新生儿凝血指标及部分生化指标检测参考区间调查

目的:调查分析新生儿凝血指标及部分生化指标检测参考区间。方法:以十所三甲医院2012年1月~2014年6月收治的新生儿2683例为研究对象,其中足月儿1700例,早产儿983例,选择同期十所医院职工健康体检1000例为对照组,通过全自动血凝仪、全自动生化分析仪测定所有对象凝血指标及12项生化指标,并建立相关指标参考区间。结果:足月新生儿PT、TT、APTT凝血指标较对照组延长,Fib较对照组降低,差异均有统计学意义(P=0.000);早产儿PT、TT、APTT较足月儿延长(P=0.000),Fib(P=0.001)降低;足月新生儿Glc水平较对照组低(P=0.000),早产儿Glc水平较足月新生儿更低(P=0.000);足月新生儿血钙水平低于对照组,血清TC、Cr、BUN、ALT含量均在对照组之下(P=0.000),早产儿相对更低(P均0.05);足月新生儿LDH、CK酶活性及K+水平均高于对照组(P均0.05),早产儿水平更高(P0.05);足月儿血清Alb、TP及Na+水平低于对照组(P0.05),早产儿更低(P均0.05)。结论:新生儿凝血表达与成人不同,凝血及部分生化指标参考区间的变化与年龄有联系,有必要为新生儿建立与年龄相关的凝血、生化指标参考区间。     

超高龄患者填充骨水泥型人工股骨头置换术后的凝血功能变化及意义

目的：观察骨水泥填充对人工股骨头置换术术后超高龄老年患者凝血系统的影响。方法：选择80岁以上骨水泥型人工股骨头置换术患者29例,于术前、术后当天及术后第3天空腹抽取静脉血,测定凝血功能相关指标,包括凝血酶原时间（PT）、部分凝血活酶时间（APTT）、凝血酶时间（TT）、凝血酶原活动度（PTA）、国际标准化比值（INR）、纤维蛋白原（FIB）、D二聚体（DD）、抗凝血酶Ⅲ（ATⅢ）、血小板（PLT）水平,并对结果进行比较分析。结果：患者术后当天FIB、DD、显著升高（P〈0.05）,ATⅢ降低（P〈0.05）,提示高凝状态,且纤溶亢进,此时段TT、PT延长（P〈0.05）,血小板明显降低,提示存在出血风险;术后第3天TT、PT显著延长（P〈0.05）,ATⅢ恢复到术前水平,FIB,DD水平较手术后当天下降,提示术后第3天有明显的出血倾向,凝血与纤溶系统逐渐恢复平衡。结论：骨水泥型人工股骨头置换术对80岁以上超高龄患者凝血功能有显著影响,术后当天高凝状态、纤溶亢进,存在潜在出血风险,术后第3天有明显出血倾向,提示高龄患者术后应适当补充凝血因子且须谨慎使用抗凝药物。     

Obesity-related derangements of coagulation and fibrinolysis: a study of obesity-discordant monozygotic twin pairs

Coagulation and fibrinolytic activities are under strong genetic control. We studied the effects of acquired obesity, independent of genetic factors on coagulation and fibrinolysis activities in obesity-discordant healthy monozygotic (MZ) twin pairs. Fourteen obesity-discordant (BMI within-pair difference >3 kg/m(2)) and 10 concordant (BMI difference <2 kg/m(2)) MZ twin pairs were identified from the nationwide FinnTwin16 study. Body composition (dual-energy x-ray absorptiometry), abdominal fat distribution (magnetic resonance imaging), liver fat (magnetic resonance spectroscopy), high sensitivity C-reactive protein, insulin sensitivity (euglycemic hyperinsulinemic clamp), and a panel of different markers of blood coagulation and fibrinolysis in the fasting state were measured. Strong resemblance was observed in most coagulation factors within all twin pairs, with the intraclass correlations ranging from 0.73 to 0.97, P < 0.03. However, the activities of fibrinogen and FIX, FXI, and FXII, and plasminogen activator inhibitor-1 (PAI-1) activities were increased in the obese co-twins (P < 0.05) and strongly correlated with the measures of adiposity, inflammation, and insulin resistance (r = 0.32-0.73, P < 0.05) among the twin individuals. Intrapair differences in fibrinogen and PAI-1 correlated with those in BMI, adiposity, and fasting insulin levels (r = 0.40-0.58, P < 0.05) indicating the independent effect of obesity. Derangements of blood coagulation and fibrinolysis are present already in early adulthood in obese subjects. Acquired obesity, independent of genetic factors, increases the activities of fibrinogen and activities of FIX, FXI, FXII, and PAI-1. This study confirms the mechanisms of simultaneous activities of intrinsic coagulation factors and impaired fibrinolysis predisposing obese subjects to thrombosis.     

