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1.  Comparison of Plateletpheresis on the Fenwal Amicus and Fresenius Com.Tec Cell Separators 
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).
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).
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.
PMCID: PMC3076329  PMID: 21512626
Plateletpheresis; Apheresis; Amicus; COM.TEC; Cell separator
2.  Comparison of plateletpheresis on three continuous flow cell separators 
Platelet concentrate (PC) remains one of the most important support measures in thrombocytopenic patients. An efficient cell separator is a prerequisite for an optimally functioning apheresis setup. Donor blood count may undergo a temporary reduction after the procedure.
The aim was to find the extent of reduction in donor blood count (hemoglobin, hematocrit, white blood cell, and platelet) after plateletpheresis and to evaluate the cell separator for collection efficiency, processing time, and leukoreduction.
Study Design and Methods:
Two hundred and thirty seven procedures performed on the Amicus (N = 121), Fenwal CS-3000 Plus (N = 50) and Cobe spectra (N = 66) in a one year period were evaluated. The procedures performed on the continuous flow centrifugation (CFC) cell separators and donor blood counts (pre and post donation) done were included in the study.
The percent reduction in hemoglobin (HB), hematocrit (HCT), white blood cell (WBC) and platelet count ((PLT ct) was 2.9, 3.1, 9, 30.7 (Mean, N = 237) respectively after the procedure. The post donation PLT ct reduced to < 100×109/L (range 80-100) in five donors (N = 5/237, Amicus). The pre donation PLT ct in them was 150-200×109/L. Collection efficiency (percent) of Amicus (79.3) was better as compared to the other two machines (CS: 62.5, Cobe: 57.5). PC collected on Cobe spectra had <1×106 WBC. The donor pre donation PLT levels had a positive correlation to the product PLT yield (r = 0.30, P = 0.000).
Monitoring donor blood counts helps to avoid pheresis induced adverse events. A cautious approach is necessary in donors whose pre donation PLT ct is 150-200×109/L. The main variable in PLT yield is donor PLT ct (pre donation). High collection efficiency is a direct measure of an optimally functioning cell separator.
PMCID: PMC2920476  PMID: 20808650
Continuous flow cell separator; donor blood count; plateletpheresis; platelet yield; Blood donor; apheresis
3.  Red Cell Apheresis with Automated In-Line Filtration 
The aim of this study was to provide data on concurrent red blood cell (RBC) and platelet (PLT) apheresis with RBC in-line leukoreduction and automated addition of saline-adenine-glucose-mannitol (SAGM) using the new version (V6.0) of Trima Accel®.
In this two-center paired study, each subject completed a test and a control procedure with an interval of 9 weeks between procedures. In the test arm, single RBC and PLT units were collected on the Trima Accel V6.0 (in-line leukofiltration and automated addition of SAGM). In the control arm, they were collected on Trima Accel V5.1/V5.2 (post-collection leukoreduction, manual SAGM addition). RBC percent hemolysis, potassium concentration and adenosine triphosphate over storage, hemoglobin (Hb) yield, and residual white blood cells (WBC) were determined.
34 subjects successfully completed both test and control procedures. Post-storage hemolysis was similar in both groups, and all values were less than 0.8% for both arms. Residual WBC counts in all RBC units were less than 1 × 106/unit. In-line processed RBC units (V6.0) have a significantly higher volume and more Hb/unit due to filtration recovery improvements. All procedures were well tolerated by the subjects.
In-line filtration and automated addition of storage solution on Trima Accel V6.0 allows collection of ready-to-use RBC units that meet EU requirements.
PMCID: PMC4025052  PMID: 24847185
Red blood cell; Apheresis; In-line filtration; Leukoreduction; Multicomponent collection; Blood storage
4.  Evaluation of White Blood Cell- and Platelet-Derived Cytokine Accumulation in MIRASOL-PRT-Treated Platelets 
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.
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.
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.
PMCID: PMC2928824  PMID: 20823992
Pathogen reduction; Mirasol-PRT; Ccytokines; Transfusion reaction
5.  Effect of storage on levels of nitric oxide metabolites in platelet preparations 
Transfusion  2012;53(3):637-644.
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).
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.
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.
