PeerJ Preprints: Hematologyhttps://peerj.com/preprints/index.atom?journal=peerj&subject=5000Hematology articles published in PeerJ PreprintsIdentification of reference genes in blood before and after entering the plateau for SYBR green RT-qPCR studieshttps://peerj.com/preprints/29292017-04-172017-04-17Jun XiaoXiaowei LiJuan LiuXiu FanHuifen LeiCuiying Li
Background: Tibetans have lived at high altitudes for thousands of years, and they have a unique composition of physiological traits that enable them to tolerate this hypoxic environment. However, the genetic basis of these traits is still unknown. As a sensitive and highly efficient technique, RT-qPCR is widely used in gene expression analyses to provide insight into the molecular mechanisms underlying environmental changes. However, the quantitative analysis of gene expression in blood is limited by a shortage of stable reference genes for the normalization of mRNA levels. Thus, systematic approaches were used to select potential reference genes. Results: Eight candidate reference genes (GAPDH, ACTB, 18S RNA, β2-MG, PPIA, RPL13A, TBP and SDHA) from humans were selected to assess their expression levels in blood under hypoxic environments. The expression stabilities of these candidate reference genes were evaluated using BestKeeper, geNorm and NormFinder programs. Interestingly, RPL13A was selected as the ideal reference gene to normalize the target gene expression in human blood before and after moving to the plateau. Conclusion: These results indicate that different reference genes should be selected for the normalization of gene expression in blood based on the environmental setting.
Background: Tibetans have lived at high altitudes for thousands of years, and they have a unique composition of physiological traits that enable them to tolerate this hypoxic environment. However, the genetic basis of these traits is still unknown. As a sensitive and highly efficient technique, RT-qPCR is widely used in gene expression analyses to provide insight into the molecular mechanisms underlying environmental changes. However, the quantitative analysis of gene expression in blood is limited by a shortage of stable reference genes for the normalization of mRNA levels. Thus, systematic approaches were used to select potential reference genes. Results: Eight candidate reference genes (GAPDH, ACTB, 18S RNA, β2-MG, PPIA, RPL13A, TBP and SDHA) from humans were selected to assess their expression levels in blood under hypoxic environments. The expression stabilities of these candidate reference genes were evaluated using BestKeeper, geNorm and NormFinder programs. Interestingly, RPL13A was selected as the ideal reference gene to normalize the target gene expression in human blood before and after moving to the plateau. Conclusion: These results indicate that different reference genes should be selected for the normalization of gene expression in blood based on the environmental setting.Differential gene expression analysis by RNA-seq reveals the importance of actin cytoskeletal proteins in leukemia cellshttps://peerj.com/preprints/27312017-01-182017-01-18Vanessa Fernández-CallejaPablo HernándezJorge B SchvartzmanDora B Krimer
Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of an erythroleukemia progenitor cell line (MEL-DS19) and a derived cell line with induced resistance to differentiation (MEL-R). RNA-seq analysis identified a total of 596 genes that were differentially expressed by more than two-fold, of which 486 genes were up-regulated in MEL-DS19 cells and 110 up-regulated in MEL-R cells. These observations revealed that the number of genes expressed in the parental cell line decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related with the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome), Btk (Bruton tyrosine kinase) and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, a significant percentage (16%) corresponded to genes coding for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed.
