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1.  Effect of storage on levels of nitric oxide metabolites in platelet preparations 
Transfusion  2012;53(3):637-644.
Background
Nitric oxide (NO), a potent signaling molecule, is known to inhibit platelet function in vivo. We investigated how the levels of NO and its metabolites change during routine platelet storage. We also tested whether the material of platelet storage containers affects nitrite content since many plastic materials are known to contain and release nitrite.
Study design and methods
For nitrite and nitrate measurement, leukoreduced apheresis platelets (PLT) and concurrent plasma (CP) were collected from healthy donors using the Trima Accel. Sixty mL aliquots of PLT or CP were stored in CLX or PL120 Teflon containers at 20–24°C with agitation and daily samples were processed to yield PLT pellet and supernatant. In a separate experiment, PLT was stored in PL120 Teflon to measure NO generation using electron paramagnetic resonance (EPR).
Results
Nitrite level increased markedly in both PLT supernatant and CP stored in CLX containers at a rate of 58 nM/day and 31 nM/day respectively. However, there was a decrease in nitrite level in PLT stored in PL120 Teflon containers. Nitrite was found to leach from CLX containers and this appears to compensate for nitrite consumption in these preparations. Nitrate level did not significantly change during storage.
Conclusion
Platelets stored at 20–24°C maintain measurable levels of nitrite and nitrate. Nitrite decline in non-leachable Teflon containers in contrast to increases in CLX containers which leach nitrite, suggests that it is consumed by platelets, residual leukocytes or erythrocytes. These results suggest NO-related metabolic changes occur in platelet units during storage.
doi:10.1111/j.1537-2995.2012.03777.x
PMCID: PMC3548060  PMID: 22804724
nitric oxide; nitrite; platelet storage; transfusion
2.  Comparison of Plateletpheresis on the Fenwal Amicus and Fresenius Com.Tec Cell Separators 
Summary
Background
A variety of apheresis devices are now available on the market for plateletapheresis. We compared two apheresis instruments (Fenwal Amicus and Fresenius COM.TEC) with regard to processing time, platelet (PLT) yield and efficiency, and white blood cell (WBC) content.
Material and Methods
Donors undergoing plateletpheresis were randomly separated into two groups (either the Amicus or the COM.TEC cell separator).
Results
In the pre-apheresis setting, 32 plateletpheresis procedures performed with each instrument revealed no significant differences in donors’ sex, age, weight, height and total blood volume between the two groups. However, the pre-apheresis PLT count was higher with the COM.TEC than with the Amicus (198 × 103/μl vs. 223 × 103/μl; p = 0.035). The blood volume processed to reach a target PLT yield of ≥3.3 × 1011 was higher in the COM.TEC compared to the Amicus (3,481 vs. 2,850 ml; p < 0.001). The median separation time was also significantly longer in the COM.TEC than in the Amicus (61 vs. 44 min; p < 0.001). 91 and 88% of the PLT products collected with the Amicus and the COM.TEC, respectively, had a PLT count of >3.3 × 1011 (p = 0.325). All products obtained with both instruments had WBC counts lower than 5 ↔ 106, as required. There was no statistical difference with regard to collection efficiency between the devices (55 ± 15 vs. 57 ± 15%; p = 0.477). However, the collection rate was significantly higher with the Amicus compared to the COM.TEC instrument (0.077 ± 0.012 × 1011 vs. 0.057 ± 0.008 × 1011 PLT/min; p < 0.001).
Conclusion
Both instruments collected platelets efficiently. Additionally, consistent leukoreduction was obtained with both instruments; however, compared with the COM.TEC instrument, the Amicus reached the PLT target yield more quickly.
doi:10.1159/000151351
PMCID: PMC3076329  PMID: 21512626
Plateletpheresis; Apheresis; Amicus; COM.TEC; Cell separator
3.  Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets 
Summary
Background
Soluble mediators in platelet concentrates (PCs) released from contaminating white blood cells (WBCs) and platelets (PLTs) themselves are supposed to promote allergic and non-hemolytic febrile transfusion reactions in the recipient. Pathogen reduction technologies (PRTs) prevent replication and proliferation of pathogens as well as of WBCs, and may reduce cytokine accumulation in PCs during storage and prevent adverse events after PLT transfusion. On the other hand, such treatments may also lead to increased cytokine production by stimulation of WBCs or PLTs due to the photochemical or photodynamical process itself.
Material and Methods
12 triple-dose PLT apheresis collections were leukoreduced by the process-controlled leukoreduction system of the Trima Accel machine and split into 3 units undergoing Mirasol-PRT treatment (M) or gamma irradiation (X) or remaining untreated (C). During storage for up to 7 days, PLT activation, WBC-derived Th-1/2, and inflammatory as well as PLT-derived cytokines were measured by cytometric bead array and enzymelinked immunosorbent assay, respectively.
Results
Independent of treatment, all PLT products exhibited low levels of WBC-associated cytokines near or below assay detection limits. WBC-associated cytokines were not elevated by Mirasol-PRT treatment. PLT-derived cytokines were detected at higher levels and increased significantly during storage in all units. Most likely due to higher PLT activation, M units showed significantly higher levels of PLT-derived cytokines compared to untreated and gamma-irradiated units on day 5 of storage.
