Variation In Platelet Count Research Articles

Prevalence of Low Platelet Count and Identification of Associating Determinants and Genetic Polymorphism in Healthy Individuals of Upper Assam, India.

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.

Early platelet variation during concomitant chemo-radiotherapy predicts adjuvant temozolomide-induced thrombocytopenia in newly diagnosed glioblastoma patients.

Temozolomide (TMZ) is known to induce thrombocytopenia but no early predictive test has yet been clearly established. The aim of the study was to retrospectively identify and validate a threshold of early platelet variation predicting TMZ-induced thrombocytopenia during the TMZ phase in patients treated according to the Stupp protocol for glioblastoma. A training set was used to analyze variations in platelet count occurring from the first week (W1) to week 6 (W6) during radiotherapy. Our aim was to identify the most relevant platelet decrease associated with TMZ-induced thrombocytopenia ≤ 100G/L at day 28 during the TMZ phase. The performance of the threshold was confirmed in an independent validation set. Overall, 147 patients were included, 85 and 62 in the training and validation sets, respectively. Twenty-seven patients (18%) experienced at least one TMZ-induced thrombocytopenia in the TMZ phase. A platelet decrease at W6 ≥ 35% (∆W6 ≥ 35%) was identified as the best predictive variation with an AUC of 0.83, a sensitivity of 65%, and a specificity of 96%. In the validation set, ∆W6 ≥ 35% platelet variation was identified as an independent marker of TMZ-induced thrombocytopenia during the TMZ phase (OR 15.23 (95% CI 3.5-107.5)) corresponding to sensitivity of 77% (66-87%), specificity of 73% (62-84%), a positive predictive value of 42% (29-54%), and a negative predictive value of 92% (86-99%). Platelet decrease at W6 ≥ 35% during the RT-TMZ phase is an early and simple predictive marker of clinically relevant TMZ-induced thrombocytopenia during TMZ maintenance.

Correlation of platelet count and platelet indices with neonatal sepsis-diagnostic and prognostic indicator

Introduction: To evaluate variations in platelet count and platelet indices- mean platelet volume (MPV) and platelet distribution width (PDW) in neonatal sepsis. Methodology: This study was conducted over a period of one year in Neonatal Intensive Care Unit of Mata Chanan Devi Hospital, New Delhi. Neonates with confirmed as well as probable sepsis were included in the study. Platelet count, MPV and PDW were monitored three times: at diagnosis (1st day), 3rd day and 7th day of sepsis. Results: Among 100 cases, culture proven sepsis was present in17 neonates. Fungal sepsis occurred in 2 cases (11.76%), 7 neonates (41.18%) had gram positive sepsis and 8 neonates (47.06%) had gram negative sepsis. Thrombocytopenia was present in 38% and thrombocytosis in 6% cases. Mild thrombocytopenia was noted in 55.26%, moderate thrombocytopenia in 31.58% and severe thrombocytopenia in 13.16% babies. Culture positive neonates had high prevalence of thrombocytopenia. High mortality was found in moderate to severe thrombocytopenic neonates, and these babies also had high MPV and high PDW. Conclusions: Thrombocytopenia was more common than thrombocytosis in neonatal sepsis. Prevalence of thrombocytopenia was significantly high in culture proven sepsis (64.7%). There was statistically significant difference in mean platelet count on day 1, day 3 and day 7 of sepsis among culture positive and culture negative neonatal sepsis. Neonates with culture proven sepsis had high MPV on day 7 and high PDW on day 1 of sepsis. There was high MPV and high PDW in neonates who developed thrombocytopenia and also in expired babies. Platelet count and platelet indices can be used as early diagnostic and prognostic biomarkers for neonatal sepsis.

