with reduced levels of FVIIIRP, concentrates were prepared by precipitation with 3% ethanol at -3°C. The results showed that in three of the patients with “typical vWd” in whom levels of procoagulant factor VIII and FVIIIRP were parallel and both always reduced the latter had abnormal electrophoretic mobility indistinguishable from that of the “atypical” cases. In all patients in whom abnormal FVIIIRP was demonstrated the bleeding time was grossly prolonged and ristocetin platelet aggregation grossly impaired. In patients in whom the mobility of FVTIIRP was indistinguishable from normal the bleeding times and ristocetin platelet aggregation were sometimes less severely impaired despite gross reduction of the circulating level of FVIIIRP. It is suggested that in vWd synthesis of abnormal variants cf FVIIIRP is relatively common but that in some patients there is reduced syntehsis of normal FVIIIRP.

1-Desamino-8-D-Arginine Vasopressin (DDAVP) Infusion in Type IIB von Willebrand’s Disease: Shortening of Bleeding Time and Induction of a Variable Pseudothrombocytopenia

1990 ◽  
Vol 64 (01) ◽  
pp. 117-120 ◽  
Author(s):  
Alessandra Casonato ◽  
M Teresa Sartori ◽  
Luigi de Marco ◽  
Antonio Girolami
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Count ◽  
Arginine Vasopressin ◽  
Calcium Concentration ◽  
Sodium Citrate ◽  
Bleeding Time ◽  
Blood Collection ◽  
Von Willebrand's Disease ◽  
Blood Samples ◽  
Von Willebrand’S Disease

SummaryWe have investigated the effects of 1-desamino-8-D-arginine vasopressin (DDAVP) infusion on platelet count and bleeding time in 4 patients with type IIB von Willebrand’s disease (vWd). Three of four patients showed a normalization of the bleeding time within 1 h after the infusion, while bleeding time was not modified in the fourth. In accordance with the literature, thrombocytopenia was observed after DDAVP infusion, but this thrombocytopenia was due to the anticoagulants used for blood collection. In two patients (F. I., G. F.) no thrombocytopenia was observed when platelets were counted by fingerstick method but there was a 20% platelet decrease in blood samples collected in sodium citrate and a 50% decrease in samples collected in EDTA. Dramatic falls in platelet counts (70–95%) were observed in the additional two patients (C. A., D.Z.) after DDAVP infusion, when both sodium citrate or EDTA were used as anticoagulants. In the latter two patients there was also a 50% decrease in platelet count when the fingerstick method was used. The decrease in the patient’s platelet count in EDTA samples after DDAVP infusion could be prevented, in part, by the previous additions of an anti GPIb monoclonal antibody and an anti GPIIb-IIIa monoclonal antibody.Thus, the thrombocytopenia observed in the four IIB vWd patients studied after DDAVP infusion seems to be, at least partially, a pseudothrombocytopenia depending on the calcium concentration in the blood samples and the availability of GPIb and GPIIb-IIIa receptors. These findings and the normalization of the bleeding time observed in three of the four patients has led us to reconsider the possible use of DDAVP in the treatment of our IIB vWd patients.

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.

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 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 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.

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