Fib Levels Research Articles

Efficacy of 20% albumin infusion on coagulation and pulmonary fibrosis in rabbits with ARDS

To observe the efficacy of 20% albumin infusion on coagulation and pulmonary fibrosis in rabbits with acute respiratory distress syndrome (ARDS) induced by two-hit of intravenous infusion of oleid acid (OA) and lipopolysaccharide (LPS). Forty healthy adult male rabbits were randomly divided into five groups, namely sham group, model group, albumin group (20% albumin), saline group (0.9% sodium chloride injection) and Ringer group (lactate Ringer solution), with 8 rabbits in each group. ARDS model was reproduced by 0.1 mL/kg of OA and 500 μg/kg of LPS through left auricular vein, and the rabbits in sham group were intravenously infused a same volume of saline as the LPS volume given in model group. The rabbits in the three treatment groups were intravenously given corresponding drugs by micro scale pumping following LPS and OA injection through left auricular vein for 210 minutes, but no infusion was given in sham and model groups. The right internal jugular vein blood was collected, and the prothrombin time (PT), active partial prothrombin time (APTT), antithrombin III (ATIII), fibrinogen (Fib) and serum procollagen peptide III (PIIIP) levels were determined at 5, 30, 120 and 210 minutes after model reproduction respectively. Expressions of collagen I and collagen III of lung tissue were observed by immunohistochemical staining. The correlations between coagulation indexes and PIIIP levels were analyzed by partial correlation analysis. Compared with sham group, APTT in model animal was dynamically prolonged at 30 minutes, with a peak at the 120 minutes and then a little fall at the 210 minutes. PT had a tendency of prolongation, but no difference was found as compared with that of sham group. Fib and ATIII levels were seen to decrease gradually till 210 minutes in model group. PIIIP began to rise at 30 minutes, then decreased a little. Both the collagen I and III levels in pulmonary tissue were increasingly expressed in model rabbits. Compared with model group, the rabbits in albumin and saline groups had a similar APTT changes as that in model rabbits, but APTT in Ringer group was dynamically prolonged. PT changed more obviously in treatment groups, especially in saline group. Fib, ATIII as well as collagen I and III levels were lowered in the treatment groups, especially in albumin group [210-minute ATIII: (64.50±17.94)% vs. (85.00±18.36)%, 210-minute collagen I (A value): 0.20±0.01 vs. 0.37±0.04, collagen III (A value): 0.19±0.02 vs. 0.38±0.04, all P < 0.05]. Serum PIIIP levels in treatment groups got obviously decreased, especially in saline group [210-minute PIIIP (μg/L): 222.76±18.69 vs. 295.45±42.75, P < 0.01]. It was shown by correlation analysis that the PIIIP in model group was positively correlated with APTT (r = 0.458, P = 0.021), but they had some negative correlation in fluid treatment groups (r = -0.194, P = 0.092). It was shown that 20% albumin infusion are more effective to promote oxygenation improvement as compared with saline and Ringer solution in rabbits with ARDS, and obviously decrease pulmonary collagen I and III levels in lung tissue, which indicate that hypoxemia improvement maybe related with pulmonary fibrosis alleviation.

Effect of stress level on blood coagulation and fracture healing in fracture patients

Objective To investigate the effect of stress level on blood coagulation and fracture healing in fracture patients. Methods The clinical data of 50 fracture patients (fracture group) and 50 healthy volunteers (control group) were analyzed retrospectively. The oxidative stress indexes [superoxide dismutase (SOD) and malondialdehyde (MDA)] and blood coagulation indexes [plasma fibrinogen (Fib), activated partial thromboplastin time (APTT), thrombin time (TT), and prothrombin time (PT)] were compared between the 2 groups. Correlation between stress level and coagulation indexes in the fracture patients was analyzed by Spearman correlation coefficient. The correlation between stress level and the progress of fracture healing in fracture patients was analyzed. Results There were no significant differences in APTT, TT, PT or other blood co-agulation indexes between the 2 groups (P >0.05). The fracture group had a significantly lower SOD level but significantly higher MDA and Fib levels than the control group (P< 0.05). Spearman analysis showed that the SOD level was negatively correlated to the Fib level (P < 0.05) while the MDA level was positively correlated to the Fib level in the fracture group (P< 0.05). The MDA level was negatively correlated to the process of fracture healing (P< 0.05) while the SOD level was positively correlated to the process of fracture healing in the fracture group (P< 0.05). Conclusions Traumatic fracture can cause stress reaction. It should be kept in mind that the severity of stress reaction is closely related to the Fib level and the process of fracture healing. Key words: Fractures, bone; Oxidative stress; Thrombin time; Fracture healing

