Venous thromboembolism (VTE) in pediatrics is quickly becoming a well-recognized cause of significant morbidity and mortality in children. Most children diagnosed with VTE have a serious underlying primary illness such as cancer, chronic total parenteral nutrition (TPN) dependency, or congenital heart disease. Infants and adolescents are most at risk of developing VTE, and the most significant risk factor is the presence of a central venous line (CVL). The incidence of VTE varies widely with study design and the diagnostic test used to detect thrombosis. Venography remains the gold standard diagnostic test, although ultrasound is increasingly used due to its noninvasive nature, despite concern regarding the sensitivity in upper system VTE. The treatment of uncomplicated VTE in children consists primarily of unfractionated heparin (UFH) initially, followed by oral anticoagulation or low molecular weight heparin (LMWH) for 3 months. LMWH offers many advantages over UFH due to the longer half-life, increased bioavailability, and ease of administration and monitoring in children. Acute complications of VTE in children are numerous and include pulmonary embolism (PE), chylothorax, and superior vena cava syndrome. Long-term morbidity includes recurrent VTE, postthrombotic syndrome, repeat general anesthetics for CVL placement, and eventual destruction of the upper venous system in children with repeat CVL-related VTE. Death from VTE is rare and is primarily due to PE.

BACKGROUND

The authors compared the relative efficacy and safety of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) for the initial treatment of venous thromboembolism (VTE) between patients with and without cancer.

METHODS

By using Cochrane methodology for systematic reviews, separate meta-analyses were conducted for subgroups of patients with and without cancer, and relative risks (RRs) were compared for statistical significance. The methodologic quality for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

RESULTS

LMWH reduced mortality significantly compared with UFH in patients with cancer (RR of 0.71; 95% confidence interval [95% CI], 0.52-0.98 [moderate-quality evidence]) but not in patients without cancer (RR of 0.97; 95% CI, 0.65-1.46 [low-quality evidence]). However, the difference in the RR for the 2 subgroups did not reach statistical significance (P = .113). The difference between LMWH and UFH in the effect on recurrent VTE was not statistically significant in the subgroup with cancer (RR of 0.78; 95% CI, 0.29-2.08 [low-quality evidence]), in the subgroup without cancer (RR of 0.94; 95% CI, 0.60-1.46 [low-quality evidence]), or between the 2 subgroups (P = .367). No data were available for bleeding outcomes, thrombocytopenia, or postphlebitic syndrome.

CONCLUSIONS

The current results indicated that LMWH most likely is superior to UFH in reducing mortality in the initial treatment of VTE for patients with cancer. There is a need for more and better designed trials to confirm these findings.

BACKGROUND

Venous thromboembolism is a major cause of postoperative morbidity and mortality in neurosurgery. The use of low-dose unfractionated heparin therapy perioperatively for prophylaxis against deep vein thromboses and pulmonary embolism has been well demonstrated in many other surgical specialties but is less commonly used in neurosurgery because of fears of devastating postoperative hematomas.

METHODS

The safety of such therapy has been analyzed in 950 patients undergoing an inpatient neurosurgical procedure. 872 patients (152 cranial procedures) completed treatment with 5000 U sodium heparin subcutaneously twice a day, commencing before surgery and continuing till patients were ambulatory.

RESULTS

There were three minor hemorrhagic complications-two superficial wound hematomas (one requiring treatment) and one gastrointestinal hemorrhage-identified. Three clinically significant major complications developed, two epidural hematomas after spinal surgery requiring evacuation and one intraventricular hemorrhage after brain biopsy.

CONCLUSIONS

This report, along with an analysis of previously published reports of low-dose perioperative heparin therapy in neurosurgical patients, suggests that such therapy is unlikely to be associated with increased morbidity. Given the known efficacy of low-dose heparin in reducing venous thromboembolism in other surgical patients, such therapy may reduce mortality and morbidity from thromboembolic complications in neurosurgical patients with minimal risk.