Presence of factors that activate platelet aggregation in mitral stenotic patients' plasma

BACKGROUND: Although the association between mitral stenosis (MS) and increased coagulation activity is well recognized, it is unclear whether enhanced coagulation remains localized in the left atrium or whether this represents a systemic problem. To assess systemic coagulation parameters and changes in platelet aggregation, we measured fibrinogen levels and performed in vitro platelet function tests in plasma obtained from mitral stenotic patients' and from healthy control subjects' peripheral venous blood. METHODS: Sixteen newly diagnosed patients with rheumatic MS (Group P) and 16 healthy subjects (Group N) were enrolled in the study. Platelet-equalized plasma samples were evaluated to determine in vitro platelet function, using adenosine diphosphate (ADP), collagen and epinephrine in an automated aggregometer. In vitro platelet function tests in group N were performed twice, with and without plasma obtained from group P. RESULTS: There were no significant differences between the groups with respect to demographic variables. Peripheral venous fibrinogen levels in Group P were not significantly different from those in Group N. Adenosine diphosphate, epinephrine and collagen-induced platelet aggregation ratios were significantly higher in Group P than in Group N. When plasma obtained from Group P was added to Group N subjects' platelets, ADP and collagen-induced, but not epinephrine-induced, aggregation ratios were significantly increased compared to baseline levels in Group N. CONCLUSION: Platelet aggregation is increased in patients with MS, while fibrinogen levels remain similar to controls. We conclude that mitral stenotic patients exhibit increased systemic coagulation activity and that plasma extracted from these patients may contain some transferable factors that activate platelet aggregation.     

Effects of induced hypothermia on organ blood flow in a hibernator and a nonhibernator

Regional blood flow and hemodynamic variables during induced hypothermia were compared in six guinea pigs and four hedgehogs. Tracer microspheres were used for blood flow measurements, since this technique is more accurate than the earlier method (86Rb+ distribution) used for cardiac output distribution measurements in hibernators. Heart rate and blood pressure decreased with reduced temperature in a comparable fashion in the two species, while cardiac output was less affected in the hedgehogs than in the guinea pigs. Total peripheral resistance increased in both species. At 34 degrees C the hedgehogs had a higher myocardial blood flow per gram tissue than the guinea pigs and it was not reduced in the hedgehogs when the body temperature was lowered to 22 degrees C, whereas in the guinea pigs it was markedly reduced. The brown adipose tissue of the hedgehogs showed a fourfold increase in blood perfusion at 22 degrees C when compared with 34 degrees C. In the hedgehogs the fractional distribution of cardiac output to the myocardium increased with decreasing body temperature, while the renal fraction decreased. In the guinea pigs, on the other hand, the fractional distribution of cardiac output to the myocardium remained unchanged but increased to the kidneys.     