Genetic characterization of fecal impacts of seagull migration on an urban scenery lake

A microbial source tracking scheme was devised to differentiate fecal impacts of seagulls from that of human activities on an urban scenery lake in southern China, which is a major wintering ground for the black-headed seagull. Fecal contamination of seagulls was characterized by quantifying a novel genetic marker targeting Catellicoccus marimamalium. Quantification of this marker was combined with those of Escherichia coli, human-associated Bacteroidales, thermophilic Campylobacter and Helicobacter. Findings of a year-round study indicate that C. marimamalium levels correlated strongly, both spatially and temporally, with seagull migration. A steady increase in C. marimammalium concentrations was recorded between October 2014 and March 2015, which peaked at about 5-log copies/100 mL in January. However, a background level of about 2.1-log copies/100 mL was noticeable from April through September when seagulls were absent, probably due to other host sources or secondary habitats for C. marimammalium. Seagull migration also caused an apparent elevation of E. coli concentrations (86% and 60%, respectively for qPCR and culture method; p < 0.001) as well as Campylobacter and Helicobacter (66% and 68%, respectively; p < 0.001). Nonetheless, in contrast to the declining levels of E. coli, Campylobacter and Helicobacter, the human-specific Bacteroidales marginally increased in the seagull-absent season, indicating a limited influence of human activities, compared with seagull migration, on the seasonal variations in microbial water quality of the lake. The elevated levels of FIB, Campylobacter and Helicobacter along with C. marimammalium may imply human health risk of the lake water due to seasonal seagull migration, which requires further investigation for risk assessment.

Fibrinogen is related to long-term mortality in Chinese patients with acute coronary syndrome but failed to enhance the prognostic value of the GRACE score.

Fibrinogen (Fib) is considered to be a potential risk factor for the prognosis of patients with acute coronary syndrome (ACS), but it is unclear whether Fib level have synergistic effects to enhance the prognostic value of the GRACE score in patients with ACS. A retrospective analysis was conducted from a single registered database. 2253 consecutive patients with ACS confirmed by coronary angiography were enrolled and were grouped into 3 categories by the tertiles of admission plasma Fib levels. The end points were all-cause mortality and cardiac mortality. The mean follow-up time was 27.2 ± 13.1 months and death events occurred in 223 cases and cardiac death events occurred in 130 cases. Cumulative survival curves indicated that the risk of all-cause death increased with increasing Fib level (mortality rates for Tertile 1 vs. Tertile 2 vs. Tertile 3 = 6.6% vs. 10.8 %vs. 12.3%, p < 0.001). Cox multivariate regression analysis indicated that compared with other traditional risk factors, plasma Fib level is independently correlated with all-cause death (HR 1.33, 95% CI 1.04-1.70). However, incorporating elevated Fib level into the GRACE model did not significantly increase the predictive value of the GRACE score; for instance, AUC only increased from 0.703 to 0.713 (p = 0.765). In conclusion, Fib level at admission was independently associated with death risk among Chinese patients with ACS. However, the incorporation of Fib level at admission into the GRACE score did not improve this score’s predictive value for death risk among these patients.

Physiological role of erythrocyte nitric oxide.

Nitric oxide (NO) produced by endothelial cells interacts with erythrocyte through band 3 protein, being scavenged by haemoglobin. A signal transduction mechanism involving protein Gi and protein band 3 stimulates erythrocyte NO efflux when acetylcholine (ACh) binds to erythrocyte membrane acetylcholinesterase. Binding of normal plasma fibrinogen (Fib) levels, to erythrocyte membrane CD47 decreases the NO efflux. When high Fib concentration and ACh were present the efflux of NO from erythrocytes was normalized. The increased NO efflux from erythrocytes in presence of high Fib concentration and band 3 phosphorylation is reinforced in the presence of 4N1K an agonist peptide of CD47. When both Fib and 4N1K are present the NO efflux from erythrocytes is higher or not affected according lower or high levels of cAMP. Erythrocyte NO efflux in patients with systemic lupus erythematous and rheumatoid attrite was significantly negative associated with carotid intima-media thickness. In patients with amyotrophic lateral sclerosis erythrocyte NO content is preserved and an inverse association between respiratory function and NO efflux from the erythrocyte was verified. Sepsis patients before dead at 24 h showed higher efflux of NO from erythrocytes that worsening the blood sub lingual microcirculation observed by high unequal blood flow and high microvascular flow index. The in vivo animal models either of inflammation or of hypertension evidenced that the NO efflux from erythrocyte decrease as a compensatory mechanism. All studies conducted since 2000 where we demonstrated the existence NO inside the erythrocyte by fluorescence microscopy, and after their signaling pathway needs more development translational research for news therapeutics and further application in not invasive therapy to vascular inflammatory diseases.

