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Alterations in the free radical generation and nitric oxide release from rat peripheral polymorphonuclear leukocytes following thrombosis.

The present investigation was undertaken to study the alterations in free radical generation and release of nitric oxide (NO) from polymorphonuclear leukocytes (PMNLs) following thrombosis. Thrombosis was induced in rats by intravenous injection of collagen and adrenaline. PMNLs were separated from rat blood by using dextran sedimentation and Ficoll-Hypaque. Arachidonic acid (AA), formyl methionine leucine phenylalanine (FMLP) and opsonized zymosan (OZ) induced free radical generation was estimated as luminol (LCL) and Lucigenin (LUCDCL) dependent chemiluminescence. PMNLs nitric oxide synthase (NOS) activity and NO release were measured by using [14C] L-Arginine (L-Arg) and oxy-hemoglobin respectively. LCL and LUCDCL responses in rat PMNLs were significantly attenuated following thrombosis. There was no change in the release of myeloperoxidase enzyme (MPO) from PMNLs obtained following thrombosis. PMNLs NOS activity and NO release were also found to be increased after thrombosis. Pretreatment of rat PMNLs with 10 mM L-NAME (NO precursor) or 100 microM sodium nitroprusside (NO donor), resulted in significant reduction of AA induced LCL response. Results obtained indicate that NO release form PMNLs was augmented while free radical generation response was attenuated after the induction of thrombosis.

Animals↗

Treatment of deep cerebral venous thrombosis by local infusion of tissue plasminogen activator.

BACKGROUND: Treatment of extensive intracranial venous sinus thrombosis with thrombolytic drugs is described, although the indications for and most efficacious technique for achieving thrombolysis remain uncertain. We report the successful lysis of superficial and deep venous system thrombosis by infusion of recombinant human tissue-type plasminogen activator (rt-PA) into the anterior superior sagittal sinus. CASE DESCRIPTION: A 34-year-old man presented with headaches followed by decreased level of consciousness and left hemiplegia. Angiography showed thrombosis of the superior sagittal and both transverse and straight sinuses with extension into the internal cerebral veins. The superior sagittal sinus was catheterized via a transfemoral route and rt-PA, 25 mg, was infused. There was no significant change in the thrombosis. The catheter was left in place and rt-PA was infused at 1 mg/minute for 19 hours. Repeat angiography showed resolution of the thrombosis. The patient was placed on heparin and then coumadin. He recovered completely. CONCLUSIONS: This report suggests that superselective infusion of thrombolytics into thrombosed intracranial venous sinuses can lyse intracranial venous sinus thrombosis. The thrombolytic agent must be infused for hours. The apparent successful lysis of clot in the deep venous system when infusion was into the superior sagittal sinus might be related to diffusion of rt-PA throughout the intracranial venous system or to improved venous outflow caused by lysis of clot in superficial dural sinuses.

Adult↗

Accuracy of clinical assessment of deep-vein thrombosis.

The clinical diagnosis of deep-vein thrombosis is generally thought to be unreliable. From experience, we hypothesised that this widely held view might be incorrect. We developed a clinical model and prospectively tested its ability in three tertiary care centres to stratify symptomatic outpatients with suspected deep-vein thrombosis into groups with high, moderate, or low probability groups of deep-vein thrombosis. We evaluated our clinical model in combination with venous ultrasonography to determine the potential for an improved and simplified diagnostic approach in patients with suspected deep-vein thrombosis. All patients were clinically assessed to determine the probability for deep-vein thrombosis before they had ultrasonography and venography. All tests were performed and interpreted by independent observers. In 529 patients, the clinical model predicted prevalence of deep-vein thrombosis in the three categories: 85% in the high pretest probability category, 33% in the moderate, and 5% in the low category. There was no statistical difference in the performance of the model in the three centres. The model demonstrated excellent interobserver reliability (Kappa = 0.85). There were important differences with ultrasonography between the high and low pretest probability groups for both positive predictive values (100% (95% CI, 94-100%) vs (63% [35-85%], respectively). Thus, use of the clinical model combined with ultrasonography would decrease the number of false positive and negative diagnosis if venography were done when the ultrasound result and pretest probability were discordant. The diagnostic process could be simplified by excluding those patients with low pretest probability and normal ultrasound results from serial testing.

