Determinants of platelet count in humans.
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ABSTRACT:
SUBMITTER: Daly ME
PROVIDER: S-EPMC3012758 | biostudies-literature | 2011 Jan
REPOSITORIES: biostudies-literature
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Project description:The last decade has witnessed an explosion in the depth, variety, and amount of human genetic data that can be generated. This revolution in technical and analytical capacities has enabled the genetic investigation of human traits and disease in thousands to now millions of participants. Investigators have taken advantage of these advancements to gain insight into platelet biology and the platelet's role in human disease. To do so, large human genetics studies have examined the association of genetic variation with two quantitative traits measured in many population and patient based cohorts: platelet count (PLT) and mean platelet volume (MPV). This article will review the many human genetic strategies-ranging from genome-wide association study (GWAS), Exomechip, whole exome sequencing (WES), to whole genome sequencing (WGS)-employed to identify genes and variants that contribute to platelet traits. Additionally, we will discuss how these investigations have examined and interpreted the functional implications of these newly identified genetic factors and whether they also impart risk to human disease. The depth and size of genetic, phenotypic, and other -omic data are primed to continue their growth in the coming years and provide unprecedented opportunities to gain critical insights into platelet biology and how platelets contribute to disease.
| S-EPMC6214346 | biostudies-literature
Project description:Purpose of the reviewThis review highlights recent advancements in understanding the regulation of platelet numbers, focusing on mechanisms by which carbohydrates (glycans) link platelet removal with platelet production in the bone marrow in health and disease.Recent findingsThis review is focused on the role of carbohydrates, specifically sialic acid moieties, as a central mediator of platelet clearance. We discuss recently identified novel mechanisms of carbohydrate-mediated platelet removal and carbohydrate-binding receptors that mediate platelet removal.SummaryThe platelet production rate by megakaryocytes and removal kinetics controls the circulating platelet count. Alterations in either process can lead to thrombocytopenia (low platelet count) or thrombocytosis (high platelet count) are associated with the risk of bleeding or overt thrombus formation and serious complications. Thus, regulation of a steady-state platelet count is vital in preventing adverse events. There are few mechanisms delineated that shed light on carbohydrates' role in the complex and massive platelet removal process. This review focuses on carbohydrate-related mechanisms that contribute to the control of platelet numbers.
| S-EPMC8641398 | biostudies-literature
Project description:Thrombocytosis is associated with cancer progression and death for many cancer types. It is unclear if platelet count is also associated with cancer survival. We conducted a cohort study of 112,231 adults in Ontario with a diagnosis of cancer between January 2007 and December 2016. We included patients who had a complete blood count (CBC) completed in the 30 days prior to their cancer diagnosis. Subjects were assigned to one of three categories according to platelet count: low (≤25th percentile), medium (>25 to <75th percentile), and high (≥75th percentile). Study subjects were followed from the date of their cancer diagnosis for cancer-specific death. Of the 112,231 eligible cancer patients in the cohort study, 40,329 (35.9%) died from their cancer in the follow-up period. Relative to those with a medium platelet count, the rate of cancer-specific death was higher among individuals with a high platelet count (HR 1.52; 95%CI 1.48-1.55) and was lower among individuals with a low platelet count (HR 0.91; 95%CI 0.88-0.93). A high platelet count was associated with poor survival for many cancer types. Platelet count could potentially be used as a risk stratification measure for cancer patients.
| S-EPMC8833779 | biostudies-literature
Project description:An elevated platelet count has been associated with an increased incidence of cancer and poor survival for many cancer types. In this study, platelet levels were captured among cancer patients in the 2 years prior to and following a cancer diagnosis. I investigated if the trends in platelet count differ between patients that died or did not die from their cancer. For many cancer types, including colon, lung, ovary, and stomach, platelet counts rose as they approached the date of diagnosis. Patients that died from their cancer within 3 years of diagnosis had a higher peak platelet count than those who survived. Following diagnosis, platelet count was elevated among patients that died from their cancer as compared to patients who survived. An elevated platelet count could potentially indicate the presence of an occult cancer or be used as a prognostic measure for cancer-specific survival.
| S-EPMC8944120 | biostudies-literature
Project description:The purpose of the study was to assess the prevalence of low platelet count among the healthy population of upper Assam, India. The impact of socio-demographic features was moreover pointed to evaluate. Additionally, Mean platelet volume (MPV) and Interleukin-6 gene polymorphism (-174 G > C) were also determined to speculate their effect on the basal platelet count. For determination of hematological indices, CBC was done and genetic polymorphism was identified by ARMS-PCR technique. Out of 510 study subjects, 25.3% (n = 129) had low platelet count, and females were recorded with significantly higher mean platelet count as compared to their male counterpart (p < 0.001). A progressive decline in platelet count was observed with ageing and more significantly noticed in females across the various age groups (p < 0.001). The mean MPV was significantly higher in low platelet count group as compared to the normal group (p < 0.001). Both platelet count and MPV differed significantly among the individuals with varied ethnicity. An inverse correlation between platelet count and its volume was reported, and such observation was continued to persist in every age-group under the study. However, no significant differences were observed for other hematological indices between the studied groups except for platelet indices and RBC count. Moreover, the peripheral blood smear examined for cellular morphology and in vitro platelet clumping did not report any significant aberrancy. No significant penetrance of the risk allele was revealed in the studied groups. However, ARMS-PCR confirmed 6% (n = 8/129) of the low platelet count subjects with heterozygous for G allele. This happens to be the first description of low platelet count among the healthy population of upper Assam, where age, gender, ethnicity, and MPV are significantly associated with platelet count variation. Heterozygosity of the risk allele does not contribute to the low platelet count condition.