Variations in Platelet Count and Total Protein in Relation to Differences in Sex, Age, Breed and Reproductive Status of Goats during the Cold-Dry Season (Harmattan)

Variations in Platelet Count and Total Protein in Relation to Differences in Sex, Age, Breed and Reproductive Status of Goats during the Cold-Dry Season (Harmattan)

Interest in Initiating Corticosteroids By Intravenous Methylprednisolone at Standard Dose in Newly Diagnosed Immune Thrombocytopenia Adults: Results of the Prospective Carmen Registry

Introduction. In France as in many other countries, first-line treatment of adult immune thrombocytopenia (ITP) is based on conventional dose (1 mg/kg/d) oral steroids (CDOS) during 3 weeks. Intravenous polyvalent immunoglobulin (IVIg) is added in case of severe bleeding. However, conventional dose (1 mg/kg/d) intravenous methylprednisolone (CDMP) is often used as a first-line treatment during a few days before continuation with oral prednisone. Indeed, CDMP may induce earlier response in comparison with CDOS due to the absence of intestinal absorption and of hepatic metabolism to be converted in the active substance. No study has assessed the benefits and the safety of this strategy in comparison with CDOS. This was the aim of this study.Methods. This study was conducted within the CARMEN registry. It is the cohort of all newly diagnosed ITP adults (≥ 18 years) recorded in the Midi-Pyrénées region, South of France, from June 2013 (still ongoing). For the present study, we selected all ITP adults included in the CARMEN registry between 05/01/2013 and 12/31/2015 with platelet count <30 x 109/L and treated with corticosteroids. All patients were hospitalized at treatment initiation. We compared two groups: the patients treated by CDOS since ITP diagnosis (CDOS group) and those treated primarily by CDMP followed by CDOS (CDMP group). The primary outcome was the time to response, defined as the time between treatment initiation and response (no bleeding and platelet count >30 x 109/L twice 7 days apart). Secondary outcomes were: the time to complete response, defined as the time between treatment initiation and complete response (no bleeding and platelet count >100 x 109/L twice 7 days apart); the rates of response and of complete response; and the occurrence of adverse drug reactions (ADRs) due to corticosteroids, analyzed by a pharmacologist and an internal medicine physician using the WHO causality scale. The primary outcome and the time to complete response were assessed using Kaplan-Meier curves. The index date was the date of start of treatment. Follow-up was censored in case of occurrence of the outcome, date of start of second-line treatment, death or date of last follow-up, whichever occurred first. All analyzes were adjusted using a propensity score (PS) assessing the probability of being exposed to CDMP vs. CDOS as well as for concurrent IVIg use. The PS included the following variables: age, gender, comorbidity Charlson score, bleeding score, platelet count before treatment and secondary vs. primary ITP. Log-rank tests were used to compare the 2 groups. Hazard ratios (HRs) were calculated using Cox models.Results. The study included 87 patients (24 in the CDMP group and 63 in the CDOS group). Mean age was 67 years (± 22) and 48% were females. ITP was primary in 84% of patients. Mean platelet count was 9.7 x 109/L (± 8.2). Thirty-four patients were also exposed to IVIg. CDMP was prescribed for 3 days in median (range: 1-10). Mean follow-up was 9.4 months (± 8.5). The overall response and complete response rates were 88.5% and 67%, respectively. The median time to response was 3 days in the CDMP group and 4 days in the CDOS group. It was 6.5 and 17 days for complete response, respectively. Response and complete response occurred earlier in the CDMP group (Figure 1A and 1B). However, only a statistical trend was observed for the time to response (adjusted HR: 1.35, 95% confidence interval - CI: 0.76 - 2.41, p<0.3). The adjusted HR for complete response was 2.29 (95% CI: 1.20 - 4.36, p<0.02). Response rates were 87.5% in the CDMP group and 89.0% in the CDOS group (p=1). Complete response rates were 71.0% and 65.0%, respectively (p=0.6). ADRs occurred in 29 (33.3%) patients who experienced 37 corticosteroid-related ADRs. These were mainly infections and diabetes mellitus. There was no difference between the 2 groups.Conclusions. CDMP resulted in an earlier response and complete response than CDOS. Only a trend was observed for the time to response probably due to lack of power to detect smaller variations in platelet counts. In hospitalized patients at ITP onset, initiating CDMP may reduce hospital stay duration. [Display omitted] DisclosuresBeyne-Rauzy:Celgene, Novartis: Honoraria.

