Quasi-phase-matched laser wakefield acceleration of electrons in an axially density-modulated plasma channel.

Quasi-phase matching in corrugated plasma channels has been proposed as a way to overcome the dephasing limitation in laser wakefield accelerators. In this study, the phase-lock dynamics of a relatively long electron bunch injected in an axially-modulated plasma waveguide is investigated by performing particle simulations. The main objective here is to obtain a better understanding of how the transverse and longitudinal components of the wakefield as well as the initial properties of the beam affect its evolution and qualities. The results indicate that the modulation of the electron beam generates trains of electron microbunches. It is shown that increasing the initial energy of the electron beam leads to a reduction in its final energy spread and produces a more collimated electron bunch. For larger bunch diameters, the final emittance of the electron beam increases due to the stronger experienced transverse forces and the larger diameter itself. Increasing the laser power improves the maximum energy gain of the electron beam. However, the stronger generated focusing and defocusing fields degrade the collimation of the bunch.

Energy efficiency and net energy prediction of feed in laying hens.

Using accurate nutrient values for ingredients is of vital importance for efficient diet formulation. The net energy (NE) system accounts for the real available amount of feedstuff energy for body maintenance and production as it considers energy dissipated as heat increment. The NE content of diets for pigs and broilers has been estimated from their nutrient contents. However, such estimates have not been made specifically for laying hens. This study reports the development of equations to predict NE for laying hens based on the chemical composition of 16 different diets meeting minimum nutrient specifications but varying in nutrient composition. Heat production and energy metabolism were measured in layers ranging from 32 to 62 weeks of age in closed-circuit calorimetry chambers with 8 replicates per diet in a randomized design. Each replicate consisted of a chamber with 3 layers that were adapted for 4 D to diets and chambers prior to measurement. The measurements included feed intake, metabolizable energy (ME) content, nitrogen balance, egg production, gas exchange, heat production, energy efficiency, and energy partition for a 3-D period. The average AME/GE and NE/AME ratios of the 16 diets were 77 and 74%, respectively. The latter ratio increased with energy efficiency (EE) content and decreased with CP content of diets. The results indicate that diet NE content can be predicted from AME, CP, and EE contents and the NE/AME ratio varied positively with EE and negatively with CP. A validation experiment with 2 diets fed to layers in calorimetry chambers confirmed the estimation from NE prediction equations. In conclusion, NE of diets can be predicted in laying hens from equations based on AME and CP and EE contents in laying hens being similar to those reported in broilers.

Temperature-Dependent Development Modeling of the Phorid Fly Megaselia halterata (Wood) (Diptera: Phoridae).

The effect of temperature on the development of Megaselia halterata (Wood) (Diptera: Phoridae) on A15 variety of button mushroom in the stages of casing and spawn-running was investigated at eight constant temperatures (10, 12.5, 15, 18, 20, 22.5, 25, and 27°C) and developmental rates were modeled as a function of temperature. At 25 and 27°C, an average of 22.2 ± 0.14 and 20.0 ± 0.10 days was needed for M. halterata to complete its development from oviposition to adult eclosion in the stages of casing and spawn-running, respectively. The developmental times of males or females at various constant temperatures were significantly different. Among the linear models, the Ikemoto and Takai linear model in the absence of 12.5 and 25°C showed the best statistical goodness-of-fit and based on this model, the lower developmental threshold and the thermal constant were estimated as 10.4°C and 526.3 degree-days, respectively. Twelve nonlinear temperature-dependent models were examined to find the best model to describe the relationship between temperature and development rate of M. halterata. The Logan 10 nonlinear model provided the best estimation for T opt and T max and is strongly recommended for the description of temperature-dependent development of M. halterata.

The toxic effects of silver nanoparticles on blood mononuclear cells.