Conclusion
In all PCs, PLTs themselves were the main source of cytokine release. Mirasol-PRT treatment was associated with a significantly increased PLT activation and accumulation of PLT-derived cytokines during storage, without affecting WBC-derived cytokines relative to controls.
doi:10.1159/000203359
PMCID: PMC2928824  PMID: 20823992
Pathogen reduction; Mirasol-PRT; Ccytokines; Transfusion reaction
4.  Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction 
Summary
Background
In vitro function of stored platelet (PLT) con-centrates was analyzed after applying two different techniques of pathogen reduction technology (PRT) treatment, which could increase cellular injury during processing and storage.
Methods
Nine triple-dose PLT apheresis donations were split into 27 single units designated to riboflavin-UVB (M) or psoralen-UVA (I) treatment or remained untreated (C). Throughout 8 days of storage, samples were analyzed for annexin V release, the mitochondrial transmembrane potential (Δψ) and some classical markers of PLT quality (pH, LDH release, hypotonic shock response (HSR)).
Results
PLT count and LDH release of all units maintained initial ranges. All units exhibited a decrease in pH and HSR and an increase in annexin V release and Δψ disruption. Notably, throughout the entire storage period, annexin V release re-mained lowest in M units. Throughout 7 days of storage, M units remained comparable to C units (p > 0.05), whereas inferior values were observed with I units. Here, differences to C units reached significance by day 1 (pH: p < 0.0001), day 5 (annexin V release: p < 0.014), and day 7 (HSR, Δψ: p ≤ 0.003). After PRT treatment, annexin V release and Δψ disruption were significantly (p < 0.001) correlated with pH and HSR.
Conclusion
During storage, all units showed a de-crease in HSR and an increase in acidity, annexin V release and Δψ disruption. While M units remained comparable to C units, I units demonstrated significantly inferior values during terminal storage. This could have resulted from differences in PRT treatment or simply be due to differences in storage media and should be analyzed for clinical relevance in future investigations.
doi:10.1159/000264666
PMCID: PMC2914403  PMID: 20737011
Pathogen reduction technology; Platelet in vitro function; Endogenous annexin V; Transmembrane mitochondrial potential; INTERCEPT BLOOD SYSTEM; MIRASOL-PRT
5.  Electron microscopic observation in case of platelet activation in a chronic haemodialysis subject 
Hematology Reports  2011;3(2):e15.
During haemodialysis (HD), platelets (PLTs) are activated and release granule contents. As HD treatment occurs three times a week, it has been demonstrated that PLTs are exhausted due to the repetitive character of the treatment. To identify PLT depletion morphologically, PLT evaluation was performed by light microscopy and electron microscopy (EM) in a chronic HD subject and a healthy reference subject. Blood samples were taken before the start of HD treatment for measurement of PLT count, PLT volume and size parameters. Blood smears were screened by light microscopy for qualitative evaluation of PLT granule containing cytoplasm, as indicated by its staining density. Morphological PLT parameters of surface area and size of dense bodies were assessed by EM. Data were compared with results of a group of 20 chronic HD subjects and a group of 20 healthy reference subjects. With respect to the percentage of PLTs with appropriate staining density (>75%), light microscopic evaluation showed that this value (9%) was within the range of a group of chronic HD subjects, but considerably below the reference range (70%). EM evaluation revealed an average PLT surface area and dense bodies area of respectively 42% and 31%, if the healthy reference subject was set on 100%. PLTs from a chronic HD subject are considerably smaller and substantially less granular than PLTs from a healthy reference subject. These findings support the hypothesis of PLT depletion in chronic HD subjects due to frequent PLT activation and/or increased urea concentrations.
doi:10.4081/hr.2011.e15
PMCID: PMC3238486  PMID: 22184536
electron microscopy; platelet activation; platelet degranulation; haemodialysis.
6.  A General Change of the Platelet Transfusion Policy from Apheresis Platelet Concentrates to Pooled Platelet Concentrates is Associated with a Sharp Increase in Donor Exposure and Infection Rates 
Summary
Background
We compare the actual with the potential donor exposure and possible infection rates in the Hanover Medical School (MHH) platelet (PLT) transfusion recipients if the current MHH standard of apheresis PLT concentrate (A-PC) supply would be replaced by a pooled PLT concentrate (P-PC) transfusion regimen.
Donors, Patients, and Methods
The electronic records of the MHH Institute of Transfusion Medicine and the MHH Department of Medical Controlling were evaluated to assess the development of PLT needs and supply at MHH from 2003–2006. For 2006, we evaluated all PLT transfusion recipients with respect to their overall transfusion needs, classified them for low and high PLT transfusion needs, and related them to the diagnostic groups that underlie their PLT demands. We assumed a P-PC preparation procedure using 4 whole blood-derived buffy coats for all calculations for potential donor exposure. To predict the possible infection rates of an unrecognized viral infection with low prevalence in the general population to A-PC or to P-PC recipients and the influence of neutralizing agent specific antibodies (NAB), we established a mathematical contamination/infection model based on the current PLT transfusion mode and data about GBV-C virus infection among Hanover blood donors.
Results
From 2003 to 2006, the 1,300–1,400 persons comprising MHH apheresis donor pool covered a 36% increase in PC transfusions. The exclusive use of P-PCs instead of A-PC would require a total of 36,240–49,276 whole blood donations to meet MHH demands, corresponding to a more than 1 log step increase in donor exposure. For individual hematological patients, the change to P-PCs would imply an 80–125%, for individual surgical patients a 40–50% higher donor exposure. Our infection model revealed an approximately 4 times higher infection.