BACKGROUND

Four recent reports of the retrieval of optional vena cava filters (VCF) in trauma patients had average implant durations of 10, 19, and 19 days (one not specified). Two patients in these studies had pulmonary emboli after VCF removal. No evidence-based guidelines exist on the appropriate time to remove optional VCF. The purpose of this study was to examine the timing of pulmonary emboli (PE) and determine the optimal time to remove optional VCFs.

METHODS

A multicenter retrospective chart review of trauma patients who had a postinjury PE between January 2001 and December 2004 was performed. We examined the demographics, prophylaxis at the time of PE (pharmacologic [unfractionated or low molecular weight heparin] or sequential compression devices [SCD]), diagnostic test used, timing of PE from the date of injury, and survival outcome.

RESULTS

In all, 146 patients were identified, mean age 45.1 (+/- 21.1 SD); Injury Severity Score 18.0 (+/- 12.1 SD). Diagnosis was obtained by spiral computed tomography (N = 93), pulmonary arteriogram (N = 18), V/Q (N = 26), autopsy (N = 6), clinical (N = 6), and unknown (N = 3). Overall mortality was 17.8% (N = 26). Pulmonary embolism was felt to contribute to or was the cause of death in 85% (N = 22) of these patients. Two late PE deaths occurred (days 21 and 43). Sixty (37%) patients had pharmacologic prophylaxis at the time of PE and 83 (50.9%) had SCDs. Average time from injury to PE was 7.9 days (+/- 8.1 SD), the longest being 43 days postinjury. Eleven percent of PE occurred after 21 days, including fatal PE.

CONCLUSIONS

Clinical criteria defining the time to remove optional VCFs without exposing patients to the risk of PE by removing a filter too soon should be determined.

A patient with anginal chest pain and electrocardiographic changes suggesting ischemia was referred to our hospital. Coronary angiography revealed no significant stenosis or ectasia but only slow flow in all 3 coronary arteries. After infusion of unfractionated heparin for 24 hours, negative T waves became less deep, and repeated coronary angiography showed significant improvement of the coronary flow. The coronary slow flow phenomenon, together with the associated ischemic electrocardiographic changes, should be considered as a separate entity in the differential diagnosis of acute coronary syndromes. Additional clinical research is required to better understand the syndromes of chest pain with normal coronary arteries.

BACKGROUND

In the absence of high-dose thienopyridines, placebo-controlled trials have demonstrated a reduction in ischemic events with intravenous glycoprotein IIb/IIIa antagonists during percutaneous coronary intervention (PCI). One head-to-head trial comparing abciximab and tirofiban among PCI patients found tirofiban to be inferior, and laboratory evidence confirmed that the bolus dose of tirofiban tested in that trial to be less effective than abciximab. Whether a higher bolus dose of tirofiban would be as efficacious as abciximab during PCI is uncertain.

RESULTS

Patients undergoing PCI were randomized equally to abciximab or to tirofiban, given as high-dose bolus (25 μg/kg) plus 12-hr infusion (0.15 μg/kg/min). All patients received aspirin and clopidogrel and were additionally randomized to unfractionated heparin or bivalirudin. Approximately 8,000 patients were to be studied, but after 383 were enrolled, the study sponsor discontinued the trial for financial reasons. The primary endpoint of 30-day death, myocardial infarction, or urgent target vessel revascularization occurred in 8.8% of patients randomized to abciximab and 6.9% of those randomized to tirofiban. The respective rates of major bleeding were 1.5 and 1.6%. Additionally, the primary endpoint occurred in 8.1% of patients randomized to unfractionated heparin and 7.6% of those randomized to bivalirudin. The respective rates of major bleeding were 2.5% and 0.5%.

CONCLUSIONS

With limited assessment, this direct comparison of high-dose bolus tirofiban versus abciximab produced encouraging results and suggests that further study of this tirofiban dose regimen is warranted. The limited assessments comparing heparin and bivalirudin are consistent with prior observations.

