Ristocetin - A New Tool in the Investigation of Platelet Aggregation

1971 ◽  
Vol 26 (02) ◽  
pp. 362-369 ◽  
Author(s):  
Margaret A. Howard ◽  
B. G Firkin
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Von Willebrand's Disease ◽  
Platelet Poor Plasma ◽  
Von Willebrand’S Disease ◽  
The Third ◽  
Ristocetin A ◽  
Adp Release

Summary1. The antibotic, Ristocetin, causes precipitation of fibrinogen from platelet poor plasma, as well as platelet aggregation.2. The precise mechanism of Ristocetin’s effect on platelets has not been elucidated, but it has been shown to initiate ADP release, which may contribute in part to its aggregating ability.3. Ristocetin has been shown to produce aggregation in platelet rich plasma from thrombasthenic patients.4. Three patients with Von Willebrand’s disease were examined. In 2, Ristocetin caused no platelet aggregation whatsoever, whilst the third aggregated normally. It is suggested, on this basis, that Von Willebrand’s disease may be subdivided into two types and that Ristocetin could prove to be a valuable technique for further study of this group of disorders.

Differing Susceptibilities of Platelets from Normal Individuals and Patients with von Willebrand’s Disease to Attack by Quinine- and Quinidine-Dependent Antiplatelet Antibodies

1989 ◽  
Vol 61 (01) ◽  
pp. 111-116
Author(s):  
Sharron L Pfueller ◽  
Robyn A Bilston ◽  
Dana Logan ◽  
Rosemary David ◽  
Ian G Sloan ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Serotonin Release ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Antiplatelet Antibodies ◽  
Normal Plasma ◽  
Igg Binding ◽  
Normal Individuals ◽  
Drug Dependent

SummaryReactivity of quinine- and quinidine-dependent antiplatelet antibodies has been compared in platelet-rich-plasma (PRP) from normal donors and from patients with von Willebrand’s disease (vWd). One quinine-dependent antibody (Q. Ab) caused platelet aggregation and [14C] serotonin release with only 7 of 12 normal donors, while another Q. Ab and a quinidine-dependent antibody (Qd. Ab) caused aggregation and release with all 12. Drug- dependent IgG binding and PF 3 availability induced by the antibodies were, however, comparable in all donors. Differences in responsiveness were associated with platelets and not plasma. vWd platelets showed normal drug-dependent IgG binding, but decreased aggregation and serotonin release to most drug- dependent antibodies. Responsiveness was not restored by purified vWf:Ag, but, in one case, was corrected by normal plasma or cryoprecipitate. Drug-dependent binding of the Q. Ab which caused variable responsiveness in normals was to the same platelet antigens (GPIb and GPIIIa) in both normal and vWd platelets and did not require plasma components. Reduced PF 3 availability was seen with some antibodies in some vWd patients. Plasma from two of these patients inhibited aggregation of normal platelets to Q. Ab and one of these inhibited aggregation to ADP. Antiplatelet antibodies were detected in these two plasmas by ELISA. Thus some Q. Ab produce different responses with platelets from different donors. In vWd, reduced responsiveness to Q.Ab and Qd. Ab may result from production of inhibitory antiplatelet antibodies.

scholarly journals Ristocetin: A Means of Differentiating Von Willebrand’s Disease Into Two Groups

Blood ◽  
1973 ◽  
Vol 41 (5) ◽  
pp. 687-690 ◽  
Author(s):  
Margaret A. Howard ◽  
R. J. Sawers ◽  
B. G. Firkin
Keyword(s):  
Platelet Aggregation ◽  
Plasma Protein ◽  
Platelet Adhesiveness ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Ristocetin A

Abstract Earlier studies have shown that patients with von Willebrand’s disease are considered to have normal platelets, but they lack at least one plasma protein. Results are presented indicating that ristocetin, known to aggregate normal platelets, fails to cause platelet aggregation in the group of von Willebrand’s disease patients exhibiting no platelet adhesiveness. It is postulated that there may be two groups of patients within von Willebrand’s disease and, further, that ristocetin will provide a useful approach to study the plasma deficiency or abnormality in von Willebrand’s disease.