BACKGROUND: Nanoparticles have become one of the leading technologies over the past two years. The extensive use of nanoparticles has raised great concern about their occupational fate and biological effects. With an increase in the production and use of nanomaterial, it is more likely to get exposed to them occupationally and environmentally. OBJECTIVE: To assess the toxicity of silver nanoparticles on human mononuclear cells. METHODS: In this in vitro experimental study, suspensions of blood mononuclear cells from 10 young healthy men were incubated with 10-nm silver nanoparticles in different concentrations (range: 1-500 µg/mL) for 6 and 24 hours by MTT assay. Positive and negative controls were used for comparison. RESULTS: After 6 hours of exposure, 10.9% to 48.4% of the cells died. After 24 hours of exposure, the rate ranged from 56.8% to 86.3%. Regardless of the exposure time, the maximum cytotoxicity was observed at the concentration of 500 µg/mL of silver nanoparticles. By increasing the exposure time to 24 hours, the cytotoxicity of nanoparticles substantially increased at all concentrations. Cell death was significantly higher when compared to the controls (p<0.01). CONCLUSION: Silver nanoparticles possess both time- and dose-dependent cytotoxicity and can thus be considered as very toxic for mononuclear cells.

Twin's sex and risk of pre-term birth.

Male sex is a risk factor for pre-term birth (PTB) among singleton pregnancies; however, in twin pregnancies, the effect of sex on PTB is not yet clear. The aim of this study was to evaluate the effect of twin's sex on risk of PTB. During this analytical cross-sectional study, we evaluated the effect of twin's sex, chorionicity and other factors on risk of PTB in 676 pregnant women in a university hospital in Tehran, Iran. Existence of male gender in pregnancy was a risk factor for PTB. Comparing same sex twins together, male-male gender was a risk factor for PTB (OR = 1.67 (1.19-2.34), p = 0.002), early PTB (OR = 1.18 (1.04-1.34), p = 0.01) and very early PTB (OR = 1.06 (1-1.13), p = 0.04). Monoamnion twins were at higher risk for early PTB (OR = 1.44 (1.08-1.92), p = 0.02), and very early PTB (OR = 1.95 (1.1-3.44), p = 0.03) but the risk did not increase in monochorion twins. History of abortion was also shown to be a risk factor (p < 0.05). Maternal age, multiparity, body mass index (BMI) and assisted reproductive techniques (ART) did not reach the significance levels to be considered as risk factors.

Non-extraction flow injection determination of cationic surfactants using eriochrome black-T.

A new, rapid, sensitive, non-extraction batch, and flow injection spectrophotometric method for the determination of cationic surfactants (CSs) such as cetyltrimethyl ammonium bromide (CTAB), tetra-n-butyl ammonium chloride (TBAC) and cetylpyridinium chloride (CPC) is proposed. The method is based on the interaction of cationic surfactants with eriochrome black-T to form an ion-association complex. This complex has strong absorbance at 708 nm. The effects of chemical parameters and FIA variables on the determination of cationic surfactants were studied in detail, especially for CTAB. Under optimum conditions, the two linear calibration ranges of the method are 3.0 x 10(-6) to 5.0 x 10(-3)mol L(-1) CTAB, CPB and DTAB for the batch spectrophotometric method and 2.0 x 10(-6) to 2.0 x 10(-4)mol L(-1) CTAB, CPB and TBC for the flow injection spectrophotometric method. The sample throughput was 35+/-5 samples h(-1) at room temperature. The relative standard deviations for 10 replicates of analysis of (2.0, 0.6 and 0.2)x10(-4)mol L(-1) CTAB were 1.2, 1.3, and 0.8%, respectively. In addition, the influence of potential interfering substances on the determination of cationic surfactants was studied. The proposed method is simple and rapid, using no toxic organic solvents. It was applied to the determination of trace CS in industrial wastewater with satisfactory results.

Thrombin generation in non-cardioembolic stroke subtypes: the Hemostatic System Activation Study.

