Investigations on the Importance and Prevalence of the Acquired von Willebrand Syndrome in Patients with Myeloproliferative Disease.

Abstract The acquired von Willebrand syndrome (AVWS) is a bleeding disorder, which is amongst others associated with myeloproliferative diseases. Its prevalence varies from 0,04–0,13% in literature. Typical laboratory findings such as a low VWF:RCo/VWF:Ag- Ratio, a prolonged aPTT, PFA and bleeding time, a decrease of VWF:RCo, FactorVIII:, VWF:Ag, typical VWF multimeric structure and the absence of a family history of bleeding are the basis for the diagnosis of AVWS. Bleeding episodes are typical for AVWS and are mostly of the mucocutaneous type (epistaxis, heavy menstrual bleeding, gingival and postoperative bleedings). Myeloproliferative diseases, particularily essential thrombocythemia, are with 15–18% the third most frequent observed comorbidity of patients with AVWS, but the prevalence of AVWS in patients with MPS is -at our knowledge- still unknown. We investigated 54 patients with the diagnosis of myeloproliferative disease (44 ET, 9 PV, 1 IMF), which was established according to the WHO-criteria over a period of 6 years (2000–2006). By analysing the typical laboratory parameters for AVWS, the VWF multimeric structure and the own and family history of bleeding we detected that 67% (36/45) of these patients had an AVWS: 27/44 ET (61%), 8/9 PV (89%), 1/1 IMF. The two most sensitive parameters in this context were VWF:RC/vWF:Ag- Ratio and VWF:RCo. It is well known that AVWS can disappear by treating the MPD. We could also show that treating the MPD with Hydroxycarbamid platelets, VWF multimeric structure, VWF:RCo/VWF:Ag-Ratio and VWF:RCo and the bleeding tendency were normalized. The JAK2-V617F mutation is frequently found in myeloproliferative disorders (MPD): Up to 97% patients with polycythemia vera (PV) and about 50% of patients with essential thrombocythemia (ET) carry this mutation. A further goal in this investigation was to find out a correlation between JAK2-V617F mutation, MPD and AVWS. JAK2-V617F diagnosis was performed in 27 of the 54 patients with MPD. 10 of these 27 patients carried a mutated JAK2-allele. However we observed no significant difference between mutated and unmutated patients in correlation to AVWS. In our investigation the high prevalence of 67% AVWS in patients with MPD confirm the hypothesis that until now AVWS is an underdiagnosed disease. Because of this high prevalence, the possibility of regression by treating MPD and the importance of early diagnosis for prevention of unexpected, sometimes letal bleeding complications, it would be benefical to introduce the AVWS- diagnosis-procedure as a routine step for patients with MPD.

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Factors Related to the Development of Acquired Von Willebrand Syndrome in Patients with Essential Thrombocythemia and Polycythemia Vera

Blood ◽

10.1182/blood.v128.22.5466.5466 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5466-5466

Author(s):

Amihai Rottenstreich ◽

Geffen Kleinstern ◽

Svetlana Krichevsky ◽

David Varon ◽

David Lavie ◽

...

Keyword(s):

Platelet Count ◽

Polycythemia Vera ◽

Essential Thrombocythemia ◽

Multivariable Analysis ◽

Jak2 V617f ◽

Jak2 V617f Mutation ◽

Acquired Von Willebrand Syndrome ◽

Platelet Counts ◽

V617f Mutation ◽

Von Willebrand

Abstract Objective: We characterized acquired von Willebrand syndrome (AVWS) among essential thrombocythemia (ET) and polycythemia vera (PV) patients. Methods: A review of patients with ET or PV evaluated for AVWS. Results: Of 116 patients with ET, 64 (55%) developed AVWS; of 57 with PV, 28 (49%) developed AVWS. Median platelet counts of ET and PV patients who developed AVWS were 920 X 109/L and 679 X 109/L, respectively (P=0.01). Of patients who developed AVWS, 69.5% had platelet counts below 1000 X 109/L. Bleeding was more common in patients with AVWS, among both ET and PV patients (P<0.001). VWF:RCo levels and VWF:RCo/VWF:Ag ratio were lower among JAK2 V617F positive- vs. JAK2 V617F negative- ET patients (P=0.02 and P=0.002, respectively); whereas VWF:Ag levels were comparable (P=0.96). ET patients harboring the JAK2 V617F mutation were more likely to develop AVWS than were calreticulin-positive patients (70.3% vs. 45.7%, P=0.02), despite lower platelet counts (median 773 vs. 920 X 109/l, P=0.05). In multivariable analysis, age (β=0.26, P=0.002), platelet count (β=-0.38, P<0.001), hemoglobin level (β=-0.22, P=0.01) and JAK2 V617F mutation (β=-0.23, P=0.01) independently predicted VWF:RCo, among ET patients; whereas only platelet count predicted VWF:RCo among PV patients (β=-0.49, P<0.001). Conclusion: Among ET and PV patients, AVWS was common and associated with higher bleeding rates and higher platelet count; nonetheless, most AVWS patients had platelet counts under 1000 X 109/L. Thus, AVWS screening should be included in routine assessment of ET and PV patients. Among ET patients, JAK2 V617F was a main driver for the development of AVWS. Disclosures No relevant conflicts of interest to declare.

