Association of Gene Polymorphisms and Leukocytosis with Thrombotic Complications in Essential Thrombocytemia and Polycythemia Vera

Aim: The assessment of angiogenic parameters in so-called “liquid tumors”, such as myeloproliferative neoplasms, remains an open clinical issue. The aim of the study is to evaluate the concentration of vascular endothelial growth factor (VEGF-A) and soluble receptors sVEGFR-1 and sVEGFR-2 in relations to risk factors of thrombosis in patients with polycythemia vera (PV). Material/Methods: A total of 45 patients suffering from newly diagnosed PV and 30 healthy volunteers were enrolled into the study. Polycythemia vera was diagnosed according to the WHO (2008) criteria. In the citrated plasma samples VEGF-A, sVEGFR-1 and sVEGFR-2 were measured using ELISA tests. Results: VEGF-A concentration was three-fold higher and sVEGFR-2 significantly lower in PV patients as compared to the control group. VEGF-A concentration was significantly higher in PV patients with JAK2V617F mutation, as compared to patients without this mutation. SVEGFR-1 and sVEGFR-2 concentrations were similar in the analyzed subgroups. In PV patients with an increased number of white blood cells (WBCs), the above upper reference value (≥10 G/l), VEGF-A concentration was two-fold higher than in patients with WBCs number <10 G/l. However, sVEGFR-1 and sVEGFR-2 concentrations did not differ between the analyzed subgroups. Analysis of correlations revealed only one relation between VEGF-A and WBCs number. Conclusions: Increased VEGF-A and decreased sVEGFR-2 concentrations in polycythemia vera patients as compared to the control group indicate an intensification of the process of angiogenesis. A higher concentration of VEGF-A in PV patients with leukocytosis and a positive correlation between WBCs number and VEGF-A reflect the potential role of VEGF-A in the pathogenesis of thrombotic complications in hypercoagulable state in PV patients.

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Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo [see comments]

Blood ◽

10.1182/blood.v80.8.1965.1965 ◽

1992 ◽

Vol 80 (8) ◽

pp. 1965-1971 ◽

Cited By ~ 93

Author(s):

R Landolfi ◽

G Ciabattoni ◽

P Patrignani ◽

MA Castellana ◽

E Pogliani ◽

...

Keyword(s):

Polycythemia Vera ◽

Clinical History ◽

Current Treatment ◽

Lipoxygenase Pathway ◽

Binding Characteristics ◽

History Of ◽

Thrombotic Complications ◽

Excretion Rates

Abstract Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.

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Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo [see comments]

Blood ◽

10.1182/blood.v80.8.1965.bloodjournal8081965 ◽

1992 ◽

Vol 80 (8) ◽

pp. 1965-1971 ◽

Cited By ~ 1

Author(s):

R Landolfi ◽

G Ciabattoni ◽

P Patrignani ◽

MA Castellana ◽

E Pogliani ◽

...

Keyword(s):

Polycythemia Vera ◽

Clinical History ◽

Current Treatment ◽

Lipoxygenase Pathway ◽

Binding Characteristics ◽

History Of ◽

Thrombotic Complications ◽

Excretion Rates

Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.

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Essential thrombocythemia – Incidence of thrombotic complications

ARS Medica Tomitana ◽

10.1515/arsm-2016-0019 ◽

2016 ◽

Vol 22 (2) ◽

pp. 108-112

Author(s):

Mihaela Maria Ghinea ◽

Zizi Niculescu ◽

C. Niculescu ◽

M. Grigorian

Keyword(s):

Risk Factors ◽

Coronary Thrombosis ◽

Myeloproliferative Disease ◽

Vein Thrombosis ◽

Background Therapy ◽

Thrombotic Complications ◽

The Moment ◽

The One ◽

Associated Risk Factors ◽

Essential Thrombocytemia

Abstract Essential thrombocytemia is a classic negative chronic myeloproliferative disease BCR-ABL characterized by global myeloid proliferation but mainly on the megacariocitary series. Most symptomatic patients show manifestations due to the vascular thromboses or haemorrhages. The objective of the paper is to evaluate the incidence of thrombotic complications. The study was carried out in the Haematology Compartment of Constanta County Clinical Hospital on a lot of 60 cases with essential thrombocytemia. The diagnosis criteria were OMS 2008 criteria. On the studied lot, on the diagnosis, 45 patients (75%) were symptomatic. Among the symptomatic ones 27 patients (60%) showed thromboembolic manifestations in the moment of the diagnosis or after diagnosis. The thrombotic manifestations present at the patients with essential thrombocytemia taken for the study were: cerebral micro thromboses - 10 cases; peripheral micro thromboses - 3 cases; erythromelalgia - 6 cases; acrocyanosis - 2 cases; coronary thrombosis - 1 case; portal vein thrombosis - 2 cases; pulmonary thromboembolism - 1 case; thrombosis of placenta vessels- 2 cases. The thrombocytosis degree is not the only important risk factor for thrombosis. The age over 60 years, arterial hypertension, dyslipidemia, smoking, atherosclerosis, are associated risk factors (independent from thrombocytosis) for the frequency and severity of the thromboses. In this framework, on the one hand the increase of accessibility to the background therapy proven efficient (interferon, anagrelide) and on the other hand the mentioning in the cardiovascular pathology guides of primary and secondary thromboses as risk factors along with hypertension, diabetes, dyslipidemias, etc is required.