Conclusions
A change to P-PC would imply a more than one log step higher donor exposure, and an unrecognized infection with a prevalence around 1% leads to an up to 4 times higher infection rate. A general change in the PC transfusion policy that favors P-PCs is dangerous and must be avoided.
doi:10.1159/000117788
PMCID: PMC3076344  PMID: 21512637
Donor exposure; Apheresis platelet concentrates; Pooled platelet concentrates; Infection rates from apheresis platelet concentrates; Infection rates from pooled platelet concentrates
7.  An Inhibition of p38 Mitogen Activated Protein Kinase Delays the Platelet Storage Lesion 
PLoS ONE  2013;8(8):e70732.
Background and Objectives
Platelets during storage undergo diverse alterations collectively known as the platelet storage lesion, including metabolic, morphological, functional and structural changes. Some changes correlate with activation of p38 mitogen activated protein kinase (p38 MAPK). Another MAPK, extracellular signal-related kinase (ERK), is involved in PLT activation. The aim of this study was to compare the properties of platelets stored in plasma in the presence or absence of p38 and ERK MAPK inhibitors.
Materials and Methods
A single Trima apheresis platelet unit (n = 12) was aliquoted into five CLX storage bags. Two aliquots were continuously agitated with or without MAPK inhibitors. Two aliquots were subjected to 48 hours of interruption of agitation with or without MAPK inhibitors. One aliquot contained the same amount of solvent vehicle used to deliver the inhibitor. Platelets were stored at 20–24°C for 7 days and sampled on Days 1, 4, and 7 for 18 in vitro parameters.
Results
Inhibition of p38 MAPK by VX-702 leads to better maintenance of all platelet in vitro storage parameters including platelet mitochondrial function. Accelerated by interruption of agitation, the platelet storage lesion of units stored with VX-702 was diminished to that of platelets stored with continuous agitation. Inhibition of ERK MAPK did not ameliorate decrements in any in vitro platelet properties.
Conclusion
Signaling through p38 MAPK, but not ERK, is associated with platelet deterioration during storage.
doi:10.1371/journal.pone.0070732
PMCID: PMC3742641  PMID: 23967093
8.  ALLOREACTIVE T LYMPHOCYTES CULTURED FROM LIVER TRANSPLANT BIOPSIES: ASSOCIATIONS OF HLA SPECIFICITY WITH CLINICOPATHOLOGICAL FINDINGS 
Clinical transplantation  1988;2(1):70-75.
Lymphocyte cultures grown from liver allograft biopsies were shown to exhibit alloreactivity towards donor cells as measured by primed lymphocyte testing (PLT). The PLT specificity was determined in assays using HLA typed panel cells and/or by inhibition testing with HLA specific monoclonal antibodies. Certain cultures exhibited PLT specificity towards class I HLA antigens of the donor, whereas others were specific for class II HLA antigens or recognized mixtures of class I and II antigens. These PLT specificity patterns were compared with clinical, histological and laboratory findings on the liver transplant patients at the time of the biopsy. Biopsies yielding class I specific PLT cells were taken generally during the earlier posttransplant period, whereas class II specific cells were grown from later biopsies. There was no significant correlation of the PLT specificity towards class I vs II antigens with the levels of total or direct bilirubin, serum glutamate oxaloacetic transaminase (SGOT), and serum glutamate pyruvate transaminase (SGPT), although a trend towards higher values was noted for biopsies presenting with a class II specific infiltrate. However, the levels of gamma glutamyl transpeptidase (GGTP) and alkaline phosphatase (AP) were significantly increased when biopsies yielded class II specific rather than class I specific PLT cells. Biopsy histology showed more damage to bile duct epithelium in association with class II PLT specificity whereas intense but often reversible infiltrates were found in biopsies yielding class I specific cells. The elevated GGTP and AP levels are probably related to the interaction of class II specific T cells with bile duct epithelium, which has been shown to express induced class II HLA antigens on their cell surface.
PMCID: PMC3000170  PMID: 21151800
T-lymphocytes; liver transplants; donor HLA alloreactivity; liver function tests; histopathology; bile duct damage
9.  Globulin-platelet model predicts minimal fibrosis and cirrhosis in chronic hepatitis B virus infected patients 
AIM: To establish a simple model consisting of the routine laboratory variables to predict both minimal fibrosis and cirrhosis in chronic hepatitis B virus (HBV)-infected patients.
METHODS: We retrospectively investigated 114 chronic HBV-infected patients who underwent liver biopsy in two different hospitals. Thirteen parameters were analyzed by step-wise regression analysis and correlation analysis. A new fibrosis index [globulin/platelet (GP) model] was developed, including globulin (GLOB) and platelet count (PLT). GP model = GLOB (g/mL) × 100/PLT (× 109/L). We evaluated the receiver operating characteristics analysis used to predict minimal fibrosis and compared six other available models.
