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Inflammatory bowel disease-like colitis in a young Turkish child with glycogen storage disease type 1b and elevated platelet count.

Inflammatory bowel disease (IBD)-like colitis is a known entity in glycogen storage disease (GSD) type 1b patients. The mean age of the reported cases with IBD-like colitis was 12 +/- 5 years, and all had absolute neutrophil count (ANC) less than 1,000 cells/microl. We report a three-year-old girl with GSD type 1b that was dignosed by mutation analysis. The patient was hospitalized with fever, diarrhea, and perioral and anal ulcers. Colonoscopy was performed and IBD-like colitis was diagnosed. The patient had elevated platelet count beyond the age of three months, but IBD-like colitis was diagnosed at three years of age. An elevated platelet count may be a warning sign for the IBD-like colitis in young patients with GSD type 1b.

Child, Preschool↗

Hepatic imaging in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count).

OBJECTIVES: Our objective was to describe the hepatic imaging findings in selected patients with HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count) and to correlate these findings with the severity of concurrent clinical and laboratory abnormalities. STUDY DESIGN: Patients with laboratory criteria for HELLP syndrome with complaints of severe right upper quadrant abdominal pain in association with either shoulder pain, neck pain, or relapsing hypotension underwent imaging of the liver. Clinical and laboratory parameters were then correlated with the hepatic imaging findings. RESULTS: Thirty-four patients were evaluated in this study. Computed tomographic scanning of the liver was used for 33 patients. Additional imaging evaluations included magnetic resonance imaging for 4 patients and ultrasonographic evaluation of the liver for 5 patients. In 15 cases (45%) the computed tomographic results were abnormal. The most frequent abnormal hepatic imaging findings were subcapsular hematoma (n = 13) and intraparenchymal hemorrhage (n = 6). There was no statistically significant correlation between the presence of an abnormal hepatic imaging finding and the severity of liver function test abnormalities. However, the severity of thrombocytopenia did correlate with hepatic imaging findings (p = 0.04). In particular, an abnormal hepatic imaging finding was noted for 10 of 13 patients (77%) with a platelet count of < or = 20 x 10(9)/L (p = 0.012). CONCLUSIONS: Abnormalities in liver function test results do not accurately reflect the presence of abnormal hepatic imaging findings in HELLP syndrome. Patients with HELLP syndrome having complaints of right upper quadrant pain and neck pain, shoulder pain, or relapsing hypotension should undergo imaging of the liver.

Adolescent↗

Correlations among age, cytokines, lymphocyte subtypes, and platelet counts in autoimmune thrombocytopenic purpura.

While autoimmune thrombocytopenic purpura is mediated by autoantibodies, accumulating evidence suggests that T helper cells and the cytokines they produce also play a key role. We determined correlations among age, serum cytokine concentrations, circulating lymphocyte, and platelet counts in adult (n=19) and children (n=29) with autoimmune thrombocytopenic purpura. Correlations between age and cytokine levels were also assessed in healthy controls (n=50). Significant positive correlations between age and serum levels of interferon-gamma, age and CD4+ lymphocytes, age and natural killer cell count were observed in these patients. Absolute lymphocyte and CD8+ cell count was significantly inversely correlated with age. In adult patients, a significant inverse correlation between platelet and absolute lymphocyte count was observed. In pediatric patients, an inverse correlation of platelet count with serum concentration of interleukin-3 was recorded. In 50 healthy volunteers there were significant positive correlations between age and interleukin-3, -4, -6, and interferon-gamma, and significantly negative correlations with interleukin-2, tumor necrosis factor-alpha, and interferon-alpha. Additional evaluations are necessary to identify the impact of age-related changes in immune function on the clinical course of autoimmune thrombocytopenic purpura.

Adolescent↗

Effects of intravenous immunoglobulin on platelet count and antiplatelet antibody disposition in a rat model of immune thrombocytopenia.