Development of drug resistance limits the effectiveness of anticancer treatments. Understanding the molecular mechanisms triggering this event in tumor cells may lead to improved therapeutic strategies. Here we used RNA-seq to compare the transcriptomes of an erythroleukemia progenitor cell line (MEL-DS19) and a derived cell line with induced resistance to differentiation (MEL-R). RNA-seq analysis identified a total of 596 genes that were differentially expressed by more than two-fold, of which 486 genes were up-regulated in MEL-DS19 cells and 110 up-regulated in MEL-R cells. These observations revealed that the number of genes expressed in the parental cell line decreased as the cells acquired the resistant phenotype. Clustering analysis of a group of genes showing the highest differential expression allowed identification of a sub-group among genes up-regulated in MEL cells. These genes are related with the organization of the actin cytoskeleton network. Moreover, the majority of these genes are preferentially expressed in the hematopoietic lineage and at least three of them, Was (Wiskott Aldrich syndrome), Btk (Bruton tyrosine kinase) and Rac2, when mutated in humans, give rise to severe hematopoietic deficiencies. Among the group of genes that were up-regulated in MEL-R cells, a significant percentage (16%) corresponded to genes coding for histone proteins, both canonical and variants. A potential implication of these results on the blockade of differentiation in resistant cells is discussed.The effects of cooling conditions on EDTA whole canine blood sampleshttps://peerj.com/preprints/23982016-08-282016-08-28Karen M TobiasLeslie SerranoXiaocun SunBente Flatland
Background. Preanalytic factors such as time and temperature can have significant effects on laboratory test results. For example, ammonium concentration will increase 31% in blood samples stored at room temperature for 30 minutes before centrifugation. To reduce preanalytic error, blood samples may be placed in precooled tubes and chilled on ice or in ice water baths; however, the effectiveness of these modalities in cooling blood samples has not been formally evaluated. The purpose of this study was to evaluate the effectiveness of various cooling modalities on reducing temperature of EDTA whole blood samples.
Methods. Pooled samples of canine EDTA whole blood were divided into two aliquots. Saline was added to one aliquot to produce a packed cell volume (PCV) of 40% and to the second aliquot to produce a PCV of 20% (simulated anemia). Thirty samples from each aliquot were warmed to 37.7°C and cooled in 2 ml allotments under one of three conditions: in ice, in ice after transfer to a precooled tube, or in an ice water bath. Temperature of each sample was recorded at one minute intervals for 15 minutes.
Results. Within treatment conditions, sample PCV had no significant effect on cooling. Cooling in ice water was significantly faster than cooling in ice only or transferring the sample to a precooled tube and cooling it on ice. Mean temperature of samples cooled in ice water was significantly lower at 15 minutes than mean temperatures of those cooled in ice, whether or not the tube was precooled. By 4 minutes, samples cooled in an ice water bath had reached mean temperatures less than 4°C (refrigeration temperature), while samples cooled in other conditions remained above 4.0°C for at least 11 minutes. For samples with a PCV of 40%, precooling the tube had no significant effect on rate of cooling on ice. For samples with a PCV of 20%, transfer to a precooled tube resulted in a significantly faster rate of cooling than direct placement of the warmed tube onto ice.
Discussion. Canine EDTA whole blood samples cool most rapidly and to a greater degree when placed in an ice-water bath rather than in ice. Samples stored on ice water can rapidly drop below normal refrigeration temperatures; this should be taken into consideration when using this cooling modality.
Background. Preanalytic factors such as time and temperature can have significant effects on laboratory test results. For example, ammonium concentration will increase 31% in blood samples stored at room temperature for 30 minutes before centrifugation. To reduce preanalytic error, blood samples may be placed in precooled tubes and chilled on ice or in ice water baths; however, the effectiveness of these modalities in cooling blood samples has not been formally evaluated. The purpose of this study was to evaluate the effectiveness of various cooling modalities on reducing temperature of EDTA whole blood samples.Methods. Pooled samples of canine EDTA whole blood were divided into two aliquots. Saline was added to one aliquot to produce a packed cell volume (PCV) of 40% and to the second aliquot to produce a PCV of 20% (simulated anemia). Thirty samples from each aliquot were warmed to 37.7°C and cooled in 2 ml allotments under one of three conditions: in ice, in ice after transfer to a precooled tube, or in an ice water bath. Temperature of each sample was recorded at one minute intervals for 15 minutes.Results. Within treatment conditions, sample PCV had no significant effect on cooling. Cooling in ice water was significantly faster than cooling in ice only or transferring the sample to a precooled tube and cooling it