The antithrombotic effect of a novel hirudin derivative after reconstruction of carotid artery in rabbits

Introduction

Hirudin is a direct thrombin inhibitor that has potential mechanistic advantages over indirect inhibitors. Peptides containing the RGD motif competitively inhibit binding of fibrinogen to glycoprotein IIb/IIIa on platelets, thus inhibiting platelet aggregation. A novel hirudin derivative, recombinant RGD-hirudin (r-RGD-hirudin), was engineered by fusing the tripeptide RGD sequence to the native hirudin. We tested the antithrombotic effect of r-RGD-hirudin using a carotid artery reconstruction model in rabbits.

Materials and methods

A fusion gene encoding r-RGD-hirudin was constructed and expressed at high levels in Pichia pastoris. Following traumatic injury and anastomosis, 42 New Zealand White rabbits were randomized to receive normal saline, abciximab, wild-type hirudin, or r-RGD-hirudin. Fibrinogen concentration, aPTT, TT, PT, and PAGm were measured prior to and following the operation. Carotid angiography and pathological examination of the anastomotic site were performed to compare patency rates among the groups.

Results

The r-RGD-hirudin significantly prolonged aPTT, TT, PT and inhibited PAGm following carotid anastomosis in rabbits. The median dose of r-RGD-hirudin (0.5 mg/kg) had a therapeutic effect equal to that of wild-type hirudin (1.0 mg/kg) and higher than that of abciximab (0.2 mg/kg) with regard to patency rates.

Conclusions

Compared to wild-type hirudin or antiplatelet agent, the novel anticoagulant, r-RGD-hirudin was capable of inhibiting both thrombin activity and platelet aggregation, and was demonstrated to be effective in the prevention of thrombosis.     

Inhibition of factor XI reduces thrombus formation in rabbit jugular vein under endothelial denudation and/or blood stasis

Introduction

In addition to acquired and inherited risk factors, the growth of venous thrombus under static conditions and endothelial injury play important roles in the development of deep venous thrombosis (DVT), for which risk factors include increased plasma levels of coagulation factor XI (FXI). The aim of this study is to understand the role of FXI in venous thrombus formation under conditions of endothelial denudation and/or blood stasis.

Materials and methods

The contribution of FXI to venous thrombus formation was investigated in a rabbit model and a flow chamber system. Thrombi were induced in the rabbit jugular veins by (1) endothelial denudation, (2) vessel ligation (blood stasis) or (3) by combined endothelial denudation and vessel ligation. Blood samples were perfused on immobilized type III collagen at a wall shear rate of 70/s and then the surface area covered by platelets and fibrin was morphometrically evaluated. Prothrombin fragment 1 + 2 (F1 + 2) generation was also measured before and after perfusion.

Results

All thrombi induced in rabbit jugular veins were composed of platelets, fibrin and erythrocytes. Anti-FXI antibody significantly reduced ex vivo plasma thrombin generation initiated by ellagic acid but not by tissue factor, and in vivo thrombus formation under endothelial denudation and/or vessel ligation. The antibody significantly reduced surface areas covered by platelets and fibrin, as well as F1 + 2 generation at a wall shear rate of 70/s in flow chambers.

Conclusion

These results suggest that FXI contributes to venous thrombus growth under conditions of endothelial denudation and/or blood stasis, and that thrombin generation by FXI interaction promotes further platelet aggregation and fibrin formation at low shear rates.     

Association of the ZNF804A gene polymorphism rs1344706 with white matter density changes in Chinese schizophrenia

Background

ZNF804A gene polymorphism rs1344706, the first genetic risk variant to achieve genome wide significance for schizophrenia, has been linked to neural functional connectivity. Dysconnectivity of WM may be the primary pathological mechanism of schizophrenia. Association of this variant with regional WM density has not been investigated in schizophrenic patients.