Decision Trees↗

Comparison of splenoportography and transhepatic portography in the diagnosis of portal vein thrombosis.

Accurate diagnosis and localization of thrombosis in the portal venous system is essential for proper surgical treatment. We compared the results of percutaneous transhepatic portography and splenoportography in 66 patients with cirrhosis of the liver. The two methods agreed on absence of thrombosis in 48, and in presence of thrombosis (verified later by surgery/autopsy) in four patients. In 12 patients an apparent thrombosis diagnosed by splenoportography was disproved by transhepatic portography, and vice versa in two patients. Free portal pressure and splenic pulp pressure did not differ significantly irrespective of the 'diagnosis' of thrombosis. We conclude, that transhepatic portography is better than splenoportography in making the diagnosis of thrombosis in the portal venous system although failure to visualize the splenic vein may indicate splenoportography.

Female↗

Incidence of deep venous thrombosis and pulmonary embolism in otolaryngology-head and neck surgery.

OBJECTIVE: Postoperative deep venous thrombosis and pulmonary embolus are major causes of morbidity and mortality in patients undergoing surgical procedures. In contrast to other surgical fields, the incidence of these life-threatening conditions has not been studied in our specialty. The purposes of this study were to elucidate the incidence of deep venous thrombosis and pulmonary embolus in patients after otolaryngologic operations and to identify specific risk factors that may contribute to the development of these conditions. METHODS: A retrospective analysis was done of 12,805 total operations on adults done by the Department of Otolaryngology at our institution from January 1987 to December 1994 to determine the number of patients in whom postoperative deep venous thrombosis and pulmonary embolus developed. Patients in whom a postoperative thromboembolic event developed after an otolaryngologic surgical procedure were identified by the medical records department with use of an abstracting database. This search cross-referenced disease-specific codes for otolaryngologic procedures with the codes for deep venous thrombosis and pulmonary embolus to identify the 34 patients in this report. Results (rounded to the nearest decimal point) were then categorized according to the different subspecialties within otolaryngology, and appropriate statistical analysis tests were performed on the resulting data. RESULTS: Thirty-four patients with postoperative deep vein thrombosis were identified during the study period, for an overall incidence of 0.3%. Of these 34 patients, 24 also had a pulmonary embolus for an overall incidence of 0.2%. The incidence of deep venous thrombosis (and pulmonary embolus) in the subspecialties was as follows: head and neck surgery, 0.6% (0.4%); otology/neurotology, 0.3% (0.2%); head and neck trauma and plastic surgery, 0.1% (0.1%); and general otolaryngology, 0.1% (0.04%). Only the patient's age and the presence or absence of pneumatic compression devices were identified as independent risk factors for the development of a thromboembolic event. CONCLUSIONS: Postoperative pulmonary embolus is a rare occurrence in the field of otolaryngology-head and neck surgery. When it does occur, it causes significant morbidity and increases the cost of care for that patient. We discuss our approach to categorizing patients into low-, intermediate-, and high-risk groups, as well as prophylaxis against pulmonary embolus.

Adult↗

[High levels of factor VIIIc and risk of venous thrombosis: critical analysis of case-control studies].

INTRODUCTION: Deep venous thrombosis is a frequent and potentially serious disease. Its causes are multifactorial, associating facilitating circumstances and genetic or acquired coagulation abnormalities. Genetic currently well known abnormalities are quantitative deficiencies of some natural anticoagulants (proteins C and S, antithrombin), and mutations of V and II (G20210-A) genes. The Leiden group has recently shown that the elevation of some coagulation factors level could also constitute a risk factor for deep venous thrombosis. CURRENT KNOWLEDGE AND KEY POINTS: Elevation of factor VIIIc is associated with a higher risk for thrombosis than in the general population but the threshold for normality of this factor is difficult to define. It is a probable constitutional abnormality whose prevalence in the general population vary from 6 to 36%. Risks of deep venous thrombosis associated to this factor elevation is more elevated in patients who have this anomaly (odds ratios vary from 2,2 to 10,3) (95% CI). FUTURE AND PROJECTS: The frequency of this anomaly and its association with a high risk for thrombosis are reasons to assess the potential usefulness of screening for these anomalies in patients who had thrombosis or in their family. The probable genetic origin of these anomalies has to be confirmed by other studies.

