21 research outputs found
Brak wpływu stopnia zwężenia zastawki aortalnej na standardowe parametry płytek krwi — kluczowa rola innych czynników ryzyka sercowo-naczyniowego
Introduction. Calcification of the aortic valve, the main component of degenerative aortic stenosis (AS), results in turbulent blood flow, higher shear stress and may have an effect on the platelet (PLT) parameters. Platelet function and size, which are easily measured automatically during a complete blood count, are proposed as markers of platelet reactivity and risk factors for cardiovascular diseases.
Material and methods. 143 patients with AS (mean age: 70 ± 13 y., males 76/53%) were enrolled into the study and divided according to the AS severity: severe AS (n = 89; males 43/48.3%; age IQR: 70 [63–75] y.) and non-severe AS (n = 54; males 63/61.1%; age IQR: 70 [62–76] y.). The clinical data were collected and analyzed with special attention being paid to the cardiovascular risk factors, concomitant diseases (coronary artery disease [CAD], diabetes mellitus, arterial hypertension, obesity). Laboratory tests and echocardiography were assessed in all subjects. Routine admission complete blood cell count was obtained — PLT count, mean PLT volume (MPV), PLT distribution width (PDW) and percentage of giant PLT (giant PLT%) were analyzed.
Results. There were no differences between the PLT count, MPV, PDW and giant PLT% when comparing the group with severe AS to the non-severe AS group. Multivariate analysis showed a significant effect of CAD coincidence (β = –0.2, SE = 0.09, p = 0,03) and active smoking (β = –0.2, SE = 0.09, p = 0.03) on the PLT count; obesity (β = 0.2, SE = 0.09, p = 0.03) and CAD (β = –0.2, SE = 0.09, p = 0.03) on MPV; obesity (β = 0.21, SE = 0.09, p = 0.02), thienopyridines (β = 0.19, SE = 0.09, p = 0.03) and LMWH intake (β = 0.21, SE = 0.09, p = 0.02) on PDW; and similarly, obesity (β = 0.23, SE = 0.09, p = 0.01), thienopyridines (β = 0.18, SE = 0.09, p = 0.046) and LMWH intake (β = 0.23, SE = 0.09, p = 0.01) on giant PLT%.
Conclusions. Aortic stenosis severity has no effect on PLT count and morphology that are automatically measured. The coincidence of standard cardiovascular risk factors and the CAD effects on the PLT parameters that are established during a standard complete blood count.Wstęp. Kalcyfikacje zastawki aortalnej, będące głównym komponentem degeneracyjnego zwężenia zastawki aortalnej (AS), skutkują turbulentnym przepływem krwi, co z kolei może wpływać na parametry płytek krwi (PLT). Funkcja i wielkość PLT, łatwo oznaczane podczas rutynowej morfologii krwi obwodowej, mogą być markerami aktywności PLT i potencjalnymi czynnikami ryzyka chorób układu sercowo-naczyniowego.
Materiał i metody. Do badania włączono 143 pacjentów z AS (średni wiek: 70 ± 13 l., mężczyźni 76/53%) i podzielono na dwie podgrupy zależnie od ciężkości AS — z ciężką AS (mediana wieku: 70 [63–75] l., n = 89, mężczyźni 43/48,3%) oraz nieciężką AS (mediana wieku: 70 [62–76] l., n = 54, mężczyźni 63/61,1%). U wszystkich chorych wykonano przezklatkowe badanie echokardiograficzne oraz zebrano wywiad lekarski, ze szczególnym uwzględnieniem czynników ryzyka chorób układu sercowo-naczyniowego i schorzeń współistniejących (choroby wieńcowej [CAD], cukrzycy typu 2, nadciśnienia tętniczego, otyłości, palenia tytoniu). W wykonanej rutynowo morfologii krwi obwodowej analizie poddano następujące parametry płytkowe: liczbę płytek (PLT count), średnią objętość płytek (MPV), wskaźnik anizocytozy płytek (PDW), odsetek płytek olbrzymich (giant PLT%).