on ice. Mean temperature of samples cooled in ice water was significantly lower at 15 minutes than mean temperatures of those cooled in ice, whether or not the tube was precooled. By 4 minutes, samples cooled in an ice water bath had reached mean temperatures less than 4°C (refrigeration temperature), while samples cooled in other conditions remained above 4.0°C for at least 11 minutes. For samples with a PCV of 40%, precooling the tube had no significant effect on rate of cooling on ice. For samples with a PCV of 20%, transfer to a precooled tube resulted in a significantly faster rate of cooling than direct placement of the warmed tube onto ice. Discussion. Canine EDTA whole blood samples cool most rapidly and to a greater degree when placed in an ice-water bath rather than in ice. Samples stored on ice water can rapidly drop below normal refrigeration temperatures; this should be taken into consideration when using this cooling modality.A gene expression signature for defining aggressive phenotype and prognosis in intermediate-risk acute myeloid leukemiahttps://peerj.com/preprints/18332016-03-072016-03-07Ailing Deng
Intermediate-risk AML is a group of heterogeneous disease, complete and accurate understanding of their molecular pattern are urgent. We downloaded gene expression profile from TCGA, and performed the differential gene expression analysis of 98 intermediate-risk AML patients according to the different clinical outcome. By studying the overlap of differential genes based on OS and EFS classification, we identified 6 distinct genes (SPANXC, ADAMTS15, C8B, FAM183A, FLJ42875 and PXDN). Only FLJ42875 and PXDN were relatively widely expressed in intermediate-risk AML. Moreover, Q1 (0-25%) of PXDN was associated significantly shortened OS and EFS (P=0.0001, P=0.0032, respectively), while OS and EFS of Q2 (25-50%) of FLJ42875 expression group were significantly longer than that of low FLJ42875 expression patients (P=0.0157, P=0.0074, respectively). In the multivariable model of OS, PXDN Q1 group had a shorter OS and EFS (P < 0.001, P =0.009; respectively). While FLJ42875 Q2 group had a tendency of prolonged OS and EFS (P=0.050, P=0.023; respectively). Our results suggest that FLJ42875 and PXDN may play a role in the leukemogenesis of intermediate-risk AML.
Intermediate-risk AML is a group of heterogeneous disease, complete and accurate understanding of their molecular pattern are urgent. We downloaded gene expression profile from TCGA, and performed the differential gene expression analysis of 98 intermediate-risk AML patients according to the different clinical outcome. By studying the overlap of differential genes based on OS and EFS classification, we identified 6 distinct genes (SPANXC, ADAMTS15, C8B, FAM183A, FLJ42875 and PXDN). Only FLJ42875 and PXDN were relatively widely expressed in intermediate-risk AML. Moreover, Q1 (0-25%) of PXDN was associated significantly shortened OS and EFS (P=0.0001, P=0.0032, respectively), while OS and EFS of Q2 (25-50%) of FLJ42875 expression group were significantly longer than that of low FLJ42875 expression patients (P=0.0157, P=0.0074, respectively). In the multivariable model of OS, PXDN Q1 group had a shorter OS and EFS (P < 0.001, P =0.009; respectively). While FLJ42875 Q2 group had a tendency of prolonged OS and EFS (P=0.050, P=0.023; respectively). Our results suggest that FLJ42875 and PXDN may play a role in the leukemogenesis of intermediate-risk AML.The atherosclerosis of the sinus node artery is associated with an increased history of supra-ventricular arrhythmias: A retrospective study on 541 standard coronary angiogramshttps://peerj.com/preprints/12042015-07-012015-07-01Michele M CiullaMatteo AstutiStefano Carugo
BACKGROUND: The ischemic damage of the sinus node (SN) is a well known cause of cardiac arrhythmias and can be a consequence of any flow abnormality in the sinus node artery (SNA). Accordingly we aimed this retrospective study to: 1. evaluate the suitability of the standard coronary angiography to study the SNA and 2. determine if the percentage of subjects with a positive retrospective history of supra-ventricular arrhythmias (SVA) differs in patients with normal and diseased SNA ascertained at the time of coronary angiography. METHODS and RESULTS: out of the 541 coronary angiograms reviewed the SNA was visible for its entire course in 486 cases (89.8%). It was found to arise from the right side of the coronary circulation in 266 cases (54.7%) slightly more often than from the left, 219 cases (45.1%). One patient had 2 distinct SNA arising from either side of the coronary circulation. For the second objective we studied the 333 patients with: a. coronary artery disease (CAD), b. properly evaluable SNA and c. complete clinical history available. In 51 (15.3%) a SNA disease was found, the 41.2% of them had a positive SVA history, mainly atrial fibrillation (AF), whereas only the 7.4% of patients with a positive history of SVA could be found in the non-SNA diseased. This difference was statistically significant (P< 0.001). CONCLUSIONS: 1- The evaluation of the SNA is feasible in clinical practice during a standard coronary angiography; 2- this may be relevant since angiographically detectable SNA disease was significantly associated with a positive history of SVA .