PMCID: PMC3548060  PMID: 22804724
nitric oxide; nitrite; platelet storage; transfusion
6.  Thrombocytosis is a significant indictor of hypercoagulability, prognosis and recurrence in gastric cancer 
Although thrombocytosis has been reported in a variety of cancer types, the standard of thrombocytosis in gastric cancer (GC) and the association between thrombocytosis and the clinicopathological features of patients with GC remain unclear. In the present study, 1,763 GC patients were retrospectively filtered by preoperative thrombocytosis and compared with control group A (n=107) that had benign gastric lesions and control group B (n=100) that were GC patients with a normal platelet (PLT) count. Associations between clinical variables and preoperative PLT counts were assessed by univariate and multivariate analyses. Kaplan-Meier survival curves and Cox regression were used to evaluate the effect of thrombocytosis on prognosis. Sensitivities and specificities of the PLT counts in predicting recurrence were analyzed via area under the receiver operating characteristic curve (AUROC). The results indicated that the incidence of thrombocytosis in GC patients was higher than in benign gastric lesion patients, with 4.03% of GC patients having a PLT count >400×109/l (P=0.014) and 12.08% had a PLT count >300×109/l (P<0.001). For the patients with a PLT count >400×109/l, the frequency of abnormal PLT counts in GC correlated with tumor size (P<0.001), tumor, node and metastasis (TNM) classification (P=0.002), invasive degree (P=0.003) and D-dimer (P=0.013) and fibrinogen concentrations (P=0.042). Tumor size (P=0.002), TNM classification (P<0.001) and depth of penetration (P=0.001) were independent factors for thrombocytosis. However, thrombocytosis functioned as an independent prognostic factor for GC patients with a PLT count >400×109/l (relative risk, 1.538; 95% confidence interval, 1.041–2.271). In the majority of patients (17/24) with a high preoperative PLT count that decreased to a normal level following resection, PLT levels increased again at recurrence. Sensitivities and specificities of thrombocytosis for recurrence in those patients were 70.8 and 83.3%, respectively (AUROC, 0.847; P=0.01). Therefore, a PLT count of 400×109/l is a suitable threshold for defining thrombocytosis in GC. Thrombocytosis was shown to affect the blood hypercoagulable state and also have a negative prognostic value for GC patients. PLT monitoring following surgery was useful to predict the recurrence for specific GC patients that suffered preoperative thrombocytosis but had restored PLT levels following resection.
PMCID: PMC4061185  PMID: 24944610
gastric cancer; thrombocytosis; recurrence; survival analysis
7.  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 
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.
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.
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.
PMCID: PMC3076344  PMID: 21512637
Donor exposure; Apheresis platelet concentrates; Pooled platelet concentrates; Infection rates from apheresis platelet concentrates; Infection rates from pooled platelet concentrates
8.  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.
PMCID: PMC3374981  PMID: 22719186
Globulin; Platelet; Globulin/platelet model; Liver fibrosis; Noninvasive fibrosis biomarker; Chronic hepatitis B virus
9.  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.
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.
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.
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.
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.
PMCID: PMC3919131  PMID: 18315528
10.  Annexin V Release and Transmembrane Mitochondrial Potential during Storage of Apheresis-Derived Platelets Treated for Pathogen Reduction 
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.
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)).
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.
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.
PMCID: PMC2914403  PMID: 20737011
Pathogen reduction technology; Platelet in vitro function; Endogenous annexin V; Transmembrane mitochondrial potential; INTERCEPT BLOOD SYSTEM; MIRASOL-PRT
11.  Pretreatment platelet count as a predictor for survival and distant metastasis in nasopharyngeal carcinoma patients 
Oncology Letters  2015;9(3):1458-1466.