Drug Inhibition of Ristocetin-induced Platelet Aggregation

1975 ◽  
Author(s):  
G. Tann ◽  
P. T. Flute
Keyword(s):  
Platelet Aggregation ◽  
Density Gradient ◽  
Platelet Rich Plasma ◽  
Normal Subjects ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Drug Inhibition

Administration of aspirin or phenylbutazone to normal subjects inhibits ristocetin-induced platelet aggregation in their platelet-rich plasma for periods up to two weeks. Two patterns of response have been observed, a complete lack of aggregation or an absence of secondary aggregation. Either can be overcome by increased amounts of ristocetin. Gel-filtered and albumin-density gradient washed platelets have also been investigated. A similar but transient inhibition has also been observed in some normal subjects due to an unknown cause. These results are important when considering the diagnosis of von Willebrand’s disease.

scholarly journals Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 786-789 ◽  
Author(s):  
ME Rick ◽  
SB Williams ◽  
RA Sacher ◽  
LP McKeown
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Glycoprotein ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Platelet Counts ◽  
Endogenous Production ◽  
Platelet Aggregate ◽  
Spontaneous Platelet Aggregation ◽  
Von Willebrand

Thrombocytopenia may accompany variant (type IIB) von Willebrand's disease (vWD) and is thought to result from binding of the abnormal von Willebrand factor (vWF) to the patient's platelets with subsequent platelet aggregate formation and clearance. We have studied a patient with type IIB vWD who became thrombocytopenic during two pregnancies. During the third trimester of pregnancy, her platelet counts dropped to 20,000 to 30,000/microL, and an increase in the intermediate-sized vWF multimers was seen on agarose gel electrophoresis. During this time her platelet-rich plasma showed spontaneous platelet aggregation, and her plasma caused spontaneous aggregation of normal washed platelets. Antibody to platelet glycoprotein Ib completely blocked the spontaneous platelet aggregation, while antibody to platelet glycoprotein IIb/IIIa did not block the response at the concentrations used. Inhibitors of platelet function that elevate platelet cyclic AMP also blocked the response, but aspirin had no effect on the spontaneous platelet aggregation. The patient illustrates that the platelet counts in one individual can vary greatly in type IIB vWD and that the thrombocytopenia that occurs can appear under physiologic conditions that stimulate the endogenous production of the patient's abnormal vWF. The mechanisms leading to spontaneous platelet aggregation and thrombocytopenia appear to be similar to those described for other patients with type IIB vWD.

scholarly journals Abnormalities of factor VIII and platelet aggregation--use of ristocetin in diagnosing the von Willebrand syndrome

Blood ◽  
1975 ◽  
Vol 45 (3) ◽  
pp. 403-412 ◽  
Author(s):  
HJ Weiss
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Second Phase ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Low Concentrations ◽  
Platelet Defects ◽  
Von Willebrand ◽  
Induced Aggregation

Ristocetin was used to study platelet aggregation in platelet-rich plasma and to assay the von Willebrand factor activity of factor VIII (VIII-VWF). Ristocetin-induced platelet aggregation (RIPA) was decreased in 13 of 18 patients with von Willebrand's disease (VWD) who had decreased plasma levels of VIII-VWF. The five patients with normal RIPA appeared to have mild VWD but did not constitute a separate subclass. RIPA was also abnormal in some patients with intrinsic platelet defects, but in no case was the defect corrected by normal plasma. The latter type of correction appears to be specific for VWD. Aspirin ingestion inhibited the second phase of RIPA (at low concentrations of ristocetin only) but did not affect the initial phase of aggregation or the level of VIII-VWF. We also studied a group of patients who had both abnormalities of the factor VIII complex and intrinsic platelet defects, such as impaired collagen-induced aggregation, as well. The findings in these patients and in those with typical von Willebrand's disease appear to comprise a spectrum of disorders (the von Willebrand syndrome) in which some abnormality of the factor VIII complex is associated with impaired platelet function. At present, ristocetin would appear to be a useful reagent for evaluating patients with bleeding disorders and for studying patients with the von Willebrand syndrome.