Experiments were conducted to investigate the effects of intravenous immunoglobulin (IVIG) in a rat model of immune thrombocytopenia (ITP). Rats were pretreated with 0 to 2 g/kg IVIG and then challenged with an antiplatelet antibody (7E3, 8 mg/kg). IVIG effects on 7E3-induced thrombocytopenia and on 7E3 pharmacokinetics were determined. IVIG pretreatment led to significant changes in the degree and time-course of 7E3-induced thrombocytopenia (P =.031). Nadir percent platelet counts were 121% to 279% greater in animals treated with IVIG (0.4-2 g/kg) than in animals receiving 7E3 alone. IVIG treatment also led to dose-dependent increases in 7E3 clearance (P <.001), with more than 2-fold increases in 7E3 clearance seen following the highest dose of IVIG. In vitro experiments showed that IVIG effects on platelet count are not likely due to anti-idiotypic inhibition of 7E3-platelet binding and that IVIG did not directly bind to 7E3. Consequently, IVIG-7E3 binding cannot explain the increase of 7E3 clearance following IVIG treatment. We propose that the observed increase in 7E3 clearance with IVIG therapy is due to saturation of the FcRn salvage receptor for IgG. The importance of the effect of IVIG on 7E3 clearance to the prevention of thrombocytopenia in these animals is unclear at present; nonetheless, these data provide experimental support for a new mechanism of IVIG action in ITP (ie, IVIG-mediated increases in antiplatelet antibody elimination). This model of ITP will be useful for further investigations of IVIG mechanism of action and for development of new therapies for ITP.

Animals↗

Platelet aggregation in whole blood--studies with a platelet counting technique--methodological aspects and some applications.

We describe a method for measuring platelet aggregation in whole blood by single platelet counting. The importance of a low stirring speed (100 rpm) to obtain agonist-specific aggregation is stressed. Despite this low stirring speed, the sensitivity to agonists equals that of the turbidometric technique in platelet-rich plasma. The optimal concentration of formaldehyde for fixing the aggregates, the effects of storage times and anticoagulant are studied. Applicability to the study of platelet function inhibitors or of inherited platelet function disorders is illustrated. It is concluded that this technique, used under the appropriate conditions, combines the advantage of measuring platelet aggregation in a more physiologic environment with the advantages of the turbidometric technique such as high sensitivity.

Adenosine Diphosphate↗

A prospective, randomized trial comparing the efficacy of dexamethasone and betamethasone for the treatment of antepartum HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.

OBJECTIVE: This study was undertaken to determine whether dexamethasone or betamethasone is superior for the antepartum treatment of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. STUDY DESIGN: This prospective, randomized, clinical investigation compared intravenously administered dexamethasone and intramuscularly administered betamethasone in the treatment of gravid women with HELLP syndrome. Efficacy end points included laboratory values (platelet count, lactate dehydrogenase activity, aspartate aminotransferase activity) and clinical parameters (mean arterial pressure, urinary output). RESULTS: Forty patients were enrolled in the study, 19 in the dexamethasone arm and 21 in the betamethasone arm. The adjusted time-averaged changes from baseline were significant for aspartate aminotransferase activity (dexamethasone, -20.4 +/- 9.6 U/L; betamethasone, 9.9 +/- 8.9 U/L; P =.029), mean arterial pressure (dexamethasone, -15.6 +/- 1.4 mm Hg; betamethasone, -8.1 +/- 1.4 mm Hg; P <.001), and urinary output (dexamethasone, 12.9 +/- 8.6 mL/h; betamethasone, -11.9 +/- 8.2 mL/h; P =.043). CONCLUSION: Intravenously administered dexamethasone appears to be more effective than intramuscularly administered betamethasone for the antepartum treatment of mothers with HELLP syndrome.

Adult↗

Estimation of platelet counts on feline blood smears.

