Browse
Submit Data
Databases
API
Help

Dataset Information

21 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding.

ABSTRACT: Over the past decade, new insights have emerged on the pathophysiology of essential thrombocythemia (ET), its clinical management, and associated thrombohemostatic disturbances. Here, we review the latest diagnostic and risk stratification modalities of ET and its therapeutics. Moreover, we discuss the clinical evidence-based benefits, deriving from major clinical trials, of using cytoreductive therapy and antiplatelet agents to lower the risk of fatal vascular events. Also, we focus on the condition of extreme thrombocytosis (>1000 × 109/L) and bleeding risk, the development and pathogenesis of acquired von Willebrand syndrome, and the clinical approach to this paradoxical scenario in ET.

SUBMITTER: Awada H

PROVIDER: S-EPMC7407619 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Essential Thrombocythemia and Acquired von Willebrand Syndrome: The Shadowlands between Thrombosis and Bleeding.

Awada Hassan H Voso Maria Teresa MT Guglielmelli Paola P Gurnari Carmelo C

Cancers 20200630 7

Over the past decade, new insights have emerged on the pathophysiology of essential thrombocythemia (ET), its clinical management, and associated thrombohemostatic disturbances. Here, we review the latest diagnostic and risk stratification modalities of ET and its therapeutics. Moreover, we discuss the clinical evidence-based benefits, deriving from major clinical trials, of using cytoreductive therapy and antiplatelet agents to lower the risk of fatal vascular events. Also, we focus on the cond ...[more]

PMID: 32629973

Similar Datasets

Hypertrophic obstructive cardiomyopathy, bleeding history, and acquired von Willebrand syndrome: response to septal myectomy.

Project description:Bleeding with severe aortic stenosis is linked to acquired von Willebrand syndrome and loss of high-molecular-weight multimers of von Willebrand factor. Valve replacement resolves bleeding tendency and loss of high-molecular-weight multimers. We report outcomes in 5 patients with symptomatic obstructive hypertrophic cardiomyopathy and spontaneous gastrointestinal, mucosal, or excessive postsurgical bleeding in whom acquired von Willebrand syndrome was documented. All 5 patients underwent surgical septal myectomy with resolution of acquired von Willebrand syndrome.

| S-EPMC3046942 | biostudies-literature

Porcine and canine von Willebrand factor and von Willebrand disease: hemostasis, thrombosis, and atherosclerosis studies.

Project description:Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), and coronary artery thrombosis. First, in humans, pigs, and dogs, VWF is essential for normal hemostasis; without VWF bleeding events are severe and can be fatal. Second, the ADAMTS13 cleavage site is preserved in all three species suggesting all use this mechanism for normal VWF multimer processing and that all are susceptible to TTP when ADAMTS13 function is reduced. Third, while the role of VWF in atherogenesis is debated, arterial thrombosis complicating atherosclerosis appears to be VWF-dependent. The differences in the VWF gene and protein between humans, pigs, and dogs are relatively few but important to consider in the design of VWF-focused experiments. These homologies and differences are reviewed in detail and their implications for research projects are discussed. The current status of porcine and canine VWD are also reviewed as well as their potential role in future studies of VWF-related disorders of hemostasis and thrombosis.

| S-EPMC3211078 | biostudies-literature

Perioperative onset of acquired von Willebrand syndrome: Comparison between HVAD, HeartMate II and on-pump coronary bypass surgery.