Upper extremity deep vein thrombosis (UEDVT) should no longer be regarded as an uncommon and benign disease, as previously reported. It is usually associated with risk factors, as central venous lines, malignancy, and coagulation defects; however, up to 20% of UEDVTs are apparently spontaneous. The clinical picture is characterized by swelling, pain, and functional impairment, albeit UEDVT may be completely asymptomatic. Objective testing is mandatory prior to instituting anticoagulation because the prevalence of UEDVT is less than 50% in symptomatic subjects, and compression ultrasound or color Doppler represents the preferred diagnostic methods. Up to 36% of the patients develop pulmonary embolism, which may be fatal; postthrombotic sequelae and recurrent thromboembolism are also frequent complications. Unfractionated or low-molecular-weight heparin followed by oral anticoagulation should be regarded as the treatment of choice; thrombolysis and surgery may be indicated in selected cases. Prophylaxis with low-dose heparin or low-dose warfarin is necessary whenever central venous catheters are positioned.

In an open, randomised controlled study, 101 patients with phlebographically diagnosed deep vein thrombosis of the leg, not extending into more than two thirds of the femoral vein, were randomised to receive Fragmin (a low molecular weight heparin) administered subcutaneously either once or twice daily in doses of 200 U(anti-FXa)/kg/24h or 100 U(anti-FXa)/kg/12h respectively. Prior to Fragmin unfractionated heparin had been administered by continuous iv infusion for not longer than 24h. Warfarin was administered from the first treatment day. Fragmin was administered for at least 5 days or until the prothrombin complex had been within the therapeutic range for at least 2 days. Patients were kept in bed for the first day but thereafter were ambulant. Phlebography was repeated at 5-7 days. Comparison of the phlebograms revealed a similar improvement (reduction in Marder score) in both groups. There were 5 cases of bleeding: 1 major and 3 minor in the twice daily group and 1 minor bleed in the once daily group. There were no cases of clinical pulmonary embolism. It is concluded that Fragmin, administered as a single daily subcutaneous injection, is effective in the treatment of deep vein thromboses, and offers the advantages of reduced costs, despite higher price of the drug, including reduced nursing time.

BACKGROUND

Uninterrupted anticoagulation with warfarin during radiofrequency catheter ablation (RFA) of atrial fibrillation is associated with a lower risk of periprocedural complications than when warfarin is temporarily discontinued. However, the optimal international normalized ratio (INR) levels during RFA have not been defined.

RESULTS

In this retrospective analysis, RFA was performed in 1133 consecutive patients (mean age, 61±10 years) with paroxysmal (550) or persistent atrial fibrillation (583). Patients were grouped based on the INR on the day of RFA. There was a quadratic relationship between the INR and bleeding and vascular complications (P<0.001). Complications were less prevalent when INR was ≥2.0 and ≤3.0 (5% [31/572]) than when INR was <2.0 (10% [49/485]; P=0.004) and >3.0 (12% [9/76]; P=0.03). The prevalence of pericardial tamponade (1%) was similar at all INRs. From the quadratic model, the optimal range of INR was calculated as 2.1 to 2.5. INRs<2.0 and >3.0 were associated with a >2-fold increase in complications, with a further steep rise beyond an INR>3.5. Concomitant clopidogrel use was associated with a significant increase in complications at all INRs (odds ratio=3.1; ±95% confidence interval, 1.4-7.4). Unfractionated heparin requirements to maintain a therapeutic activated clotting time during RFA was reduced by 50% in patients with an INR>2.0.

CONCLUSIONS

The optimal INR range during uninterrupted periprocedural anticoagulation using warfarin is narrow. Therefore, INR levels should be carefully monitored in preparation for RFA of atrial fibrillation.

Efficacy and safety of a low molecular weight heparin (Alfa LMWH) was compared with unfractionated heparin (UFH) in the prevention of post-operative venous thromboembolism after hip fractures. Forty-nine patients were randomized to treatment with Alfa LMWH 7500 anti-Xa coagulometric units twice daily or with UFH 5000 IU t.i.d. Screening for thrombosis was performed with 125-I-fibrinogen leg scanning and strain-gauge plethysmography. Positive results were confirmed by venography. Five patients in the Alfa LMWH group (20 per cent) developed venographycally proven deep vein thrombosis (DVT) versus seven (29 per cent) in the UFH group. One pulmonary embolism and two deaths occurred in the UFH group and none in the LMWH group. No differences in haemorrhagic complications and blood loss indices were observed. Alfa LMWH appears to be a promising drug for prevention of venous thromboembolism after orthopaedic surgery. A "flexible" schedule of administration is proposed on the basis of the results of plasma anti-Xa assays.