Thrombocytopenia after sutureless aortic valve implantation: Comparison between Intuity and Perceval bioprostheses

Thrombocytopenia after sutureless aortic valve implantation: Comparison between Intuity and Perceval bioprostheses

Variation in platelet count with gestational age, weight and sex in hospitalized newborns

Introduction: Platelet count &amp; CRP are diagnostic markers of neonatal sepsis. Though the platelet count remains the same throughout the neonatal period, variations in platelet count have been noted based on gestational age, weight &amp; sex of neonates. Beside other hematological findings, changes in platelet count induced by neonatal sepsis have been the focus of many studies. Objective: To analyze the variation in platelet count with gestational age, weight and sex in hospitalized newborns. Methods: This is a retrospective case analysis of 533 neonates between January-2012 to December-2014. The parameters examined were Baseline Platelet Count, Change In Platelet Count, (Baseline Platelet Count- Change In Platelet Count)/ Baseline Platelet Count, Platelet Nadir, Incidence, Duration &amp; Severity of Thrombocytopenia. Statistical Analysis: All data were collected in validated preformatted proforma sheet &amp; analysed using appropriate statistical methods. Results: 533 babies were studied. About 21.2% had Culture negative sepsis, 9.75% had culture positive sepsis &amp; 69.04% had no sepsis. No difference in any platelet parameter was noted between female &amp; male babies. The prevalence of early onset sepsis in our study was 17.44% &amp; late onset sepsis was 13.50%. Significant variations of all platelet indices were noted among lower gestational age babies. Significant variations in the Incidence, Prevalence &amp; duration of thrombocytopenia were noted depending on the weight of the baby. Conclusion: The baseline platelet count of the neonates remains uniform irrespective of sex, weight or gestational age. There are quantitative differences in the platelet response based on weight and gestational age

Circadian variation of growth factor levels in platelet-rich plasma.

The influence of circadian rhythms has recently been considered in advanced studies of chronopharmacology and chronotherapeutics. Although emerging studies have reported the usefulness of platelet-rich plasma (PRP), no reports have described the diurnal variations in PRP growth factor levels. In the present study, we hypothesized that growth factor levels in PRP show a significant diurnal variation. Controlled laboratory study. Institutional. Ten adult male volunteers (mean age, 30.0 ± 2.6 years; range, 26-34 years). Each subject donated a 20-mL sample of fasting blood, 4 times per day (7 AM, 11 AM, 3 PM, and 7 PM). Each blood sample was processed to produce PRP. Complete blood counts of peripheral blood (PB) and PRP, as well as quantitative determination of PRP growth factor levels (platelet-derived growth factor and transforming growth factor) were performed. Statistical analyses were conducted using a one-way repeated measures analysis of variance. No significant differences were observed in platelet, white blood cell, and red blood cell counts in the PB or in the PRP samples throughout the course of the day. In addition, there were no significant differences in PRP growth factor levels at the various time points. Significant diurnal variations in platelet counts and growth factor levels were not observed in PRP. Therefore, adjustments for diurnal variation in chronotherapy may not be important when PRP is used in clinical practice.