BACKGROUND: The ischemic damage of the sinus node (SN) is a well known cause of cardiac arrhythmias and can be a consequence of any flow abnormality in the sinus node artery (SNA). Accordingly we aimed this retrospective study to: 1. evaluate the suitability of the standard coronary angiography to study the SNA and 2. determine if the percentage of subjects with a positive retrospective history of supra-ventricular arrhythmias (SVA) differs in patients with normal and diseased SNA ascertained at the time of coronary angiography. METHODS and RESULTS: out of the 541 coronary angiograms reviewed the SNA was visible for its entire course in 486 cases (89.8%). It was found to arise from the right side of the coronary circulation in 266 cases (54.7%) slightly more often than from the left, 219 cases (45.1%). One patient had 2 distinct SNA arising from either side of the coronary circulation. For the second objective we studied the 333 patients with: a. coronary artery disease (CAD), b. properly evaluable SNA and c. complete clinical history available. In 51 (15.3%) a SNA disease was found, the 41.2% of them had a positive SVA history, mainly atrial fibrillation (AF), whereas only the 7.4% of patients with a positive history of SVA could be found in the non-SNA diseased. This difference was statistically significant (P< 0.001). CONCLUSIONS: 1- The evaluation of the SNA is feasible in clinical practice during a standard coronary angiography; 2- this may be relevant since angiographically detectable SNA disease was significantly associated with a positive history of SVA .Low serum albumin and total lymphocyte count as predictors of 30 day hospital readmission in patients 65 years of age or olderhttps://peerj.com/preprints/11862015-06-182015-06-18Robert Robinson
Introduction: Hospital readmission within 30 days of discharge is a target for health care cost savings through the medicare Value Based Purchasing initiative. Because of this focus, hospitals and health systems are investing considerable resources into the identification of patients at risk of hospital readmission and designing interventions to reduce the rate of hospital readmission. Malnutrition is a known risk factor for hospital readmission.
Materials and Methods: All medical patients 65 years of age or older discharged from Memorial Medical Center from January 1, 2012 to March 31, 2012 who had a determination of serum albumin level and total lymphocyte count on hospital admission were studied retrospectively. Admission serum albumin levels and total lymphocyte counts were used to classify the nutritional status of all patients in the study. Patients with a serum albumin less than 3.5 grams/dL and/or a TLC less than 1,500 cells per mm3 were classified as having protein energy malnutrition. The primary outcome investigated in this study was hospital readmission for any reason within 30 days of discharge.
Results: The study population included 1,683 hospital discharges with an average age of 79 years. The majority of the patients were female (55.9%) and had a DRG weight of 1.22 (0.68). 219 patients (13%) were readmitted within 30 days of hospital discharge. Protein energy malnutrition was common in this population. Low albumin was found in 973 (58%) patients and a low TLC was found in 1,152 (68%) patients. Low albumin and low TLC was found in 709 (42%) of patients. Kaplan-Meier analysis shows any laboratory evidence of PEM is a significant (p < 0.001) predictor of hospital readmission. Low serum albumin (p < 0.001) and TLC (p = 0.018) show similar trends. Cox proportional-hazards regression analysis showed low serum albumin (Hazard Ratio 3.27, 95% CI: 2.30-4.63) and higher DRG weight (Hazard Ratio 1.19, 95% CI: 1.03-1.38) to be significant independent predictors of hospital readmission within 30 days.
Discussion: This study investigated the relationship of PEM to the rate of hospital readmission within 30 days of discharge in patients 65 years of age or older. These results indicate that laboratory markers of PEM can identify patients at risk of hospital readmission within 30 days of discharge. This risk determination is simple and identifies a potentially modifiable risk factor for readmission: protein energy malnutrition.