Prognostic value of combined preoperative fibrinogen and neutrophil-lymphocyte ratio in patients with hepatocellular carcinoma after liver transplantation.

ObjectivesElevated plasma fibrinogen (Fib) correlated with patient's prognosis in several solid tumors. However, few studies have illuminated the relationship between preoperative Fib and prognosis of HCC after liver transplantation. We aimed to clarify the prognostic value of Fib and whether the prognostic accuracy can be enhanced by the combination of Fib and neutrophil–lymphocyte ratio (NLR).ResultsFib was correlated with Child-pugh stage, alpha-fetoprotein (AFP), size of largest tumor, macro- and micro-vascular invasion. Univariate analysis showed preoperative Fib, AFP, NLR, size of largest tumor, tumor number, macro- and micro- vascular invasion were significantly associated with disease-free survival (DFS) and overall survival (OS) in HCC patients with liver transplantation. After multivariate analysis, only Fib and macro-vascular invasion were independently correlated with DFS and OS. Survival analysis showed that preoperative Fib > 2.345 g/L predicted poor prognosis of patients HCC after liver transplantation. Preoperative Fib showed prognostic value in various subgroups of HCC. Furthermore, the predictive range was expanded by the combination of Fib and NLR.Materials and MethodsData were collected retrospectively from 130 HCC patients who underwent liver transplantation. Preoperative Fib, NLR and clinicopathologic variables were analyzed. The survival analysis was performed by the Kaplan-Meier method, and compared by the log-rank test. Univariate and multivariate analyses were performed to identify the prognostic factors for DFS and OS.ConclusionsPreoperative Fib is an independent effective predictor of prognosis for HCC patients, higher levels of Fib predict poorer outcomes and the combination of Fib and NLR enlarges the prognostic accuracy of testing.

Analysis of coagulation related parameters between patients with advanced schistosomiasis cirrhosis and hepatitis B cirrhosis

To analyze the differences of coagulation parameters between patients with advanced schistosomiasis cirrhosis and hepatitis B cirrhosis under different degrees of liver function, so as to provide the evidence for further guidance of judging clinical condition and prognosis. Sixty-three patients with advanced schistosomiasis cirrhosis and eighty patients with hepatitis B induced cirrhosis hospitalized in Jingzhou Central Hospital from January 2014 to June 2016 were served as an advanced schistosomiasis cirrhosis group and a hepatitis B cirrhosis group, respectively, and ninety-six gastropathy patients excluded from other diseases that might affect coagulation in the same period were served as a control group. The levels of PT, INR, Fib, TT, APTT, and PLT of the patients among the above 3 groups and the cirrhosis patients with different Child-Pugh classes were detected and compared. The differences of the levels of PT, INR, Fib, TT, APTT, and PLT among the 3 groups were statistically significant (F = 84.512, 81.672, 37.612, 104.475, 52.497, 102.233; all P ＜0.05). The further analysis showed that PT, INR, TT, and APTT of both the advanced schistosomiasis cirrhosis and hepatitis B induced cirrhosis groups were longer than those of the control group, and the PLT levels of both the former 2 groups were lower than that of the control group (all P < 0.05). Compared with the advanced schistosomiasis cirrhosis group, PT, INR, TT, and APTT of the hepatitis B induced cirrhosis group were longer, and the levels of Fib and PLT were lower (all P < 0.05). Among those with the liver function of Grade A, the reduced degree of PLT in the patients with hepatitis B induced cirrhosis was more serious, while for those with the liver function of Grade B and C, the difference between the patients with advanced schistosomiasis cirrhosis and hepatitis B induced cirrhosis was not statistically significant (both P > 0.05). Under all the grades of liver function, TT and APTT of the hepatitis B induced cirrhosis group was longer than those of the advanced schistosomiasis cirrhosis group, and the Fib level of the former was lower than that of the latter. Among those with the liver function of Grade A and B, PT and INR of the hepatitis B induced cirrhosis group were longer than those of the advanced schistosomiasis cirrhosis group; while for those with the liver function of Grade C, the difference between the two groups was not statistically significant (all P > 0.05). There exist differences of the damage degrees of coagulation function between the patients with advanced schistosomiasis cirrhosis and hepatitis B cirrhosis. When the damage degree of the liver function is lighter, the coagulation function in the patients with hepatitis B cirrhosis decreases more significantly; when the damage degree becomes more severe, APPT in the patients with hepatitis B cirrhosis extends more significantly, while the differences of PLT and PT between them are little.