Methods

69 healthy controls and 80 patients with schizophrenia underwent genotyping of rs1344706 SNPs, and were examined for WM density (T1-weighted MRI). The association of rs1344706 with WM changes in schizophrenia patients and healthy controls was analyzed using a full-factorial 2 × 2 analysis of variance.

Results

1. There was an interaction on WM density in the left prefrontal lobe between the rs1344706 genotype and schizophrenic diagnosis, where the risk T allele carriers presented higher WM density in the schizophrenia patients and lower WM density in healthy controls in comparison with the non-risk allele carriers.2. The risk allele was associated with an increased WM density of the bilateral hippocampus in both the patients and the healthy group.

Limitation

The influence of antipsychotics to the white matter in schizophrenic patients was not fully eliminated.

Conclusions

The ZNF804A variant may confer risk for schizophrenia by exerting its effects on the WM in the left prefrontal lobe together with other risk factors for schizophrenia.     

Purification, biochemical properties and antithrombotic effect of a novel Streptomyces enzyme on carrageenan-induced mice tail thrombosis model

Introduction

The prevalence of cardiovascular diseases, one of the major causes of worldwide mortality, is being increasingly reported. Safer, more effective, and less expensive thrombolytic drugs can possibly overcome the underlying problems associate with current thrombolytic drugs.

Methods

A thrombolytic enzyme was purified and characterized from a Streptomyces strain. Carrageenan induced tail-thrombosis mice model was used to evaluate in vivo antithrombotic effect of the enzyme.

Results

First 15 N-terminal amino acids of the purified enzyme were IAGGQAIYAGGGRRS, which are significantly different from the reported fibrinolytic enzymes. The enzyme exhibited 14.3 ± 2.3-fold stronger thrombolytic activity than that of plasmin. In carrageenan induced tail-thrombosis model, the enzyme caused reduction in frequency of thrombus. Tail-thrombus of the enzyme treated group was significantly shorter than the physiological saline treated group and the thrombus decrement was correlated with the enzyme dose.

Conclusions

The enzyme purified from the Streptomyces strain can be a potential candidate for the treatment of thrombosis.     

Effect on perfusion chamber thrombus size in patients with atrial fibrillation during anticoagulant treatment with oral direct thrombin inhibitors, AZD0837 or ximelagatran, or with vitamin K antagonists

Introduction

AZD0837 and ximelagatran are oral direct thrombin inhibitors that are rapidly absorbed and bioconverted to their active forms, AR-H067637 and melagatran, respectively. This study investigated the antithrombotic effect of AZD0837, compared to ximelagatran and the vitamin K antagonist (VKA) phenprocoumon (Marcoumar^®), in a disease model of thrombosis in patients with non-valvular atrial fibrillation (NVAF).

Methods

Open, parallel-group studies were performed in NVAF patients treated with VKA, which was stopped aiming for an international normalized ratio (INR) of ≤ 2 before randomization. Study I: 38 patients randomized to AZD0837 (150, 250 or 350 mg) or ximelagatran 36 mg twice daily for 10-14 days. Study II: 27 patients randomized to AZD0837 250 mg twice daily or VKA titrated to an INR of 2-3 for 10-14 days. A control group of 20 healthy elderly subjects without NVAF or anticoagulant treatment was also studied. Size of thrombus formed on pig aorta strips was measured after a 5-minute perfusion at low shear rate with blood from the patient/control subject.

Results

Thrombus formation was inhibited by AZD0837 and ximelagatran. Relative to untreated patients, a 50% reduction of thrombus size was estimated at plasma concentrations of 0.6 and 0.2 μmol/L for AR-H067637 and melagatran, respectively. For patients receiving VKA treatment, the thrombus size was about 15% lower compared with healthy elderly controls.

Conclusions

Effects of AZD0837 and ximelagatran on thrombus formation were similar or greater than for VKA therapy and correlated with plasma concentrations of their active forms.     