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

Case Reports in Hematology ◽

10.1155/2017/9862620 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 1

Author(s):

Zachary Wolfe ◽

Bradley Lash

Keyword(s):

Family History ◽

Monoclonal Gammopathy ◽

Rare Case ◽

Autoimmune Disorders ◽

Von Willebrand Disease ◽

Lymphoplasmacytic Lymphoma ◽

Acquired Von Willebrand Syndrome ◽

Treatment And Prevention ◽

History Of ◽

Von Willebrand

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.

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Season of birth interacts with measures of inbreeding in multiplex schizophrenia pedigrees: evidence from genetic isolates in Daghestan

Open Medicine ◽

10.2478/s11536-006-0041-8 ◽

2006 ◽

Vol 1 (4) ◽

pp. 392-398

Author(s):

Kazima Bulayeva ◽

John McGrath

Keyword(s):

Genetic Diversity ◽

Family History ◽

Age Of Onset ◽

Population Genetic Study ◽

Season Of Birth ◽

High Genetic Diversity ◽

Low Genetic Diversity ◽

High Prevalence ◽

History Of ◽

Genetic Isolates

AbstractWhile the season-of-birth effect is one of the most consistent epidemiological features of schizophrenia, there is a lack of consistency with respect to the interaction between season of birth and family history of schizophrenia. Apart from family history, measures related to consanguinity can be used as proxy markers of genomic heterogeneity. Thus, these measures may provide an alternate, indirect index of genetic susceptibility. We had the opportunity to explore the interaction between season of birth and measure of consanguinity in well-described genetic isolates in Daghestan, some of which are known for their relatively high prevalence of schizophrenia. Our previous population-genetic study showed Daghestan has an extremely high genetic diversity between the ethnic populations and a low genetic diversity within them. The isolates selected for this study include some with more than 200 and some with less than 100 generations of demographical history since their founding. Based on pedigrees of multiply-affected families, we found that among individuals with schizophrenia, the measure of consanguinity was significantly higher in the parents of those born in winter/spring compared to those born in summer/autumn. Furthermore, compared to summer/autumn born, winter/spring born individuals with schizophrenia had an earlier age-of-onset, and more prominent auditory hallucinations. Our results suggest that the offspring of consanguineous marriages, and thus those with reduced allelic heterogeneity, may be more susceptible to the environmental factor(s) underpinning the season-of-the effect in schizophrenia.

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Acquired von Willebrand Syndrome associated to secondary IgM MGUS emerging after Autologous Stem Cell Transplantation for AL Amyloidosis

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2017.034 ◽

2017 ◽

Vol 9 (1) ◽

pp. e2017034 ◽

Cited By ~ 2

Author(s):

Victor H Jimenez-Zepeda ◽

Hina Qamar ◽

Adrienne Lee ◽

Karen Valentine ◽

Leslie Skeith

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Conditioning Regimen ◽

Al Amyloidosis ◽

Acquired Von Willebrand Syndrome ◽

First Case ◽

History Of ◽

Von Willebrand

Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic disorder that occurs in patients with no prior personal or family history of bleeding. Here, we describe a case of AVWS occurring after autologous stem cell transplantation (ASCT). Interestingly, AVWS developed after bortezomib-based induction and conditioning regimens. Recent evidence suggests that the proximity of the bortezomib therapy to the collection of stem cells with consequent depletion of regulatory T cells after the conditioning regimen could explain some of the unusual autoimmune complications reported in patients receiving bortezomib prior to ASCT. In addition, this patient developed a secondary MGUS post-ASCT, which may have also contributed to the AVWS. To the best of our knowledge, this is the first case of post-ASCT AVWS reported. Prospective data is needed to better elucidate the mechanisms by which these unusual complications occur in patients receiving bortezomib prior to ASCT.

