The reduction of large von Willebrand factor multimers in plasma in essential thrombocythaemia is related to the platelet count

Genderen, Perry J.J. van; Budde, Ulrich; Michiels, Jan; Strik, R. Van; Vliet, H. H. D. M. Van

doi:10.1046/j.1365-2141.1996.d01-1729.x

Cited by 105 publications

(102 citation statements)

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Section: Discussionsupporting

confidence: 72%

“…Plasma vWF:Ag and vWF:CBA levels were significantly higher in RT patients as compared with both ET patients (p~0.05) and normal individuals (p~0.05). In contrast, per-centages of plasma large vWF multimers were higher in normal individuals as compared with both RT patients (p~0.01) and ET patients (p~0.01), consistent with previous observations [4,16]. There were no significant differences in pre-ASA values of Ivy BT, plasma vWF:RCoF, plasma vWF:RCoF/vWF:Ag ratio, plasma vWF:CBA/vWF:Ag ratio, MDA-AA, platelet vWF:Ag and vWF:CBA (data not shown) between ET and RT patients and normal subjects.…”

Section: Pre-asa Treatment Valuessupporting

confidence: 80%

“…In a previous study we showed that plasma vWF:CBA/ vWF:Ag ratios are tightly correlated to the percentage of plasma large vWF multimers [16]. The ristocetin cofactor activity, which is usually used to test vWF function in vitro, appeared to be a less sensitive parameter for detecting modest reductions of large vWF multimers in plasma, consistent with previous observations [7,14,16]. The influence of a decreased level of large vWF multimers in plasma on the excessive ASA-induced BT prolongation was stressed by manipulating the plasma levels of large vWF multimers by the infusion of DDAVP.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in patients with congenital von Willebrand disease type 3 who lack the ability to synthesize von Willebrand factor (vWF), a normalization of the prolonged BT may be obtained with transfusion of normal platelets after prior cryoprecipitate infusion, suggesting an important role of platelet vWF in plateletvessel wall interactions [6]. Since ET patients may exhibit abnormalities of plasma vWF (in particular, reduction of large vWF multimers) [3,4,14,16], as well as abnormalities of platelet vWF [5], a study was designed to find out whether the excessive BT prolongation after treatment with ASA in ET patients was related to abnormalities of plasma or platelet vWF.…”

Section: Introductionmentioning

confidence: 99%

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Excessive prolongation of the bleeding time by aspirin in essential thrombocythemia is related to a decrease of large von Willebrand factor multimers in plasma

Genderen¹,

Vliet²,

Prins³

et al. 1997

Annals of Hematology

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Patients with essential thrombocythemia (ET), who frequently have bleeding complications, may manifest an excessive prolongation of the bleeding time (BT) after ingestion of aspirin (ASA). The reason for this excessive prolongation of the BT is unknown, but it is attributed to qualitative platelet defects. Since patients with ET may also have acquired abnormalities of plasma and platelet von Willebrand factor (vWF), we questioned whether the excessive prolongation of the BT by ASA was related to changes in either plasma or platelet vWF. To that end, we studied BT and plasma and platelet vWF in ten ET patients, ten patients with reactive thrombocytosis (RT), and ten normal individuals, both before and after administration of 500 mg ASA for 7 days. In a second study, the effect of DDAVP infusion on plasma vWF in relation to the BT was studied in ten normal individuals and ten ET patients after treatment with 100 mg ASA for 3 days. In the first study, treatment with ASA resulted in a significant prolongation of the BT in normal subjects, RT patients, and ET patients. However, in five ET patients an excessive (`2 SD) prolongation of the BT by ASA was observed. Although ASA induced no direct changes in either plasma or platelet vWF levels in either normal subjects, RT patients, or ET patients, all five ET patients who showed an excessive prolongation of the BT by ASA had significantly decreased levels of large vWF multimers in plasma. In the second study, infusion with DDAVP resulted in a significant increase in plasma large vWF multimers, paralleled by a normalization of (excessively) prolonged BT. Our data suggest that in ET inhibition of platelet function by ASA in the presence of concurrently decreased levels of large vWF multimers in plasma may have provoked the excessive BT prolongation.