Fibrinogen-Fibrin Degradation Product Levels in Different Types of Intravascular Haemolysis

To examine the possibility that intravascular haemolysis may lead to intravascular coagulation we have compared the degree of fibrin deposition, as measured by levels of serum fibrinogen-fibrin degradation products (F.D.P.), in two different types of intravascular haemolysis associated with red cell fragmentation. F.D.P. levels in 56 patients with intravascular haemolysis secondary to prosthetic heart valves were compared with those in 18 patients who had microangiopathic haemolytic anaemia (M.H.A.) associated with malignant hypertension or renal disease. F.D.P. levels were raised in almost all the patients with M.H.A., and this group had significantly higher levels than any of the valve replacement groups. In contrast, in the prosthetic valve patients F.D.P. levels were usually normal and bore no relation to the degree of haemolysis. It is suggested that in the absence of other precipitating factors intravascular haemolysis will not initiate intravascular coagulation. In M.H.A., while the intravascular haemolysis appears to be a consequence of an underlying intravascular coagulation, it is likely that persistence of the coagulation disturbance is related more to factors such as small vessel damage than to the release of any thromboplastic substances from fragmented red cells.     

Biological Rhythms in the Physiology and Pharmacology of Blood Coagulation

This article reviews the current knowledge on time-dependent variations in the physiology of blood coagulation and in the anticoagulant effect of heparin and warfarin. Animal data indicated that the shortest blood clotting time and the highest levels of coagulation factors II, VII, and IX were recorded during the resting period of the animal. These circadian rhythms were not altered by modifications of the lighting regimens. In healthy volunteers, the prothrombin time was longer at the end of the afternoon than early in the morning; the acro-phases of activated partial thromboplastin time and thrombin time occurred in the evening or during the night. The acrophases of fibrinogen, factors II, VII, VIII, and a-1-antitrypsin were obtained in the morning. There is no agreement on the chronobiology of platelet aggregation, and differences can be found in the time of maximal aggregability. The chronopharmacological studies of heparin infused at a constant rate to patients with thromboembolic diseases suggested that maximal effectiveness occurred at 04:00, while it was minimal at 08:00. Animal data indicated that oral administration of warfarin at the end of the activity period of rats produced maximal inhibition of vitamin K-dependent factors. This was the time of day when warfarin interference with the vitamin K cycle of the liver was highest. Further studies are needed to determine the clinical significance of biological rhythms in the physiology and pharmacology of blood coagulation.     

Biological Rhythms in the Physiology and Pharmacology of Blood Coagulation

This article reviews the current knowledge on time-dependent variations in the physiology of blood coagulation and in the anticoagulant effect of heparin and warfarin. Animal data indicated that the shortest blood clotting time and the highest levels of coagulation factors 11, VII, and IX were recorded during the resting period of the animal. These circadian rhythms were not altered by modifications of the lighting regimens. In healthy volunteers, the prothrombin time was longer at the end of the afternoon than early in the morning; the acrophases of activated partial thromboplastin time and thrombin time occurred in the evening or during the night. The acrophases of fibrinogen, factors 11, VII, VIII, and α-1-antitrypsin were obtained in the morning. There is no agreement on the chronobiology of platelet aggregation, and differences can be found in the time of maximal aggregability. The chronopharmacological studies of heparin infused at a constant rate to patients with thromboembolic diseases suggested that maximal effectiveness occurred at 04:00, while it was minimal at 08:00. Animal data indicated that oral administration of warfarin at the end of the activity period of rats produced maximal inhibition of vitamin K-dependent factors. This was the time of day when warfarin interference with the vitamin K cycle of the liver was highest. Further studies are needed to determine the clinical significance of biological rhythms in the physiology and pharmacology of blood coagulation.     

Non-invasive methods of separating hedgehog (Erinaceus europaeus) age classes and an investigation into the age structure of road kill