Introduction: Hospital readmission within 30 days of discharge is a target for health care cost savings through the medicare Value Based Purchasing initiative. Because of this focus, hospitals and health systems are investing considerable resources into the identification of patients at risk of hospital readmission and designing interventions to reduce the rate of hospital readmission. Malnutrition is a known risk factor for hospital readmission.Materials and Methods: All medical patients 65 years of age or older discharged from Memorial Medical Center from January 1, 2012 to March 31, 2012 who had a determination of serum albumin level and total lymphocyte count on hospital admission were studied retrospectively. Admission serum albumin levels and total lymphocyte counts were used to classify the nutritional status of all patients in the study. Patients with a serum albumin less than 3.5 grams/dL and/or a TLC less than 1,500 cells per mm3 were classified as having protein energy malnutrition. The primary outcome investigated in this study was hospital readmission for any reason within 30 days of discharge.Results: The study population included 1,683 hospital discharges with an average age of 79 years. The majority of the patients were female (55.9%) and had a DRG weight of 1.22 (0.68). 219 patients (13%) were readmitted within 30 days of hospital discharge. Protein energy malnutrition was common in this population. Low albumin was found in 973 (58%) patients and a low TLC was found in 1,152 (68%) patients. Low albumin and low TLC was found in 709 (42%) of patients. Kaplan-Meier analysis shows any laboratory evidence of PEM is a significant (p < 0.001) predictor of hospital readmission. Low serum albumin (p < 0.001) and TLC (p = 0.018) show similar trends. Cox proportional-hazards regression analysis showed low serum albumin (Hazard Ratio 3.27, 95% CI: 2.30-4.63) and higher DRG weight (Hazard Ratio 1.19, 95% CI: 1.03-1.38) to be significant independent predictors of hospital readmission within 30 days.Discussion: This study investigated the relationship of PEM to the rate of hospital readmission within 30 days of discharge in patients 65 years of age or older. These results indicate that laboratory markers of PEM can identify patients at risk of hospital readmission within 30 days of discharge. This risk determination is simple and identifies a potentially modifiable risk factor for readmission: protein energy malnutrition.Oxygen transport and release of adenosine triphosphate in micro-channelshttps://peerj.com/preprints/10032015-04-242015-04-24Terry Moschandreou
The governing nonlinear steady equations for oxygen transport in a microfluidic channel are solved analytically. The Lagrange inversion theorem is used which admits complete integrable solutions in the channel. Considering a cell-rich and cell free region with RBCs and blood plasma, we obtain results showing clearly that there is a significant decrease in oxygen tension in the vicinity of an oxygen permeable membrane placed on the upper channel/tube wall and to the right side of it in the downstream field. The purpose of the membrane is to cause a rapid change in oxygen saturation as RBC’s flow through channel/tube. To the right of the membrane downstream the greatest amount of ATP is released. The method of solution is compared to numerical results. The analytical results obtained could prove useful for the corresponding time dependent problem in future studies.
The governing nonlinear steady equations for oxygen transport in a microfluidic channel are solved analytically. The Lagrange inversion theorem is used which admits complete integrable solutions in the channel. Considering a cell-rich and cell free region with RBCs and blood plasma, we obtain results showing clearly that there is a significant decrease in oxygen tension in the vicinity of an oxygen permeable membrane placed on the upper channel/tube wall and to the right side of it in the downstream field. The purpose of the membrane is to cause a rapid change in oxygen saturation as RBC’s flow through channel/tube. To the right of the membrane downstream the greatest amount of ATP is released. The method of solution is compared to numerical results. The analytical results obtained could prove useful for the corresponding time dependent problem in future studies.Placental vascular pathology and increased thrombin generation as mechanisms of disease in obstetrical syndromeshttps://peerj.com/preprints/487v12014-09-042014-09-04Salvatore Andrea MastroliaMoshe MazorGiuseppe LoverroVered KlaitmanOffer Erez
Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e. infection inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti-thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal-fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.
Obstetrical complications including preeclampsia, fetal growth restriction, preterm labor, preterm prelabor rupture of membranes and fetal demise are all the clinical endpoint of several underlying mechanisms (i.e. infection inflammation, thrombosis, endocrine disorder, immunologic rejection, genetic, and environmental), therefore, they may be regarded as syndromes. Placental vascular pathology and increased thrombin generation were reported in all of these obstetrical syndromes. Moreover, elevated concentrations of thrombin-anti-thrombin III complexes and changes in the coagulation as well as anticoagulation factors can be detected in the maternal circulation prior to the clinical development of the disease in some of these syndromes. In this review, we will assess the changes in the hemostatic system during normal and complicated pregnancy in maternal blood, maternal-fetal interface and amniotic fluid, and describe the contribution of thrombosis and vascular pathology to the development of the great obstetrical syndromes.MicroRNAs expression profile in CCR6+ regulatory T cellshttps://peerj.com/preprints/471v22014-08-222014-08-22Juanjuan ZhaoYongju LiYan HuChao ChenYa ZhouYijin TaoMengmeng GuoNalin QinLin Xu
Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.