Coagulation status after therapeutic plasma exchange using citrate in kidney transplant recipients.

Therapeutic plasma exchange (TPE) is increasingly used for treatment of antibody-mediated rejection (AMR) after solid organ transplants. There is concern that TPE may increase risk of bleeding, although data are limited. After TPE, clot-based coagulation tests may not accurately represent the levels of coagulation factors due to the effect of citrate. We investigated protein levels of fibrinogen using antigen detection method (FibAg) and correlated results with a clot-based fibrinogen activity test (Fib). Nine kidney transplant recipients who received TPE for AMR were investigated. Fib, FibAg, prothrombin time/international normalized ratio (PT/INR), partial thromboplastin time (PTT), coagulation factor X chromogenic activity (CFX), and ionized calcium (iCa) were measured at pre- and post-TPE and 1, 3, 6, 9, 24, and 48 hours after the first TPE. Mean Fib/FibAg ratio before TPE was 1.08; therefore, all Fib values were normalized (n) by dividing by 1.08. Overall, the mean normalized Fib (nFib)/FibAg ratio at post-TPE was 0.89 and returned to close to 1.0 at 6 hours after the first TPE. Decreases in nFib, FibAg, and CFX and increases in PT/INR and PTT post-TPE were observed. The lowest Fib, FibAg, CFX, platelet, and iCa levels were still at levels that would be considered sufficient for hemostasis at all time points. The mean nFib/FibAg ratio after TPE was 0.89 and normalized in 6 hours, which demonstrates a persistent effect of citrate for up to 6 hours. Therefore, similar data observed in clot-based tests of PT/INR and PTT may be falsely elevated up to 6 hours after TPE due to the citrate effect.

Characterization of nanobodies binding human fibrinogen selected by E. coli display

Abnormal levels of fibrinogen (Fib) in blood plasma are associated with several pathological conditions and hence methods for its detection in blood and body fluids are essential. Nanobodies (Nbs) or (VHHs) are single domain antibodies derived from camelids with excellent biophysical and antigen-binding properties, showing great promise in diagnostics and therapy. In this work, we select and characterize high affinity Nbs binding human Fib employing an E. coli cell surface display system based on the fusion of an immune library of VHH domains with the β-domain of Intimin. Bacteria displaying high-affinity Nbs against Fib were selected using magnetic cell sorting (MACS). Specific binding of the selected clones to Fib was confirmed by flow cytometry of E. coli bacteria, as well as by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) with the purified Nbs. E. coli display also provided an excellent estimation of the affinity of the selected Nbs by flow cytometry analysis under equilibrium conditions, with equilibrium constant (KD) values very similar to those obtained by SPR analysis. Finally, pairwise epitope-scouting studies revealed that the selected Nbs bound distinct epitopes on Fib. The selected Nbs are promising diagnostic tools for determination of human Fib levels.

Understanding the controversy surrounding the correlation between fibrinogen level and prognosis of coronary artery disease—The role of the subtypes of coronary artery disease

BackgroundThere is a controversy surrounding the correlation between fibrinogen (Fib) level and prognosis of coronary artery disease (CAD). We try to investigate the role of the subtypes of CAD in this controversy. MethodsA retrospective analysis was conducted from a single center CAD registered database. 3020 consecutive patients with CAD confirmed by coronary angiography were enrolled. The end points were all-cause mortality. ResultsThe mean follow-up time was 27.2±13.1months and death events occurred in 258 cases. Mortality rates for patients with CAD and those in the stable coronary artery disease (SCAD) and unstable angina pectoris (UAP) groups exhibited an overall rising trend as Fib levels increased (log rank test, all p<0.05). However, similar trends were not detected in patients with acute myocardial infarction (AMI). The results of a Cox proportional-hazards regression analysis showed that Fib level was independently correlated with the risk of death in patients with CAD as well as those in the SCAD and UAP groups (CAD, HR 1.40, CI 1.16–1.68; SCAD, HR 1.86, CI 1.24–2.79; UAP, HR 1.42, CI 1.06–1.90). In the AMI group, however, no independent correlation was observed between Fib level and mortality. ConclusionThe different proportions of subtypes of CAD affected the correlation between Fib level and the clinical prognosis of patients with CAD. This is maybe a clue to explain the controversy.