Decline in platelet count as a prognostic marker in critically ill children

Objectives: To study the variation in platelet count in critically ill children and correlate its association with their outcomes Methods: This was a prospective cross-sectional analysis of 150 critically ill children admitted in PICU of tertiary care hospital over period of 1 year. Laboratory data was collected with daily platelet counts from day of admission till death or discharge whichever was earlier in all patients. The study population was grouped as thrombocytopenic (platelet count < 150 χ 10 /L) and nonthrombocytopenic. They were compared with each other with respect to laboratory parameters and risk factors. Survivor and non survivors were compared with variation in platelet count. Decline in platelet count was correlated with mortality. Chi-square test, median test, ROC curve and forward stepwise binary logistic regression was used for statistical analysis. Results: Forty eight (32%) children had thrombocytopenia. They had significantly higher mortality [14(29.16%) vs 14(1372%)] and bleeding tendency [13(28.08%) vs 4(3.92%) than non- thrombocytopenic children. Admission thrombocytopenia was not found to be risk factor for mortality. Though survivors and non-survivors had decline in platelet count in first four days, non-survivors had significantly higher drop. Platelet counts decline >30% at 72 hours was independent risk factor (odds ratio 4.126) for mortality with high sensitivity(91.7%) and specificity (84.4%) with area under ROC curve of 0.898 which was associated with PRISMII. Conclusion: Decline in platelet count can be used as prognostic marker of poor outcome in critically ill children.

Mean platelet volume and platelet counts in type 2 diabetes: mellitus on treatment and non-diabetic mellitus controls in Lagos, Nigeria.

IntroductionThe Mean platelet volume and platelet counts are indicators of thrombotic potentials, and risk factors for microvascular complications in diabetics. This study aimed to establish variations in platelet counts and mean platelet volume in type 2 diabetic patients on treatment and non-diabetic controls.MethodsThis was an unmatched case-control study involving 200 participants consisting of 100 diabetics and 100 non-diabetic controls. Four and half milliliters of blood was collected from diabetics and non diabetic controls into EDTA anticoagulant tubes. Full blood count was performed using the Sysmex KN-21N, (manufactured by Sysmex corporation Kobe, Japan) a three- part auto analyzer able to run 19 parameters per sample including platelet counts and mean platelet volume.ResultsThe mean fasting blood sugar for the diabetics was 147.85±72.54 mg/dl and the controls 95.20±30.10 mg/dl. The mean platelet count for the diabetics was 235.29±76.81*109/L and controls, 211.32±66.44*109/L. The mean platelet volume, for the diabetics was 8.69±0.67 fl and the controls, 8.91±0.80 fl. There was a statistically significant difference in platelet counts of diabetics and healthy controls p =0.038 while none existed between the mean platelet volume in diabetics and healthy controls p = 0.593.ConclusionThis study revealed a higher mean platelet count for diabetics on treatment than for non diabetic controls while mean platelet volume was lower in cases than controls. However, both parameters in diabetics on treatment were within the normal reference range for healthy individuals.

Age- And Sex-Related Variations in Platelet Count in Italy: A Proposal of Reference Ranges Based on 40987 Subjects' Data

Background and ObjectivesAlthough several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150–400×109 platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count.MethodsWe analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles.ResultsPlatelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×109/L in children (176–452), adult men (141–362), adult women (156–405), old men (122–350) and, old women (140–379). Moreover, we calculated an “extended” reference interval that takes into account the differences in platelet count observed in different geographic areas.ConclusionsThe age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy.