BACKGROUND: The association between hemostatic activation, stroke mechanism, and outcome is poorly defined. The Hemostatic System Activation Study (HAS) investigators measured serial levels of prothrombin fragment F1.2, a marker of thrombin generation, in patients enrolled in the Warfarin Aspirin Recurrent Stroke Study (WARSS). METHODS: HAS enrolled 631 of the 2,206 patients in WARSS. Strokes were subtyped according to inferred mechanism. Plasma was collected for F1.2 at randomization (within 30 days of stroke), 3 months, 12 months, and 18 months. The 3 to 6 month samples in aspirin-treated patients were used for the primary analysis. RESULTS: The authors analyzed 3 to 6 month samples on 320 patients. Higher F1.2 levels were associated with older age, female sex, and hypertension. There was no difference between mean F1.2 levels in 56 cryptogenic (0.9 +/- 0.32 nmol/L) and 114 non-cryptogenic (1.13 +/- 0.74 nmol/L) patients or across specific stroke subtypes. There was an 8.8%/year (p = 0.006) increase in mean F1.2 levels. There was a trend toward higher risk of recurrent stroke or death as F1.2 levels increased in aspirin (RR: 1.30, 95% CI: 0.57 to 2.94, p = 0.53) and warfarin treated patients (RR: 1.68, 95% CI: 0.48 to 5.94, p = 0.42). F1.2 levels were reduced on average 70% in warfarin-treated patients in a dose-dependent fashion. CONCLUSION: F1.2 levels did not appear to differ by stroke subtype, suggesting that factors other than underlying stroke pathophysiology influence thrombin generation in the post-acute stroke period. F1.2 levels were suppressed by warfarin in a dose-dependent fashion. Additional research is needed to determine the predictive value of F1.2 after stroke.

Ability of recombinant factor VIIa to generate thrombin during inhibition of tissue factor in human subjects.

BACKGROUND: In view of the central role of the tissue factor-factor VIIa pathway in the initiation of blood coagulation, novel therapeutic strategies aimed at inhibiting this catalytic complex are currently being evaluated. A limitation of this new class of anticoagulants may be the lack of an appropriate strategy to reverse the effect if a bleeding event occurs. The aim of this study was to investigate the in vivo potential of recombinant factor VIIa (rVIIa) to induce thrombin generation in healthy subjects pretreated with recombinant nematode anticoagulant protein c2, a specific inhibitor of the tissue factor-factor VIIa complex, in a double-blind randomized crossover study. METHODS AND RESULTS: Administration of nematode anticoagulant protein c2 (3.5 microgram/kg) caused a prolongation of the prothrombin time from 13.7+/-0.6 to 16.9+/-1.2 seconds. The subsequent injection of rVIIa (90 microgram/kg) resulted in an immediate and complete correction of the prothrombin time and a marked generation of thrombin, reflected by increased levels of prothrombin activation fragment F1+2 and thrombin-antithrombin complexes from 0.75+/-0.64 to 3.29+/-6.3 nmol/L and from 2.4+/-0.6 to 10.7+/-3.9 microgram/mL, respectively. Factor X and IX activation peptides showed a 3.5-fold and a 3.8-fold increase, respectively, after the administration of rVIIa in the presence of nematode anticoagulant protein c2. CONCLUSIONS: During treatment with an inhibitor of the tissue factor-factor VIIa complex, the infusion of rVIIa resulted in thrombin generation. Our results indicate that rVIIa may be a good candidate as an antidote for inhibitors of tissue factor.

Activation of clotting factors XI and IX in patients with acute myocardial infarction.