Project description:ObjectivesAcquired von Willebrand syndrome (AvWS) is associated with postoperative bleeding complications in patients with continuous flow left ventricular assist devices (CF-LVADs). The aim of this study is to analyze the perioperative vWF profile comparing an axial pump (HMII) to a centrifugal pump (HVAD) regarding the correlation between perioperative occurrence of AvWS, early- and late-postoperative bleeding events.MethodsFrom July 2013 until March 2015 blood samples of 33 patients (12 HMII/ 8 HVAD/ 13 controls) were prospectively collected at 12 different time points and analyzed for the vWF antigen (vWF:Ag), its activity (vWF:Ac) and the vWF:Ac/vWF:Ag-ratio (vWF:ratio). The follow up period for postoperative bleeding events was from July 2013 until July 2016.ResultsPostoperatively, there was no difference in the vWF-profile between HVAD and HMII groups. However, a subgroup of patients already had significantly lower vWF:ratios preoperatively. Postoperatively, both CF-LVAD groups presented significantly lower vWF:ratios compared to the control group. Bleeding events per patient-year did not differ between the two groups (HMII vs. HVAD: 0.67 vs. 0.85, p = 0.685). We detected a correlation between vWF:ratio <0.7at LVAD-start (r = -0.583, p = 0.006) or at the end of surgery (r = -0.461, p = 0.035) and the occurrence of pericardial tamponade. In the control group, the drop in both vWF:Ag and vWF:Ac recovered immediately postoperatively above preoperative values.ConclusionA subgroup of patients with end-stage heart failure already suffers AvWS preoperatively. In both CF-LVAD groups, AvWS begins immediately after surgery. Intraoperative vWF:ratios <0.7 correlate with higher incidences of pericardial tamponade and re-operation. The presumably dilutive effect of the heart lung machine on vWF vanishes immediately at the end of surgery, possibly as part of an acute-phase response.

| S-EPMC5325196 | biostudies-literature

Longitudinal bleeding assessment in von Willebrand disease utilizing an interim bleeding score.

Project description:BackgroundAssessment of bleeding phenotype is critically important in the diagnosis of von Willebrand disease (VWD). Despite advances in bleeding assessment tools (BATs), standardized tools to evaluate bleeding following diagnosis (interim bleeding) are lacking.ObjectivesWe assessed the clinical utility of an interim bleeding protocol in a multicenter, international study involving patients with VWD.MethodsThe enrolment ISTH BAT formed the original bleeding score (0 BS). At follow-up, the International Society on Thrombosis and Haemostasis BAT was repeated but included only interval bleeding (Interim BS, 1 BS). Both scores were annualized (0 BS/yr, 1 BS/yr). BS were analyzed by VWD subtype, plasma VWF level, sex, and age.ResultsInterim BS discriminated by subtype, with significantly increased 0 BS and 1 BS in patients with type 3 VWD. In patients with type 1 VWD, a positive or negative 0 BS did not predict future bleeding, with similar 1 BS/yr (median 1.0 vs. 0.7, p = .2). Despite significantly higher 0 BS in females with type 1 VWD than males (median 7 vs. 5, p = .0012), 1 BS were not significantly different (median 4 vs. 4, p = .16). While 0 BS were lower in children than adults with type 1 VWD, interim BS were similar (median 5 vs. 3, p = .5; 1BS/yr, median 1 vs. 0.8, p = .7). Interestingly, in those with plasma von Willebrand factor:ristocetin cofactor levels >50 IU/dl, interim BS rates were similar to those 30-50 IU/dl (1 BS/yr 0.8 vs. 1.3, p = .5).ConclusionThis study provides both a new approach to longitudinal bleeding assessment and insights into the evolution of bleeding in VWD.

| S-EPMC10193460 | biostudies-literature

ADAMTS-13 and bleeding phenotype in von Willebrand disease.