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Two CML patients who subsequently developed features of essential thrombocythemia with JAK2-V617F mutation while in complete cytogenetic remission after treatment with imatinib mesylate

International Journal of Hematology ◽

10.1007/s12185-013-1326-8 ◽

2013 ◽

Vol 97 (6) ◽

pp. 804-807 ◽

Cited By ~ 9

Author(s):

Yoo Jin Lee ◽

Joon Ho Moon ◽

Ho Cheol Shin ◽

Jong Won Seo ◽

Seo Ae Han ◽

...

Keyword(s):

Imatinib Mesylate ◽

Essential Thrombocythemia ◽

Jak2 V617f ◽

Jak2 V617f Mutation ◽

Cytogenetic Remission ◽

V617f Mutation

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Increased risk of heparin induced thrombocytopenia and thrombosis in patients with essential thrombocythemia carrying the homozygous JAK2 V617F mutation

Journal of Thrombosis and Thrombolysis ◽

10.1007/s11239-018-1773-4 ◽

2018 ◽

Vol 47 (1) ◽

pp. 155-156 ◽

Cited By ~ 1

Author(s):

Roberto Castelli ◽

Paolo Gallipoli ◽

Riccardo Schiavon ◽

Thomas Teatini ◽

Giorgio Lambertenghi Deliliers ◽

...

Keyword(s):

Essential Thrombocythemia ◽

Jak2 V617f ◽

Jak2 V617f Mutation ◽

Heparin Induced Thrombocytopenia ◽

Increased Risk ◽

V617f Mutation

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Evaluation of the JAK2 V617F gene mutation in myeloproliferative neoplasms cases: a one-center study from Eastern Anatolia

Turkish Journal of Biochemistry ◽

10.1515/tjb-2018-0054 ◽

2019 ◽

Vol 44 (4) ◽

pp. 492-498

Author(s):

Gonca Gulbay ◽

Elif Yesilada ◽

Mehmet Ali Erkurt ◽

Harika Gozukara Bag ◽

Irfan Kuku ◽

...

Keyword(s):

Blood Cell ◽

Essential Thrombocythemia ◽

Myeloproliferative Neoplasms ◽

Hematological Parameters ◽

Jak2 V617f ◽

Primary Myelofibrosis ◽

Myeloproliferative Disorders ◽

Jak2 V617f Mutation ◽

V617f Mutation ◽

The Difference

AbstractObjectiveDetection ofJAK2V617F in myeloproliferative neoplasms (MPNs) is very important in both diagnosis and disease progression. In our study, we investigated the frequency ofJAK2V617F mutation in patients with myeloproliferative disorders.MethodsWe retrospectively reviewed the records of 720 patients (174 females and 546 males) who were tested for JAK2 V617F mutation from January 2007 to December 2017.ResultsIn our patients were determined 22.6%JAK2V617F mutation. 33.3% in women, 19.2% in men have been positive forJAK2V617F mutation. In our studyJAK2V617F present in 48.6% of essential thrombocythemia, 80.5% of polycythemia rubra vera (PV), 47.5% of primary myelofibrosis, 10% of MPNs, unclassifiable, 0.8% of others. We also investigated the difference in hematological parameters [white blood cell, hemoglobin (Hb), hematocrit (HCT), red blood cell distribution widths (RDW) and platelets count (PLT)] betweenJAK2V617F positive andJAK2V617F negative patients.ConclusionsInvestigation of the JAK2 V617F mutation is very important in cases of MPNs. In our study JAK2 V617F mutation was higher in PV, essential thrombocythemia, and primary myelofibrosis patients. However, there were significant differences in Hb, HCT, RDW and PLT levels in mutation-positive patients.

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Metatarsalgia Caused by an Increase in Circulating Platelets: A Case Report

Foot & Ankle ◽

10.1177/107110078400400414 ◽

1984 ◽

Vol 4 (4) ◽

pp. 216-217

Author(s):

Leon Rosenkranz ◽

M. Michael Cataletto

Keyword(s):

Platelet Count ◽

Case Report ◽

Essential Thrombocythemia ◽

Foot Pain ◽

Myeloproliferative Disease ◽

Disease Reduction ◽

History Of ◽

Work Up

A patient with a year-long history of metatarsalgia was found to have an elevated platelet count due to essential thrombocythemia, a benign myeloproliferative disease. Reduction of the platelet count with chemotherapy eliminated the foot pain. The authors recommend that a platelet count be part of the work-up of patients with metatarsalgia when the etiology of the foot pain is unclear.

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