The aim of the present study was to investigate the prognostic value of different pretreatment platelet (PLT) counts on the treatment outcome in nasopharyngeal carcinoma (NPC) patients receiving concurrent chemoradiotherapy (CCRT) or radiotherapy (RT) alone. A total of 1,501 NPC patients, including 412 receiving CCRT and 1,089 receiving RT, were enrolled in the present study. The PLT count cut-off points for the CCRT and RT groups were 150 and 300×109/l, respectively, and the PLT counts were categorized it into three groups: Low (PLT≤150×109/l), moderate (150×109/l300×109/l). To identify independent predictors of overall survival (OS), the Cox proportional hazards model was used to determine local-regional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) rates in the CCRT and RT patients. Furthermore, univariate and multivariate analysis indicated that compared with a moderate PLT count, a low PLT count was an independent unfavorable prognostic factor for OS rate in CCRT patients [hazard ratio (HR), 2.024; 95% confidence interval (CI), 1.165–3.516], and a high PLT count was an independent unfavorable prognostic factor for OS and DMFS rates in CCRT (OS: HR, 1.742; 95% CI, 1.090–2.786; DFMS: HR, 2.110; 95%CI, 1.084–4.108) and RT (OS: HR, 1.740; 95%CI, 1.283–2.362; DMFS: HR, 2.819; 95% CI, 1.766–4.497) patients. Compared with a low PLT count, a high PLT count was significantly and independently associated with a poor DMFS rate in the RT patients (P=0.025; HR, 2.454; 95% CI, 1.121–5.372). Therefore, the present study indicates that low and high PLT counts may be useful indicators of survival and distant metastasis in NPC patients who have undergone radiation treatment.
PMCID: PMC4314978  PMID: 25663931
platelet count; nasopharyngeal carcinoma; radiotherapy; concurrent chemoradiotherapy; predictor; prognosis
12.  The determinants of granulocyte yield in 1198 granulocyte concentrates collected from unrelated volunteer donors mobilized with dexamethasone and granulocyte–colony-stimulating factor: a 13-year experience 
Transfusion  2008;49(3):421-426.
The combination of granulocyte–colony-stimulating factor (G-CSF [filgrastim]) and dexamethasone (G-CSF/dex) is an effective granulocyte mobilization regimen, but the variables that affect donor neutrophil response and granulocyte collection yield are not well characterized.
A computerized database containing records of 1198 granulocyte collections from 137 unrelated volunteer apheresis donors during a 13-year period was retrospectively analyzed. Donors were categorized by age, sex, and cumulative number of granulocyte donations. Complete blood counts at baseline and after G-CSF/dex stimulation were recorded. The outcome variables include the pre-procedure absolute neutrophil count (preANC), which reflects G-CSF/dex stimulation, and the granulocyte product yield per liter processed (BagGranYield/L).
Higher baseline ANC and platelet (PLT) counts were significantly associated with higher preANC while a larger number of prior granulocytapheresis procedures was associated with lower preANC. Total filgrastim dose (used in weight-based dosing) did not significantly impact preANC or the granulocyte yield; weight-based dosing at 5 μg per kg and a uniform 480-μg dose produced equivalent preANC. PreANC and weight were the key determinants of granulocyte yield (BagGranYield/L).
Apheresis donors with higher baseline PLT counts and ANCs have higher ANCs after G-CSF/dex stimulation; donor age, weight, and sex do not have a significant impact. A uniform G-CSF dose of 480 μg is as effective as weight-based dosing at 5 μg per kg. Donor ANC monitoring should be considered after serial granulocytapheresis procedures.
PMCID: PMC3421027  PMID: 19040597
13.  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.
PMCID: PMC3446987  PMID: 23028636
14.  The association between red blood cell and platelet transfusion and subsequently developing idiopathic pneumonia syndrome after hematopoietic stem cell transplantation 
Transfusion  2013;54(4):1071-1080.
Blood transfusions are common during hematopoietic stem cell transplantation (HSCT) and may contribute to lung injury.
This study examined the associations between red blood cell (RBC) and platelet (PLT) transfusions and idiopathic pneumonia syndrome (IPS) among 914 individuals who underwent myeloablative allogeneic HSCT between 1997 and 2001. Patients received allogeneic blood transfusions at their physicians' discretion. RBCs, PLTs, and a composite of “other” transfusions were quantified as the sum of units received each 7-day period from 6 days before transplant until IPS onset, death, or Posttransplant Day 120. RBC and PLT transfusions were modeled as separate time-varying exposures in proportional hazards models adjusted for IPS risk factors (age, baseline disease, irradiation dose) and other transfusions. Timing of PLT transfusion relative to myeloid engraftment and PLT ABO blood group (match vs. mismatch) were included as potential interaction terms.
Patients received a median of 9 PLT and 10 RBC units. There were 77 IPS cases (8.4%). Each additional PLT unit transfused in the prior week was associated with 16% higher IPS risk (hazard ratio, 1.16; 95% confidence interval, 1.09–1.23; p < 0.001). Recent RBC and PLT transfusions were each significantly associated with greater risk of IPS when examined without the other; only PLT transfusions retained significance when both exposures were included in the model. The PLT association was not modified by engraftment or ABO mismatch.