Blood samples were obtained from 50 cats admitted for hematologic evaluation at the Royal (Dick) School of Veterinary Studies. Manual platelet counts were done using a hemacytometer, and the average number of platelets per oil immersion field (1,000X magnification) was determined on stained blood smears. A hemacytometer count was not obtained for one sample because of a failure in erythrocyte lysing. In nine samples, obvious platelet clumps in the blood smear prevented accurate determination of the number of platelets per oil immersion field. Hemacytometer counts on these nine samples ranged from 260-587 X 10 (3) platelets/microliter, suggesting that platelet clumps on a blood smear were usually associated with adequate platelet numbers. Simple regression analysis of hemacytometer counts and the average umber of platelets per oil immersion field for the remaining 40 samples yielded correlation coefficients (r) of 0.776 on untransformed data, and 0.892 on log10-transformed data. Each platelet per oil immersion field represented a circulating platelet count of approximately 20 X 10(3)/microliter, similar to conversion factors reported for dogs and human beings. It was concluded that estimation of platelet number on stained blood smears is a simple and quick method that appears to be reliable over a wide range of platelet counts in cats.

Journal Article↗

Mobilization of CD34+ cells in elderly patients (>/= 70 years) with multiple myeloma: influence of age, prior therapy, platelet count and mobilization regimen.

The mobilization of peripheral blood stem cells was studied in 984 multiple myeloma patients, including 106 patients aged >/= 70 years. Increasing age correlated inversely with CD34+ yield (P < 0.0001), but also with >/= 12 months of prior standard chemotherapy (P = 0.0001), < 200 x 10(9)/l platelets (P = 0.0006) premobilization and mobilization with growth factors only (P = 0.0001). After controlling for these age covariates, multivariate analysis identified </= 12 months standard therapy and platelet count >/= 200 x 10(9)/l premobilization as favourable variables (both P < 0.0001), while increasing patient age remained an unfavourable factor (P = 0.0009). With both favourable variables, 85% of elderly patients collected >/= 4 x 10(6)/kg CD34+ cells in a median of one collection. The effect of age was incremental with no age threshold showing acceleration in the decline of CD34+ yield. Chemotherapy significantly increased CD34+ yield compared with growth factors only. However, the subgroup of patients with > 12 months prior therapy and premobilization platelet count < 200 x 10(9)/l mobilized as many CD34+ cells with granulocyte colony-stimulating factor (G-CSF) alone as with chemotherapy and haematopoietic growth factors. Increasing patient age had no effect on post-transplant neutrophil recovery, but significantly delayed platelet recovery (>/= 50 x 10(9)/l) if < 2 x 10(6)/kg CD34+ cells were infused, but this effect was eliminated completely with infusion of >/= 4 x 10(6)/kg CD34+ cells. Increasing age adversely affected CD34+ yield even with limited premobilization therapy, indicating that early collection is important in elderly patients.

Adult↗

Bleeding on patients with autoimmune thrombocytopenic purpura and normal platelet count.

80% of patients with chronic autoimmune thrombocytopenic purpura (ATP) may reach normalization of platelet count after steroids or splenectomy. In some of these cases a bleeding tendency may still persist and this has been attributed to abnormalities of platelet function resulting from the effect of platelet-bound antibodies. We have studied 49 ATP patients in order to assess the frequency and the pattern of this immune thrombopathia, and the correlation with the levels of platelet associated IgG (PAIgG). Only 3 patients (6%) had prolonged bleeding time and persistence of mucocutaneous haemorrhages, whereas 36% presented an altered platelet aggregation pattern. Platelet serotonin content, platelet and plasma beta-thromboglobulin concentration, and malondialdehyde generation after thrombin stimulus were found also altered, but the findings were not clearly correlated with the concentration of PAIgG.

Adolescent↗

High-resolution particle analysis--its application to platelet counting and suggestions for further application in blood cell analysis.

The characteristics of an instrument for high-resolution particle analysis in flow are discussed. It employs a combination of hydrodynamic focusing, fluid resistors, and electronic techniques to achieve precision and ease of use heretofore unobtainable in a moderate-cost clinical instrument. Its application to whole blood platelet counting is discussed, and suggestions are made for its possible application to a wide variety of blood cell measurements.

Animals↗

Relationship of mean platelet volume to platelet count in morphologic evaluation of thrombopoiesis.