Case-Control Studies↗

[A common mutation C677T in the 5,10-methyltetrahydrofolate reductase gene is associated to idiopathic deep venous thrombosis].

PURPOSE: Moderate hyperhomocysteinemia is a risk factor for deep venous thrombosis. The homozygous C677T methylenetetrahydrofolate reductase (MTHFR) mutation is associated with increased level of total plasma homocysteine. The association between homozygous C677T mutation and deep venous thrombosis is still controversial. METHOD: In order to evaluate this association, we studied the prevalence of C677T mutation in 168 patients with confirmed deep venous thrombosis; 31 with an idiopathic deep venous thrombosis (group A) and 137 with thromboembolic event explained by one or more clinical and/or biological risk factors (group B). RESULTS: The distribution of genotypes was different between group A and B [++/+ -/- -(n(%))] : 9(29)/10(32)/12(39) vs 16(12)/57(42)/64(46) (chi(2) : 6.03; P: 0.049). The comparison between homozygotes and the two other genotypes showed significant statistical relationship between homozygous genotype and idiopathic character of deep venous thrombosis (chi(2) : 6.01; P : 0.014; OR : 3.09 [IC 95% : 1.06-8.53]). CONCLUSION: These results suggest that homozygous C677T methylenetetrahydrofolate reductase mutation could be considered as a genetic risk factor for venous thrombosis.

Adult↗

[Homocysteine, 5,10-methylenetetrahydrofolate reductase and deep venous thrombosis. Survey of 120 patients in internal medicine].

BACKGROUND: In the last few years, the association of deep vein thrombosis with frequent biological risk factors and genetic polymorphisms has significantly modified the field of venous thrombosis. In this study, we measured plasma homocysteine levels and tested the C677T methylenetetrahydrofolate reductase (MTHFR) mutation. PATIENTS AND METHODS: Plasma homocysteine levels and test for C677T MTHFR mutation were performed in 120 consecutive patients with objectively diagnosed deep vein thrombosis, and in 120 controls. RESULTS: We found a strong association between hyperhomocysteinemia and thrombosis (odd ratio: 2.43 IC 95% [1.27-4.7]). Conversely the C677T MTHFR gene polymorphism is only associated with hyperhomocysteinemia but not associated with thrombosis. CONCLUSION: This is a preliminary study to the ongoing international multicentric study of SNFMI (Société nationale française de m0+edecine interne) concerning hyperhomocysteinemia and venous thrombosis.

Adult↗

Antibodies to topical bovine thrombin correlate with access thrombosis.

Bovine thrombin is often used topically to promote hemostasis during vascular surgery, including dialysis-access placement. Patients frequently develop antibodies to bovine thrombin preparations, and some may develop antiphospholipid antibodies. We evaluated 88 hemodialysis patients for the presence of antibodies to topical bovine thrombin to determine if elevated antibody levels correlated with vascular access thrombosis. Twenty-seven patients (30.7%) had elevated antibody levels to topical bovine thrombin. More patients with elevated antibody levels had prior vascular access thrombosis than patients with normal antibody levels (13 of 27 versus 5 of 61 patients; P < 0.001). This difference was almost entirely the result of greater levels of thrombosis in patients with polytetrafluoroethylene (PTFE) grafts and elevated antibody levels. In these patients, 11 of 13 patients (84.6%) with elevated antibody levels had a previous thrombosis compared with 2 of 15 patients (13. 3%) with normal antibody levels (P < 0.001). Patients with elevated antibody levels and PTFE grafts also had more prior thromboses (1.92 +/- 1.60 versus 0.133 +/- 0.35 thromboses; P < 0.01) and a greater thrombosis rate (66.89 +/- 63.71 versus 4.65 +/- 12.05 thromboses/100 patient-years; P < 0.01) than patients with normal antibody levels. There were no differences in the frequency of myocardial infarction, coronary artery bypass, access age, presence of diabetes mellitus, platelet counts, anticardiolipin antibody, albumin, lactate dehydrogenase, or C-reactive protein levels. In conclusion, patients with PTFE grafts and elevated antibody levels to topical bovine thrombin had significantly more vascular access thrombosis.