PLT transfusions are associated with greater risk of IPS after myeloablative HSCT. RBCs may also contribute; however, these findings need confirmation.
PMCID: PMC4059041  PMID: 24033082
15.  Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure 
Transfusion  2010;51(6):1197-1206.
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.
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.
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.
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.
PMCID: PMC3606016  PMID: 21182532
16.  Differences in Platelet Indices between Healthy Han Population and Tibetans in China 
PLoS ONE  2013;8(6):e67203.
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.
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.
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).
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.
PMCID: PMC3691229  PMID: 23826234
17.  Human platelets inhibit liver fibrosis in severe combined immunodeficiency mice 
AIM: To investigate the role of human platelets in liver fibrosis.
METHODS: Severe combined immunodeficiency (SCID) mice were administered CCl4 and either phosphate-buffered saline (PBS group) or human platelet transfusions (hPLT group). Concentrations of hepatocyte growth factor (HGF), matrix metallopeptidases (MMP)-9, and transforming growth factor-β (TGF-β) in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay (ELISA) and Western blotting. The effects of a human platelet transfusion on liver fibrosis included the fibrotic area, hydroxyproline content, and α-smooth muscle actin (α-SMA) expression, which were evaluated by picrosirius red staining, ELISA, and immunohistochemical staining using an anti-mouse α-SMA antibody, respectively. Phosphorylations of mesenchymal-epithelial transition factor (Met) and SMAD3, downstream signals of HGF and TGF-β, were compared between the two groups by Western blotting and were quantified using densitometry. Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Furthermore, the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.
RESULTS: The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group (fibrotic area, 1.7% ± 0.6% vs 2.5% ± 0.6%, P = 0.03; hydroxyproline content, 121 ± 26 ng/g liver vs 156 ± 47 ng/g liver, P = 0.04). There was less α-smooth muscle actin staining in the hPLT group than in the PBS group (0.5% ± 0.1% vs 0.8% ± 0.3%, P = 0.02). Hepatic expression levels of mouse HGF and MMP-9 were significantly higher in the hPLT group than in the PBS group (HGF, 109 ± 13 ng/g liver vs 88 ± 22 ng/g liver, P = 0.03; MMP-9, 113% ± 7%/GAPDH vs 92% ± 11%/GAPDH, P = 0.04). In contrast, the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group (22 ± 5 ng/g liver vs 39 ± 6 ng/g liver, P = 0.02). Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group (37% ± 4%/GAPDH vs 20% ± 8%/GAPDH, P = 0.03). Phosphorylation of SMAD3 was weaker in the hPLT group than in the PBS group (60% ± 12%/GAPDH vs 84% ± 12%/GAPDH, P = 0.1), although this difference was not significant. Furthermore, a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group (5.9% ± 1.7% vs 2.9% ± 2.1%, P = 0.02). Significant human platelet accumulation was observed in the fibrotic liver tissues, whereas few platelets accumulated in the normal liver.
CONCLUSION: Human platelets inhibit liver fibrosis in SCID mice. Increased concentration of HGF in the liver suppresses hepatic stellate cell activation, induces MMPs, and inhibits hepatocyte apoptosis.
PMCID: PMC3752558  PMID: 23983427
Human platelet; Liver fibrosis; Hepatocyte apoptosis; Hepatocyte growth factor; Transforming growth factor-β; Matrix metallopeptidases
18.  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.
PMCID: PMC3238486  PMID: 22184536
electron microscopy; platelet activation; platelet degranulation; haemodialysis.
19.  Blood platelet and monocyte activations and relation to stages of liver cirrhosis 
AIM: Blood platelets (plt) and monocytes are the cells that play a crucial role in the pathogenesis of liver damage and liver cirrhosis (LC). In this paper, the analysis of mutual relationship between platelets and monocytes activation in LC was conducted.
METHODS: Immunofluorescent flow cytometry was used to measure the percentage of activated platelet populations (CD62P, CD63), the percentage of plt-monocyte aggregates (pma) (CD41/CD45), and activated monocytes (CD11b, CD14, CD16) in the blood of 20 volunteers and 40 patients with LC. Platelet activation markers: sP-selectin, platelet factor 4 (PF4), beta-thromboglobulin (βTG) and monocyte chemotactic peptide-1 (MCP-1) were measured and compared in different stages of LC.