Relationship between metabolites of arachidonic acid and prognosis in patients with acute coronary syndrome

ObjectiveTo investigate the correlation of arachidonic acid (ARA) metabolites and prognosis in ACS patients. Methods and resultsThis is a mono-center retrospective nested case-control study. We followed up 470 ACS patients, of whom 39 patients had MACE in a mean follow up time of 1037days (identified as MACE group). Another 39 clinically matched patients without MACE were selected from the 470 ACS patients (Non-MACE group). Thirty-nine subjects without Coronary Heart Disease were enrolled as Control group. Metabolites of ARA were determined by LC-MS/MS. We found that plasma levels of LTB4, 8-HETE, 11-HETE, 12-HETE, and 15-HETE were significantly increased in MACE and Non-MACE groups, 5-HETE and 9-HETE were significantly increased in MACE group comparing with Control group (P<0.05). Importantly, plasma level of 19-HETE in MACE group was significantly lower than Non-MACE and Control groups. 19-HETE significantly correlated with the prognosis of ACS after adjustment for clinical characteristics (HR=0.103, 95% C.I.: 0.014–0.766). The AUC for ROC curve of 19-HETE in predicting MACE was 0.637 (P<0.05). Survival analysis showed that ACS patients with 19-HETE levels higher than 0.13ng/ml tend to have better prognosis than those lower than 0.13ng/ml (P<0.05). GRACE score and serum Fib levels were also significantly correlated with MACE. 20-HETE level was found significantly higher in STEMI group comparing with NSTE-ACS group (P<0.05). ConclusionPlasma arachidonic acid metabolites may act as prognostic markers for ACS patients.

Relationship between fibrinogen and tumor and the mechanism

Fibrinogen (Fib) is one of the most common coagulation proteins, plays an important role in the coagulation cascade, and has a closed relationship with tumor. Studies indicate that the level of Fib has elevated in many kinds of cancer, and Fib is also closely correlated with the progression, metastasis and prognosis of tumor. Though the mechanism of the interaction of Fib and tumor is still unclear, Fib as a tumor marker and new therapy for these malignancies has been a new hotspot. Key words: Fibrinogen; Neoplasms; Tumor metastasis; Prognosis

Evolution of procalcitonin, C-reactive protein and fibrinogen levels in neutropenic leukaemia patients with invasive pulmonary aspergillosis or mucormycosis.

Unlike bacterial infections, the value of procalcitonin (PCT) in detecting fungal infections in leukaemia patients is not clear. To determine whether the monitoring of PCT coupled with C-reactive protein (CRP) and fibrinogen (Fib) could be helpful in the management of pulmonary aspergillosis (IPA) or mucormycosis (PM), we retrospectively analysed the evolution of PCT, CRP and Fib levels in 94 leukaemia patients with proven/probable IPA (n=77) or PM (n=17) from D-12 to D12 relative to IFI onset defined as D0. Overall, 2140 assays were performed. From D-12 to D0, 12%, 5% and 1.4% of patients had PCT >0.5, 1 and 1.5μgl(-1) , respectively, while CRP was >50, 75 and 100mgl(-1) in 84%, 70% and 57% and Fib was >4, 5 and 6gl(-1) in 96%, 80% and 61% of cases respectively (P<10(-7) ). The same trends were observed from D1 to D12. Overall, between D-12 and D12, only 6.4% of patients had PCT >1.5μgl(-1) , while CRP >100mgl(-1) and Fib >6gl(-1) were observed in 80% and 75% of cases respectively (P<10(-7) ). In leukaemia patients, IPA or PM was accompanied by a significant increase in CRP and Fib while PCT remained low.