Two sessions of sleep-focused mind-body bridging improve self-reported symptoms of sleep and PTSD in veterans: A pilot randomized controlled trial

Objective

Sleep disturbance is highly prevalent among veterans. As an alternative to sleep medications with their undesirable side effects, nonpharmacological mind-body interventions may be beneficial for sleep management in primary care. The aim of this pilot study was to investigate whether a novel mind-body intervention, mind-body bridging (MBB), focusing on sleep, could improve self-reported sleep disturbance and comorbid symptoms in veterans.

Methods

This pilot study was a randomized controlled trial at the Veterans Affairs Salt Lake City Health Care System in which 63 veterans with self-reported sleep disturbance received MBB or an active sleep education control. Both interventions were conducted in two sessions, once per week. Patient-reported outcomes included the following: primary—Medical Outcomes Study (MOS) Sleep Survey, MOS Short Form-36V; secondary—Center for Epidemiological Studies-Depression, PTSD Check List-Military, Five-Factor Mindfulness Questionnaire.

Results

At both Week 1 (1 week after the first session) and post-intervention assessments, while sleep disturbance decreased in both groups, MBB performed significantly better than did the control group. Furthermore, self-reported PTSD symptoms improved in MBB, while they remained unchanged in the control. Overall mindfulness increased in MBB, while it remained unchanged in the control.

Conclusions

This study provides preliminary evidence that a brief sleep-focused MBB could be a promising intervention for sleep and potentially other comorbid symptoms (e.g., PTSD). MBB could help patients develop awareness skills to deal with sleep-related symptoms. Integration of MBB into primary care settings may enhance care of patients with sleep disturbance and co-morbid symptoms.     

Does personality disorder decrease the likelihood of remission in early-onset chronic depression?

Background

The impact of personality disorders (PD) on the course of depression has been gaining interest among clinical researchers over the past decade. Recent observational studies have found that PD was associated with impaired social functioning and reduced likelihood of depression recovery. Elevated rates of PD have been noted in early-onset and chronic forms subtypes of depression. However, scant data exist regarding the link between PD and outcome for this depression subtype.

Methods

The National Epidemiological Survey on Alcohol and Related Conditions database was analyzed. This survey included 43 093 respondents, 18 years and older, conducted in 2001 through 2002. Logistic regression was used to identify demographic and clinical predictors of remission in early-onset chronic depression.

Results

The absence of PD, having more years of education, and being married considerably improved the likelihood of remission. Paranoid personality disorder and obsessive-compulsive disorder were the only specific PD found to be associated with a reduced probability of remission.

Limitations

Depression remission status may have biased the recollection of PD symptoms. Borderline personality disorder, narcissistic personality disorder, and schizotypal personality disorder were not assessed.

Conclusions

This study suggests that PD are significant predictors of remission in early-onset chronic depression.     

A potential thrombus diagnosis reagent based on P-selectin monoclonal antibody SZ-51 light chain

Introduction

P-selectin is a well characterized platelet adhesion molecule that can shift from the secretory granules to the surface of activated platelets, which makes it a potential target in thrombus diagnosis and therapy. SZ-51 is a monoclonal antibody against P-selectin.

Materials and methods

To build a potential thrombus diagnosis reagent, we expressed the light chain of SZ-51 (SZ-LC) in P. pastoris and the protein was highly purified by the procedure combining nickel affinity purification, Q-column and Superdex 75 column chromatography. The purified recombinant SZ-LC was labeled with ^99mTc and used for blood clearance, in vitro platelet binding and dog thrombus binding assay.

Results and conclusion

The yield of SZ-LC by the expression and purification method reached above 70 mg/L culture. We found that the nucleotide from ^99mTc-SZ-LC was removed quickly through animal kidney, and ^99mTc-SZ-LC could bind specifically to the activated human platelet in vitro. More importantly, with this recombinant protein, we successfully detected the fresh thrombus that was induced in dog vein. These results suggested that the recombinant SZ-LC expressed by P. pastoris was functional active and a potential reagent for thrombus diagnosis.     