RESULTS: Platelet activation with the increase in both βTG serum concentration and elevation of plt population (CD62P and CD63 as well as MIF CD62P and CD63) is elevated as LC develops and thrombocytopenia rises. There is a positive correlation between medial intensity of fluorescence (MIF) CD62P and MIF CD63 in LC. We did not show any relationship between monocyte activation and pma level. SP-selectin concentration correlates positively with plt count and pma, and negatively with stage of plt activation and MIF CD62P and MIF CD63. There was no correlation between MCP-1 concentration and plt, monocyte activation as well as pma level in LC. CD16 monocytes and MIF CD16 populations are significantly higher in the end stage of LC. A positive correlation occurs between the value of CD11b monocyte population and MIF CD14 and MIF CD16 on monocytes in LC.
CONCLUSION: Platelet and monocyte activation plays an important role in LC. Platelet activation stage does not influence monocyte activation and production of plt aggregates with monocytes in LC. With LC development, thrombocytopenia may be the result of plt consumption in platelet-monocyte aggregates.
PMCID: PMC4305910  PMID: 15884116
Blood platelet; Monocyte; Liver cirrhosis; Flow cytometry
20.  Enhanced shear-induced platelet aggregation due to low-temperature storage 
Transfusion  2012;53(7):1520-1530.
Refrigeration of platelets (PLTs) offers an attractive alternative to the currently practiced storage at room temperature since it may mitigate problems associated with bacterial contamination and extend storage lifetime. Refrigeration causes a number of biophysical and biochemical changes in PLTs and decreases PLT circulation time in vivo. However, the effect of refrigeration on PLT hemostatic functions under physiologic and pathophysiologic shear conditions has not been adequately characterized.
Washed PLTs prepared from either fresh PLT-rich plasma (PRP) or PRP stored at 4°C for 2 days was mixed with exogenous von Willebrand factor (VWF) and fibrinogen and sheared in a cone-and-plate viscometer. PLT aggregation, activation, and VWF binding after shear and glycoprotein (GP) Ibα receptor expression and ristocetin-induced PLT agglutination were measured.
PLTs stored at 4°C for 2 days aggregated significantly more than fresh PLTs particularly at high shear rates (10,000/sec), and this increase was independent of PLT concentration or suspension viscosity. Further, refrigerated PLTs showed a greater increase in GP Ibα–dependent PLT activation under shear and also bound more VWF than fresh PLTs. However, the GP Ibα expression levels as measured by three different antibodies were significantly lower in refrigerated PLTs than in fresh PLTs, and refrigeration resulted in a modest decrease in ristocetin-induced PLT agglutination.
The combined results demonstrate that refrigeration increases PLT aggregation under high shear, but not static, conditions and also increases shear-induced VWF binding and PLT activation. Clinically, enhanced shear-induced PLT aggregation due to low temperature storage may be a beneficial strategy to prevent severe bleeding in trauma.
PMCID: PMC4321779  PMID: 23043289
21.  Significance of eosinophil accumulation in the thrombus and decrease in peripheral blood in patients with acute coronary syndrome 
Coronary Artery Disease  2015;26(2):101-106.
Background and aims
It is well known that the interaction between platelets (PLTs), endothelial cells, and leukocytes contributes to thrombosis in patients with acute coronary syndrome. The aim of this study was to investigate the significance of PLTs and eosinophils (EOS) in coronary arterial thrombi.
PLT count, mean PLT volume, PLT mass, EOS count, EOS percentage, and troponin I level in peripheral blood were determined in 81 patients with angina pectoris (AP) and 49 patients with acute myocardial infarction (AMI). A total of 12 thrombus specimens from AMI patients were submitted for histopathological analysis. EOS presence in thrombectomy specimens were checked by hematoxylin–eosin staining and confirmed by Luna staining.
Results showed that EOS were present in all 12 samples (100%). Cell count and percentage of EOS in peripheral blood of patients with AMI were lower than those in patients with AP (both P<0.00001). A higher PLT count was observed in AMI patients (243±70), especially among female patients or those who were older than 60 years, when compared with AP patients (216±60; all P<0.05). According to the troponin I level, we divided AMI patients into groups I (≥20 ng/ml) and II (<20 ng/ml). Group I had a lower EOS percentage compared with group II (P=0.0496). PLT count was also lower in group I with no statistical difference found (P=0.1202). Moreover, there was an inverse correlation between the EOS percentage and the troponin I level (r=−0.434).