The separation of animals into age classes is often fraught with difficulties, but is essential for the interpretation of survival rates and population structure. This study investigated both live hedgehogs and road kill in order to develop techniques that could be utilised to separate age classes in the field. Body measurements were taken from 24 live hedgehogs caught at a site in County Cork, Ireland over a three year period. Additionally, carcasses from around Ireland were collected and measured. There was a significant correlation between the weight and hind foot length of both live and dead hedgehogs. The weight of individuals was also significantly correlated with the body length and jaw length of hedgehogs. In all of these correlations, the sample clustered clearly into two groups with ‘juveniles’ meeting all of the following criteria: a hind foot length of <3.6 cm, a body length of <?16 cm and a jaw length of below 4.5 cm. It is suggested that these parameters, combined with the presence of growing spines, could provide a way of separating age classes in the field. This would be of particular benefit to short term studies, allowing the population structure to be accurately assessed and the reproductive success and sustainability of a population to be investigated. Road kill were also aged using the dentary bone in order to investigate the age profiles of hedgehogs killed on the road. Amongst those killed, 54 % of hedgehogs were 1-year-old or less. The majority of hedgehogs (87 %) were between 0–3-years-old, the oldest females were nine (n?=?2), and the oldest males were eight years old (n?=?2), respectively. Road kill hedgehogs had an average longevity of 1.94 years, and the mean age of females was higher (2.10 years) than males (1.87 years).     

The Effect of Sulfinpyrazone (Anturan) on Platelet Economy and Blood Coagulation in Man

Sulfinpyrazone (Anturan) administered in therapeutic doses over a period of several weeks produced prolongation of platelet survival and reduced turnover but with little change in blood coagulation. The changes in platelet survival and turnover were associated with reduced platelet adhesiveness. It is therefore possible to affect platelet economy in man significantly, without producing corresponding effects on blood coagulation.     

The Influence of Helicobacter pylori Status on Circulating Levels of the Coagulation Factors Fibrinogen, von Willebrand Factor, Factor VII, and Factor VIII

Background. Helicobacter pylori (H. pylori) infection has been associated with an increased risk of developing ischemic heart disease (IHD). It has been suggested that a persisting low-grade acute phase response results from the chronic inflammation caused by H. pylori infection, which may give rise to increased circulating levels of certain coagulation factors.
Materials and Methods. One hundred three (53 male) nonconsecutive, randomly selected white subjects with symptoms of dyspepsia were recruited for study from an outpatient endoscopy clinic at Leeds General Infirmary. The presence of H. pylori was determined by histological and microbiological investigation, a rapid urease test, and a ¹³carbon urea breath test (¹³C-UBT). Fibrinogen was measured by the Clauss method, factor VIII:C (FVIII:C) and factor VII:C (FVII:C) were measured by clotting rate assays, and the von Willebrand factor (vWF) was determined by an enzyme-linked immunosorbent assay.
Results. No difference was found in levels of coagulation factors according to H. pylori status. Multiple regression models were used to account for the effect of covariates and H. pylori status on levels of FVII:C, FVIII:C, vWF, and fibrinogen, and again H. pylori status was not a significant determinant of levels of any of these coagulation factors. No difference occurred in full blood count, platelet count, white cell count, or plasma viscosity in individuals who were H. pylori -positive compared with those who were negative.
Conclusions. H. pylori infection is not associated with increased circulating levels of fibrinogen, FVII:C, vWF.Ag, or FVIII:C or hemorrheology in this patient group.     

Blood viscosity factor in persons with high and low risk of ischemic heart disease]

In the years 1986-1987, the blood viscosity factor, the content of haemoglobin in erythrocytes, the concentration of glucose in blood, the lipids and the blood coagulation system were examined in 180 subjects. They were divided into three groups according to the exposure to risk factors: group performing light manual work (L), group performing hard manual work (C) and group of engine drivers (M). No statistically significant differences in regard to age, employment period, number of cigarettes smoked, as well as arterial systolic and diastolic blood pressure were found between the subjects. Workers from group M had the highest body weight (P > 99%) and increased concentration in blood of triglycerides (P > 99% and Apo B (P > 99%. Subjects from group C had the lowest concentration of cholesterol in blood (P > 99%) and the smallest number of members with hypertensions (3.8%) and overweight (7.5%). Group L included the highest percentage of persons with arterial hypertension (17.5%), the highest, among all examined, blood viscosity factor determined at the coagulation rate of 18.6 s-1, and the lowest prothrombin factor (P > 99%).     

Testing the role of intraguild predation in regulating hedgehog populations.