RESULTS: Thirteen clinical biochemical and hematological variables [sex, age, PLT, alanine aminotransferase, aspartate aminotransferase (AST), albumin, GLOB, total bilirubin (T.bil), direct bilirubin (D.bil), glutamyltransferase, alkaline phosphatase, HBV DNA and prothrombin time (PT)] were analyzed according to three stages of liver fibrosis (F0-F1, F2-F3 and F4). Bivariate Spearman’s rank correlation analysis showed that six variables, including age, PLT, T.bil, D.bil, GLOB and PT, were correlated with the three fibrosis stages (FS). Correlation coefficients were 0.23, -0.412, 0.208, 0.220, 0.314 and 0.212; and P value was 0.014, < 0.001, 0.026, 0.018, 0.001 and 0.024, respectively. Univariate analysis revealed that only PLT and GLOB were significantly different in the three FS (PLT: F = 11.772, P < 0.001; GLOB: F = 6.612, P = 0.002). Step-wise multiple regression analysis showed that PLT and GLOB were also independently correlated with FS (R2 = 0.237). By Spearman’s rank correlation analysis, GP model was significantly correlated with the three FS (r = 0.466, P < 0.001). The median values in F0-F1, F2-F3 and F4 were 1.461, 1.720 and 2.634. Compared with the six available models (fibrosis index, AST-platelet ratio, FIB-4, fibrosis-cirrhosis index and age-AST model and age-PLT ratio), GP model showed a highest correlation coefficient. The sensitivity and positive predictive value at a cutoff value < 1.68 for predicting minimal fibrosis F0-F1 were 72.4% and 71.2%, respectively. The specificity and negative predictive value at a cutoff value < 2.53 for the prediction of cirrhosis were 84.5% and 96.7%. The area under the curve (AUC) of GP model for predicting minimal fibrosis and cirrhosis was 0.762 [95% confidence interval (CI): 0.676-0.848] and 0.781 (95% CI: 0.638-0.924). Although the differences were not statistically significant between GP model and the other models (P all > 0.05), the AUC of GP model was the largest among the seven models.
CONCLUSION: By establishing a simple model using available laboratory variables, chronic HBV-infected patients with minimal fibrosis and cirrhosis can be diagnosed accurately, and the clinical application of this model may reduce the need for liver biopsy in HBV-infected patients.
doi:10.3748/wjg.v18.i22.2784
PMCID: PMC3374981  PMID: 22719186
Globulin; Platelet; Globulin/platelet model; Liver fibrosis; Noninvasive fibrosis biomarker; Chronic hepatitis B virus
10.  Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure 
Transfusion  2010;51(6):1197-1206.
BACKGROUND
Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States.
STUDY DESIGN AND METHODS
We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type.
RESULTS
A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively.
CONCLUSION
A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI.
doi:10.1111/j.1537-2995.2010.02991.x
PMCID: PMC3606016  PMID: 21182532
11.  Differences in Platelet Indices between Healthy Han Population and Tibetans in China 
PLoS ONE  2013;8(6):e67203.
Introduction
The present data on the evaluation of platelet (PLT) parameters in Chinese Han population and Tibetans are still limited. The objective of this study was to determine the differences in common PLT indices between Han population and Tibetans in China, through a large-scale investigation of healthy people.
Methods
2131 Han people from Chengdu Plain, 1099 Tibetans from Qinghai-Tibet Plateau and 956 Plateau Han migrants were included in this study. All the subjects were healthy people through the health screening. PLT indices were measured with Sysmex XE-2100 and XT-1800i blood cell automatic analyzer.
Results
Compared with Han people in Chendu Plain, Tibetans had higher PLT count (P<0.01) but lower mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR) (P<0.01); while Plateau Han migrants had lower PLT count, MPV and P-LCR (P<0.05). When compared with Tibetans, Plateau Han migrants had lower levels of mean PLT count but higher PDW and P-LCR (P<0.05).
Conclusions
There are ethnic differences in PLT indices between Chinese Han population and Tibetans. Based on this finding, it would be reasonable to conduct formal prospective studies to determine the clinical significance of these differences and to explore the effects of genetic background on these indices.
doi:10.1371/journal.pone.0067203
PMCID: PMC3691229  PMID: 23826234
12.  Performance of automated platelet quantification using different analysers in comparison with an immunological reference method in thrombocytopenic patients 
Blood Transfusion  2009;7(1):43-48.
Background
Rapidly available and accurate platelet counts play an important role in the evaluation of haemorrhagic status and in assessing the need for platelet transfusions. We, therefore, evaluated platelet counting performance of haematology analysers using optical, impedance and immunological methods in thrombocytopenic patients.
Materials and Methods
We considered 99 patients with a platelet (plt) count under 50x109 plt/L. We compared the platelet counts obtained using ADVIA 2120 (optical method), Cell-Dyn Sapphire (optical, impedance and immunological methods with CD61) and a reference, double staining (CD41+CD61) immunological method.
Results
The platelet counts of all the considered methods showed good correlation with those of the reference method, despite an overestimation in platelet quantification. The degree of inaccuracy was greater for platelet counts under 20 x109 plt/L.
Conclusions
Clinicians who use platelet thresholds below 20 x109 plt/L for making clinical decisions must be aware of the limitations in precision and accuracy of cell counters at this level of platelet count. Inaccurate counts of low platelet numbers could create problems if attempts are made to reduce the threshold below 20x109 plt/L.
doi:10.2450/2008.0039-08
PMCID: PMC2652236  PMID: 19290080
Platelet count; Accuracy; Thrombocytopenia; Method's correlation
13.  Efficacy and Side Effects of Granulocyte Collection in Healthy Donors 
Summary
Background
We report on the efficacy and side effects of granulocyte collection, which is comparatively infrequently performed in Germany.
Methods
Data from 378 healthy donors who underwent 914 granulocyte collections between 1999 and 2007 were retrospectively analyzed. Donors received G-CSF (lenograstim) at a median dose of 5.58 (3.25–7.36) μg/kg body weight with (n = 243) or without (n = 57) 4 mg dexamethasone. Side effects were recorded by donor monitoring and interview (questionnaire).