Aged↗

Forecasting thrombosis of vascular access with Doppler color flow imaging.

A noninvasive technique, color Doppler flow imaging, was used to study the predictive value for future episodes of thrombosis in vascular access (polytetrafluoroethylene [PTFE] grafts and radial-cephalic fistulae) in a series of chronic hemodialysis patients. Patients with grafts were classified into three groups based on maximum constriction of the vascular access diameter: narrowing of greater than 50% (group I), narrowing of 30% to 50% (group II), and no narrowing or narrowing less than 30% (group III). More than half of the patients in group I suffered vascular access thrombosis within 6 months, while only 9% to 13% of patients in groups II and III had episodes of thrombosis during the same time interval. Decreased access volume flow (AVF) also correlated with episodes of thrombosis in these patients. No correlation could be demonstrated between recirculation and future thrombosis. No patient with a fistula had narrowing greater than 30% and none had vascular access thrombosis during the 6-month follow-up.

Arteriovenous Shunt, Surgical↗

S-nitrosoglutathione reduces nonocclusive thrombosis rate following balloon overstretch injury and intracoronary irradiation of porcine coronary arteries.

PURPOSE: Intracoronary radiation (IR) suppresses neointima formation following balloon injury in animal models. High doses of radiation exacerbate thrombosis and delay re-endothelialization. The free radical nitric oxide (NO) has been reported to inhibit platelet aggregation, reduce neointimal hyperplasia, and stimulate re-endothelialization. This study examined the effects of a chemical NO donor on neointima formation, thrombosis, and healing of irradiated porcine coronary arteries. METHODS AND MATERIALS: Vascular lesions were created in the coronary arteries of 59 domestic swine by overstretch balloon injury. Arteries were then left untreated or were treated with intracoronary gamma-radiation using Iridium-192 in each artery to deliver 5 or 15 Gy at 2 mm from the center of the source. The chemical NO donor S-nitrosoglutathione (GSNO) was infused i.v. at a rate of 250 microg/min for 10 min before injury, followed by a continuous infusion for 60 min. Animals were euthanized at 14 days and their arteries were analyzed for histomorphometric indices of proliferation and thrombosis. RESULTS: A dose of 15 Gy reduced the ratio of intimal area to medial fracture length (IA/FL) versus control (0.06 +/- 0.05 0.54 +/- 0.10 [p < 0. 001]) but increased the nonocclusive thrombosis rate compared to controls (85% vs. 30%; p < 0.05). A low dose of 5 Gy did not affect neointima formation. Treatment with GSNO reduced thrombosis in all treated groups: control, 15%; 5 Gy, 18%; and 15 Gy, 35% (p < 0.05) without affecting neointima formation. CONCLUSION: Systemic administration of GSNO during balloon injury and IR was tolerated well by the swine and resulted in reduction of the thrombosis rate, especially at high doses, without apparent effect on neointima formation.

Animals↗

Management of patients with suspected deep vein thrombosis in the emergency department: combining use of a clinical diagnosis model with D-dimer testing.

