Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

Sixma, Jan J.; Sakariassen, Kjell S.; Beeser‐Visser, Nel H.; Ottenhof-Rovers, Mieke; Bolhuis, P. A.

doi:10.1182/blood.v63.1.128.128

Cited by 139 publications

(39 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of perfusion studies for the differentiation of such patients has a definite advantage in that it may help to determine the optimal treatment. Previous studies from our laboratory have shown a close association between the bleeding time and adherence of platelets in a perfusion model (Sixma et al, 1984;Sakariassen et al, 1984b). Normalization of platelet adherence in mixed reconstituted blood may help to provide clues for successful treatment of this baffling and heterogeneous group of patients.…”

Section: Discussionmentioning

confidence: 68%

“…FVIII-VWF was purified from human cryoprecipitate as indicated by Bolhuis et a1 (1 98 1). The assay of FVIII-VWF related properties was performed as described elsewhere (Sixma et al, 1984). The multimeric structure of plasma FVIII-VWF was studied by electrophoresis in 1% agarose followed by incubation with 251-radiolabelled heterologous antibodies (Ruggeri & Zimmerman, 1980).…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Differentiation of patients with subtype IIb‐like von Willebrand's disease by means of perfusion experiments with reconstituted blood

Sakariassen¹,

Nieuwenhuis²,

Sixma³

1985

Br J Haematol

View full text Add to dashboard Cite

Four unrelated patients with a bleeding diathesis (bleeding time longer than 30 min), some spontaneous platelet aggregation, thrombocytopenia and large platelets, had decreased levels of factor VIII-von Willebrand factor (FVIII-VWF) related properties and impaired platelet adherence to human artery subendothelium. The largest multimers of plasma FVIII-VWF were absent and enhanced ristocetin induced platelet aggregation in platelet-rich plasma was observed. 'Pseudo-von Willebrand's disease' was excluded, because FVIII-VWF from normal subjects did not initiate platelet aggregation. Perfusion studies with reconstituted blood, consisting of respectively patient platelets in normal plasma or normal platelets in patient plasma, yielded evidence for an intrinsic platelet abnormality in two out of the four patients and a plasma defect in the other two patients. Similar experiments with platelets and plasma from four patients with von Willebrand's disease (VWD) subtype I and four patients with VWD subtype IIa showed that the impaired platelet adherence in blood from these patients was caused by a plasma defect. These experiments indicate that patients with laboratory findings in many respects similar to those originally reported for patients with VWD subtype IIb may represent a heterogeneous group of individuals. The data derived from our study imply that perfusion experiments with reconstituted blood offer a new approach in characterization of these patients, which may be more relevant for the treatment of the patients than characterization by ristocetin induced adsorption of FVIII-VWF to platelets.

show abstract

Section: Discussionmentioning

confidence: 68%

Section: Methodsmentioning

confidence: 99%

Differentiation of patients with subtype IIb‐like von Willebrand's disease by means of perfusion experiments with reconstituted blood

Sakariassen¹,

Nieuwenhuis²,

Sixma³

1985

Br J Haematol

View full text Add to dashboard Cite

show abstract

“…Pathologically high shear stress may, conversely, enhance proteolysis of vWf, which reduces the largest and most functional vWf multimers and can cause a qualitative loss of function. 28,29 This effect has been observed in some platelet assays at high shear rates (eg, PFA-100, filterometer). 10,11 Whereas the consequences of acquired von Willebrand syndrome in dogs with SAS or MR are not yet clear and it is not known whether or not the hemostatic disturbances should be taken into account in the management of these conditions, recent studies suggest that bleeding may be a problem in human patients with aortic stenosis.…”

Section: Discussionmentioning

confidence: 90%

Dogs with Heart Diseases Causing Turbulent High-Velocity Blood Flow Have Changes in Platelet Function and von Willebrand Factor Multimer Distribution