Wyniki. Nie obserwowano istotnej różnicy pod względem PLT count, MPV, PDW ani giant PLT%, porównując grupy pod względem ciężkości AS. W przeprowadzonej analizie wieloczynnikowej wykazano istotny wpływ współwystępowania CAD (β = –0,2; SE = 0,09; p = 0,03) i palenia tytoniu (β = –0,2; SE = 0,09; p = 0,03) na PLT count; otyłości (β = 0,2; SE = 0,09; p = 0,03) i CAD (β = –0,2; SE = 0,09; p = 0,03) na MPV; otyłości (β = 0,21; SE = 0,09; p = 0,02), stosowania pochodnych tienopirydyn (β = 0,19; SE = 0,09; p = 0,03) oraz heparyn drobnocząsteczkowych (β = 0,21; SE = 0,09; p = 0,02) na PDW; i podobnie, otyłości (β = 0,23; SE = 0,09; p = 0,01), stosowania pochodnych tienopirydyn (β = 0,18; SE = 0,09; p = 0,046) oraz heparyn drobnocząsteczkowych (β = 0,23; SE = 0,09; p = 0,01) na giant PLT%.
Wnioski. Stopień AS nie wpływa na automatycznie mierzoną liczbę i morfologię PLT. Współwystępowanie czynników ryzyka chorób układu sercowo-naczyniowego oraz CAD wpływa na rutynowo oznaczane w morfologii krwi obwodowej parametry płytkowe
Association of thrombocytosis with COPD morbidity: The SPIROMICS and COPDGene cohorts
Background: Thrombocytosis has been associated with COPD prevalence and increased all-cause mortality in patients with acute exacerbation of COPD (AECOPD); but whether it is associated with morbidity in stable COPD is unknown. This study aims to determine the association of thrombocytosis with COPD morbidity including reported AECOPD, respiratory symptoms and exercise capacity. Methods: Participants with COPD were included from two multi-center observational studies (SPIROMICS and COPDGene). Cross-sectional associations of thrombocytosis (platelet count ≥350×109/L) with AECOPD during prior year (none vs. any), exertional dyspnea (modified Medical Research Council (mMRC) score≥2), COPD Assessment Test (CAT) score≥10, six-minute-walk distance (6MWD), and St. George Respiratory questionnaire (SGRQ) were modeled using multivariable logistic or linear regression. A pooled effect estimate for thrombocytosis was produced using meta-analysis of data from both studies. Results: Thrombocytosis was present in 124/1820 (6.8%) SPIROMICS participants and 111/2185 (5.1%) COPDGene participants. In meta-analysis thrombocytosis was associated with any AECOPD (adjusted odds ratio [aOR] 1.5; 95% confidence interval [95% CI]: 1.1-2.0), severe AECOPD (aOR 1.5; 95% CI: 1.1-2.2), dyspnea (mMRC≥2 aOR 1.4; 95% CI: 1.0-1.9), respiratory symptoms (CAT≥10 aOR 1.6; 95% CI: 1.1-2.4), and higher SGRQ score (β 2.7; 95% CI: 0.5, 5). Thrombocytosis was also associated with classification into Global Initiative for Chronic Obstructive Lung Disease (GOLD) group D (aOR 1.7 95% CI: 1.2-2.4). Conclusions: Thrombocytosis was associated with higher likelihood of prior exacerbation and worse symptoms. Platelet count, a commonly measured clinical assay, may be a biomarker for moderate-severe COPD symptoms, guide disease classification and intensity of treatment. Future longitudinal studies investigating the role of platelets in COPD progression may be warranted. Trial registration: ClinicalTrials.gov: NCT01969344(SPIROMICS) and NCT00608764(COPDGene)
Thyroid Disorders
The thyroid disorders are one of the most common and exciting areas of endocrinology. Hypothyroidism, multinodular goiter, hyperthyroidism and thyroid cancer are only few of the several implications that the thyroid disorders have in health. In fact, thyroid hormones regulate not only metabolism process, but also many other molecular and physiological systems. From this point of view, hyperthyroidism complications are a good example of the significance of thyroid hormone actions. This book aims to provide a general view of thyroid disorders, and a deeper explanation of hyperthyroidism and its complications and impact in health
Thrombocytosis: an important marker of cancer in primary care
Thrombocytosis (raised platelet count) has recently been identified as a prediagnostic
risk marker of cancer; however, the association has not been fully
investigated. This thesis aimed to explore the relationship between thrombocytosis
and a future diagnosis of cancer through three complementary
pieces of research.