Stent implantation in the superficial femoral artery: Short thrombelastometry-derived coagulation times identify patients with late in-stent restenosis

Introduction

The mechanisms of restenosis, the recurrence of luminal narrowing, are complex and incompletely understood to date. Thrombin, the pivotal enzyme in haemostasis, presumably contributes to the formation of in-stent restenosis (ISR). It was therefore the aim of our study to investigate whether blood coagulation/thrombin generation plays a critical role in the formation of ISR in peripheral artery disease patients with stent angioplasty in the superficial femoral artery.

Materials and Methods

We aimed to examine in this retrospective study whether patients with high-degree restenosis (50-75% lumen diameter reduction, n = 20) are in a hypercoaguable state implying enhanced readiness to generate thrombin compared to patients with low-degree restenosis (< 50% lumen diameter reduction, n = 14).

Results

The coagulation tests calibrated automated thrombography, activated partial thromboplastin time, platelet aggregation, platelet adhesion, fibrinogen, and microparticles’ procoagulant activity did not indicate a different coagulation status in the two patient groups. However, the thrombelastometry-derived value Coagulation Time (CT) was significantly shorter in the high-degree restenosis group (p = 0.012), indicating a hypercoagulable state of patients with high-degree restenosis. Under our experimental conditions, CTs shorter than 444.5 s identify patients at high risk (sensitivity = 95%) for luminal narrowing.

Conclusions

Our study supports the assumption that blood coagulation/thrombin generation plays a critical role in the development of ISR in peripheral arteries after stent insertion and that the thrombelastometry-derived CT might be a suitable value to identify peripheral artery disease patients at risk for development of high-degree in-stent restenosis in the superficial femoral artery.     

Plasma factor and inhibitor composition contributes to thrombin generation dynamics in patients with acute or previous cerebrovascular events

Introduction

More than 80% of cerebrovascular events are ischemic and largely thromboembolic by nature. We evaluated whether plasma factor composition and thrombin generation dynamics might be a contributor to the thrombotic phenotype of ischemic cerebrovascular events.

Materials and Methods

We studied (1) 100 patients with acute ischemic stroke (n = 50) or transient ischemic attack (TIA) (n = 50) within the first 24 hours from symptom onset, and (2) 100 individuals 1 to 4 years following ischemic stroke (n = 50) or TIA (n = 50). The tissue factor pathway to thrombin generation was simulated with a mathematical model using plasma levels of clotting factors (F)II, V, VII, VIII, IX, X, antithrombin and free tissue factor pathway inhibitor (TFPI).

Results

The plasma levels of free TFPI, FII, FVIII, and FX were higher, while antithrombin was lower, in the acute patients compared to the previous event group (all p ≤ 0.02). Thrombin generation during acute events was enhanced, with an 11% faster maximum rate, a 15% higher maximum level and a 26% larger total production (all p < 0.01). The increased thrombin generation in acute patients was determined by higher FII and lower antithrombin, while increased free TFPI mediated this effect. When the groups are classified by etiology, all stroke sub-types except cardioembolic have increased TFPI and decreased AT and total thrombin produced.

Conclusion

Augmented thrombin generation in acute stroke/TIA is to some extent determined by altered plasma levels of coagulation factors.     

Seasonal variation in the incidence of superficial venous thrombophlebitis

Introduction

Previous studies have demonstrated an increased frequency and severity of symptoms due to varicose veins during summer. However there is no data on their complications, including superficial venous thrombophlebitis (SVT). The aim of this study was to test the hypothesis that SVT follows a seasonal pattern.

Materials and Methods

During the two-year period between January 2007 and December 2008, inclusive, 123 patients with SVT were evaluated, including 60 females and 63 males. In 8 patients (6.5%) an additional and/or other predisposing factor was present. On presentation, SVT was complicated by thrombus extension to the proximal deep system in 5 cases (4.1%); above-knee SVT was present in 4 of these 5 cases.

