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 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

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.

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.

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 Characterization of the defect of the factor VIII/von Willebrand factor protein in von Willebrand's disease

Blood ◽  
1982 ◽  
Vol 59 (3) ◽  
pp. 542-548 ◽  
Author(s):  
HR Gralnick ◽  
MC Cregger ◽  
SB Williams
Keyword(s):  
Sialic Acid ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Platelet Rich Plasma ◽  
Molecular Forms ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Platelet Receptor ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The factor VIII/von Willebrand factor (f.VIII/vWf) protein was purified from the plasma of a patient with von Willebrand's disease (vWd). The patient had all of the classic laboratory findings of vWd except for the ristocetin-induced platelet aggregation of his own platelet-rich plasma. The disease has been documented in three generations. Comparison of the purified normal and vWd f.VIIi/vWf protein revealed several abnormalities, including decreased concentration of f.VIII/vWf antigen; decreased specific vWf activity; absence of the larger molecular forms of the f.VIII/vWf protein; carbohydrate deficiencies affecting the sialic acid, penultimate galactose and N- acetylglucosamine moieties; and decreased binding of the f.VIII/vWf protein to its platelet receptor. These studies indicate the multiplicity of biochemical and functional abnormalities associated with the f.VIII/vWf protein in vWd. f.VIII/vWf protein to normal f.VIII/vWf protein that had been treated with 2-mercaptoethanol (2-ME) to reduce the multimer size and then treated with specific exoglycosidases to remove the sialic acid and penultimate galactose residues revealed similar biologic properties.

IMPORTANCE OF LARGE VON WILLEBRAND FACTOR (vWF) MULTIMERS IN vWF INTERACTION WITH PLATELET GLYCOPROTEIN IIb/IIIa

1987 ◽  
Author(s):  
M Yamamoto ◽  
Y Ando ◽  
K Watanabe ◽  
H Iri ◽  
Y Araki ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Platelet Rich Plasma ◽  
Platelet Glycoprotein ◽  
Induce Platelet Aggregation ◽  
Maximum Extent ◽  
Physiological Relevance ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

Recently it has been reported that, in addition to binding to glycoprotein (GP) lb, vWF also interacts with GPIIb/IIIa, although the physiological relevance of this interaction is not completeley clear. In this paper, we have investigated the role of different size of vWF multimers in vWF-mediated platelet aggregation. Different size of vWF multimers were purified from human plasma through Sephacryl S-1000 column according to the method of Fowler et al. Fractions were analysed by SDS-agarose gel electrophoresis by the method of Ruggeri et al. When each fraction was examined for ristocetin cofactor activity (RCo), only larger multimers exhibited significant RCo. The maximum extent of ristocetin-induced platelet agglutination by larger multimers (10 μg/ml) was 80%, while that of intermediate and lower multimers at the same concentration was 20% and 0%, respectively. Each fraction was then added to washed platelet suspensions in the presence of 10 μM ADP and 0.3 mM CaCl2. Only larger multimers induced platelet aggregation, while intermediate and lower multimers failed to induce platelet aggregation. The maximum extent of aggregation in the presence of larger multimers (10 μg/ml) was 70% of that in the presence of fibrinogen instead. Similar experiments were peformed using platelet-rich plasma from a patient with afibrinogenemia in stead of washed normal platelets. ADP caused significant aggregation only when purified vWF larger multimers or fibrinogen was added. This vWF-mediated aggregation was completely inhibited by monoclonal antibody to GPIIb/IIIa (1 μg/ml) and synthetic peptide, Arg-Gly-Asp-Ser, (1 mM).Our results indicate that larger multimers of vWF play major roles in vWF interaction with GPIIb/IIIa.

scholarly journals von Willebrand's disease characterized by increased ristocetin sensitivity and the presence of all von Willebrand factor multimers in plasma

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 668-672 ◽  
Author(s):  
L Holmberg ◽  
E Berntorp ◽  
M Donner ◽  
IM Nilsson
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Rich Plasma ◽  
Severe Bleeding ◽  
Molecular Defect ◽  
Von Willebrand's Disease ◽  
Von Willebrand’S Disease ◽  
Coagulant Activity ◽  
The One ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract In eight members of one family, platelets in platelet-rich plasma aggregated at much lower ristocetin concentrations than normal. Ivy bleeding time was variously prolonged, and von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity, and factor VIII coagulant activity were decreased. Most of the affected members had had slight to rather severe bleeding symptoms. Platelet-type von Willebrand's disease (vWD) could be ruled out. All multimers of vWF:Ag were found in plasma as well as platelets. Administration of 1-desamino- 8-D-arginine vasopressin (DDAVP) to the propositus did not cause thrombocytopenia, and platelet-poor plasma obtained immediately after did not aggregate normal platelets. The molecular defect in this family, inherited as an autosomal dominant, resembles the one in type IIB because of the response to ristocetin but differs from IIB because all vWF:Ag multimers are present in plasma and the response to DDAVP is atypical. We conclude that this family has a new subtype of vWD and propose that structural as well as functional criteria should be used for a proper classification of vWD.

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.

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