Project description:BackgroundThe bleeding phenotype of von Willebrand disease (VWD) varies highly between patients and can only partly be explained by von Willebrand factor (VWF) parameters. By cleaving large VWF multimers into smaller, less active multimers, ADAMTS-13 is an important regulator of VWF activity. However, it is unknown what the role of ADAMTS-13 is in individuals with VWD.ObjectivesWe therefore studied how ADAMTS-13 activity is associated with the laboratory and bleeding phenotype in individuals with VWD.MethodsWe measured ADAMTS-13 activity using the fluorescence resonance energy transfer substrate VWF 73 assay in 638 individuals with VWD in the nationwide cross-sectional Willebrand in the Netherlands study and in 36 healthy controls. The bleeding phenotype was assessed using the Tosetto bleeding score.ResultsADAMTS-13 activity was similar in individuals with VWD (109% ± 20.6%) and controls (110% ± 19.7%). ADAMTS-13 activity was higher in individuals with VWD with type 3 than those with type 1 (mean difference, 11.8%; 95% confidence interval [CI], 2.9%-20.8%) or type 2 (mean difference, 16.1%; 95% CI, 7.1%-25.1%). ADAMTS-13 activity was not associated with the Tosetto bleeding score (0.1 Tosetto bleeding score increase per 10% ADAMTS-13 increase, 95% CI, -0.2 to 0.3). Furthermore, ADAMTS-13 activity did not differ between individuals with and without a bleeding event during the year preceding blood sampling (mean difference, 1.4%; 95% CI, -2.1% to 4.9%).ConclusionADAMTS-13 activity was highest in individuals with type 3 VWD, but it had only minor associations with VWF parameters. ADAMTS-13 activity does not influence the bleeding phenotype in individuals with VWD.

| S-EPMC7695560 | biostudies-literature

Acquired von Willebrand syndrome in cardiogenic shock patients on mechanical circulatory microaxial pump support.

Project description:Early use of mechanical circulatory support, e.g. veno-arterial extracorporeal membrane oxygenation (ECMO) or left ventricular unloading by microaxial pump in refractory cardiogenic shock is recommended in current guidelines. Development of acquired von Willebrand Syndrome (AVWS) in patients with left ventricular assist devices (LVADs) and ECMO has been reported. There is an increasing number of patients treated with the Impella® CP microaxial pump for left ventricular unloading. However, the prevalence of AVWS in these high risk patients is unknown and needs to be determined. We therefore screened 21 patients (68 ± 11years) treated with Impella® (17 for cardiogenic shock, 4 for protected PCI) for the presence of AVWS by determining von Willebrand factor multimers, VWF collagen binding capacity and VWF antigen. During the time course of Impella® support, 20/21 patients (95%) developed AVWS (mean duration of support: 135 ± 114 hours, mean time from device implantation to first diagnosis of AVWS: 10.6 ± 10.8 hours). Our data indicate that AVWS is a common phenomenon during left ventricular unloading via microaxial pump support. Thus, AVWS has to be considered as contributing factor for potential bleeding complications in this high risk patient population, especially in the context of dual antiplatelet therapy.

| S-EPMC5555672 | biostudies-literature

Bleeding assessment tools to predict von Willebrand disease: Utility of individual bleeding symptoms.

Project description:BackgroundBleeding assessment is part of the diagnostic workup of von Willebrand disease (VWD). Bleeding assessment tools (BATs) have standardized obtaining this information but have been criticized because they are time consuming.ObjectiveTo use our legacy data to determine which questions from BATs are the strongest predictors of a VWD diagnosis.Patients/methodsBleeding score data from 3 different BATs were used. Patients aged <12 years were excluded. Questions on BATs relate to different bleeding symptoms, and each symptom is scored by severity. Scores for each symptom were sorted based on whether they indicated clinically significant bleeding, and nonsignificant scores were set as the reference category. Multivariable logistic regression was used to determine the symptoms that were the strongest predictors of a laboratory-confirmed VWD diagnosis.ResultsA total of 927 participants were included; 144 (16%) were patients with VWD, and 783 (84%) were healthy controls. The top 3 symptoms for which a clinically significant positive response increased the likelihood of VWD were hemarthrosis (odds ratio [OR], 19.2; 95% confidence interval [CI], 3.7-100.4), postsurgical bleeding (OR, 15.2; 95% CI, 5.9-38.9), and menorrhagia (OR, 10.3; 95% CI, 4.9-21.9). With each increase in number of bleeding symptom categories with clinically significant scores, subjects had a stepwise increase in odds of a VWD diagnosis.ConclusionsOur results suggest that most of the bleeding symptoms on BATs are significant predictors of VWD, and there is value in assessing multiple bleeding symptoms when eliciting a bleeding history. Certain bleeding symptoms are more useful predictors than others. Future BAT revisions may consider adding a relative weighting to each symptom.

| S-EPMC6971303 | biostudies-literature

Acquired von Willebrand Syndrome in IgM Monoclonal Gammopathy as the Presentation of Lymphoplasmacytic Lymphoma.