Results

SVT occurred more often during the months of May through October (monthly incidence of 7.3 cases) compared to remaining of the year (monthly incidence of 2.9 cases). SVT showed a peak in June and July with 33.3% of all SVTs occurring during these two months (monthly incidence of 10.25 cases). Using time-series statistics SVT occurrence showed a periodical seasonal pattern (p = 0.003). Although a seasonal pattern was evident in all patient subgroups, this was significant only in males and patients with below-knee SVT.

Conclusions

SVT showed a clear seasonal pattern of occurrence, with a significant rise during summer time. Although a possible explanation of this observation could be poor patient compliance and suboptimal usage of elastic stockings during the hot Mediterranean summer, further studies to investigate the cause, clinical significance and preventive methods of this complication are justified.     

No evidence for an association between ABO blood group and overall ischemic stroke or any of the major etiologic subtypes

Introduction

The ABO blood group system is encoded by one gene, ABO. Previous studies have reported an association between blood group non-O (i.e. phenotype A, B or AB) and myocardial infarction. Studies on stroke and ABO are, however, more scarce. Therefore, we aimed to investigate whether ABO phenotype or genotype is associated with ischemic stroke and/or etiologic subtypes of ischemic stroke.

Materials and methods

The study was performed in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS), which comprises 600 patients with ischemic stroke before the age of 70 years, and 600 matched controls. Patients were classified according to the TOAST criteria.

Results

There was no significant association between ABO phenotype (blood group O vs. non-O) and overall ischemic stroke (multivariable odds ratio of 0.9, 95% confidence interval 0.7-1.2). This was also true for blood group O vs. A and O vs. B. Furthermore, no association between ABO genotypes and ischemic stroke was detected. The ischemic stroke subtype analysis was confined to large-vessel disease, small-vessel disease, cardioembolic stroke and cryptogenic stroke. In this analysis, there was no significant association between any ischemic stroke subtype and ABO phenotype or genotype.

Conclusions

The findings in this study suggest that ABO phenotype or genotype does not have a major impact in the pathophysiology of ischemic stroke or any of the ischemic stroke subtypes.     

A porcine model of massive, totally occlusive, pulmonary embolism

Background

A reliable, animal model of massive, totally occlusive, pulmonary embolism (PE) is lacking.

Objectives

To design an animal model of totally occlusive PE and to challenge the model by a plasminogen activator.

Methods

In eight anaesthetized pigs (~ 90 kg) a massive preformed autologous thrombus was injected into the caval vein. One animal was autopsied to assess the extent of injected clot, whereas in the other animals extracorporeal life support (ECLS) was initiated and continued for three hours. These animals received 100 mg rt-PA. Blood gases, coagulation tests, creatine kinase (CK), lactate dehydrogenase (LDH), end-tidal CO2, systemic and pulmonary artery blood pressures and flow were registered.

Results

All animals went into circulatory arrest within 2 minutes after injection of the thrombus. In the animal where ECLS was not started, autopsy relieved a totally occlusive embolus of the pulmonary artery. The ECLS maintained a systemic blood flow of 6-8 L/min with adequate oxygenation and CO2-removal. However, lactate increased and base-excess became negative. Ddimer increased, fibrinogen decreased, and CK and LDH increased. All seven animals were weaned from ECLS. Despite the rt-PA treatment, the animals had at that time low end tidal CO2/PaCO2 ratio and increased mean pulmonary arterial pressure, suggesting a significant amount of embolic material remaining in the pulmonary artery.

Conclusion

This model of massive, totally occlusive, pulmonary embolism mimics well fatal PE seen in the clinic, and has the potential for use in testing of new therapeutic interventions.     

Single-prolonged stress induces apoptosis in the amygdala in a rat model of post-traumatic stress disorder

Objective

To detect the apoptosis-related Bax and Bcl-2 gene expression and apoptotic cell death in the amygdala region in the single-prolonged stress (SPS) rats.