Plasma VEGF levels may not accurately reflect the truth all the time

To the editor, We read with great interest the study by She-Juan An et al., which showed that posttreatment plasma VEGF levels associated with the overall survival of patients with advanced non-small-cell lung cancer treated with bevacizumab plus chemotherapy. In this study, before and 6 weeks after treatment, vascular endothelial growth factor (VEGF) levels measured. Also, this study showed that low posttreatment VEGF levels associated with better overall survival (OS) [1]. We have some insights for this decrease in serum VEGF levels. VEGF circulating in the blood of patients with cancer may be derived from various sources, as depicted in Fig. 1. Circulating levels of VEGF are dependent on the amount released from tumor cells (Fig. 1A) and/or platelets activated at the tumor-vessel endothelium. Activated platelets release VEGF (Fig. 1B), and platelet consumption causes increased levels of thrombopoietin, which in turn stimulates megakaryopoiesis and platelet production in the bone marrow. Newly produced platelets are larger in size than those produced during steady-state thrombopoiesis, and therefore contain an elevated amount of VEGF (Fig. 1C). Finally, host immune cells as macrophages that infiltrate tumor tissues can be an additional source of VEGF (Fig. 1 D) [2]. Serum VEGF levels have also been found to correlate with platelet count in a mixed population of metastatic cancers and renal cancer, and some investigators have also stated that VEGF should be corrected for platelet counts. To correct for variation in platelet counts between patients, it has been proposed that the concentration of VEGF per platelet (pg/10) can be calculated by dividing the serum VEGF concentration (pg/ml) by the platelet count (910/ml) [3]. In the study, She-Juan An et al., mean VEGF levels decreased from 81.5 pg/ml to 50.5 pg/ml after 6 weeks of treatment (P = 0.08), with a mean reduction of 31 pg/ml in overall. The relationship of the plasma VEGF levels with OS and progression-free survival (PFS), the patients were divided in the two groups based on their median VEGF value. The OS differed significantly between the low and high posttreatment VEGF levels (25.6 months vs. 13.4 months, P = 0.0284). No other relationship was found with plasma VEGF levels. It is known that most cytotoxic chemotherapeutics decrease the platelet count. In this study, thrombocytopenia was developed in 27.3% patients treated with bevacizumab plus chemotherapy. The association between VEGF levels and thrombocytopenia was not reported. Also, it is possible that platelet counts decreased with chemotherapy, but remained within normal limits. Because platelet counts before and after therapy has not been reported, the possible contribution of platelets on the decreasing VEGF levels remains obscure. We believe that the decrease in serum VEGF levels may at least in part be due to decreased platelet counts secondary to chemotherapy, and plasma VEGF levels may not accurately reflect the truth all the time before correcting the VEGF levels for platelet counts. M. A. N. Şendur S. Aksoy (&) Ş. Yaman Z. Arik N. Y. Ozdemir N. Zengin Department of Medical Oncology, Ankara Numune Education and Research Hospital, 06100 Sihhiye, Ankara, Turkey e-mail: saksoy07@yahoo.com

Psychological Stress and Psychosomatic Treatment: Major Impact on Serious Blood Disorders?

Objective: To demonstrate evidence of possible major impacts of psychological stress and psychosomatic interventions on myeloproliferative blood disorders and develop new approaches for the unification and quantified analysis of stress and psychosomatic treatments. Methods: This 3.5- year longitudinal study was based upon the regular blood tests of a person with myelofibrosis who experienced severe and repeated work-related psychological stress and was subjected to psychosomatic treatment in the form of regular (∼4 h per day) self-hypnosis sessions. Statistical data analysis was conducted on the basis of an introduced concept of generalized stress that mathematically unifies psychological stress and psychosomatic treatment. Results: Severe stress and psychosomatic treatment were statistically shown to have a major (dominant) impact on blood platelet counts well described by an exponential dependence on cumulative levels of generalized stress. The typical relaxation time for the impacts of both stress and treatment was shown to be ∼2 months. Only ∼12% of the total variation in platelet counts could be attributed to factors other than psychological stress and psychosomatic treatment. The psychosomatic intervention resulted in a consistent reduction of high platelet counts from ∼1,400 × 10⁹ l^–1 to approximately the middle of the normal range, with other blood parameters being either approximately stable or showing indications of a strengthening immune system. Conclusions: Our findings give hope for a possible development of psychosomatic treatments of at least some blood disorders. They also indicate a highly instrumental role of platelets in the quantified analysis of stress, psychosomatic interventions, and their neuroimmunological pathways.