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Thrombosis RelatedABO,F5,MTHFR,andFGGGene Polymorphisms in Morbidly Obese Patients

Disease Markers ◽

10.1155/2016/7853424 ◽

2016 ◽

Vol 2016 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Kristina Kupcinskiene ◽

Martyna Murnikovaite ◽

Greta Varkalaite ◽

Simonas Juzenas ◽

Darius Trepenaitis ◽

...

Keyword(s):

Morbid Obesity ◽

Risk Factor ◽

Gene Polymorphisms ◽

Morbidly Obese ◽

Similar Distribution ◽

Obese Patients ◽

Rt Pcr ◽

European Descent ◽

Thrombotic Complications ◽

The Difference

Objective. Obesity is a well-known risk factor for thrombotic complications. The aim of the present study was to determine the frequency of thrombosis relatedABO,F5,MTHFR,andFGGgene polymorphisms in morbidly obese patients and compare them with the group of nonobese individuals.Methods. Gene polymorphisms were analyzed in 320 morbidly obese patients (BMI > 40 kg/m2) and 303 control individuals (BMI < 30 kg/m2) of European descent.ABOC>T (rs505922),F5C>G (rs6427196),MTHFRC>T (rs1801133), andFGGC>T (rs6536024) SNPs were genotyped by RT-PCR.Results. We observed a tendency forMTHFRrs1801133 TT genotype to be linked with morbid obesity when compared to CC genotype; however, the difference did not reach the significantPvalue (OR 1.84, 95% CI 0.83–4.05,P=0.129). Overall, the genotypes and alleles of rs505922, rs6427196, rs1801133, and rs6536024 SNPs had similar distribution between morbidly obese and nonobese control individuals. Distribution of height and weight means among individuals carrying different rs505922, rs6427196, rs1801133, and rs6536024 genotypes did not differ significantly.Conclusions. Gene polymorphismsABOC>T (rs505922),F5C>G (rs6427196),MTHFRC>T (rs1801133), andFGGC>T (rs6536024) were not associated with height, weight, or morbid obesity among European subjects.

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CYP1AI, glutathione S-transferase gene polymorphisms and risk of Polycythemia vera

Cancer Epidemiology ◽

10.1016/j.canep.2011.05.001 ◽

2012 ◽

Vol 36 (1) ◽

pp. 68-72 ◽

Cited By ~ 1

Author(s):

Randa G. Naffa ◽

Abdalla S. Awidi ◽

Al-Motassem F. Yousef ◽

Said I. Ismail

Keyword(s):

Polycythemia Vera ◽

Gene Polymorphisms ◽

Glutathione S Transferase ◽

Transferase Gene

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Could hypoxia increase the prevalence of thrombotic complications in polycythemia vera?

Blood Coagulation & Fibrinolysis ◽

10.1097/mbc.0b013e32835bfdb9 ◽

2013 ◽

Vol 24 (3) ◽

pp. 311-316 ◽

Cited By ~ 9

Author(s):

Maurizio Zangari ◽

Louis Fink ◽

Giulia Tolomelli ◽

Jasmine C.H. Lee ◽

Brady L. Stein ◽

...

Keyword(s):

Polycythemia Vera ◽

Thrombotic Complications

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Superior Vena Cava Syndrome in a Patient with Polycytemia Vera: Diagnosis and Treatment

Cardiology Research and Practice ◽

10.4061/2010/791648 ◽

2010 ◽

Vol 2010 ◽

pp. 1-3 ◽

Cited By ~ 4

Author(s):

Salvatore Lentini ◽

Mario Barone ◽

Filippo Benedetto ◽

Francesco Spinelli

Keyword(s):

Polycythemia Vera ◽

Superior Vena Cava ◽

Superior Vena Cava Syndrome ◽

Superior Vena ◽

Vena Cava ◽

Diagnosis And Treatment ◽

Air Bubble ◽

Vena Cava Syndrome ◽

Thrombotic Complications ◽

Tomography Scan

Polycythemia vera is a myeloproliferative disorder characterized by thrombotic complications both in the arterial and venous systems. We report the case of a 55-year-old patient affected by polycythemia vera, presenting with acute superior vena cava syndrome due to thrombosis of the upper part of the superior vena cava. Diagnosis was done clinically and by computed tomography scan and showed an unusual finding: an air bubble trapped in the brachiocephalic venous trunk. The patient underwent emergency surgery. Diagnosis and treatment of the case are discussed.

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