Potential competitors that eat each other can engender patterns of spatial segregation similar to those produced by competition, and distinguishable only by field manipulation. This paper reports the results of a perturbation experiment to test the factors responsible for small-scale discontinuities in the distribution of a common insectivore. Populations of hedgehogs (Erinaceus europaeus) were monitored following their introductions into an area where they had been absent, and into a neighbouring area where they were known to persist. The two sites had a similar availability of preferred habitat, and the growth rates of introduced hedgehogs were similar. The density of badgers (Meles meles), larger members of the same guild, appears to produce differences in mortality and dispersal, which returned the populations close to their original levels within 2 months of the transplant.     

Use of p-aminobenzamidine to monitor activation of trypsin-like serine proteases

The fluorescent compound p-aminobenzamidine was used to monitor activation of the trypsin-like serine proteases trypsin, thrombin, and blood coagulation factors IXa and Xa. p-Aminobenzamidine, when bound to the activated forms of these proteases but not the corresponding zymogens, displayed an increase in fluorescence. This fluorescence increase was coincident with activation as measured by synthetic substrate hydrolysis, physiological coagulation activity, and the appearance of activation products on gel electrophoresis. The activation of proteolytically modified factor X was also monitored. These results suggest that following p-aminobenzamidine fluorescence is a convenient procedure for monitoring activation of trypsin-like serine proteases.     

Design of constructs for the expression of biologically active recombinant human factors X and Xa. Kinetic analysis of the expressed proteins

Activation of vitamin K-dependent plasma proteases occurs by specific interaction with components of the blood coagulation cascade. In this report, we describe the direct expression and enzymatic characterization of the human coagulation zymogen factor X and its activated form, factor Xa, from transformed Chinese hamster ovary fibroblast cell lines. Expression was achieved using either a full-length factor X cDNA or a unique mutant factor Xa cDNA. The functional factor Xa precursor contained a novel tripeptide bridge in place of the native 52-amino acid activation peptide. This mutation allowed for intracellular processing and secretion of the activated form of factor X. Secreted recombinant factors X (rX) and Xa (rXa) were purified by sequential anion-exchange and immunoaffinity chromatography. The enzymatic activities of factors rX and rXa were compared with those of plasma factors X and Xa in three independent assay systems. In comparison to human plasma factor X, the amidolytic, prothrombinase complex, and plasma clotting activities of factor rX were 50, 85, and 43%, respectively. The corresponding comparative activities for factor rXa were 32, 64, and 48%, respectively. The ability to directly express mutant forms of biologically active human factor X will facilitate the structure/function analysis of this important blood coagulation protein and may lead to the development of novel coagulation inhibitors.     

非冬眠期刺猬血液生理生化指标季节变化

目的了解刺猬的血液生理生化参数正常值及其季节性差异。方法采用BC-3000 Plus全自动血液细胞分析仪和BAYER-ADVIA-1650全自动生化分析仪,分别对刺猬的13项生理指标和15项生化指标进行了测定,并比较分析了春季、夏季和秋季的血液生理生化指标。结果刺猬雌体和雄体的平均红细胞体积（MCV）在夏季均显著小于秋季,雄体夏季的平均红细胞血红蛋白（MCH）小于秋季,说明刺猬秋季的血液载氧能力高于夏季。白细胞数目（WBC）没有季节和性别的显著差异,说明刺猬在三个季节的免疫能力差别不大。在血液生化指标中,刺猬（雌雄）春季和秋季的葡萄糖（GLU）含量均显著高于夏季;雌性刺猬春季的谷草转氨酶（AST）显著大于夏季和秋季;雄性刺猬的总胆固醇（CHOL）和低密度脂蛋白（LDLC）均表现为秋季的显著高于春季和夏季的。结论生理生化指标的不同反映了刺猬在活动能力、代谢水平、营养状况、健康状况等方面存在性别和季节性差异。     