Effect of platelet turnover on whole blood platelet aggregation in patients with coronary artery disease

Previous studies have demonstrated considerable variation in the antiplatelet effect of aspirin. To investigate the impact of platelet turnover on the antiplatelet effect of aspirin in patients with stable coronary artery disease (CAD) and to identify determinants of platelet turnover. Platelet turnover was evaluated by measurements of immature platelets and thrombopoietin in 177 stable CAD patients on aspirin monotherapy, including 85 type 2 diabetics and 92 non-diabetics. Whole blood platelet aggregation was determined using the VerifyNow(®) Aspirin test and multiple electrode aggregometry (MEA, Multiplate(®) ) induced by arachidonic acid (AA) (1.0 mm), adenosine diphosphate (ADP) (10 μm) and collagen (1.0 μg mL(-1) ). Immature platelet levels significantly correlated with MEA (r = 0.31-0.36, P-values < 0.0001) and the platelet activation marker sP-selectin (r = 0.19, P = 0.014). Contrary to the VerifyNow(®) test, MEA significantly correlated with variations in platelet count (r = 0.45-0.68, P-values < 0.0001). Among patients with residual platelet reactivity according to AA, there were significantly more diabetics (61% vs. 41%, P = 0.027) and higher levels of sP-selectin (77.7 ± 29 vs. 70.2 ± 25 ng mL(-1) , P = 0.070) and serum thromboxane B(2) (0.81 [0.46; 1.70] vs. 0.56 [0.31; 1.12] ng mL(-1) , P = 0.034). In a multivariate regression analysis, immature platelet levels were determined by thrombopoietin levels (P < 0.001), smoking (P = 0.020) and type 2 diabetes (P = 0.042). The antiplatelet effect of aspirin was reduced in CAD patients with an increased platelet turnover. Once-daily dosing of aspirin might not suffice to adequately inhibit platelet aggregation in patients with an increased platelet turnover.

Accuracy of Platelet Counting by Automated Hematologic Analyzers in Acute Leukemia and Disseminated Intravascular Coagulation

Platelet counting in patients with acute leukemia or disseminated intravascular coagulation (DIC) may have a risk for erroneous counts owing to the presence of nonplatelet particles or platelet activation. We evaluated automated platelet counting methods using the Abbott Cell-Dyn Sapphire (Abbott Diagnostics, Santa Clara, CA), Sysmex XE-2100 (Sysmex, Kobe, Japan), ADVIA 2120 (Siemens Diagnostics, Tarrytown, NY), and Beckman Coulter LH 750 (Beckman Coulter, Miami, FL) compared with the international reference method (IRM). Automated platelet counting methods were inaccurate compared with the IRM, without evidence of interfering nonplatelet particles. It is interesting that platelet activation markers were associated with DIC severity and erroneous platelet counting, suggesting that platelet activation is a potential source of inaccuracy. Furthermore, the artifactual in vitro platelet activation induced a high degree of intermethod variation in platelet counts. The inaccuracy of automated platelet counts increased the risk for misdiagnosis of DIC. More attention needs to be given to the accuracy of platelet counts, especially in clinical conditions with florid platelet activation.

Minor diurnal and activity-induced variations in daytime peripheral blood platelet counts do not have any major impact on platelet yield by platelet apheresis

Physical activity alters systemic levels of several angioregulatory cytokines that affect microvascular endothelial cells and can be assumed to influence vascular permeability. This may alter platelet release to the bone marrow microcirculation and thereby the levels of circulating platelets. We investigated effects of physical activity on angioregulatory chemokines (CXCL8, 9, 10 and 11) and peripheral blood platelet counts before and after intensive physical activity in young adults, and also compared platelet yields obtained by platelet apheresis performed in the morning and in the afternoon in 20 healthy donors. Physical activity increased serum CXCL10 levels and platelet counts but did not alter the other chemokine concentrations. In the apheresis donors, there was only a minor increase in platelet counts during the day, and the platelet yields did not differ significantly between platelet concentrates collected early in the morning and late in the afternoon. In conclusion, minor intra-individual variations in platelet counts do not seem to have major influence on platelet yields by platelet apheresis.