Hypercoagulable state as demonstrated by thromboelastometry in hemoglobin E/beta-thalassemia patients: Association with clinical severity and splenectomy status

IntroductionPatients with hemoglobin E/beta-thalassemia disease (E/β) are at risk of thromboembolism. Rotational thromboelastometry (ROTEM®) can be used to determine a hypercoagulable state. The objective was to describe the hemostatic and thromboelastometric changes in pediatric patients with E/β with different clinical severity, in comparison with healthy children as controls. Materials and methodsFifty-three pediatric patients with E/β and 21 healthy children were enrolled. The clinical severity of E/β was categorized by using the clinical severity scores. All subjects were tested for complete blood count, protein C activity (PC), total protein S (PS), antithrombin (AT), D-dimer and fibrinogen (Fib) levels and thromboelastometry, measured by ROTEM®. ResultsThe levels of PC (65.7 vs 118.5%), PS (46.8 vs 78.4%), AT (95.7 vs 105.7%) and Fib (217 vs 294mg/dL) were significantly lower, and the platelet count (PLT) was significantly higher in the patient group than the controls. The maximum clot firmness (MCF) of patients with moderate disease who were previously splenectomized (seven patients) and patients with severe disease (nine patients) were higher than patients who had intact spleen with moderate disease, patients with mild disease and controls (P<0.05). Only PLT had significant correlation with MCF (P<0.05). ConclusionsHypercoagulable state was demonstrated by ROTEM® in patients with E/β with severe disease and who were previously splenectomized. The hypercoagulable state was associated with the higher numbers of PLT rather than the decrease of PC, PS, and AT.

Research on hemostasis of hemocoagulase in patients with hemorrhagic cystitis post-allogeneic hematopoietic stem cell transplantation

Research on hemostasis of hemocoagulase in patients with hemorrhagic cystitis post-allogeneic hematopoietic stem cell transplantation

Selection in sugarcane based on inbreeding depression.

This study aimed to evaluate the gene action associated with yield-related traits, including mean stalk weight (MSW), tons of sugarcane per hectare (TCH), and fiber content (FIB) in sugarcane. Moreover, the viability of individual reciprocal recurrent selection (RRSI-S1) was verified, and the effect of inbreeding depression on progenies was checked. The results were also used to select promising genotypes in S1 progenies. Eight clones (RB925345, RB867515, RB739359, SP80-1816, RB928064, RB865230, RB855536, and RB943365) and their respective progenies, derived from selfing (S1), were evaluated. Several traits, including the number of stalks, MSW, soluble solids content determined in the field, stalk height, stalk diameter, TCH, soluble solids content determined in the laboratory, sucrose content, and FIB were evaluated in a randomized block design with hierarchical classification. The results showed that the traits with predominant gene action associated with the dominance variance of MSW and TCH were most affected by inbreeding depression. The FIB, with predominant additive control, was not affected by selfing of the clones, and the RB867515⊗, RB928064⊗, RB739359⊗ and RB925345⊗ progenies performed best. Therefore, the use of S1 progenies for RRSI-S1 in sugarcane breeding programs is promising, and it should be explored for the future breeding of clones with high FIB levels.

A High Incidence of Disseminated Intravascular Coagulation in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia and Its Management