In conclusion, patients with AMI presented with a decreased EOS percentage and an increased PLT count. The decreased EOS percentage suggested serious myocardial damage. The study indicated that EOS play an important role in thrombosis in patients with acute coronary syndrome.
PMCID: PMC4323555  PMID: 25340316
acute coronary syndrome; eosinophils; platelets; thrombosis
22.  Prominent features of platelet count, plateletcrit, mean platelet volume and platelet distribution width in pulmonary tuberculosis 
We aimed to investigate the relation of platelet count (PLT) and plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) with other acute phase reactants and radiological extent in pulmonary tuberculosis (PTB).
One hundred patients with PTB (Group 1), 50 patients with community-acquired pneumonia (Group 2) and 28 healthy control individuals (Group 3) were included in this analytic study.
WBC (White Blood Cell), ESR (Eritrocyte Sedimentation Rate), CRP (C-Reactive Protein), PLT and PCT values were both in Group 1 and Group 2 than in Group 3. PDW values were significantly higher in Group 1 than Group 3. WBC, ESR and CRP values were lower, while PLT and PCT values were higher in the Group 1 compared to Group 2 (p < 0.001). PLT was positively correlated with CRP and ESR values in the tuberculosis group (p < 0.001), while it was not correlated with CRP and ESR in the pneumonia group (p > 0.05). ESR, CRP, PLT and PCT values were found higher in radiological advanced stage (Stage 3) patients with PTB, while hemoglobin (Hb) was found lower (p < 0.05). Higher WBC, ESR, CRP and PCT values as well as radiological advanced stage were more common in PTB patients with thrombocytosis compared to the patients with normal platelet count, whereas Hb was found lower in these patients.
This study indicates that reactive thrombocytosis and higher PCT and PDW develop frequently in PTB and there is a relation between thrombocytosis and acute phase reactants, that is the inflammatory response. In addition, tuberculosis with radiological advanced stage is seen more frequently in the patients with thrombocytosis and higher PCT, drawing attention to the possible role of platelets in the cell-based immune process of tuberculosis.
PMCID: PMC3529701  PMID: 23114411
Mean platelet volume; Platelet; Plateletcrit; Platelet distribution width; Pneumonia; Pulmonary tuberculosis; Thrombocytosis
23.  The usefulness of transient elastography, acoustic-radiation-force impulse elastography, and real-time elastography for the evaluation of liver fibrosis 
Clinical and molecular hepatology  2013;19(2):156-164.
Several noninvasive methods have recently been developed for the evaluation of liver fibrosis. The accuracy of transient elastography (TE), acoustic-radiation-force impulse (ARFI) elastography, and real-time elastography (RTE) in predicting liver fibrosis were evaluated.
Seventy-four patients who had undergone a liver biopsy within the previous 6 months were submitted to evaluation with TE, ARFI, and RTE on the same day.
There were significant correlations between fibrosis stage and liver stiffness measurement (LSM) using the three tested methods: TE, r2=0.272, P=0.0002; ARFI, r2=0.225, P=0.0017; and RTE, r2=0.228, P=0.0015. The areas under the receiver operating characteristic curves (AUROC) for the diagnosis of significant fibrosis (≥F2, Metavir stage) by TE, ARFI, RTE, TE/platelet count (PLT), velocity of shear wave (Vs)/PLT, and elasticity score (Es)/PLT were 0.727, 0.715, 0.507, 0.876, 0.874, and 0.811, respectively. The AUROC for the diagnosis of cirrhosis by TE, ARFI, RTE, TE/PLT, Vs/PLT, and Es/PLT were 0.786, 0.807, 0.767, 0.836, 0.819, and 0.838, respectively. Comparisons of AUROC between all LSMs for predicting significant fibrosis (≥F2) produced the following results: TE vs. RTE, P=0.0069; ARFI vs. RTE, P=0.0277; and TE vs. ARFI, P=0.8836. Applying PLT, the ability of each LSM to predict fibrosis stage significantly increased: TE/PLT vs. TE, P=0.0004; Vs/PLT vs. ARFI, P=0.0022; and Es/PLT vs. RTE, P<0.0001. However, the ability to predict cirrhosis was not enhanced, combining LSM and PLT.