Factor VII-activating protease (FSAP) circulates as an inactive zymogen in the plasma. FSAP also regulates fibrinolysis by activating pro-urokinase or cellular activation via cleavage of platelet-derived growth factor BB (PDGF-BB). As the Marburg I polymorphism of FSAP, with reduced enzymatic activity, is a risk factor for atherosclerosis and liver fibrosis, the regulation of FSAP activity is of major importance. FSAP is activated by an auto-catalytic mechanism, which is amplified by heparin. To further investigate the structural requirements of polyanions for controlling FSAP activity, we performed binding, activation and inhibition studies using heparin and derivatives with altered size and charge, as well as other glycosaminoglycans. Heparin was effective in binding to and activating FSAP in a size- and charge density-dependent manner. Polyphosphate was more potent than heparin with regard to its interactions with FSAP. Heparin was also an effective co-factor for inhibition of FSAP by plasminogen activator inhibitor 1 (PAI-1) and antithrombin, whereas polyphosphate served as co-factor for the inhibition of FSAP by PAI-1 only. For FSAP-mediated inhibition of PDGF-BB-induced vascular smooth muscle cell proliferation, heparin as well as a polyphosphate served as efficient co-factors. Native mast cell-derived heparin exhibited identical properties to those of unfractionated heparin. Despite the strong effects of synthetic polyphosphate, the platelet-derived material was a weak activator of FSAP. Hence, negatively charged polymers with a high charge-to-size ratio are responsible for the activation of FSAP, and also act as co-factors for its inhibition by serine protease inhibitors.

We assessed the impact of smoking on outcomes in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention using alternative antithrombotic regimens and stent types. In the HORIZONS-AMI trial 3,602 patients were randomly assigned to unfractionated heparin (UFH) plus a glycoprotein IIb/IIIa inhibitor (GPI) or bivalirudin alone and paclitaxel-eluting stents or bare-metal stents. Compared to nonsmokers, smokers had significantly lower rates of mortality and major bleeding at 30 days and at 1 year; however, the differences were no longer significant after covariate adjustment. Smoking was associated with increased rates of definite/probable stent thrombosis (ST) at 1 year (adjusted RR 1.99, 95% confidence interval 1.28 to 3.10) mainly because of a higher rate of late ST after paclitaxel-eluting stent implantation (1.9% vs 0.4%, p = 0.0006). In smokers bivalirudin monotherapy compared to UFH plus a GPI was associated with lower mortality at 30 days (0.5% vs 2.2%, p = 0.002) and at 1 year (1.8% vs 4.0%, p = 0.008). No decrease in mortality was seen with bivalirudin in nonsmokers. Major bleeding was significantly decreased with bivalirudin regardless of smoking status (smokers 3.7% vs 8.9%, p <0.0001; nonsmokers 6.5% vs 9.6%, p = 0.01). In conclusion, in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention, smoking is an independent predictor of definite/probable ST at 1 year. Bivalirudin monotherapy compared to UFH plus a GPI decreased major bleeding regardless of smoking status but may have different effects on individual components of ischemic events.

BACKGROUND

Unfractionated heparin (UFH) is a mainstay of treatment for patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), but the practice of weight-adjusted bolus and infusion dosing has not been carefully evaluated.

METHODS

Using data from 31,445 high-risk patients with NSTE ACS enrolled at 420 hospitals in the CRUSADE initiative, we evaluated initial UFH dosing relative to guideline recommendations and determined factors associated with excess weight-adjusted dosing and major bleeding, overall and among subgroups. Excess dose was defined as >70 U/kg for bolus or >15 U/kg per hour for infusion.