Hydroxycarbamide associated platelet count oscillations in a patient with polycythaemia vera. A case report and review of the literature

We describe an unusual case of oscillating platelet counts in a patient with polycythaemia vera. Following commencement of cytoreductive hydroxycarbamide therapy, episodes of thrombocytopenia were followed regularly by thrombocytosis. Platelet counts fluctuated periodically between approximately 200 and 800 × 109/l, with a 28 day cycle duration. Frequent adjustment of the hydroxycarbamide dose was not successful in preventing the oscillations in platelet count. In contrast, maintenance of a constant dose led to a gradual damping of the cycles and thus termination of the large oscillations. The case further implicates hydroxycarbamide as a potential cause of cyclic variations in platelet counts, and demonstrates that cessation of this drug is not always necessary in order to treat this phenomenon.

Platelet counts and outcome in the pediatric intensive care unit

Objectives:Thrombocytopenia is commonly observed in critically ill patients. This study was undertaken to evaluate the variation in platelet counts and the risk factors associated with thrombocytopenia and mortality in pediatric intensive care patients. In addition, prognostic value of platelet counts for outcome in pediatric intensive care unit was studied.Study Design:Prospective, observational cohort analysis.Setting:8- bedded pediatric intensive care unit of a tertiary care teaching hospital.Patients:All consecutively admitted patients (n=138) staying in the pediatric intensive care unit (PICU) for at least 48h over a 7 months period were studied.Measurements and Main Results:Thrombocytopenia was defined as platelet counts <150.0/nL. Median 1st day Pediatric Risk of Mortality Score (PRISM) was 5 (range 0-30) and median ICU stay was 4 days (range 2-98 days). Twenty five percent patients had at least one episode of thrombocytopenia during the stay. Twenty percent of these patients had thrombocytopenia on admission and rest (80%) developed it during the PICU stay. Seventy one percent (19) of the patients developed thrombocytopenia by fourth day of admission. Patients with PICU acquired thrombocytopenia had statistically significant lower baseline, nadir and 4th day platelet counts and a significantly higher drop in platelet counts (56% vs. 6% P<0.001) as compared to non thrombocytopenic patients. PRISM score, long PICU stay, sepsis, coagulopathy, and creatinine levels were significantly associated with occurrence of thrombocytopenia. Patients with thrombocytopenia had higher probability of bleeding (34% vs. 15%, P=0.01). Higher platelet counts on admission were associated with significantly reduced risk of thrombocytopenia (P=0.00) Baseline, nadir and day-4 platelet counts, presence of thrombocytopenia on admission, sepsis, coagulopathy and a higher mean PRISM score on univariate analysis were significantly associated with mortality. Leucopenia or leucocytosis, thrombocytopenia and coagulopathy were found to significantly affect outcome. Drop in platelet counts was found to have slightly higher discriminative value for mortality prediction than PRISM on the ROC curve. The survivors had higher platelet counts throughout the PICU stay and after an initial fall in platelet counts in the PICU showed a significantly higher rise in the platelet counts in the following days than the non-survivors.Conclusions:Thrombocytopenia is common in PICU. Patients requiring cardiopulmonary resuscitation or with circulatory shock, coagulopathy, sepsis and with more severe disease have higher risk of developing thrombocytopenia. Thrombocytopenic patients have a higher risk of bleeding. Drop in platelet counts >27% and thrombocytopenia were independently related to mortality. Serial measurements of platelet counts are better predictors of pediatric intensive care outcome than one-time values. Any drop in platelet counts even without thrombocytopenia needs an urgent and extensive evaluation.

Two Candidate Genes for Low Platelet Count Identified by Genome-Wide Linkage Analysis: Glycoprotein IX and Thrombopoietin.