Ristocetin in the Diagnosis of von Willebrand’s Disease: A Comparison of Rate and Percent of Aggregation with Levels of the Plasma Factor(s) Necessary for Ristocetin Aggregation

1975 ◽  
Vol 34 (02) ◽  
pp. 465-474 ◽  
Author(s):  
S. V Dowling ◽  
R. H Muntz ◽  
S D’Souza ◽  
H Ekert
Keyword(s):  
Acetylsalicylic Acid ◽  
Platelet Rich Plasma ◽  
Von Willebrand's Disease ◽  
Platelet Poor Plasma ◽  
Von Willebrand’S Disease ◽  
Aggregation Rate ◽  
Corrective Effect ◽  
Plasma Factor ◽  
Von Willebrand’S Factor

SummaryPercent aggregation and the aggregation rate of platelet rich plasma (PRP) in response to ristocetin (1.75 mg/ml) were measured in 20 normals and 16 patients with von Willebrand’s disease (vWd), with and without the addition of acetylsalicylic acid (ASA). Percent aggregation did not clearly distinguish between normals and patients with vWd. Aggregation rate was normal in only 2 of 16 patients, and after incubation of PRP with ASA 1 of these 2 remained normal.The corrective effect of dilutions of platelet poor plasma (PPP) on the ristocetin response of washed platelets (von Willebrand’s factor, vWf ) was measured in 21 normals and 12 patients with vWd. All patients with vWd had abnormal levels. There was a significant correlation between aggregation rate and vWf in patients with vWd but not in normals. Both tests appear to measure closely related defects, and the aggregation rate is as specific as the vWf level for the diagnosis of clinically affected patients.

scholarly journals Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 786-789 ◽  
Author(s):  
ME Rick ◽  
SB Williams ◽  
RA Sacher ◽  
LP McKeown
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Glycoprotein ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Platelet Counts ◽  
Endogenous Production ◽  
Platelet Aggregate ◽  
Spontaneous Platelet Aggregation ◽  
Von Willebrand

Abstract Thrombocytopenia may accompany variant (type IIB) von Willebrand's disease (vWD) and is thought to result from binding of the abnormal von Willebrand factor (vWF) to the patient's platelets with subsequent platelet aggregate formation and clearance. We have studied a patient with type IIB vWD who became thrombocytopenic during two pregnancies. During the third trimester of pregnancy, her platelet counts dropped to 20,000 to 30,000/microL, and an increase in the intermediate-sized vWF multimers was seen on agarose gel electrophoresis. During this time her platelet-rich plasma showed spontaneous platelet aggregation, and her plasma caused spontaneous aggregation of normal washed platelets. Antibody to platelet glycoprotein Ib completely blocked the spontaneous platelet aggregation, while antibody to platelet glycoprotein IIb/IIIa did not block the response at the concentrations used. Inhibitors of platelet function that elevate platelet cyclic AMP also blocked the response, but aspirin had no effect on the spontaneous platelet aggregation. The patient illustrates that the platelet counts in one individual can vary greatly in type IIB vWD and that the thrombocytopenia that occurs can appear under physiologic conditions that stimulate the endogenous production of the patient's abnormal vWF. The mechanisms leading to spontaneous platelet aggregation and thrombocytopenia appear to be similar to those described for other patients with type IIB vWD.

scholarly journals Abnormalities of factor VIII and platelet aggregation--use of ristocetin in diagnosing the von Willebrand syndrome

Blood ◽  
1975 ◽  
Vol 45 (3) ◽  
pp. 403-412 ◽  
Author(s):  
HJ Weiss
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Second Phase ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Low Concentrations ◽  
Platelet Defects ◽  
Von Willebrand ◽  
Induced Aggregation

Abstract Ristocetin was used to study platelet aggregation in platelet-rich plasma and to assay the von Willebrand factor activity of factor VIII (VIII-VWF). Ristocetin-induced platelet aggregation (RIPA) was decreased in 13 of 18 patients with von Willebrand's disease (VWD) who had decreased plasma levels of VIII-VWF. The five patients with normal RIPA appeared to have mild VWD but did not constitute a separate subclass. RIPA was also abnormal in some patients with intrinsic platelet defects, but in no case was the defect corrected by normal plasma. The latter type of correction appears to be specific for VWD. Aspirin ingestion inhibited the second phase of RIPA (at low concentrations of ristocetin only) but did not affect the initial phase of aggregation or the level of VIII-VWF. We also studied a group of patients who had both abnormalities of the factor VIII complex and intrinsic platelet defects, such as impaired collagen-induced aggregation, as well. The findings in these patients and in those with typical von Willebrand's disease appear to comprise a spectrum of disorders (the von Willebrand syndrome) in which some abnormality of the factor VIII complex is associated with impaired platelet function. At present, ristocetin would appear to be a useful reagent for evaluating patients with bleeding disorders and for studying patients with the von Willebrand syndrome.

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.

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