Results
The median granulocyte yield in apheresis products was 8.47 × 1010 (3.07–14.92 × 1010). Granulocyte yields correlated significantly with gender, baseline WBC, PMN and PLT counts, and nicotine consumption. Dexamethasone and lenograstim administration was more effective than lenograstim administration alone (p < 0.001). Side effects of granulocyte mobilization were generally mild: bone pain in 31.4%, headache in 19.6%, and fatigue in 15.7% of donors. During follow-up (4 weeks), pruritus and/or exanthema were reported in 17.6% of donors.
Conclusions
Granulocyte mobilization with lenograstim with or without dexamethasone was a safe and effective regimen for granulocyte mobilization. Side effects were tolerable and milder than those seen in peripheral blood stem cell donors. Long-term monitoring of granulocyte donors is important to establish optimal standards for the procedure.
doi:10.1159/000354093
PMCID: PMC3776445  PMID: 24179474
Granulocyte collection; Allogeneic donors; G-CSF
14.  Coagulation activation, depletion of platelet granules and endothelial integrity in case of uraemia and haemodialysis treatment 
BMC Nephrology  2013;14:72.
Background
During haemodialysis (HD) treatment, increase of platelet (PLT) activation and induction of procoagulant activity is demonstrated. Although the role of the endothelium and its direct interaction with coagulation and homeostasis is known, it is not elucidated how PLT activation markers and activation of coagulation coincide with markers of endothelial integrity during HD treatment. In the present study uraemia and HD induced changes, with particular emphasis on PLT granules depletion, activation of coagulation and endothelial integrity were investigated.
Methods
To detect depletion of PLT granules, peripheral blood slide smears were screened by light microscopy for qualitative evaluation of PLT granule containing cytoplasm, as indicated by its granules staining density. Activation of coagulation was investigated by establishement of thrombin-antithrombin (TAT) and fibrinogen concentrations. To evaluate endothelial integrity proendothelin (proET-1) plasma concentrations were established.
Results
Results of our study demonstrate that proET-1 plasma concentrations were obviously increased in the subjects’ group with end-stage chronic kidney disease (CKD) and renal failure if compared with a group of apparently healthy subjects. The amount of depleted PLT granules was obviously increased in the subjects’ group with end-stage CKD if compared with the group with renal failure. Mean plasma concentrations of TAT and fibrinogen revealed results within the reference range.
Conclusions
It is demonstrated that uraemia is associated with endothelial damage and aberrations in PLT granules morphology in subjects with HD treatment. We hypothesize that increased proET-1 concentrations reflect ongoing stress on endothelial cells amongst others due to uraemia. Biomarkers like proET-1 and aberrations in PLT granules morphology assist in the early detection of procoagulant activity of the endothelium.
doi:10.1186/1471-2369-14-72
PMCID: PMC3623653  PMID: 23537104
Platelet granules depletion; Coagulation; Proendothelin; End-stage kidney disease; Renal failure
15.  Fibrinogen mediates platelet-polymorphonuclear leukocyte cooperation during immune-complex glomerulonephritis in rats. 
Journal of Clinical Investigation  1994;94(3):928-936.
The metabolic and functional alterations which occur during the acute phase of nephrotoxic nephritis (NTN) in rats, a model of immune-mediated glomerulonephritis, result from a cooperative interaction between PMNs and platelets (PLTs). In consequence, we hypothesized that fibrinogen (Fg) might play a critical role in this process and, accordingly, we found that defibrination of animals decreased both the acute phase proteinuria in NTN (approximately 70%) as well as the influx of PLTs and PMNs into the glomerulus (approximately 40-50%). In contrast, blockade of the PLT Fg receptor, alpha IIb beta 3, with the RGD peptidomimetic SC-49992 decreased proteinuria (approximately 90%) without substantially altering the influx of PMNs or PLTs. Immunocytochemistry showed a marked increase in beta 3 integrin expression in inflamed glomeruli which was prevented either by PMN or PLT depletion before disease induction. FACS and immunocytochemical analysis of glomerular cell dissociates demonstrated that beta 3 integrin expression was predominantly on intraglomerular PLTs. In vitro, activated PLTs stimulated the PMN respiratory burst, an interaction which could be inhibited by Fg receptor blockade. In sum, acute NTN is accompanied by a marked increase in glomerular beta 3 integrin expression predominantly due to the influx of PLTs which localize to the glomerulus in a PMN-dependent fashion. Fg appears to serve a major role as a coactivating stimulus for PLT-PMNs in situ via alpha IIb beta 3, potentially mediating the PMN respiratory burst which contributes to proteinuria. Fg may also play a subsidiary role in PMN/PLT comigration.
Images
PMCID: PMC295129  PMID: 8083378
16.  Initial Values of Donor Hematocrit and Efficiency of Plateletpheresis 
Acta Informatica Medica  2013;21(2):116-119.
CONFLICT OF INTEREST: NONE DECLARED
Introduction
The collection of platelets by apheresis is considered as a very great progress in transfusion medicine. A larger yield (total number of collected platelets) is obtained if the donor has a greater number of initial platelets and if the separation is done in a shorter time. One of the parameters is also the efficiency of the platelet collection (expressed in percentage) on the value of which different factors may have direct or indirect influence.
Aims
To calculate the efficiency of platelet collection with the separator Fenval Baxter AMICUS and to compare the efficiency of platelet collection with this separator in relation to the initial value of donor hematocrit.