The management of patients presenting to hospital Emergency Departments with suspected deep vein thrombosis is problematic since urgent diagnostic imaging is at times unavailable. We evaluated the accuracy of a rapidly available D-dimer test and the potential of combining D-dimer testing with an explicit clinical model to improve the management of patients with suspected deep vein thrombosis. Two hundred and fourteen patients with suspected deep vein thrombosis presenting to the Emergency Departments of two tertiary care institutions were enrolled in this prospective cohort study. Patients were evaluated by an Emergency Physician who determined the pre-test probability for deep vein thrombosis to be either low, moderate, or high using an explicit clinical model. Patients were managed according to their pre-test probability category by specific algorithms that in all cases included venous ultrasound imaging within 24 h and a 90-day follow-up for the development of thromboembolic complications. Patients also underwent fingerstick SimpliRED(R) whole blood agglutination D-dimer testing; however, D-dimer results did not influence subsequent patient management. D-dimer had a sensitivity of 82.5% and a specificity of 84.9% for the diagnosis of deep vein thrombosis. The observed negative predictive value of D-dimer was 96.9% (95% CI, 93.0% to 99.1%) overall, and 100% (95% CI, 96.3% to 100%) in low probability patients, 94.1% (95% CI, 83.8% to 98.8%) in moderate probability patients, and 86.7% (95% CI, 59.4% to 98.3%) in high probability patients. SimpliRED(R) D-dimer has a high negative predictive value and may be useful in excluding the diagnosis in patients at low pre-test probability for deep vein thrombosis.

Agglutination Tests↗

[Risk of thrombosis in prolonged catheterization of the radial artery: comparison of 2 types of catheters].

The thrombosis rate after long-term cannulation of the radial artery was assessed prospectively in 48 intensive care patients randomly assigned to groupe A (polyethylene Leader-Cath 115-09 catheter; n = 50, aged 55 +/- 20 years, 74% male patients) or groupe B (Teflon Viggo Floswitch 4441 catheter; n = 48, aged 58.6 +/- 16 years, 73% male patients). Bedside angiography was carried out with 10 to 15 ml Hexabrix before removal of the catheter. The two groups were similar with regard to anthropometric parameters, used drugs, pathological events during the stay in ICU, arterial cannulation technique and its duration. There was no case of clinically significant ischaemia. The rate of X-ray total arterial thrombosis was 20% in group A, and 2% in group B (p less than 0.01). There was no difference in the rate of partial thrombosis (54% vs. 41.7% respectively, NS) and of lack of thrombosis (26% vs. 56.3% respectively, NS). The overall rate of thrombosis was greater in group A than in group B, but not significantly (74% vs. 43.7% respectively). The duration of arterial cannulation did not influence the rate of thrombosis. However it was higher in males of Group A than in those of Group B (p less than 0.01), when heparin was not given (p less than 0.05); when vaso-active drugs were used (p less than 0.05); and when the time required for cannula insertion was greater than 5 min (p less than 0.01). It is concluded that Teflon catheters are more biocompatible than polyethylene catheters.

Adult↗

Venous thrombosis in relation to fibrinogen and factor VII genes among African-Americans.

We evaluated the relation between venous thrombosis and plasma fibrinogen levels, the HaeIII and BcI polymorphisms of the beta fibrinogen gene, and the MspI polymorphisms of the factor VII gene in a case-control study of African-Americans. The study included 91 venous thrombosis cases and 185 control subjects obtained from a hospital in Atlanta, Georgia. High plasma fibrinogen was associated with increased risk of venous thrombosis, but the finding was not statistically significant. There was little association between the HaeIII polymorphisms and the BclI polymorphisms and the risk of venous thrombosis. The prevalence of the M2/M2 genotype of the factor VII gene was higher among cases than controls, but the difference was not statistically significant. The prevalence of the HaeIII H2 allele and the BclI B2 allele of the beta fibrinogen gene, both of which have been associated with slightly higher levels of plasma fibrinogen in most studies, is considerably lower among African-Americans in this study than it is among Whites in the United States and among Northern Europeans. The study is limited by its small size. However, despite this limitation, it supports the belief that increased plasma fibrinogen levels are associated with increased venous thrombosis risk. The study also indicated that the HaeIII and the BclI polymorphisms of the beta fibrinogen gene and the MspI polymorphisms of the factor VII gene are not strong determinants of venous thrombosis.

Adult↗

Antiphospholipid thrombosis syndromes: etiology, pathophysiology, diagnosis and management.