In acute coronary events, plaque rupture and the subsequent formation of the catalytic tissue factor-factor VIIa complex is considered to initiate coagulation. It is unknown whether clotting factors XI and IX are activated in acute coronary events. Therefore, we prospectively investigated the activation of clotting factors XI and IX as well as activation of the contact system and the common pathway in 50 patients with acute myocardial infarction (AMI), in 50 patients with unstable angina pectoris (UAP), and in 50 patients with stable angina pectoris (SAP). Factor XIa-C1 inhibitor complexes, which reflect acute activation of factor XI, were detected in 24% of the patients with AMI, 8% of the patients with UAP, and 4% of the patients with SAP (P<0.05), whereas factor XIa-alpha(1)-antitrypsin complexes, which reflect chronic activation, were observed equally in all 3 study groups. Factor IX peptide levels were significantly higher in the patients with AMI and UAP compared with the patients with SAP (P<0.01). No differences regarding markers of the common pathway were demonstrated. Fibrinopeptide A levels were elevated in patients with AMI compared with patients with UAP and those with SAP (P<0.01). Factor XIIa- or kallikrein-C1 inhibitor complexes were not increased. In conclusion, this is the first demonstration of the activation of clotting factors XI and IX in patients with acute coronary syndromes. Because these clotting factors are considered to be important for continuous thrombin generation and clot stability, their activation might have clinical and therapeutic consequences.

Prothrombin activation is increased among asymptomatic carriers of the prothrombin G20210A and factor V Arg506Gln mutations.

The risk of venous thrombosis is increased in individuals who carry specific genetic abnormalities in blood coagulation proteins. Among Caucasians, the prothrombin G20210A and factor V Arg506Gln (FV R506Q) mutations are the most prevalent defects identified to date. We evaluated their influence on markers of coagulation activation among participants in the Second Northwick Park Heart Study, which recruited healthy men (aged 50-61 years) from nine general medical practices in England and Wales. They were free of clinical vascular disease and malignancy at the time of recruitment. Genotypes for the two mutations were analyzed using microplate array diagonal gel electrophoresis, and coagulation markers (factor XIIa; activation peptides of factor IX, factor X, and prothrombin; fibrinopeptide A) were measured by immunoassay. Factor VII coagulant activity and factor VIIa levels were determined by a functional clotting assay. Among 1548 men genotyped for both mutations, 28 (1.8%) and 52 (3.4%) were heterozygous for prothrombin G202 IOA and FV R506Q, respectively. The only coagulation marker that was significantly associated with the two mutations was prothrombin activation fragment FI+2 [mean +/- SD, 0.88 +/- 0.32 nmol/L in men with prothrombin G20210A (p = 0.002) and 0.89 +/- 0.30 in men with FV R506Q (p = 0.0001) versus 0.72 +/- 0.24 among non-carriers for either mutationl. This data provides conclusive evidence that heterozygosity for the prothrombin G20210A as well as the FV R506Q mutations in the general population leads to an increased rate of prothrombin activation in vivo.

Comparison of novel hemostatic factors and conventional risk factors for prediction of coronary heart disease.

BACKGROUND: This study sought to assess whether novel markers of hemostatic activity are predictive of coronary heart disease (CHD) and improve risk assessment. METHODS AND RESULTS: Conventional CHD risk factors, the activation peptides of factor IX and factor X, factor VII activity and antigen, activated factor XII, prothrombin fragment 1+2, fibrinopeptide A, and fibrinogen were measured in 1153 men aged 50 to 61 years who were free of myocardial infarction at recruitment. Activated factor VII (VIIa) was measured in 829 men. During 7.8 years of follow-up, 104 had a CHD event. Baseline status was related to outcome by logistic regression by using a modified nested case-control design. Screening performance was judged from receiver operating characteristic curves. A high activated factor XII was associated with increased CHD risk, but low levels were not protective. Plasma VIIa and factor X activation peptide were independently and inversely related to risk. Plasma factor IX activation peptide and fibrinogen were positively associated with risk, but the relations were no longer statistically significant after adjustment for other factors, including VIIa and apoA-I. Other hemostatic markers were not associated with CHD risk. CONCLUSIONS: Hemostatic status did not add significant predictive power to that provided by conventional CHD risk factors yet was able to substitute effectively for these factors.

Increased activation of the haemostatic system in men at high risk of fatal coronary heart disease.