Although the 'normal' range of platelet count in a healthy person is quite broad (150 to 400 ×109/L), an individual's platelet count is maintained within a much narrower range, constantly balanced between thrombopoiesis and senescence. Platelet counts within the normal range have been shown to be largely determined by genetic factors with heritability estimates from twin studies ranging from 0.57 to 0.80. A genome-wide linkage analysis was carried out in a large Asian Indian kindred with β thalassemia to search for genes influencing variation in normal platelet count. Significant linkage is shown at two locations on chromosome 3q with age, sex and β thalassemia adjusted platelet counts. Linkage analysis showed one marker (D3S1309) on chromosome 3q with a lod score of 3.26 and another marker (D3S1282) approximately 30 cM centromeric, with a lod score of 2.52. Multipoint linkage analysis across 90 cM of chromosome 3q identified two peaks across the region with maximum multipoint lod scores of 3.52 and 4.11 under markers D3S1309 and D3S1282, respectively. Two strong candidate genes for platelet variation were identified in the linked region; thrombopoietin (THPO) and glycoprotein IX (GPIX). Resequencing of four individuals revealed five single nucleotide polymorphisms (SNPs) in THPO and one mutation in the transmembrane region of GPIX. Analysis of variance showed that the GPIX mutation and one THPO SNP accounted for 6% and 4% of the variation in platelet count in the kindred, respectively. The THPO SNP lies in the 3′ untranslated region (3′ UTR) of the gene and has not been previously reported.Although no function could be attributed to the THPO SNP it could potentially influence post-transcriptional control of gene expression. The G to A transition in nucleotide 653 (Ref seq NM_000174) resulted in an Ala 156 (GCC) to Thr (ACC) replacement in the GPIX protein. The GPIX mutation was recently identified in a Chinese patient with Bernard-Soulier syndrome (BSS), a rare bleeding disorder characterized by severe thrombocytopenia and giant platelets. The Chinese patient was homozygous for the mutation; however, heterozygous relatives did not show the characteristic BSS symptoms, leading the authors to conclude that the mutation acted under a recessive model of inheritance. Transient transfection studies by the same group confirmed that the mutation prevents GP Ib/IX complex insertion in the cytoplasmic membrane of platelets, and suppresses GPIbα and GPIX expression, but does not cause its intracellular degradation. One copy of the GPIX mutation was found in 300 European individuals with platelet counts within the normal clinical range.Conclusion: Although the genetic determinants of many thrombocythemias and congenital thrombocytopenias have been identified, very little is known about the genetic determinants of normal platelet count variation. The results suggest that two QTLs on chromosome 3q influence platelet count variation in the Asian Indian kindred, with the GPIX transmembrane mutation and the 3′ UTR SNP in THPO, being strong candidates.

Two candidate genes for low platelet count identified in an Asian Indian kindred by genome-wide linkage analysis: glycoprotein IX and thrombopoietin

A genome-wide linkage analysis of platelet count was carried out in a large Asian Indian kindred. Linkage analysis showed one marker (D3S1309) on chromosome 3q with a lod score of 3.26 and another (D3S1282) approximately 30 cM centromeric, with a lod score of 2.52. Multipoint analysis of chromosome 3q identified two peaks with maximum multipoint lod scores of 3.52 and 4.11 under markers D3S1309 and D3S1282, respectively. Two strong candidate genes for platelet variation were identified in the linked region; thrombopoietin (THPO) and glycoprotein IX (GPIX). Resequencing of four individuals revealed five single-nucleotide polymorphisms (SNPs) in THPO and one mutation in the transmembrane region of GPIX. Analysis of variance showed that the GPIX mutation and one THPO SNP accounted for 6 and 4% of the variation in platelet count, respectively. The THPO SNP lies in the 3' untranslated region of the gene and has not been previously reported. The G to A transition at nucleotide 653 resulted in an Ala 156 (GCC) to Thr (ACC) replacement in the GPIX protein. The GPIX mutation was recently identified in a Chinese patient with Bernard-Soulier syndrome (BSS), a rare recessive bleeding disorder characterized by thrombocytopenia and giant platelets. One copy of the GPIX mutation was found in 300 European individuals with platelet counts within the normal range. The results suggest that two QTLs on chromosome 3q influence platelet count variation in the Asian Indian kindred, with the GPIX transmembrane mutation and the 3' UTR SNP in THPO being strong candidates.