TE and ARFI may be better methods for predicting significant liver fibrosis than RTE. This predictive ability increased significantly when accounting for platelet count. However, all of the measures had comparable efficacies for predicting cirrhosis.
PMCID: PMC3701848  PMID: 23837140
Transient elastography; Acoustic-radiation-force impulse elastography; Real-time elastography; Liver fibrosis
24.  Serum Ceruloplasmin Levels Correlate Negatively with Liver Fibrosis in Males with Chronic Hepatitis B: A New Noninvasive Model for Predicting Liver Fibrosis in HBV-Related Liver Disease 
PLoS ONE  2013;8(10):e77942.
This study aimed to investigate associations between ceruloplasmin (CP) levels, inflammation grade and fibrosis stages in patients with chronic hepatitis B (CHB) and to establish a noninvasive model to predict cirrhosis.
Liver biopsy samples and sera were collected from 198 CHB patients randomized into a training group (n=109) and a validation group (n=89). CP levels were determined using nephelometric immunoassays. Relationships between CP and liver inflammation and fibrosis were analyzed by Spearman rank correlation. Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of CP for determining liver fibrosis in CHB. The liver pathology-predictive model was built using multivariate logistic regression analysis to identify relevant indicators.
CP levels were lower in males than in females, lower in patients with inflammation stage G4 compared to other stages and lower in cirrhotic compared to non-cirrhotic patients. Using area under the curve (AUC) values, CP levels distinguished different stages of inflammation and fibrosis. Multivariate analysis showed that CP levels were all significantly associated with cirrhosis in males. A model was developed combining routine laboratory markers APPCI (alpha-fetoprotein [AFP], prothrombin time, and platelets [PLT] with CP) to predict fibrosis in CHB patients. The APPCI had a significantly greater AUC than FIB-4 (aspartate aminotransferase [AST]/ alanine aminotransferase [ALT]/PLT/age), APRI (AST/PLT ratio index), GPI (globin/PLT), and APGA (AST/PLT/gammaglutamyl transpeptidase [GGT]) models (all P-values<0.001).
CP levels correlate negatively and indirectly with inflammation and fibrosis stages in male CHB patients. The APPCI model uses routine laboratory variables with CP to accurately predict liver fibrosis in CHB.
PMCID: PMC3837017  PMID: 24282481
25.  Blood product ratio in acute traumatic coagulopathy - effect on mortality in a Scandinavian level 1 trauma centre 
Trauma is the leading cause of loss of life expectancy worldwide. In the most seriously injured patients, coagulopathy is often present on admission. Therefore, transfusion strategies to increase the ratio of plasma (FFP) and platelets (PLT) to red blood cells (RBC), simulating whole blood, have been introduced. Several studies report that higher ratios improve survival in massively bleeding patients. Here, the aim was to investigate the potential effect of increased FFP and PLT to RBC on mortality in trauma patients.
In a retrospective before and after study, all trauma patients primarily admitted to a level-one Trauma Centre, receiving blood transfusion, in 2001-3 (n = 97) and 2005-7 (n = 156), were included. In 2001-3, FFP and PLT were administered in accordance with the American Society of Anesthesiologists (ASA) guidelines whereas in 2005-7, Hemostatic Control Resuscitation (HCR) entailing pre-emptive use of FFP and PLT in transfusion packages during uncontrolled haemorrhage and thereafter guided by thrombelastograph (TEG) analysis was employed. The effect of transfusion therapy and coagulopathy on mortality was investigated.
Patients included in the early and late period had comparable demography, injury severity score (ISS), admission hematology and coagulopathy (27% vs. 34% had APTT above normal). There was a significant change in blood transfusion practice with shorter time interval from admission to first transfusion (median time 3 min vs.28 min in massive bleeders, p < 0.001), transfusion of higher ratios of FFP:RBC, PLT:RBC and PLT:FFP in the HCR group but 30-day mortality remained comparable in the two periods. In the 2005-7 period, higher age, ISS and Activated Partial Thromboplastin Time (APTT) above normal were independent predictors of mortality whereas no association was fund between blood product ratios and mortality.
Aggressive administration of FFP and PLT did not influence mortality in the present trauma population.
PMCID: PMC3004812  PMID: 21138569

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