The haemostatic system was examined in 2951 men aged 50 to 61 years, clinically free of cardiovascular disease, who were ranked according to a risk score for fatal coronary heart disease (CHD). Risk was judged from their serum cholesterol concentration, systolic blood pressure, body mass index and smoking habit. The status of the factor VII-tissue factor pathway was estimated from the plasma levels of factor VII coagulant activity, factor VII antigen and activated factor VII. Activation of factor IX was assessed from the plasma concentration of factor IX activation peptide. Activity within the common pathway was measured as the plasma concentrations of prothrombin fragment 1 + 2 and fibrinopeptide A. All 6 markers of haemostatic status were positively and statistically significantly associated with risk, providing further evidence for a hypercoagulable state in men at high risk for fatal CHD. Plasma fibrinogen and serum triglyceride concentrations were also graded positively with risk.

Factor XIa induced activation of the intrinsic cascade in vivo.

Coagulation factor XI is a glycoprotein of the contact factor system. Its deficiency is associated with a highly variable bleeding tendency, thus a role in relation to hemostasis appears to exist. However, the importance of factor XI for stimulating intrinsic coagulation in vivo has not yet been determined. To study the procoagulant effects of human factor XIa in vivo, we infused the purified enzyme into normal chimpanzees (100 micrograms) in the absence or presence of the thrombin inhibitor rec-hirudin (1.0 mg/kg loading dose plus 0.3 mg/kg body wt continuous infusion). Factor XIa elicited an immediate activation of factors IX, X, and prothrombin, as measured by their respective activation fragments. However, whereas the activation of factors IX and X was immediate and shortlasting, (peak increments of 6- and 1.4-fold of baseline at 5 minutes after injection), the conversion of prothrombin gradually increased, reaching a summit of 6-fold baseline values after 60 min, and remaining elevated during the course of the experiments. Thrombin-antithrombin complexes also remained elevated during the study period. In the presence of hirudin, the initial activation of factors IX, X, and prothrombin was unchanged, however the further increment in prothrombin fragment F1 + 2 was markedly inhibited. These results demonstrate that factor XIa is a potential agonist of the intrinsic cascade in vivo, which activity is enhanced in the presence of thrombin.

The effects of quality and timing of venepuncture on markers of blood coagulation in healthy middle-aged men.

Effects of the quality and the time of venepuncture on factor VII coagulant activity (VIIc) and the concentrations of fibrinogen, prothrombin fragment 1 + 2 (F1 + 2) and fibrinopeptide A (FPA) were sought in 2665 men, of whom 2334 were re-examined after about one year. Venepunctures were categorised as satisfactory, not fully satisfactory or unsatisfactory according to pre-defined criteria. Neither the quality nor timing of the venepuncture influenced VIIc or fibrinogen concentration. However, at baseline and re-examination F1 + 2 and FPA were increased on average by about 9% and 45% respectively when venepunctures were not fully satisfactory, and by about 11% and 100% when unsatisfactory. Plasma collected after 1500 h had slightly but significantly lower levels of F1 + 2 and FPA than samples taken earlier, possibly due to circadian rhythm. The results emphasise the need for careful surveillance of the venepuncture procedure and the value of FPA when using F1 + 2 as a marker of risk of thrombosis.

Activation of the coagulation cascade after infusion of a factor XI concentrate in congenitally deficient patients.

Virally inactivated, high-purity factor XI concentrates are available for treatment of patients with factor XI deficiency. However, preliminary experience indicates that some preparations may be thrombogenic. We evaluated whether a highly purified concentrate produced signs of activation of the coagulation cascade in two patients with severe factor XI deficiency infused before and after surgery. Signs of heightened enzymatic activity of the common pathway of coagulation (elevated plasma levels of prothrombin fragment 1 + 2 and fibrinopeptide A) developed in the early post-infusion period, accompanied by more delayed signs of fibrin formation with secondary hyperfibrinolysis (elevated D-dimer and plasmin-antiplasmin complex). These changes occurred in both patients, but were more severe in the older patient with breast cancer when she underwent surgery, being accompanied by fibrinogen and platelet consumption. There were no concomitant signs of heightened activity of the factor VII-tissue factor mechanism on the factor Xase complex (plasma levels of activated factor VII and of factor IX and X activation peptides did not increase). The observed changes in biochemical markers of coagulation activation indicate that concentrate infusions increased thrombin generation and activity and that such changes were magnified by malignancy and surgery. Because some factor XI concentrates may be thrombogenic, they should be used with caution, especially in patients with other risk factors for thrombosis.

