Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: Relationship with platelet count

Genderen, Perry J.J. van; Michiels, Jan; Luytgaarde, Sonja C P A M van der Poel-van de; Vliet, H. H. D. M. Van

doi:10.1007/bf01698487

Cited by 72 publications

(70 citation statements)

References 15 publications

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“…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: Discussionsupporting

confidence: 87%

“…In previous studies we found that the reduction of large vWF multimers in plasma in ET is directly related to the number of circulating platelets [4,14,17]. The reduction of large vWF multimers in plasma becomes particularly apparent at platelet counts exceeding 1000!…”

Section: Discussionmentioning

confidence: 89%

“…For all studies involving vWF, blood was collected in one-tenth final volume of 3.8% trisodium citrate solution containing aprotinin, EDTA, and N-ethyl maleimide to give final concentrations of 500 KIU/ml, 5 mmol/l and 6 mmol/l, respectively. Ivy BT, plasma von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RCoF) and collagen binding activity (vWF:CBA) parameters were measured as described previously [14,15]. Multimeric analysis of plasma and platelet vWF and the quantification of plasma large vWF multimers was performed as reported in detail elsewhere [4].…”

Section: Methodsmentioning

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: 87%

Section: Discussionmentioning

confidence: 89%

Section: Methodsmentioning

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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“…While extreme thrombocytosis may correlate with the occurrence of hemorrhage due to an acquired von Willebrand disease, [19][20][21] the contribution of platelet number to major thrombotic events remains poorly established. 22 In a randomized clinical trial that included high-risk ET patients, HU treatment was found to be superior to anagrelide, a selective cytoreductive antiplatelet drug, in preventing arterial thrombosis.…”

Section: Discussionmentioning

confidence: 99%

Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status

Carobbio

Finazzi

Guerini

et al. 2006

Blood

285

229

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Leukocytes contribute to the pathogenesis of thrombosis in essential thrombocythemia (ET) through recently discovered mechanisms of activation and interaction with platelets and endothelial cells. To evaluate whether an increased leukocyte count was associated with thrombosis and whether this effect can be modulated by therapy, we analyzed the clinical course of 439 patients with ET followed at the Ospedali Riuniti di Bergamo. The strength of the association was measured at diagnosis or before thrombotic events by multivariable analyses carried out using data at baseline as well as time-varying covariates. The results showed that (1) an increased leukocyte count at diagnosis was associated with thrombosis during follow-up ("baseline analysis," relative risk [RR] 2.3, 95% confidence interval [CI] 1.4-3.9, P ‫؍‬ .001); (2) hydroxyurea (HU) lowered leukocytosis and reduced the strength of the association between leukocytosis and thrombosis ("time-dependent analysis," RR 1.6, 95% CI 0.9-2.0, not significant [NS]); (3) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, P ‫؍‬ .01) compared with HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, NS); and (4) the presence of JAK2 V617F was not identified as a risk factor for thrombosis during follow-up despite a significant association between the mutation and leukocytosis. We suggest validation of these findings in prospective clinical studies. (Blood.

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Acquired von Willebrand's disease: A concise review

1997

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Acquired von Willebrand's disease (AvWD), an adult-onset bleeding diathesis, has most commonly been found in patients with an underlying lymphoproliferative disease or monoclonal gammopathy. Other malignancies, autoimmune diseases, hypothyroidism, and drugs have also been associated with AvWD. We have included an illustrative case history of a patient with a bleeding diathesis consistent with AvWD and a monoclonal gammopathy who required emergent cardiac surgery. Our review of the literature determined that most cases of AvWD are due to a circulating antibody that combines with the high molecular weight multimers ( CASE HISTORY INTRODUCTIONA 55-year-old man presented with severe epistaxis reAcquired von Willebrand's disease (AvWD) is an unquiring nasal packing and balloon tamponade. The patient common bleeding disorder that has remained, until recomplained of exertional chest pain for the past 2 weeks; cently, both difficult to characterize pathophysiologically, he now noted dyspnea and chest pain at rest. He was and challenging to treat successfully. Acquired forms of found to have an hematocrit of 22% and an elevated PTT, von Willebrand's disease are usually encountered in and he was transfused to a hematocrit of 30% with relief of adults without a personal or family history of bleeding his resting pain. Stress thallium showed diffuse, reversible diatheses [1]. Laboratory examination demonstrates that perfusion defects in the anterior, apical, inferior, and septhe functional assay for von Willebrand factor (vWF), tal areas, while an echocardiogram showed normal sysristocetin cofactor activity (vWF:RiCo), is characteristitolic function. The patient was referred to the University cally low or nearly absent, while the antigen (vWF:Ag) of Maryland Medical Center for cardiac catheterization assay is low or normal [2]. Bleeding time is markedly and evaluation of his bleeding disorder. prolonged. Furthermore, electrophoresis of von WilleThe patient's past medical history and family history brand factor most commonly reveals a pattern similar to type II congenital von Willebrand's disease (vWD), with selective loss of high molecular weight multimers *Correspondence to: Henry M. Rinder, M.D., Department of Labora-(HMWM) [2,3]. In this paper, we discuss an illustrative tory Medicine, Yale University School of Medicine, New Haven, CT case and review the recent literature on AvWD, which 06520-8035. details the physiologic basic for this disease and the ratioReceived for publication 9 August 1996; Accepted 11 September 1996. nale for treatment options.ᮊ 1997 Wiley-Liss, Inc.

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Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: Relationship with platelet count

Cited by 72 publications

References 15 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

Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status

Acquired von Willebrand's disease: A concise review

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