| S-EPMC6438998 | biostudies-literature
Project description:The advanced platelet parameters Immature Platelet Fraction and Immature Platelet Fraction Count have been implemented in clinical practice as measures of thrombopoietic activity, mainly in hematologic disorders that cause thrombocytopenia. The purpose of this observational study was to examine thrombopoiesis as reflected by these 2 new CBC parameters in patients infected with dengue. The study was conducted in infectious disease referral hospital in Metro Manila, the Philippines. We enrolled hospitalized patients at admission who were diagnosed with acute dengue or community acquired bacterial infection (CABI). Immature Platelet Fraction (IPF) and Immature Platelet Fraction Count were evaluated at admission and during hospitalization. A total of 606 patients were enrolled from May 1, 2017 to June 1, 2018. The participants consisted of 152 patients with dengue infection, 180 confirmed CABI, and 274 suspected CABI patients. At admission, the percent IPF (IPF%) of the patients with dengue was significantly higher than that of the confirmed CABI patients (median 3.7% versus 1.9%; p <0.001). In a time course evaluation, there was no significant difference of IPF% between the patients with dengue infection and the confirmed CABI patients in the febrile phase (median 1.9% versus 2.4%; p = 0.488), however, the IPF% of the patients with dengue infection increased to be significantly higher than that of the confirmed CABI patients in the critical phase (median 5.2% versus 2.2%; p <0.001). Our study elucidated the unique characteristics and time-course trends of IPF percent and number (IPF#) in the patients with dengue infection. IPF% and IPF# are potentially valuable parameters in dengue and further investigation is required for the optimal use in clinical practice.
| S-EPMC8559939 | biostudies-literature
Project description:To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART.SMART patients from sites that determined platelets routinely.Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2.Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/?l (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/?l) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels.Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.
| S-EPMC4024440 | biostudies-literature
Project description: Not available
| S-EPMC6513131 | biostudies-literature
Project description:Immune thrombocytopenia (ITP) is a common platelet disorder in pediatric patients. Pediatric and adult ITP have been associated with sialic acid alterations, but the pathophysiology of ITP remains elusive, and ITP is often a diagnosis of exclusion. Our analysis of pediatric ITP plasma samples showed increased anti-Thomsen-Friedenreich antigen (TF-antigen) antibody representation, suggesting increased exposure of the typically sialylated and cryptic TF-antigen in these patients. The O-glycan sialyltransferase St3gal1 add sialic acid specifically on the TF-antigen. To understand if TF-antigen exposure associates with thrombocytopenia, we generated a mouse model with targeted deletion of St3gal1 in megakaryocytes (MK) (St3gal1MK-/-). TF-antigen exposure was restricted to MKs and resulted in thrombocytopenia. Deletion of Jak3 in St3gal1MK-/- mice normalized platelet counts implicating involvement of immune cells. Interferon-producing Siglec H-positive bone marrow (BM) immune cells engaged with O-glycan sialic acid moieties to regulate type I interferon (IFN-I) secretion and platelet release (thrombopoiesis), as evidenced by partially normalized platelet count following and inhibition of interferon and Siglec H receptors. Single cell RNAseq determined that TF-antigen exposure by MKs primed St3gal1MK-/- BM immune cells to release IFN-I. Single cell RNAseq further revealed a new population of immune cells with a plasmacytoid dendritic cell (pDC)-like signature and concomitant upregulation of immunoglobulin re-arrangement gene transcripts Igkc and Ighm, suggesting additional immune regulatory mechanisms. Thus, aberrant TF-antigen moieties, often found in pathological conditions, regulate immune cells and thrombopoiesis in the BM, leading to reduced platelet count.
2021-06-29 | GSE179067 | GEO
Project description:OBJECTIVE:Ascending thoracic aortic aneurysm (ATAA), seen in adults, is an important cause of morbidity and mortality. In this study, we aimed to evaluate the levels of mean platelet volume (MPV), mean platelet volume-to-platelet count ratio (MPVPCR), mean platelet volume-to-lymphocyte ratio (MPVLR), and red cell distribution width platelet count ratio (RDWPCR) in patients with thoracic aortic aneurysm. METHODS:105 patients admitted to the emergency department were diagnosed with thoracic aortic aneurysm between January and December 2014, and 100 healthy individuals were involved in this retrospective study. MPV, MPVLR, MPVPCR and RDWPCRs were calculated at the time of admission. RESULTS:Platelet and lymphocyte levels were found to be significantly lower in the patient group when compared to the healthy group (P<0.001, P<0.001, respectively), while MPV, MPVPCR, MPVLR and RDWPCR were found to be significantly higher (P<0.001, P<0.001, P<0.001, and P=0.013, respectively). In the patient group, the high-sensitivity C-reactive protein was significantly higher (P<0.001), and the neutrophil (P=0.062) was also higher. In ROC analysis, MPVPCR had the highest sensitivity (80%) and RDWPCR had the highest specificity (72%). CONCLUSION:The results for MPV, MPVPCR, MPVLR and RDWPCR can be evaluated as useful parameters in the emergency clinical approach in the evaluation of inflammatory activity in ATAA patients. More extensive studies are required to address the role of these parameters in determining the severity of the disease.
| S-EPMC7199975 | biostudies-literature