The activation of factor X and prothrombin by recombinant factor VIIa in vivo is mediated by tissue factor.

The human coagulation system continuously generates very small quantities of Factor Xa and thrombin. Current evidence suggests that basal level activation of the hemostatic mechanism occurs via Factor VIIa-dependent activation of Factor X, but direct proof has not been available for the participation of tissue factor in this pathway. To examine this issue, we infused relatively high concentrations of recombinant Factor VIIa (approximately 50 micrograms/kg body wt) into normal chimpanzees and observed significant increases in the plasma levels of Factor IX activation peptide, Factor X activation peptide, and prothrombin activation fragment F1+2. Metabolic turnover studies with radiolabeled Factor IX activation peptide, Factor X activation peptide, and F1+2 indicate that elevated levels of the activation peptides are due to accelerated conversion of the three coagulation system zymogens into serine proteases. The administration of a potent monoclonal antibody to tissue factor, which immediately neutralizes function of the Factor VIIa-tissue factor complex in vitro, abolishes the activation of Factor X and prothrombin mediated by the infused recombinant protein, and also suppresses basal level activation of Factor IX and Factor X. The above results suggest that recombinant Factor VIIa functions as a prohemostatic agent by interacting with endogenous tissue factor sites, but definitive proof will require studies in hemophilic animals using relevant hemostatic endpoints.

Effect of low-intensity warfarin anticoagulation on level of activity of the hemostatic system in patients with atrial fibrillation. BAATAF Investigators.

BACKGROUND AND PURPOSE: The Boston Area Anticoagulation Trial for Atrial Fibrillation (BAATAF) demonstrated that low-intensity warfarin anticoagulation can, with safety, sharply reduce the rate of stroke in patients with nonvalvular atrial fibrillation. The beneficial effect of warfarin was presumably related to a decrease in clot formation in the cardiac atria and subsequent embolization. METHODS: To assess the effect of warfarin therapy on in vivo clotting in patients in the BAATAF, we measured the plasma level of prothrombin activation fragment F1+2. One sample was obtained from 125 patients from the BAATAF; 62 were taking warfarin and 63 were not taking warfarin (control group). RESULTS: The warfarin group had a 71% lower mean F1+2 level than the control group (mean F1+2 of 1.57 nmol/L in the control group compared with a mean of 0.46 nmol/L in the warfarin group; P < .001). F1+2 levels were higher in older subjects but were consistently lower in the warfarin group at all ages. Fifty-two percent of patients in the control group were taking chronic aspirin therapy at the time their F1+2 level was measured. Control patients taking aspirin had F1+2 levels very similar to control patients not taking aspirin (mean of 1.52 nmol/L for control patients on aspirin compared with 1.64 nmol/L for control patients off aspirin; P > .1). CONCLUSIONS: We conclude that prothrombin activation was significantly suppressed in vivo by warfarin but not aspirin among patients in the BAATAF. These findings correlate with the marked reduction in ischemic stroke noted among patients in the warfarin treatment group observed in the BAATAF.

Coagulation activation following estrogen administration to postmenopausal women.

We investigated coagulation system activation following estrogen treatment in 29 healthy postmenopausal women. Study participants received conjugated estrogens at 0.625 and 1.25 mg per day, and placebo for 3-month periods in a randomized crossover protocol. Blood samples were obtained on two consecutive days at the end of each treatment period for immunoassays of F1+2 and fibrinopeptide A (FPA), markers of factor Xa action on prothrombin and thrombin action on fibrinogen in vivo, respectively. Treatment with estrogens at a dose of 0.625 or 1.25 mg resulted in significant increases in mean F1+2 levels of 40 and 98%, respectively, and in mean FPA levels of 37 and 71%, respectively. The measurements of F1+2 were significantly higher in women receiving 1.25 mg of estrogen than 0.625 mg. We also observed significant declines in the levels of antithrombin III and total protein S antigen. Immunologic levels of protein C increased modestly at only the 1.25 mg estrogen dose level. These data indicate that low doses of oral estrogens (< or = 1.25 mg per day) frequently increase the amount of thrombin generated in vivo. Our observations may help to explain the increased thrombotic risk that has been observed with higher doses of this medication (> or = 2.5 mg).

