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.

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.

Increased Ristocetin Induced Binding of Factor VIII to Platelets in Von Willebrand’s Disease (vWd)

1979 ◽  
Author(s):  
Z.M. Ruggeri ◽  
F.I. Pareti ◽  
P.M. Mannucci ◽  
T.S. Zimmerman
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Human Platelet ◽  
Bleeding Tendency ◽  
Platelet Factor ◽  
Induce Platelet Aggregation ◽  
Prolonged Bleeding Time ◽  
Crossed Immunoelectrophoresis ◽  
Ristocetin Cofactor

Initial reports of ristocetin-induced platelet aggregation (RIPA) demonstrated it to be decreased in some patients with vWd. We now report 20 patients (from five unrelated families) in whom RIP A was increased, apparently as the result of an increased ristocetin-induced binding of Factor VIIIrelated antigen (VIIIR:Ag) to platelets. All the patients had a life-long bleeding tendency, with prolonged bleeding time, and an abnormal two-dimensional crossed immunoelectrophoresis (2DCIE). Increased RIPA was demonstrated by measuring the minimum ristocetin concentration necessary to induce platelet aggregation. This was 0.42 mg/ml á 0.11 SD in the patients, and 0.91 á 0.097 SD in 17 normals (t = 13.83; P < 0.001). VIIIR:Ag binding to platelets occurred at ristocetin concentrations (0.4 mg/mI) which were ineffective in normals (who required >0.6 mg/mI). In contrast, the VIIIR:Ag of other patients with abnormal 2DCIE and markedly decreased RIP A did not bind to platelets at ristocetin concentrations as high as I mg/ml. It has been previously demonstrated that 30% to 60% of normal VIIIR:Ag binds to isolated human platelet membranes in the absence of ristocetin or any other agent, and that binding is restricted to the larger forms of VIIIR:Ag. However, VIIIR:Ag from the patients with increased RIPA, including two with normal ristocetin cofactor activity, showed decreased or undetectable binding as did all other patients with abnormal 2DCIE. This study suggests that ristocetin induced platelet Factor VIII interaction does not accurately reflect the “bleeding time factor” defect in vWd.

Thrombocytopathy Induced by Acquired Circulating Factor VIII Inhibitor

1975 ◽  
Author(s):  
M. Cortellaro ◽  
E. Pogliani ◽  
E. Cofrancesco ◽  
E. E. Polli
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Steroid Treatment ◽  
Factor Viii Inhibitor ◽  
Factor Viii Activity ◽  
Antiplatelet Antibody ◽  
Normal Platelet ◽  
Viii Inhibitor ◽  
Willebrand Factor

A reduced ADP and ristocetin platelet aggregation by acquired circulating factor VIII inhibitor (2 U/ml) was found in a young woman with S. L. E. Bleeding time was prolonged, factor VIII activity decreased (25%), Willebrand antigen and Willebrand factor were normal. PF3 assay and PF4 release were normal. Platelet (14C) - serotonin uptake, but not release, was reduced. Antiplatelet antibody was not detected.Patient’s plasma inhibited the ristocetin and ADP induced platelet aggregation of normal PRP, but not of normal and patient GFP.After steroid treatment F. VIII inhibitor and thrombocytopathy disappeared.It is suggested that the circulating inhibitor is able to coat autologous and isologous unwashed platelets, interfering with platelet function.

scholarly journals Defective Ristocetin Aggregation Not Attributable to a Von Willebrand or Bernard-Soulier Type Defect

1977 ◽  
Author(s):  
J. L. Wautier ◽  
A. T. Nurden ◽  
H. Michel ◽  
J. P. Caen
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Polyacrylamide Gel Electrophoresis ◽  
Rabbit Aorta ◽  
Sialic Acid Content ◽  
Normal Platelet ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Membrane Defect ◽  
Surface Glycoproteins

In von Willebrand’s disease the absence of platelet aggregation by ristocetin has been correlated with abnormalities in the von Willebrand factor (VIIIVWF), while in the Bernard-Soulier syndrome (BSS) a platelet membrane defect involving surface glycoproteins has been reported. During a 3 year period an absence of platelet aggregation induced by ristocetin was observed in a 53 year old Caucasian man with enlarged spleen, normal platelet count and eosinophilic leukaemia. The platelets react normally with collagen and ADP but the aggregation induced by thrombin and bovine VIIIVWF were reduced. The patient’s platelets were well agglutinated by an antibody reacting with a component absent in the BSS. The bleeding time, VIII levels, platelet adhesion to subendothelium (rabbit aorta) were normal. No abnormalities were detected in the surface glycoproteins as studied by SDS Polyacrylamide gel electrophoresis however the platelet sialic acid content was slightly reduced. It is concluded that an abnormality additional to those previously described may be the course of the defective ristocetin induced platelet aggregation in this patient.