Backgroud: CCR6+ CD4+ regulatory T cells (CCR6+Tregs), a distinct Tregs subset, played an important role in various immune diseases. Recent evidence showed that microRNAs (miRNAs) are vital regulators in the function of immune cells. However, the potential role of miRNAs in the function of CCR6+Tregs remains largely unknown. In this study, we detected the expression profile of miRNAs in CCR6+ Tregs. Materials and Methods: The expression profile of miRNAs as well as genes in CCR6+Tregs or CCR6-Tregs from Balb/c mice were detected by microarray. The signaling pathways were analyzed using Keggs pathway library. Results: We found that there were 58 miRNAs significantly upregulated and 62 downregulated up to 2 fold in CCR6+Tregs compared with CCR6-Tregs. Moreover, 1391 genes were observed with 3 fold change and 20 signaling pathways were enriched using Keggs pathway library. Conclusion: The present data firstly showed CCR6+Tregs expressed specific miRNAs pattern, which provide an insight into the role of miRNAs in the biological function of distinct Tregs subsets.Functional enhancement of platelet activation and aggregation by erythrocytes: role of red cells in thrombosishttps://peerj.com/preprints/351v12014-04-022014-04-02Gabrielle E BrownLeslie S. RitterPaul F. McDonaghZoe Cohen
Platelets expose phosphatidylserine (PS), a component of the prothrombinase complex, on the outer surface of the plasma membrane when activated. [ref 1] The prothrombinase complex catalyzes the conversion of prothrombin to thrombin, and it has been demonstrated that an increase in PS exposure is correlated with an increase in thrombin generation by platelets. [refs 2,3] Similarly, erythrocyte (RBC) activation, or eryptosis, is also characterized by PS exposure on the plasma membrane. [ref 4] Although PS exposure on RBCs is considered a signal for splenic macrophage destruction, eryptosis may allow RBCs to contribute to thrombosis.[ref 4] The aims of this study were to determine whether the addition of RBCs to platelets increased functional platelet aggregation and coagulation properties. A ratio of 4 RBCs to 1 platelet (4:1) was evaluated for aggregation and coagulation compared to platelet control. Platelet aggregation and coagulation properties were evaluated with impedance aggregometry and thromboelastography, respectively. The 4:1 experimental group had significant increases in aggregation and coagulation relative to the platelet control. These results indicate that RBCs increase platelet aggregation and coagulation properties. This suggests that RBCs play a role in diseases traditionally thought of as associated solely via dysregulated platelet activation.
Platelets expose phosphatidylserine (PS), a component of the prothrombinase complex, on the outer surface of the plasma membrane when activated. [ref 1] The prothrombinase complex catalyzes the conversion of prothrombin to thrombin, and it has been demonstrated that an increase in PS exposure is correlated with an increase in thrombin generation by platelets. [refs 2,3] Similarly, erythrocyte (RBC) activation, or eryptosis, is also characterized by PS exposure on the plasma membrane. [ref 4] Although PS exposure on RBCs is considered a signal for splenic macrophage destruction, eryptosis may allow RBCs to contribute to thrombosis.[ref 4] The aims of this study were to determine whether the addition of RBCs to platelets increased functional platelet aggregation and coagulation properties. A ratio of 4 RBCs to 1 platelet (4:1) was evaluated for aggregation and coagulation compared to platelet control. Platelet aggregation and coagulation properties were evaluated with impedance aggregometry and thromboelastography, respectively. The 4:1 experimental group had significant increases in aggregation and coagulation relative to the platelet control. These results indicate that RBCs increase platelet aggregation and coagulation properties. This suggests that RBCs play a role in diseases traditionally thought of as associated solely via dysregulated platelet activation.