Methods

A total of 100 male Wistar rats were randomly divided into a normal control group and SPS groups of 1d, 4d, 7d, and 14d. The expression of Bax and Bcl-2 was detected using immunohistochemistry and Western Blotting; TUNEL-staining and double-labeled flow cytometry (FCM) were employed for the detection and quantification of the apoptotic cells in the amygdala; morphological change of the subcellular structure in amygdala was observed by using the transmission electron microscopy (TEM).

Results

The ratio of Bax/Bcl-2 peaked at SPS 4d and then gradually decreased. The apoptosis peaked at SPS 4d. The TUNEL-positive cells were found in each SPS group and the TUNEL-positive cells rate peaked at SPS 4d. The morphological change of amygdala cells in each SPS group bears typical apoptotic characteristics.

Conclusions

In the SPS rat brain, we found apoptotic process in the amygdala region which may relate to the pathogenesis of amygdala abnormal function in PTSD.     

Programme spécialisé pour les premiers épisodes psychotiques : analyse d’une cohorte de 100 patients

Background

The emergence of specialized programs for the treatment of first-episode psychoses in non-research settings calls for a better definition of this group of patients and of the psychological interventions offered.

Aims

The aim of this study is to describe a specialized program for first-episode psychotic patients and to define the patients referred to, their different distinguishing characteristics and their relative use of the different services offered them.

Method

From an initial population of 127 patients, 100 agreed to have their data used to determine their detailed socio-demographic and symptomatological characteristics, their treatment delays (duration of untreated psychosis, referral delay) and their use of specific treatment modalities offered.

Results

The sample is similar to others described in the current literature in terms of socio-demographics, diagnostic distribution, and duration of untreated psychosis. The referral delay is 1.66 year. The symptomatological and neuropsychological portraits observed are characterized by heterogeneity. Services offered appear clinically indicated for most patients referred to (81%), with different characteristics observed across the groups of patients referred to in the different modalities.

Conclusion

The heterogeneity of the clinical presentation and of needs observed implies that such a program has to include a detailed assessment of each patient and a basic range of interventions. The implementation of such interventions in a non-research setting, and eventually on a large scale, should be accompanied by an evaluation process that could help guide clinical work and the organization of psychiatric services for patients suffering from psychosis.     

Alterations of profibrinolytic receptor annexin A2 in pre-eclampsia: a possible role in placental thrombin formation

Introduction

Deficient fibrinolytic activity due to alterations of profibrinolytic receptor annexin A2 has been shown to be related to increased thrombosis. We compared the expression of annexin A2 in pre-eclampsia with that in normal pregnancies and investigated its relationship to placental thrombin formation.

Materials and methods

Sixty patients with pre-eclampsia and 30 matched normal pregnant controls were included in the study. Expression of annexin A2 mRNA in placental tissues was analyzed using quantitative RT-PCR. Annexin A2 protein in placentas as well as blood was determined by western blot analysis and immunohistochemistry. Enzyme-linked immunosorbent assay (ELISA) was used to detect the presence of anti- annexin A2 antibodies in peripheral maternal blood.

Results

The expression of annexin A2 mRNA in placentas was significantly decreased in pre-eclampsia compared to normal pregnancies. Levels of annexin A2 protein in placentas as well as in peripheral maternal blood were also significantly reduced in patients with pre-eclampsia compared with healthy pregnant women. High titers of anti- annexin A2 antibodies were more frequently detected in pre-eclampsia group. Decreased levels of annexin A2 expression and the presence of anti-annexin A2 antibodies were associated with increased placental thrombosis.

Conclusion

The down regulation of annexin A2 expression and the presence of anti-annexin A2 antibodies were correlated to PE and may increase placental thrombin formation.     

Diurnal variation of soluble CD40 ligand in patients with acute coronary syndrome. Soluble CD40 ligand and diurnal variation

Introduction

We sought to investigate whether day-night variations occur in the concentration of circulating soluble CD40 ligand in patients with acute coronary syndrome, as this may have practical implications.