Donors and Methods
The donors who participated in this study were divided into groups according to the value of the donor’s ‘hematocrit before separation. Group C consisted of donors whose initial value of the hematocrit was lower or equal to 46%. Group D consisted of donors whose initial value of the hematocrit was higher than 46%. The process was carried out on Fenval Baxter AMICUS. The expected efficiency of the collection was obtained by dividing the total number of collected cells by the expected total number of processed cells, i.e. the total number of cells passed through the equipment.
Results
In the 258 separations which satisfied the fixed criteria were men in 226 cases (87.6%) and women in 32 (12.4%). There is a statically significant difference in the platelet value between the groups and this value is higher in group D than in group C. The average value of platelets before separation was 46.66. The range of minimal and maximal value is from 38.8 to 52.4 ±2.78. The initial value of hematocrits of the donor does not intervene in the length of the separation, but it has a significant effect on the efficiency of the platelet collection. Increases in the number of hematocrits significantly decrease the efficiency of platelet collection. In practice it means that we can base on this fact make a better selection of donors. In this kind selection, one should prefer a donor with a higher number of initial platelets and lower levels of hematocrits. In that way we can collect a more important yield, have a shorter length of separation and increase the efficiency of platelet collection. Its advantage is as well medical because of a more important yield but also financial because of the decrease of the length of the separation and the increase in efficiency. Key words: value of hematocrits, donors, apheresis, platelets, efficiency.
doi:10.5455/aim.2013.21.116-119
PMCID: PMC3766539  PMID: 24058252
value of hematocrits; donors; apheresis; platelets; efficiency
17.  Host Platelets and, in Part, Neutrophils Mediate Lung Accumulation of Transfused UVB-Irradiated Human Platelets in a Mouse Model of Acute Lung Injury 
PLoS ONE  2012;7(9):e44829.
We previously reported that ultraviolet light B (UVB)-treated human platelets (hPLTs) can cause acute lung injury (ALI) in a two-event SCID mouse model in which the predisposing event was Lipopolysaccharide (LPS) injection and the second event was infusion of UVB-treated hPLTs. To delineate contributions of host mouse platelets (mPLTs) and neutrophils in the pathogenesis of ALI in this mouse model, we depleted mPLTs or neutrophils and measured hPLT accumulation in the lung. We also assessed lung injury by protein content in bronchoalveolar lavage fluid (BALF). LPS injection followed by infusion of UVB-treated hPLTs resulted in sequestration of both mPLTs and hPLTs in the lungs of SCID mice, although the numbers of neutrophils in the lung were not significantly different from the control group. Depletion of mouse neutrophils caused only a mild reduction in UVB-hPLTs accumulation in the lungs and a mild reduction in protein content in BALF. In comparison, depletion of mPLTs almost completely abolished hPLTs accumulation in the lung and significantly reduced protein content in BALF. UVB-treated hPLTs bound to host mPLTs, but did not bind to neutrophils in the lung. Aspirin treatment of hPLTs in vitro abolished hPLT accumulation in the lung and protected mice from lung injury. Our data indicate that host mPLTs accumulated in the lungs in response to an inflammatory challenge and subsequently mediated the attachment of transfused UVB-hPLTs. Neutrophils also recruited a small percentage of platelets to the lung. These findings may help develop therapeutic strategies for ALI which could potentially result from transfusion of UV illuminated platelets.
doi:10.1371/journal.pone.0044829
PMCID: PMC3446987  PMID: 23028636
18.  Platelet Antistaphylococcal Responses Occur through P2X1 and P2Y12 Receptor-Induced Activation and Kinocidin Release▿  
Infection and Immunity  2008;76(12):5706-5713.
Platelets (PLTs) act in antimicrobial host defense by releasing PLT microbicidal proteins (PMPs) or PLT kinocidins (PKs). Receptors mediating staphylocidal efficacy and PMP or PK release versus isogenic PMP-susceptible (ISP479C) and -resistant (ISP479R) Staphylococcus aureus strains were examined in vitro. Isolated PLTs were incubated with ISP479C or ISP479R (PLT/S. aureus ratio range, 1:1 to 10,000:1) in the presence or absence of a panel of PLT inhibitors, including P2X and P2Y receptor antagonists of increasingly narrow specificity, and PLT adhesion receptors (CD41, CD42b, and CD62P). PLT-to-S. aureus exposure ratios of ≥10:1 yielded significant reductions in the viability of both strains. Results from reversed-phase high-performance liquid chromatography indicated that staphylocidal PLT releasates contained PMPs and PKs. At ratios below 10:1, the PLT antistaphylococcal efficacy relative to the intrinsic S. aureus PMP-susceptible or -resistant phenotype diminished. Apyrase (an agent of ADP degradation), suramin (a general P2 receptor antagonist), pyridoxal 5′-phosphonucleotide derivative (a specific P2X1 antagonist), and cangrelor (a specific P2Y12 antagonist) mitigated the PLT staphylocidal response against both strains, correlating with reduced levels of PMP and PK release. Specific inhibition occurred in the presence and absence of homologous plasma. The antagonism of the thromboxane A2, cyclooxygenase-1/cyclooxygenase-2, or phospholipase C pathway or the hindrance of surface adhesion receptors failed to impede PLT anti-S. aureus responses. These results suggest a multifactorial PLT anti-S. aureus response mechanism involving (i) a PLT-to-S. aureus ratio sufficient for activation; (ii) the ensuing degranulation of PMPs, PKs, ADP, and/or ATP; (iii) the activation of P2X1/P2Y12 receptors on adjacent PLTs; and (iv) the recursive amplification of PMP and PK release from these PLTs.
doi:10.1128/IAI.00935-08
PMCID: PMC2583569  PMID: 18824536
19.  A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function 
Blood  2009;113(16):3831-3837.
Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 ± 0.001 log fL; P < 1.08 × 10−24) and PLT (per-G effect −4.55 ± 0.80 109/L; P < 7.19 × 10−8) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis.
doi:10.1182/blood-2008-10-184234
PMCID: PMC2714088  PMID: 19221038
20.  Platelet count is a sensitive predictor of autologous peripheral blood progenitor cell collection yield in previously treated plasma cell disease patients 
Transfusion  2008;48(6):1106-1114.
BACKGROUND
It is often a clinical dilemma to determine when to collect autologous peripheral blood progenitor cells (PBPCs) in patients who received prior chemotherapy. It is also challenging to predict if the collected cells will be enough for one or two transplants.
STUDY DESIGN AND METHODS
A total of 103 PBPC donors were followed to evaluate factors that predict poor autologous PBPC collection. The donors were categorized into three groups: plasma cell disorders (PCDs), lymphomas, and normal allogeneic donors.
RESULTS
Our evaluation showed that platelet (PLT) count before growth factor administration significantly correlated with total CD34+ cell yield (Spearman r = 0.38, p < 0.001). Further analysis showed this correlation was only significant in plasma cell disease patients who received prior chemotherapy (Spearman r = 0.5, p = 0.008). Baseline PLT counts did not correlate with PBPC collection yield in untreated PCD, lymphoma, and normal allogeneic donors. In addition, daily PLT count during PBPC harvest correlated with CD34+ cell yield for that day (Spearman r = 0.41, p < 0.001). With a multiple linear regression model (adjusted R2 = 0.31, AIC = 63.1), it has been determined that the baseline PLT count significantly correlates with total CD34+ cell yield in treated PCD patients.
CONCLUSION
Baseline PLT count is a sensitive indicator of autologous PBPC mobilization in PCD patients who received prior chemotherapy. This finding may be considered before growth factor administration to determine the optimal period to mobilize treated PCD patients and to predict if enough cells can be collected for one or two transplants.
doi:10.1111/j.1537-2995.2008.01651.x
PMCID: PMC3919131  PMID: 18315528
21.  Sustained remissions of immune thrombocytopenia associated with the use of thrombopoietin receptor agonists 
Transfusion  2013;53(11):2807-2812.
BACKGROUND
Thrombopoietin receptor agonists (TRAs) are effective treatments for immune thrombocytopenia (ITP). However, continuous therapy is generally required to maintain platelet (PLT) count responses.
STUDY DESIGN AND METHODS
In this case series, we describe ITP patients from our practice who achieved durable responses to the TRAs romiplostim and eltrombopag. Patients were classified as having a definite TRA-induced remission if PLT counts increased above 100 × 109/L after TRA treatment and remained above 100 × 109/L even after the medication was discontinued; or a possible TRA-induced remission if PLT counts increased above 100 × 109/L, remained elevated for at least 3 months after the medication was discontinued, but a subsequent relapse occurred or the effect of other disease-modifying therapies could not be excluded.
RESULTS
Of 31 patients with chronic ITP treated with TRAs in our practice, nine patients achieved a PLT count response with either romiplostim (n = 6) or eltrombopag (n = 3) that was maintained even after the medications were discontinued. Three patients met criteria for a definite TRA-induced remission, each after exposure to romiplostim. Patients had ITP for a median of 7.8 years and had failed a median of four prior therapies including eight patients who had a splenectomy. We documented a progressive decline in anti-glycoprotein IIbIIIa PLT autoantibodies in one patient while on treatment.
CONCLUSION
Some patients with ITP can achieve sustained PLT count responses after the use of TRAs. This observation raises the possibility that these agents may restore immune tolerance to PLT antigens in some patients and supports the practice of down titrating the dose.
doi:10.1111/trf.12139
PMCID: PMC3938454  PMID: 23451917 CAMSID: cams4132
22.  Brief Report: Normal Intestinal Permeability at Elevated Platelet Serotonin Levels in a Subgroup of Children with Pervasive Developmental Disorders in Curaçao (The Netherlands Antilles) 
This study investigated the relationship between platelet (PLT) serotonin (5-HT) and intestinal permeability in children with pervasive developmental disorders (PDD). Differential sugar absorption and PLT 5-HT were determined in 23 children with PDD. PLT 5-HT (2.0–7.1 nmol/109 PLT) was elevated in 4/23 patients. None exhibited elevated intestinal permeability (lactulose/mannitol ratio: 0.008–0.035 mol/mol). PLT 5-HT did not correlate with intestinal permeability or GI tract complaints. PLT 5-HT correlated with 24 h urinary 5-hydroxyindoleacetic acid (5-HIAA; p = .034). Also urinary 5-HIAA and urinary 5-HT were interrelated (p = .005). A link between hyperserotonemia and increased intestinal permeability remained unsupported. Increased PLT 5-HT in PDD is likely to derive from increased PLT exposure to 5-HT. Longitudinal studies, showing the (in)consistency of abnormal intestinal permeability and PLT 5-HT, may resolve present discrepancies in the literature.
doi:10.1007/s10803-007-0399-8
PMCID: PMC2226079  PMID: 17661166
Child development disorders; Pervasive; Platelets; Serotonin; Gastrointestinal; Permeability
23.  Neonatal alloimmune thrombocytopenia associated with maternal-fetal incompatibility for blood group B 
Transfusion  2007;48(2):358-364.