A graph of the relationship between mean platelet volume (MPV) and platelet count (TPK) was constructed out of 158 haematologically normal individuals, 19 patients with thrombocytopenia and 63 patients with thrombocytosis. Patients with thrombocytopenia and thrombocytosis whose bone marrows were found to show adequate or increased, morphologically normal, thrombopoiesis were included in the graph. The graph was found to exhibit the previously known inverse relationship between TPK and MPV extended into thrombocytopenic values and is thought to represent an intact marrow function capable of meeting the increased demands of thrombopoiesis. On the other hand, 15 patients whose bone marrows were showing evidence of hypoplastic thrombopoiesis fell outside the region representing intact marrow function. The position of an individual's values of MPV vs TPK in a coordinate system with these variables on the axes correlates well with the morphologic evaluation of thrombopoietic function and seems to be clinically useful.

Blood Platelets↗

Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy.

Adjuvant therapy for breast cancer with tamoxifen is suggested to be of benefit to both women with negative and women with positive axillary nodes, and treatment lasting several years is currently being investigated. Venous thrombophlebitis may complicate tamoxifen treatment at a rate of approximately one per 800 treatment-years. To explore the possible mechanisms of this effect, we evaluated changes in antithrombin III levels, fibrinogen levels, and platelet counts in 140 postmenopausal women with surgically resected breast cancer who were disease free and participating in a double-blind, placebo-controlled, randomized toxicity study of tamoxifen. Antithrombin III levels, elevated at baseline evaluation, decreased in tamoxifen-treated subjects at 6 months, but no subject exhibited a drop to clinically significant levels. Fibrinogen levels decreased 15% (0.4 g/L) in tamoxifen-treated subjects at 6 months. Platelet counts decreased 7% to 9% from baseline to evaluations at 3, 6, 12, 18, and 24 months in tamoxifen-treated subjects. While these changes do not explain the possible small thrombophlebitis-promoting effect of tamoxifen, the decrease in fibrinogen levels might be expected to be associated with a decreased risk of arterial thrombosis.

Antithrombin III↗

Adenovirus-mediated transfer of the HST-1 (FGF4) gene induces increased levels of platelet count in vivo.

The HST-1 (fibroblast growth factor 4, FGF4) protein is a potent mitogen for a variety of cell types of mesodermal and neuroectodermal origin, including fibroblasts, endothelial cells, and melanocytes in vitro. To identify the cells and tissue targets of HST-1 in vivo, adenovirus-mediated HST-1 gene transfer was performed. In nude mice, intraperitoneal injection of 3 x 10(9) plaque-forming units of adenoviruses carrying the HST-1 gene (Adex1HST-1L) caused an increase in the number of platelets in the peripheral blood. The number of platelets reached twice the pretreated level by 12 days after the virus injection and the increased level continued up to 20-30 days thereafter. Administration of recombinant HST-1 protein resulted in a transient increase in the platelet count. The number of megakaryocytes in the bone marrow and spleen of the animals with Adex1HST-1L was increased compared with the control animals. Other hematological changes attributed to HST-1 were not observed. Although the mechanisms involved in increased levels of platelet count by HST-1 protein remain to be elucidated, these findings also suggest that adenovirus with the HST-1 gene may be efficiently used for the treatment of thrombocytopenia in various diseases.

Adenoviridae↗

Clinical significance of platelet count at day +60 after allogeneic peripheral blood stem cell transplantation.