Essential Athrombia

1975 ◽  
Vol 33 (02) ◽  
pp. 278-285 ◽  
Author(s):  
Şeref Inceman ◽  
Yücel Tangün
Keyword(s):  
Platelet Aggregation ◽  
Bleeding Time ◽  
Bleeding Tendency ◽  
Clot Retraction ◽  
Platelet Factor ◽  
Prolonged Bleeding Time ◽  
Normal Platelet ◽  
Aggregation Response ◽  
Platelet Disorder ◽  
Fibrinogen Content

SummaryA constitutional platelet function disorder in a twelve-year-old girl characterized by a lifelong bleeding tendency, prolonged bleeding time, normal platelet count, normal clot retraction, normal platelet factor 3 activity and impaired platelet aggregation was reported.Platelet aggregation, studied turbidimetrically, was absent in the presence of usual doses of ADP (1–4 μM), although a small wave of primary aggregation was obtained by very large ADP concentrations (25–50 μM). The platelets were also unresponsive to epinephrine, thrombin and diluted collagen suspensions. But an almost normal aggregation response occurred with strong collagen suspensions. The platelets responded to Ristocetin. Pelease of platelet ADP was found to be normal by collagen and thrombin, but impaired by kaolin. Platelet fibrinogen content was normal.The present case, investigated with recent methods, confirms the existence of a type of primary functional platelet disorder characterized solely by an aggregation defect, described in 1955 and 1962 under the name of “essential athrombia.”

Epidemiology of Thrombosis in Nigerians. Study of Platelet and Fibrinolytic Parameters

1975 ◽  
Author(s):  
E. Dupuy ◽  
A.F. Flemming ◽  
J. P. Caen
Keyword(s):  
Platelet Aggregation ◽  
Fibrinolytic Activity ◽  
Blood Donors ◽  
Bleeding Time ◽  
Arterial Disease ◽  
Parasitic Infections ◽  
Coagulant Activity ◽  
European Values ◽  
Fibrinolytic Parameters ◽  
And Function

The infrequency of atherosclerosis and arterial disease and the relative thrombocytopenia reported in Nigerians led us to investigate platelet number and function and fibrinolytic activity in Nigerian non-elite (blood donors) Nigerian elite (hospital senior staff) and Europeans living in Zaria.The relative thrombocytopenia in Nigerians was confirmed, and counts were between 100–180 × 109/1 in 26 out of 35 subjects. Platelet aggregation using adrenaline and collagen were in the same range in all groups. An early disaggregation with ADP was found in one third of all Nigerians. Platelet aggregation with ristocetin in the Nigerian elite was less than 50 per cent of European values in 10/16 subjects; platelets of 12/17 non-elite subjects did not aggregate at all.The bleeding time (Ivy) and factor VIII coagulant activity did not differ in the three groups. Fibrinolytic activity was higher in Nigerians than Europeans.Many factors could be involved in these differences, including splenomegaly, parasitic infections, increases in immunoglobulins, greater physical activity and the healthier endothelium in Nigerians.

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.

Circulating anticoagulant in a family with prolonged bleeding time and factor VIII deficiency

Blood ◽  
1977 ◽  
Vol 49 (5) ◽  
pp. 799-806 ◽  
Author(s):  
M Diez-Ewald ◽  
EC Lian ◽  
R Nunez ◽  
D Deykin ◽  
DR Harkness
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Bleeding Time ◽  
Factor Viii Activity ◽  
Clot Retraction ◽  
Factor Viii Related Antigen ◽  
Factor Viii Deficiency ◽  
Prolonged Bleeding ◽  
Prolonged Bleeding Time ◽  
Aggregation Activity

Abstract A circulating anticoagulant against factor VIII activity was demonstrated in the plasma of a boy from a family with both factor VIII deficiency and prolonged bleeding time. However, the factor VIII- related antigen, ristocetin-induced platelet aggregation activity, platelet retention in glass bead columns, platelet aggregation with adenosine 5′-diphosphate, collagen and epinephrine, and clot retraction among affected members were normal. The electrophoretic mobility of factor VIII-related antigen on crossed immunoelectrophoresis was normal. The inactivation of factor VIII activity by the inhibitor was time dependent and was nonlinear as the concentration of the inhibitor was increased. Immunotyping showed that the inhibitor was IgG with k light chains.

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.

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