Antiphospholipid antibodies are increasingly being identified as a cause of both arterial and venous thrombosis as well as fetal wastage syndrome via placental vascular thrombosis. The antiphospholipid thrombosis syndromes should be considered and searched for when suggestive clinical findings are present or when unexplained arterial or venous thrombosis occurs. Noting the presence and type of antiphospholipid antibody thrombosis syndrome assumes major importance with respect to not only making an accurate diagnosis of cause of thrombosis but also in selecting effective antithrombotic therapy.

Animals↗

Treatment alternatives for axillary-subclavian vein thrombosis: long-term follow-up.

Spontaneous axillary-subclavian vein thrombosis in young patients produces long-term disability. Patients with secondary axillary-subclavian vein thrombosis usually require prolonged venous catheterization for chemotherapy or pacemaking. This study aimed to compare the early and late results of lytic versus anticoagulant therapy in the treatment of axillary-subclavian vein thrombosis, both spontaneous and secondary to central venous cannulation. Nine patients underwent conventional treatment (heparin and warfarin) (group 1), and 10 had initial lytic therapy followed by heparin and warfarin (group 2). Three patients had cervical or first rib resection. Thirteen patients had spontaneous thrombosis and six were secondary to central venous catheterization. The mean follow-up was 36 months. Two of nine patients (22%) in group 1 and eight of 10 patients (80%) in group 2 had total venous recanalization and symptom resolution (P = 0.018). In the spontaneous axillary-subclavian vein thrombosis subset, one of six patients (17%) in group 1 and five of seven patients (71%) in group 2 had total venous recanalization and symptom resolution (P = 0.078). The average difference in cost per patient between groups 1 and 2 was $19,039. In conclusion, lytic therapy appears superior to anticoagulation in the treatment of axillary-subclavian vein thrombosis. However, such treatment is more expensive and its benefits should be carefully weighed against the cost in each case.

Adult↗

Venous thrombosis related to peripherally inserted central catheters.

PURPOSE: To determine factors that may lead to venous thrombosis in patients with peripherally inserted central catheters (PICC). MATERIALS AND METHODS: The medical records of 678 patients with 813 PICCs during 1997 were cross-referenced with all patients receiving venous duplex examinations (1,631) during the same time period. Multiple factors were examined in the patients with catheter-related thrombosis, including diagnosis, solution infused, catheter tip position, vein accessed, and catheter diameter. RESULTS: Nurses placed 269 PICCs with 12 venous thromboses, for a rate of 4.5%. Radiologists placed 544 PICCs with 20 venous thromboses, for a rate of 3.7%. There was no significant difference in these rates. The overall thrombosis rate was 3.9%. After multivariate analysis, only catheter diameter remained significant. There were no thromboses in catheters 3 F or smaller. The thrombosis rate was 1% for 4-F catheters, 6.6% for 5-F catheters, and 9.8% for 6-F catheters. CONCLUSIONS: Thrombosis rate associated with PICCs was low (3.9%). The smallest acceptable catheter diameter should be used to decrease the incidence of venous thrombosis.

Analysis of Variance↗

Stent thrombosis: historical perspectives and current trends.

Coronary stents are now implanted in more than 70% of percutaneous coronary revascularization procedures. Early enthusiasm for improved acute angiographic results and limited restenosis was dampened initially by a high rate of stent thrombosis and later by the increased bleeding complications of aggressive and complex anticoagulation protocols designed to lower the stent thrombosis risk. More recently, routine high-pressure deployment strategies and anti-platelet drug regimens have lowered the incidence of stent thrombosis to approximately 1% without an increased bleeding risk. The timing of stent thrombosis has also changed from a median of 4-5 days to a median of 1 day after the stent procedure. Risk factors in earlier studies included stenting for threatened or abrupt closure, smaller vessels, longer lesions, and possibly left anterior descending artery lesion location. Modern studies have shown a slightly increased risk for multiple stent use, residual dissection, and smaller final lumen. Optimal therapy for stent thrombosis includes emergent revascularization and anti-thrombotic treatment, although the clinical consequences remain dire despite successful reperfusion. The use of platelet glycoprotein IIb/IIIa inhibitors, especially in high-risk situations may further reduce the incidence of stent thrombosis.

Hemorrhage↗