Tarnow¹,

Kristensen²,

Olsen³

et al. 2005

J Vet Int Med

View full text Add to dashboard Cite

The purpose of this prospective study was to investigate platelet function using in vitro tests based on both high and low shear rates and von Willebrand factor (vWf) multimeric composition in dogs with cardiac disease and turbulent high-velocity blood flow. Client-owned asymptomatic, untreated dogs were divided into 4 groups: 14 Cavalier King Charles Spaniels (Cavaliers) with mitral valve prolapse (MVP) and no or minimal mitral regurgitation (MR), 17 Cavaliers with MVP and moderate to severe MR, 14 control dogs, and 10 dogs with subaortic stenosis (SAS). Clinical examinations and echocardiography were performed in all dogs. PFA100 closure times (the ability of platelets to occlude a hole in a membrane at high shear rates), platelet activation markers (plasma thromboxane B2 concentration, platelet surface P-selectin expression), platelet aggregation (in whole blood and platelet-rich plasma with 3 different agonists), and vWf multimers were analyzed. Cavaliers with moderate to severe MR and dogs with SAS had longer closure times and a lower percentage of the largest vWf multimers than did controls. Maximal aggregation responses were unchanged in dogs with SAS but enhanced in Cavaliers with MVP (regardless of MR status) compared with control dogs. No significant difference in platelet activation markers was found among groups. The data suggest that a form of platelet dysfunction detected at high shear rates was present in dogs with MR and SAS, possibly associated with a qualitative vWf defect. Aggregation results suggest increased platelet reactivity in Cavaliers, but the platelets did not appear to circulate in a preactivated state in either disease.

show abstract

“…Previous studies had demonstrated that a group of commercial high-potency concentrates commonly used for the treatment of haemophilia A during the early 1980s had negligible eect in supporting platelet adhesion [12]. The fact that these preparations were characterized by the lack of vWF multimers of high molecular weight explained the results.…”

Section: Discussionmentioning

confidence: 97%

“…These concentrates have been shown to improve haemostasis in dierent vWD types [for review , 4]. On the other hand, a preliminary study with a group of high-potency factor VIII concentrates which lacked larger vWF multimers demonstrated that these preparations were unable to support platelet adhesion [12].…”

mentioning

confidence: 99%

An intermediate‐purity factor VIII concentrate supports platelet adhesion under flow conditions

et al. 1997

View full text Add to dashboard Cite

Von Willebrand factor (vWF) binds to platelets and mediates platelet adhesion to subendothelium to support haemostasis. Factor VIII concentrates containing vWF have been recommended for treatment of bleeding episodes in von Willebrand disease (vWD) types 2 and 3. Their clinical efficacy in normalizing FVIII coagulant levels, shortening the bleeding time, stopping or preventing clinical bleeding and safety have been tested. However, the basic mechanisms of their effects on haemostasis have not been fully characterized. We have analysed the ability of vWF present in an intermediate-purity factor VIII concentrate (Haemate-P, Centeon) to bind to platelets (ultrastructural studies) and to support platelet adhesion under flow conditions (perfusion studies). For this purpose, Haemate-P or cryoprecipitate was added to washed platelet suspensions, or to vWF-depleted reconstituted healthy anticoagulated blood. Immunoelectron microscopy (IEM) revealed vWF arrangements on platelet surfaces which have been exposed to mixtures of the vWF-rich concentrate plus ristocetin. vWF levels in perfusates were confirmed by determination of ristocetin co-factor and vWF-antigen. Baumgartner's perfusion method and computer-assisted morphometry were used to evaluate platelet adhesion of the perfusates onto everted rabbit aorta subendothelium under standardized conditions (shear rate, 800 s(-1) , 10 min, 37 °C). vWF-depleted perfusates showed 15.8% (SEM 1.7) total covered surface (CS) with platelets. An increase in CS resulted when 0.40 or 0.80 IU vWF mL(-1) from Haemate-P (30.1%, SEM 3.0, P<0.05; 39.4%, SEM 3.1, P<0.008, respectively) were added. A similar increase was observed when cryoprecipitate was added to perfusates (28.6%, SEM 2.4, P<0.05 for 0.40 IU vWF mL(-1) ; 27.2%, SEM 2.9, P<0.01 for 0.80 IU vWF mL(-1) ). IEM confirmed that vWF from concentrates binds to platelets. Furthermore, perfusion studies revealed that the fractionated vWF supports platelet adhesion, thus providing experimental evidence of the therapeutic benefits exerted by Haemate-P.

show abstract

Adhesion of platelets to human artery subendothelium: effect of factor VIII-von Willebrand factor of various multimeric composition

Cited by 139 publications

References 25 publications

Differentiation of patients with subtype IIb‐like von Willebrand's disease by means of perfusion experiments with reconstituted blood

Differentiation of patients with subtype IIb‐like von Willebrand's disease by means of perfusion experiments with reconstituted blood

Dogs with Heart Diseases Causing Turbulent High-Velocity Blood Flow Have Changes in Platelet Function and von Willebrand Factor Multimer Distribution

An intermediate‐purity factor VIII concentrate supports platelet adhesion under flow conditions

Contact Info

Product

Resources

About