Project description:Acquired von Willebrand syndrome (AVWS) is an increasingly recognized entity with numerous potential underlying etiologies. Most commonly implicated are lymphoproliferative, myeloproliferative, cardiovascular, and autoimmune disorders. Unlike inherited von Willebrand disease (vWD), AVWS tends to present at an older age and without a family history of vWD. Treatment is directed at the underlying etiology if one is uncovered, as well as treatment and prevention of bleeding. Here, we present a rare case of AVWS secondary to Waldenström macroglobulinemia which went unrecognized for several years but resolved promptly with treatment. The potential mechanisms of AVWS secondary to monoclonal gammopathies are discussed as well as strategies to treat and prevent bleeding in these patients.

| S-EPMC5485300 | biostudies-other

A rare case of acquired von Willebrand syndrome type 2B: diagnosis, treatment, and underlying pathophysiology.

Project description:BackgroundAcquired von Willebrand syndrome (AVWS) is a rare bleeding disorder that usually mimics type 1 or 2A von Willebrand disease (VWD).Key clinical questionCan AVWS mimic the phenotype of type 2B VWD?Clinical approachA 64-year-old male patient presented with thrombocytopenia, normal routine hemostasis results, and normal VWF antigen and factor VIII levels but reduced von Willebrand factor (VWF) activity (31 IU/dL). The ristocetin-induced platelet aggregation test showed paradoxical aggregation at low doses of ristocetin, suggesting type 2B VWD, but no deleterious sequence variation was found in either the VWF or GP1BA genes, compatible with AVWS. Serum protein electrophoresis revealed a monoclonal immunoglobulin G antibody.ConclusionThis AVWS with a 2B phenotype VWD was probably related to a monoclonal immunoglobulin G antibody causing a VWF conformational change, resulting in increased affinity to platelet glycoprotein-Ib. In the event of surgery or bleeding, treatment with vonicog alfa seems to be the best option for this patient.

| S-EPMC11369413 | biostudies-literature

Mild Acquired von Willebrand Syndrome and Cholestasis in Pediatric and Adult Patients with Fontan Circulation.

Project description:Background: Hemodynamic alterations in Fontan patients (FP) are associated with hemostatic dysbalance and Fontan-associated liver disease. Studies of other hepatopathologies indicate an interplay between cholestasis, tissue factor (TF), and von Willebrand factor (VWF). Hence, we hypothesized a relationship between the accumulation of bile acids (BA) and these hemostatic factors in FP. Methods: We included 34 FP (Phenprocoumon n = 15, acetylsalicylic acid (ASA) n = 16). BA were assessed by mass spectrometry. TF activity and VWF antigen (VWF:Ag) were determined by chromogenic assays. VWF collagen-binding activity (VWF:CB) was assessed via ELISA. Results: Cholestasis was observed in 6/34 FP (total BA ≥ 10 µM). BA levels and TF activity did not correlate (p = 0.724). Cholestatic FP had lower platelet counts (p = 0.013) from which 5/6 FP were not treated with ASA. VWF:Ag levels were increased in 9/34 FP and significantly lower in FP receiving ASA (p = 0.044). Acquired von Willebrand syndrome (AVWS) was observed in 10/34-FP, with a higher incidence in cholestatic FP (4/6) (p = 0.048). Conclusions: Cholestasis is unexpectedly infrequent in FP and seems to be less frequent under ASA therapy. Therefore, ASA may reduce the risk of advanced liver fibrosis. FP should be screened for AVWS to avoid bleeding events, especially in cholestatic states.

| S-EPMC9917608 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data