Firstly, a systematic review was carried out which aimed to identify studies
that had investigated thrombocytosis as a diagnostic marker of cancer. Four
case-control studies were identified that had found thrombocytosis to be a
significant predictor of lung, oesophago-gastric, uterine, and renal cancer.
A further four studies found that thrombocytosis did not predict pancreatic,
breast, ovarian, or colorectal cancer. One further study had collected, but
not analysed, platelet count data. Data from all nine studies were included
in a meta-analysis. The findings of the review suggest that thrombocytosis
is a marker of some, but not all, types of cancer.
The second study used data from the Clinical Practice Research Datalink
(CPRD) and the English cancer registry. This cohort study examined the
relationship between thrombocytosis and cancer using two groups of patients.
The first included 40,000 patients with a raised platelet count (a
platelet count of > 400 x 109/L). The second cohort included 10,000 patients
with a normal platelet count (150 - 400 x 109/L) who were age, sex,
and practice matched to a random quarter of the first cohort. This study
found that the risk of cancer was greater in patients with thrombocytosis
compared to those with a normal platelet count. The one year cancer
incidence was 11.6% (95% CI 11.0 - 12.3) for male patients with thrombocytosis,
and 4.1% (95% CI 3.4 - 4.9) in males with a normal platelet count. In
female patients, the one year cancer incidence was 6.2% (95% CI 5.9 - 6.5)
for those with thrombocytosis and 2.2% (95% CI 1.8 - 2.6) for those with
a normal platelet count. Lung and colorectal cancer were more likely to be
diagnosed in patients with thrombocytosis than in patients with a normal
platelet count, and breast and prostate cancer less likely. In patients with
a sustained increase in platelet count over six months, the risk of cancer increased
to 18.1% in males (95% CI 15.9 - 20.5) and 10.1% in females (95%
CI 9.0 - 11.3). Around a third of patients with lung or colorectal cancer
and thrombocytosis had no other symptoms prior to diagnosis that would
have prompted investigation for cancer as per current NICE guidance.
The third study compared cancer recording in the CPRD and in the English
cancer registry. The aim of this study was to examine the validity of cancer
recording in the CPRD using cancer registry recording as the gold standard,
and to estimate predictors of concordance between the two data sources. A
sensitivity analysis repeated the primary analysis from the second study
to estimate the effect of including unverified CPRD cancer diagnoses. The
CPRD identified 5,924 of 7,785 cancers recorded in the cancer registry (sensitivity
76.1%, 95% CI 75.1 - 77.0). 36,255 patients with no record of cancer
in the CPRD also had no cancer record in the cancer registry (specificity
97.0%, 95% CI 96.1 - 97.2). 5,924 of 7,028 CPRD cancer diagnoses were
confirmed by the cancer registry data; the positive predictive value (PPV)
of a CPRD recorded diagnosis was 84.3% (95% CI 83.4 - 85.1). Male cancers,
those in younger patients, and those recorded from 2005 onwards were
more likely to be recorded in both sources. In a sensitivity analysis, the
exclusion of cancer diagnoses that were only recorded in the CPRD did not
significantly alter findings from the cohort study described above.
The findings from this thesis show that thrombocytosis is an important
predictor of undiagnosed cancer in adults aged 40 years and over. Patients
with thrombocytosis are more likely to be diagnosed with lung and colorectal
cancer than other types. These results suggest that cancer should be
considered as an underlying diagnosis in patients with unexpectedly raised
platelets, even if cancer was not suspected at the time that the blood test
was ordered. For at least a third of patients with thrombocytosis and cancer,
there will be no other clinical features of malignancy; for this proportion,
thrombocytosis has great potential to expedite diagnosis and improved survival
Stepping away from pharmaceutical therapies: Exercise and supplementation with fermented red clover extract as alternative strategies to promote vascular health in postmenopausal women
Cardiovascular disease is the leading cause of death worldwide. Both aging and menopause, associated with the cessation of endogenous estrogen production, are key factors that contribute to the development of cardiovascular disease in women. Over the last few decades, an interest in alternatives to pharmaceutical interventions for promoting and/or rescuing cardiovascular health in postmenopausal women has emerged, where both exercise and phytoestrogen supplementation have been deemed effective candidates. However, due to the paucity of intervention studies in postmenopausal women, knowledge gaps remain in these strategies that need to be elucidated in the context of vascular health. This dissertation aims to answer three main questions that will refine the scientific community’s understanding of alternative interventions for vascular health in postmenopausal women: (1) Can exercise training work synergistically with in-vitro dual anti-platelet therapy to improve platelet function, as determined by basal platelet reactivity and prostacyclin sensitivity (Chapter 4)? (2) Does the timing of the initiation of exercise training after menopause affect the degree of vascular adaptations and thrombotic risk profile (Chapters 5 and 6)? (3) Can short-term supplementation with the novel phytoestrogen fermented red clover extract improve markers of vascular inflammation (Chapter 7)?