Thrombocytopenia (TP) is a frequent complication after allogeneic stem cell transplantation (SCT) and regarded as a poor prognostic factor, especially in patients with chronic graft-versus-host disease (GVHD), although various factors were related to the development of TP after allogeneic SCT. Sixty-three patients receiving allogeneic peripheral blood stem cell transplantation (PBSCT) were stratified according to platelet count (PC) at day +60 and analyzed in terms of overall survival (OS) and the incidence of non-relapse mortality (NRM). Ten patients (15.9%) were stratified in group 1 (PC </= 29 x 10(9)/L), 23 patients (36.5%) in group 2 (PC 30-79 x 10(9)/L), and 30 patients in group 3 (PC >/= 80 x 10(9)/L). Group 3 was associated with lower incidence of extensive chronic GVHD (p=0.013), better 3-yr OS (p=0.0030), and lower NRM rate (p<0.0001). In multivariate analyses, the PC at day +60 was identified as an independent prognostic factor (p=0.003) together with CD34+ cell dose (p<0.001), disease risk (p=0.004), and acute GVHD (p=0.033) in terms of NRM, and the PC (p=0.047) and CD34+ cell dose (p=0.026) in terms of incidence of infectious events. Measuring the platelet count at day +60 is a simple method for predicting the risk of chronic GVHD development and prognosis after allogeneic PBSCT.

Adolescent↗

Impact of oxygenator design on hemolysis, shear stress, and white blood cell and platelet counts.

OBJECTIVE: To determine whether relative pressure drop, shear stress, hemolysis, and white blood cell and platelet counts are influenced by different oxygenator designs. To compare the oxygenator results with the average shear stress over an arterial cannula. DESIGN: Prospective; patients enrolled consecutively. SETTING: University hospital. PARTICIPANTS: Three groups of 12 adults patients, scheduled for routine cardiac surgery. INTERVENTIONS: Each group was submitted to a different oxygenator design: group 1 to a high-pressure hollow-fiber membrane oxygenator (Sarns Turbo); group 2 to a medium-pressure hollow-fiber membrane oxygenator (Cobe optima); and group 3 to a flat-sheet membrane oxygenator (Cobe Duo). MEASUREMENTS AND MAIN RESULTS: Although the investigated oxygenators have important differences in pressure drop and shear stress, no statistical differences were found in hemolysis generation or blood handling among the different groups. Actually, the study shows much higher shear stress levels over an average arterial cannula than over any of the evaluated oxygenators. CONCLUSIONS: The pressure drop over an oxygenator does not correlate well with shear stress and hemolysis because the dimensions of the system (radius and length) must be included in the calculation of shear stress from pressure drop.

Adult↗

The peripheral platelet count in response to intravenous infusion of salbutamol.

Five healthy male volunteers received i.v. infusions of salbutamol, a relatively selective beta-2-receptor-stimulating agent, in doses of 0.03, 0.06, 0.09 and 0.27 microgram X kg-1 X min-1 over a period of 6 min. At the three low doses the heart rate remained essentially unchanged and no significant decrease in the platelet count occurred. However, in response to 0.27 microgram X kg-1 X min-1 of salbutamol the heart rate increased by 25% over basal value (p less than 0.01) and a significant lowering (p less than 0.005) of the platelet count was obtained. The present findings suggest that the drop in the peripheral platelet concentration in response to adrenergic beta-receptor stimulation is mediated via beta-1-receptors.

Adult↗

Pharmacokinetics and peripheral platelet counts after a single dose of recombinant human thrombopoietin in rhesus monkeys.

AIM: To study the pharmacokinetics and the change of peripheral platelet counts after a single dose of recombinant human thrombopoietin (rhTpo). METHODS: After i.v. or s.c. injections of rhTpo in 12 rhesus monkeys, rhTpo concentration in serum was determined by ELISA. Platelets were counted by automatic microcell counter. RESULTS: The terminal half-lives of rhTpo were 12-18 h. AUC following s.c. were linearly increased with dose, while Cls were 0.061, 0.08, and 0.07 L.kg-1.h-1 in s.c. 0.5, 2, and 8 micrograms.kg-1 groups, respectively. Bioavailability was 0.50 +/- 0.18 after s.c. Single dose of rhTpo was associated with an increase in platelets (55.9%-107.4%, P < 0.05) in a dose-related manner. The peak response and the sustained days of platelet increase were dose-related. The degree of platelet increase (% x time) correlated with the systemic exposure to rhTpo (C x time). CONCLUSION: rhTpo behaved as a linear pharmacokinetics in the monkey within dose range of 0.5-8 micrograms.kg-1.

Animals↗