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Section: Discussionsupporting

confidence: 72%

Section: Pre-asa Treatment Valuessupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Excessive prolongation of the bleeding time by aspirin in essential thrombocythemia is related to a decrease of large von Willebrand factor multimers in plasma

Genderen¹,

Vliet²,

Prins³

et al. 1997

Annals of Hematology

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“…Paradoxically, very high platelet counts can induce a bleeding tendency, mainly due to an acquired Von Willebrand's disease. 29 I fully agree with ELN recommendations that cytoreductive drugs in children with PV and ET should be prescribed as a last possibility and I suggest that, in the rare cases that need treatment, the selection of a cytotoxic or cytoreductive agent should be done after discussion with the child and parents. Hydroxyurea (HU) and interferon-alpha (IFN-a) are first line therapy at any age including children and young adults.…”

Section: How To Manage Childrenmentioning

confidence: 70%

How to manage children and young adults with myeloproliferative neoplasms

Barbui

2012

Leukemia

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On the basis of my personal clinical and research experience and validated by the current literature, my approach to the management of pediatric (age o18 years) and young patients (age o40 years) with classic myeloproliferative neoplasms is presented by focusing on diagnosis, patient communication, risk stratification and therapy. The WHO-2008 diagnostic criteria are recommended, even though in children suspected with essential thrombocythemia (ET), a specific set of diagnostic features may be required. Patient communication includes information on natural history, genetic abnormalities and counseling in all women of child-bearing age. The main challenge in children and young adults with ET and polycythemia vera (PV) is to avoid recurrence of major thrombosis by selecting those patients who ultimately can benefit from cytotoxic and antithrombotic therapy without increasing the incidence of drug-induced side effects. In asymptomatic low-risk patients no therapy is prescribed while in high-risk low-dose aspirin, hydroxyurea and interferon-alpha are my first line drugs. My first decision when considering treatment of a young patient with primary myelofibrosis (PMF) or post-PV or post ET-myelofibrosis, is whether he/she qualifies for bone marrow allotransplantation. In the remaining young PMF patients palliative therapy or experimental drugs are considered.Leukemia ( Keywords: myeloproliferative neoplasms; treatment; young people INTRODUCTION Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are currently classified among the bcr/abl-negative, 'classic' myeloproliferative neoplasms (MPNs) and represent a stem cell-derived clonal myeloproliferation. Hematopoietic progenitors derived from patients with MPNs are hypersensitive to the stimulation of physiological growth factors such as thrombopoietin or erythropoietin (EPO). 1 Since 2005, the pathophysiology of these diseases has advanced considerably with the discovery of an acquired mutation of JAK2 V617F in a vast majority of PV patients and in almost half of those with ET and PMF. 2 The mutation, located within the negative regulatory pseudokinase, or Janus homology 2 domain, causes cytokine-independent activation of several biochemical pathways implicated in EPO receptor signaling. Subsequently, mutations in MPL were reported in B4% of patients with ET or PMF. The significance of JAK2 and MPL mutations for the evolution of the MPNs and their relative roles in determining disease phenotype as well as progression to myelofibrosis and leukemic transformation are unclear at present.In this context, it should be underscored that most of the information in terms of diagnosis, prognosis and therapy focuses on the 'average' MPN patients of whom median age ranges between 60 and 65 years. On the other hand, less consistent data are available in the groups of MPN patients who are presenting below this median age such as pediatric and young adults (20% of MPN patients). This issue is now becoming more and more important, because with the ad...

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Pathophysiology, Epidemiology, Diagnosis, and Treatment of Acquired von Willebrand Syndrome

Budde

Federici

Rand

2011

Von Willebrand Disease

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The reduction of large von Willebrand factor multimers in plasma in essential thrombocythaemia is related to the platelet count

Cited by 105 publications

References 10 publications

Excessive prolongation of the bleeding time by aspirin in essential thrombocythemia is related to a decrease of large von Willebrand factor multimers in plasma

Excessive prolongation of the bleeding time by aspirin in essential thrombocythemia is related to a decrease of large von Willebrand factor multimers in plasma

How to manage children and young adults with myeloproliferative neoplasms

Pathophysiology, Epidemiology, Diagnosis, and Treatment of Acquired von Willebrand Syndrome

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