BACKGROUND
Blood group A and B antigens are expressed only weakly on platelets (PLTs) of most individuals but are very strongly expressed on PLTs from approximately 1 percent of normal subjects (Type II high expressers). The implications of this trait for transfusion medicine are undefined.
STUDY DESIGN AND METHODS
A family was studied in which two Group B infants were born with neonatal thrombocytopenia, whereas a third infant whose blood group was A2 had a normal PLT count at birth.
RESULTS
Serologic studies demonstrated a maternal antibody that reacted strongly with PLTs from the father and the two group B children in flow cytometry and with GPIIb/IIIa from their PLTs in solid-phase assays. No PLT-specific antibodies were detected in maternal serum sample, but it contained a high-titer immunoglobulin G antibody specific for blood group B. All PLT-reactive antibody in the mother’s serum was removed by absorption with pooled, washed group A and B red cells (RBCs). Studies with monoclonal anti-B and measurement of serum B-glycosyltransferase activity showed that the father and both group B children were Type II high expressers of blood group B.
CONCLUSIONS
The findings indicate that high-titer blood group antibodies acquired from the mother can cause thrombocytopenia in infants possessing the Type II high-expresser phenotype despite competition for antibody binding by blood group antigens expressed on RBCs and other tissues.
doi:10.1111/j.1537-2995.2007.01531.x
PMCID: PMC3572505  PMID: 18028270
24.  Aspects of platelet disturbances in haemodialysis patients 
Clinical Kidney Journal  2013;6(3):266-271.
Patients with mild-to-chronic kidney disease (CKD) exhibit a variety of haemostatic disorders, ranging from an increased clotting tendency and reductions in the levels of natural inhibitors of coagulation to defective fibrinolysis. In addition, platelet (PLT) abnormalities are common. In this minireview, we report on aspects of haemodialysis (HD)-induced PLT activation. It is demonstrated that PLTs from HD patients are exhausted due to repeated stimulation of HD treatment and recurrent release of PLT degranulation products. During HD, additional aberrations of the haemostatic process occur. Besides deviations of coagulation and fibrinolysis, PLT activation and a reduction in their granule content have been observed during HD treatment. As HD treatment is carried out three times per week, month after month, chronic HD patients may suffer persistently from coagulation defects and PLT disorders on top of the alterations induced by the uraemic state itself. PLT activation occurs together with thrombin and fibrin generation. However, macro fibrin depositions in clot devices are not demonstrated, microaggregates occur not only in the extracorporeal circuit (ECC) but are also present in the blood circulation. As vascular access thrombosis is a frequent complication in patients with HD treatment, it is believed that hypercoagulability could result from vascular changes combined with PLTs and activation of coagulation factors.
doi:10.1093/ckj/sft033
PMCID: PMC3941307  PMID: 24596657
coagulation; end-stage kidney disease; extracorporeal blood circulation; platelet activation
25.  Changes in the total leukocyte and platelet counts in Papuan and non Papuan adults from northeast Papua infected with acute Plasmodium vivax or uncomplicated Plasmodium falciparum malaria 
Malaria Journal  2008;7:259.
Background
There are limited data on the evolution of the leukocyte and platelet counts in malaria patients.
Methods
In a clinical trial of chloroquine vs. chloroquine plus doxycycline vs. doxycycline alone against Plasmodium vivax (n = 64) or Plasmodium falciparum (n = 98) malaria, the total white cell (WCC) and platelet (PLT) counts were measured on Days 0, 3, 7 and 28 in 57 indigenous Papuans with life long malaria exposure and 105 non Papuan immigrants from other parts of Indonesia with limited malaria exposure.
Results
The mean Day 0 WCC (n = 152) was 6.492 (range 2.1–13.4) × 109/L and was significantly lower in the Papuans compared to the non Papuans: 5.77 × 109/L vs. 6.86 × 109/L, difference = -1.09 [(95% CI -0.42 to -1.79 × 109/L), P = 0.0018]. 14 (9.2%) and 9 (5.9%) patients had leukopaenia (<4.0 × 109/L) and leukocytosis (>10.0 × 109/L), respectively. By Day 28, the mean WCC increased significantly (P = 0.0003) from 6.37 to 7.47 × 109/L (73 paired values) and was similar between the two groups. Ethnicity was the only WCC explanatory factor and only on Day 0.
The mean Day 0 platelet count (n = 151) was 113.0 (range 8.0–313.0) × 109/L and rose significantly to 186.308 × 109/L by Day 28 (P < 0.0001). There was a corresponding fall in patient proportions with thrombocytopaenia (<150 × 109/L): 119/151 (78.81%) vs. 16/73 (21.92%, P < 0.00001). Papuan and non Papuan mean platelet counts were similar at all time points. Only malaria species on Day 0 was a significant platelet count explanatory factor. The mean D0 platelet counts were significantly lower (P = 0.025) in vivax (102.022 × 109/L) vs. falciparum (122.125 × 109/L) patients.
Conclusion
Changes in leukocytes and platelets were consistent with other malaria studies. The Papuan non Papuan difference in the mean Day 0 WCC was small but might be related to the difference in malaria exposure.
doi:10.1186/1475-2875-7-259
PMCID: PMC2642516  PMID: 19094197

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