Gemfibrozil reduces plasma prothrombin fragment F1 + 2 concentration, a marker of coagulability, in patients with coronary heart disease.

The effects of gemfibrozil on several indices of haemostatic activity were explored in male patients with coronary heart disease (CHD). Sixty-three of 71 patients completed a crossover study in which gemfibrozil 1,200 mg/day and matching placebo were each taken in randomised order for 2 months in a double-blind manner, separated by a 2-month washout period. Serum cholesterol decreased by an average (95% confidence interval) of 12 (9 to 15)% and non-fasting triglyceride concentration by 43 (34 to 51)% during active treatment. Plasma prothrombin fragment F1 + 2 concentration, a marker of the in vivo rate of generation of thrombin, was 25 (12 to 37)% lower on average while on gemfibrozil than during the placebo phase. Factor VII coagulant activity (VIIc) and antigen concentration, and fibrinopeptide A concentration were not influenced by gemfibrozil in the group overall. However, the VIIc response appeared to be dependent upon the untreated cholesterol level. Hypercholesterolaemic men (cholesterol greater than 6.5 mmol/l) experienced a significant reduction in VIIc averaging 6% of standard during active therapy. Other effects of gemfibrozil were a 5 (2 to 9)% increase in plasma fibrinogen by a gravimetric method, an 11 (8 to 13)% increase in platelet count, and a 6 (2 to 10)% reduction in white cell count. The reduced incidence of CHD following gemfibrozil therapy in hyperlipidaemic patients may arise in part through a reduction in procoagulant activity and thus the risk of an occlusive coronary thrombosis.

Monitoring "mini-intensity" anticoagulation with warfarin: comparison of the prothrombin time using a sensitive thromboplastin with prothrombin fragment F1+2 levels.

Treatment with warfarin using a target International Normalized Ratio (INR) range of 1.7 to 2.5 is efficacious for many clinical indications, but the minimal intensity of anticoagulation required for antithrombotic protection has yet to be determined. To evaluate whether patients could be reliably monitored with a less intense regimen, we anticoagulated patients with warfarin for several months using a target INR range of 1.3 to 1.6 as determined by prothrombin time (PT) using a sensitive thromboplastin (Dade IS, International Sensitivity Index [ISI] = 1.3). Plasma measurements of F1+2, a marker of factor Xa action on prothrombin in vivo, were also obtained to determine the suppressive effect of warfarin on hemostatic system activity. Overall, 20 of 21 patients with a history of cerebrovascular events (mean age, 61 years) could be reliably regulated with warfarin in the target INR range. F1+2 levels were significantly suppressed from baseline in all patients, with a mean reduction of 49% (range, 28% to 78%). We found a significant relationship between the extent of suppression of prothrombin activation levels and the baseline measurements. A mean reduction of 65% was observed for those patients with baseline F1+2 greater than or equal to 1.5 nmol/L, but only 38% for baseline F1+2 less than or equal to 0.5 nmol/L. Overall, 68% of plasma samples obtained during stable anticoagulation were within the target INR range. PTs were also determined on all plasma samples with two thromboplastins of lower sensitivity (C+, ISI = 2.09; and automated simplastin, ISI = 2.10). Only 47% and 35% of PT determinations, respectively, were within the target range with these reagents. We conclude that prothrombin activation can be significantly suppressed in vivo with use of warfarin in an INR range of 1.3 to 1.6. This level of anticoagulation can be reliably achieved by monitoring PTs with a thromboplastin of high sensitivity.