IntroductionDisseminated intravascular coagulation (DIC) occurs about 10% of adult patients with acute lymphoblastic leukemia (ALL) at presentation, and develops in approximately 30-40% of adult patients after starting induction therapy. Although reports of DIC developing with a high frequency in Philadelphia chromosome-positive (Ph+) ALL are scarce, we have experienced many cases of DIC in Ph+ ALL patients.We start chemotherapy and prednisolone (PSL) at the same time after diagnosis of ALL, and give imatinib (IM) at the time it is found to be Ph+. However, we have experienced cases of early death due to severe DIC and tumor lysis syndrome (TLS) when utilizing this approach. Therefore, we have tried mild tumor reduction via initiation of PSL, IM and chemotherapy at different times.We investigated the difference in the incidence of DIC between Ph+ ALL patients and Ph negative (Ph-) ALL patients and discuss the management of DIC and its effect.Patients and methodsWe examined ALL patients who received their first treatment at our institution between January 2012 and December 2014.We monitored for DIC by twice daily blood testing, and diagnosed DIC according to the diagnostic criteria for DIC of the Japanese Ministry of Health, Labour and Welfare. When DIC developed, the patients were encouraged to rest, and we treated DIC with recombinant human soluble thrombomodulin (rTM) and/or gabexate mesylsate (FOY). To prevent bleeding episodes, platelet (Plt) and fresh frozen plasma transfusion were given to maintain Plt count >50,000/ul and fibrinogen (Fib) level >100 mg/dl.For induction therapy, to avoid rapid development of DIC and TLS, we first administered PSL 60 mg/m2. While confirming a decrease in leukocyte counts and fibrin degradation products (FDP), we started IM followed by chemotherapy (daunorubicin + vincristine + cyclophosphamide + L-asparaginase) in Ph+ ALL patients. We began PSL followed by the same chemotherapy in Ph- ALL patients as well. We used rasburicase to prevent TLS.ResultsA total of 35 patients with newly diagnosed ALL were examined: 18 patients were Ph+ and 17 were Ph-. The incidence of DIC was 82.3% (14/17) in Ph+ patients and 38.9% (7/18) in Ph- patients. The group with Ph+ showed a significantly higher rate of DIC (p value = 0.015). Duration of the treatment of DIC was 4-14 days (median, 10 days) in Ph+ patients, and 3-10 days (median, 5 days) in Ph- patients. The group with Ph+ also showed significantly longer duration of treatment (p value = 0.02).Twelve Ph+ patients developed DIC (two patients were excluded because of treatment that was different from that described above); five were men and seven were women. Median age was 61 years (range, 34-78 years). Leukocyte counts at the time of diagnosis were 4400-542100 /ul (median 34400 /ul), hemoglobin value was 6.4-15.6 g/dl (median 11.6, g/dl), Plt counts were 6000-262000 /ul (median, 56000 /ul), Fib value was 199-707 mg/dl (median, 299 mg/dl), and FDP value was 3.4-45.7 ug/ml (median, 9.7 ug/ml). DIC occurred at 1-8 days (median, 3 days) from diagnosis. One patient (8%) had DIC at presentation, and the remaining 11 patients (92%) had DIC after the initiation of induction therapy. We started IM at day 3-6 (median, day 5), DIC developed in two patients starting IM, and chemotherapy was started at day 5-10 (median, day 7). Only one patient had slight elevation of FDP, and this value decreased in a progressive fashion in the remaining 11 patients. The maximum FDP value during the treatment of DIC was 32-1162.8 ug/ml (median, 140 ug/ml). We treated DIC with FOY single agent (one patient) or a combination of rTM and FOY (10 patients); all patients showed improvement. The period for improvement of DIC was 4-14 days (median, 8 days), and none of the patients had bleeding or organ damage. Only one patient had TLS, but it immediately improved. In these Ph+ patients, 11/12 patients (92%) achieved complete remission (CR), and one patient had partial remission. Further, 5/5 patients (100%) achieved CR, and none had TLS in the group with Ph-.ConclusionDIC occurred at a high incidence in Ph+ ALL patients. By starting PSL, IM, and chemotherapy at the right time, we can perform induction therapy without generating serious complication due to DIC. DisclosuresNo relevant conflicts of interest to declare.

Regulation of UC-MSC on Immune Inflammatory Thrombophilia in MRL/lpr Mice

To study the immune repair effect of umbilical cord mesenchymal stem cells (UC-MSC) on inflammatory disorders and thrombophilia state of MRL/lpr mice by detecting the expression change of peripheral blood CD4(+) CD25(+) T cells and the levels of plasma inflammatory cytokines TNF-α, IL-6 and thrombosis indicators TF, FIB. Twenty five MRL/lpr mice were divided into control (C) group, UC-MSC one time treatment (UT1) group and UC-MSC three time treatments (UT3) group. UC-MSC cell suspension was injecled via tail vein and these mice were feeded in SPF environment. The blood samples were taken from the mice every 2 weeks after 16(th) week. FCM was used to detect the expression of CD4(+) CD25(+) T cells in peripheral blood, ELISA assay was used to detect the levels of inflammatory cytokines TNF-α, IL-6 and thrombosis indicators TF, FIB. The expression of peripheral blood CD4(+) CD25(+) T cells in treatment groups increased during 16(th) to 18(th) week, dropped and tended to be stable since 20(th) week, and lower than those in control group. The levels of plasma TNF-α and IL-6 in treatment group decreased since 16(th) week and significantly lower than those in control group (P < 0.05). The levels of plasma TF and FIB in treatment group decreased since 16(th) week. The level of plasma TF in treatment group was significantly lower than those in control group (P < 0.05) since 18(th) week. UC-MSC can repair the immune inflammatory microenvironment disorders of MRL/lpr mice through its immunomodulatory effect. UC-MSC contribute to repair of immune inflammatory thrombophilia of MRL/lpr mice.