Materials and Methods

We assessed 70 consecutive ST-segment elevation myocardial infarction patients admitted into the Coronary Care Unit and 50 control subjects. Each subject was studied under strictly controlled light/dark conditions. Blood samples were drawn at 09:00 h (light phase) and 02:00 h (dark phase). Nocturnal blood samples were drawn by a trained nurse, with the help of a minute torch with a dim red light in order to avoid any direct lighting on the patient during sleep. The soluble CD40 ligand was measured using a commercially available ELISA.

Results

Soluble CD40 ligand levels showed no diurnal variations in control subjects. In the ST-segment elevation myocardial infarction group, however, soluble CD40 ligand concentration (pg/mL) in the light phase was significantly higher than that in the dark phase (167.3 ± 63.2 vs 118.9 ± 48.3 pg/mL, p < 0.001).

Conclusions

The study shows for the first time the existence of diurnal variations in soluble CD40 ligand levels in ST-segment elevation myocardial infarction patients, which indicates the need for standardizing the time of blood sampling for the assessment of this molecule, at least in studies involving ST-segment elevation myocardial infarction patients.     

Efficacy and bleeding risk of antithrombin supplementation in septic disseminated intravascular coagulation: A prospective multicenter survey

Introduction

Although supplementation with antithrombin (AT) concentrates has been widely accepted for the treatment of disseminated intravascular coagulation (DIC) in Japan, the effects and adverse effects have not been investigated.

Materials and Methods

We conducted a nonrandomized multi-institutional survey. A total of 729 septic DIC patients with AT activity levels of 70% or lower, who had undergone AT substitution at either 1500 IU/day or 3000 IU/day for consecutive 3 days were analyzed. Of these, 650 and 79 patients had received 1500 IU/day (AT1500 group) and 3000 IU/day (AT3000 group), respectively.

Results

Bleeding events were observed in 6.52% of patients (severe bleeding, 1.71%). A significant decrease in initial AT level (below 50%) was observed in 69.6% of patients in AT3000 group and 48.2% in AT1500 group, and this difference was significant (P < 0.01). A logistic-regression analysis conducted using age, gender, body weight, initial AT activity, and supplemented AT dose, revealed that higher initial AT activity (odds ratio (OR), 1.032; P < 0.001), AT dose of 3000 IU/day (OR, 1.912; P = 0.026), and age (OR, 0.985; P = 0.023) were significant factors for improved survival.

Conclusion

The risk of severe bleeding is less than 2%, and concomitant administration of heparin did not increase the risk. The survival in AT1500 group was 65.2%, while that in AT3000 group was 74.7%.     

Risk of in-stent thrombus formation at one year after drug-eluting stent implantation

Introduction

Although very late stent thrombosis is an important problem with drug-eluting stents, risks for in-stent thrombus formation have not been clarified. Therefore, we examined the risks among patient and lesion characteristics by direct visualization of the stented lesion by angioscopy.

Materials and methods

Consecutive patients (n = 118) who received successful angioscopic examination of drug-eluting (sirolimus- or paclitaxel-eluting) stents at 1-year after implantation were included. Presence or absence of thrombus directly on the area of each condition determined by the combination of lesion color (white or yellow) and neointima coverage (grade 0 − 2) was evaluated for each stent; and the factors associated with the presence of thrombus were analyzed.

Results

Multivariate logistic regression analysis revealed lesion color (= yellow; odds ratio [OR] 5.5, 95% confidence interval [CI] 3.0-10, p < 0.001), neointima coverage (= grade 0 or 1; OR 5.5, 95% CI 2.4-13, p < 0.001), and stent type (= paclitaxel-eluting stent; OR 7.6, 95% CI 3.9-15, p < 0.001) as independent contributors for in-stent thrombus formation.

Conclusion

Yellow color of the lesion, poor neointima coverage, and use of paclitaxel-eluting stent were the risks of in-stent thrombus formation at 1 year after DES implantation.