Comparing the MicroRNA Spectrum between Serum and Plasma

MicroRNAs (miRNAs) are small, non-coding RNAs that regulate various biological processes, primarily through interaction with messenger RNAs. The levels of specific, circulating miRNAs in blood have been shown to associate with various pathological conditions including cancers. These miRNAs have great potential as biomarkers for various pathophysiological conditions. In this study we focused on different sample types' effects on the spectrum of circulating miRNA in blood. Using serum and corresponding plasma samples from the same individuals, we observed higher miRNA concentrations in serum samples compared to the corresponding plasma samples. The difference between serum and plasma miRNA concentration showed some associations with miRNA from platelets, which may indicate that the coagulation process may affect the spectrum of extracellular miRNA in blood. Several miRNAs also showed platform dependent variations in measurements. Our results suggest that there are a number of factors that might affect the measurement of circulating miRNA concentration. Caution must be taken when comparing miRNA data generated from different sample types or measurement platforms.     

Influence of age and hematocrit on the coagulation of blood

To examine the effects of age, hematocrit and the daily variation in hematocrit on coagulation of blood, the time of onset of coagulation (Ti) of whole blood obtained from donors including normal subjects and patients was measured by means of a rheological technique. The Ti value of recalcified blood decreased with an increase in age, but in donors aged 65 years or more (the elderly), the Ti value was almost independent of age. The Ti value for blood obtained from the elderly was significantly lower at lower hematocrit levels, but that for blood obtained from young donors was almost independent of hematocrit. The daily variation in hematocrit in individuals was small (maximum variation: about 4%), and the variation had little effect on the Ti value. However, a slight increase in hematocrit was considered to bring about a significant increase in viscosity at lower shear rates. Therefore, it is suggested that a slight increase in hematocrit under stagnant flow conditions is one of major risk factors for venous thrombogenesis, especially in the elderly.     

Blood coagulation system in oncological patients treated with rubomycin, adriamycin and carminomycin]

Systems of blood coagulation in patients treated with antibiotics of the anthracycline group were studied. Rubomycin was used in the treatment of patients with acute leukemia Adriamycin and carminomycin were used in the treatment of patients with solid tumors. The antibiotics affected the process of blood coagulation mainly through their cytostatic effect on thrombocytopoesis. Thrombocytopenia induced deficit of thrombocytal factors participating in the process of blood coagulation which resulted in hypocoagulation and hemorrhagic complications. The plasmic factors did not significantly change during the antibiotic therapy. A tendency to decrease in the levels of prothrombine, fibrinase and fibrinogen was noted which was possible due to an inhibitory effect of the antibiotics on the function of the reticuloendothelial tissue cells or indirectly to suppression of the tumor process. More pronounced changes in the system of blood coagulation of patients treated with rubomycin were probably associated with inferiority of the thrombocytal apparatus of the patients with acute leukemia treated with the antibiotic.     

Comparative hemostatic protein alterations accompanying pregnancy and parturition

Pregnancy and parturition represent adaptive, physiological stress situations that elicit both blood coagulation protein changes and endocrine alterations. This paper briefly reviews the interrelationships of these responses by comparing the available data in several mammalian species including man, dog, cow, and pig. Hemostasis is an enzymatically controlled cascade process involving platelets and specific coagulation proteins that results in the formation of insoluble strands of fibrin. Although qualitatively similar in most mammals, quantitative differences exist in the circulating levels of individual coagulation proteins which may contribute towards the different rates of clot formation. In the late gestation stage of human pregnancy, significant increases are observed in the circulating biological activities of the coagulation factors VII, VIII:C, IX, and X. In the dog, the activities of factors VII and IX reach peak values in midpregnancy, while in the cow little or no changes are observed except for factor VII values which show a significant increase only around the time of parturition. These coagulation changes appear to be associated with fluctuations in circulating hormone values, particularly plasma estrogen. In human pregnancy, the circulating levels of fibrinogen, the precursor of fibrin, increase during the gestation period reaching maximum values during and immediately following parturition. In the dog and the cow two distinct increases in fibrinogen values are observed, the first in the midgestation period and the second in the immediate postparturition period. In the pig, fibrinogen values also rise significantly at parturition. Oral contraceptive studies in the human female have indicated that changes in circulating activities of coagulation proteins are hormonally influenced.(ABSTRACT TRUNCATED AT 250 WORDS)