Hepatopulmonary syndrome-related changes in D-dimer, prothrombin time, fibrinogen, CD4 and CD8 in a rat model system

To determine the changes in levels of D-dimer, prothrombin time (PT), fibrinogen (Fib), CD4 and CD8 in relation to hepatopulmonary syndrome (HPS) by using a rat model system and to assess the association with pathologic changes in lung. Forty male Sprague-Dawley rats were divided into equal groups for modeling of cirrhosis and HPS. The two groups were assessed by blood gas analysis, standard biochemical tests to measure D-dimer, PT, Fib, CD4 and CD8, and pathological examination of lung tissues. The HPS rats showed significantly lower PaO2 than the cirrhosis rats (58.20+/-3.19 mmHg vs. 85.00+/-2.53 mmHg, P = 0.000). The HPS rats showed significantly higher levels of D-dimer, Fib and CD8 than the cirrhosis rats (0.39+/-0.09 mg/ml vs. 0.25+/-0.05 mg/ml, P = 0.000; 1.77+/-0.10 g/L vs. and 1.49+/-0.09 g/L, P = 0.010; 32.32+/-4.45/mm3 vs. 20.13+/-6.09/mm3, P = 0.014). The HPS rats showed significantly lower levels of PT, CD4 and CD4/CD8 than the cirrhosis rats (14.86+/-1.04 s vs. 16.23+/-0.75 s, P = 0.036; 20.45+/-3.86/mm3 vs. 26.75+/-5.32/mm3, P = 0.000; 0.64+/-0.09 vs. 1.32+/-0.13, P = 0.000). The lung tissues of the HPS rats showed microthrombosis in pulmonary vessels, which were not observed in lung tissues of the cirrhosis rats. HPS-related differential levels of D-dimer, PT, Fib, CD4, CD8 and CD4/CD8 may represent a biomarker profile suggestive of incidence of thromboembolism in lung.

Dynamic measurement of CRP, IL-6 and Fib levels of unstable angina and its clinical significance

Objective To study the clinical significance of dynamic determination of serum CRP,IL-6 and fibrinogen(Fib)levels in unstable angina pectoris(UAP) patients. Methods 162 UAP patients were selected as UAP group(including 52 cases of low risk group,53 cases in medium risk group and 57 cases in high risk group),58 healthy people were selected as control group.The CRP,IL-6 and Fib contents were observed in UAP patients after cardiac events. Results At discharge,CRP,IL-6,Fib in UAP low risk group were(3.47± 0.55)mg/L,(10.38±1.57)ng/L,(1.64±0.65)g/L,which were significantly lower than the admission contents [(6.50±0.87)mg/L,(14.35±1.22)ng/L,(3.01±0.28)g/L](t= 2.761,2.945,2.118,P= 0.028,0.003,0.031). CRP,IL-6,Fib levels in the medium risk group were(6.87±0.75)mg/L,(14.35±1.02)ng/L,(2.26±0.33) g/L,which were significantly lower than the admission contents[(9.21±1.03)mg/L,(19.24±1.58)ng/L,(4.15±0.47)g/L](t= 2.985,3.157,3.548,P= 0.003,0.001,0.000).CRP,IL-6,Fib levels in the high risk group were(8.71±0.84)mg/L,(17.37±1.26)ng/L,(4.67±0.85)g/L,which were significantly lower than the admission contents[(12.48±1.24)mg/L,(25.13±1.84)ng/L,(7.28±0.64)g/L](t= 3.472,4.018,5.097,P= 0.000,0.000,0.000).Six months after hospital discharge,in CRP,IL-6,Fib elevated groups,the incidence rates of cardiac event were 40.20%,40.35% and 47.50%,which were significantly higher than those in normal group (5.0%,4.17%,14.29%,χ2= 23.655,2.211,14.442,P= 0.000,0.000,0.000). Conclusion CRP,IL-6 and Fib levels in UAP patients were significantly higher than those in healthy people,and with remission,contents would be lower,which was the index to reflect the severity of UAP,but its specificity is bad,need to use caution. Key words: Angina,unstable; C-reactive protein; Interleukin-6; Fibrinogen