Together, the findings from this dissertation highlight that exercise and fermented red clover extract are effective alternative strategies to improving vascular health in postmenopausal women. Specifically, exercise training improves platelet function and sensitivity and can work synergistically with in-vitro dual anti-platelet therapy (Chapter 4). In addition, short-term supplementation with fermented red clover extract improves the vascular inflammatory profile in recently postmenopausal women (Chapter 7). However, the timing of exercise training after menopause may influence the magnitude of thrombogenic adaptations, as recently postmenopausal women experience more robust thrombogenic benefits than women who are a greater number of years postmenopausal (i.e., late postmenopausal women) (Chapter 5 and 6)
The Latest Clinical Advances in Thrombocytopenia
Platelets are critical elements in the blood stream, supporting hemostasis (defense against bleeding), as well as performing even more complex tasks within networks of biological (immunity) and pathophysiological processes, such as cancer and ischemia/reperfusion injury. Changes in the number (and function) of platelets may have a substantial impact on any of these processes. The “simple” finding of a reduced platelet count (thrombocytopenia) has a history (origin) and a consequence (e.g., bleeding). This book brings together international experts to provide an up-to-date overview of the impact of thrombocytopenia from a clinical perspective
Investigations into the molecular pathogenesis of essential thrombocythaemia
In order to explore the phenotypic heterogeneity of the myeloproliferative neoplasm essential
thrombocythaemia (ET), the role of the JAK2 mutation V617F in the pathogenesis of the
disease was investigated, in particular its relationship to myeloid clonality. The clinical,
haematological and molecular characteristics of 133 ET patients were studied. JAK2 V617F was
detected in 55 (41%) patients; a clonal X-chromosome inactivation pattern (XCIP) was found in
24 (39%) of the 62 evaluable female patients. There was no association between JAK2
mutational status and XCIP status or thrombotic risk, but higher JAK2 V617F mutant levels
were noted in patients who had a thrombosis. A trend towards a higher thrombotic rate was
observed in patients whose XCIP was clonal. In 10 untreated JAK2 V617F-positive ET patients,
JAK2 WT thrombopoiesis was not suppressed despite the presence of a thrombocytosis,
suggesting that the regulation of JAK2 WT thrombopoiesis was abnormal. Eleven patients were
screened for the presence of more than one JAK2 V617F-positive population using an exonic
SNP located near the mutation. In ten (91%) of these the mutation appeared to have been
independently acquired on at least two occasions. Furthermore, XCIP analysis of JAK2 V617Fpositive
erythroid colonies from six ET patients revealed that in one patient the V617F-positive
populations were not derived from a single clonal population. An association between the
reported JAK2 haplotype (known as ‘46/1’) and JAK2 V617F-positive ET patients was observed
in the cohort studied. Methylation studies indicated that this haplotype introduced additional
methylated sites near to the mutation locus, which may potentially affect conformation of the
DNA and mutability of the JAK2 locus. Together, the studies reported in this thesis suggest that
JAK2 V617F is not the initiating event at least in some cases of ET, and that its presence does
not invariably indicate the presence of a monoclonal disorder
Hematology
Hematology encompasses the physiology and pathology of blood and of the blood-forming organs. In common with other areas of medicine, the pace of change in hematology has been breathtaking over recent years. There are now many treatment options available to the modern hematologist and, happily, a greatly improved outlook for the vast majority of patients with blood disorders and malignancies. Improvements in the clinic reflect, and in many respects are driven by, advances in our scientific understanding of hematological processes under both normal and disease conditions. Hematology - Science and Practice consists of a selection of essays which aim to inform both specialist and non-specialist readers about some of the latest advances in hematology, in both laboratory and clinic