RESULTS

The most frequent bolus dose was 5,000 U (42.7%) and infusion dose was 1,000 U/h (46%). An excess weight-adjusted UFH bolus or infusion dose was administered 35% of the time. Factors strongly associated with excess weight-adjusted dosing were age (per 10-year increase) (odds ratio [OR] 1.11, 95% CI 1.08-1.15) and female sex (OR 1.45, 95% CI 1.33-1.59). Rate of major bleeding increased proportionally in relation to dose of UFH for both bolus and infusion, specifically when dose was above the recommended weight-adjusted range (>70 U/kg for bolus or >15 U/kg per hour for infusion). Both excess bolus (OR 1.03, 95% CI 1.00-1.06) and infusion (OR 1.16, 95% CI 1.05-1.28) were individually associated with increased bleeding. The relationship between weight-adjusted UFH dose and major bleeding did not vary independently by sex or age.

CONCLUSIONS

In high-risk patients with NSTE ACS, initial UFH bolus and infusion dosing were frequently higher than recommended weight-adjusted ranges, particularly in patients with lower body weight. Excess bolus and infusion rate dosing was associated with more bleeding and was common among elderly and females. Attention to dosing by weight rather than standard bolus and infusion dosing should lead to improved safety in the use of UFH.

Fondaparinux (Arixtra) is the first selective factor Xa inhibitor approved for use in thromboprophylaxis after orthopaedic surgery. New recently completed trials have also demonstrated the potential of fondaparinux in the prevention of venous thromboembolism (VTE) in other surgical and medical settings and in the treatment of established VTE. In the randomized double-blind PEGASUS study in high-risk abdominal surgery patients, fondaparinux reduced the incidence of VTE from 6.1% with dalteparin to 4.6% (odds ratio reduction = 25.8%, P = 0.14), without increasing the bleeding risk. In the randomized double-blind ARTEMIS trial in acutely ill medical patients, fondaparinux reduced the incidence of VTE from 10.5% with placebo to 5.6% (odds ratio reduction = 49.5%, P = 0.029), without increasing the bleeding risk; there was no pulmonary embolism in the fondaparinux group compared with five, all fatal, in the placebo group (P = 0.029). In the two MATISSE trials, both the efficacy and safety of once daily fondaparinux were at least as good as enoxaparin in the treatment of deep-vein thrombosis (MATISSE-DVT) and unfractionated heparin in the treatment of pulmonary embolism (MATISSE-PE). In patients with coronary artery disease, promising results were obtained in phase II trials and large phase III trials are ongoing. In conclusion, fondaparinux may further improve and simplify the prevention and treatment of thrombosis in a large range of medical and surgical settings.

OBJECTIVE

To determine the relationship between anticoagulation levels during percutaneous coronary intervention, and ischaemic events and bleeding.

RESULTS

A sub-analysis from the STEEPLE trial was conducted. Pre-defined target anticoagulation levels were achieved in 86% of patients receiving enoxaparin, compared with 20% receiving unfractionated heparin (UFH) (P < 0.001). A significant relationship was observed between anti-Xa levels>> 0.9 IU/mL and covariate-adjusted rate of non-coronary artery bypass graft-related major and minor bleeding [odds ratio (OR) 1.6, 95% CI 1.0-2.5 for each unit of anti-Xa; P = 0.03]; anti-Xa levels and covariate-adjusted incidence of death, myocardial infarction, or revascularization showed no significance (P = 0.47). Major bleeding increased significantly with an activated clotting time (ACT)>> 325 s (OR 1.6, 95% CI 1.1-2.2 per 100 s; P = 0.04). A significant relationship with increasing ischaemic events was observed when ACT was < 325 s (OR 0.7, 95% CI 0.2-0.8 per 100 s; P = 0.006) indicating a narrow therapeutic window.

CONCLUSIONS

Target anticoagulation levels were achieved more readily in patients receiving enoxaparin. An anti-Xa level of up to 0.9 IU/mL has a good safety and efficacy profile; poor achievement of target ACT with UFH makes assessing the optimal range difficult.

BACKGROUND

Procoagulant activity and oxidative stress generated by balloon injury to normal vessels promote the migration of medial smooth muscle cells and their proliferation in the intima. We hypothesised that administering levo N-acetyl-cysteine (NAC) i.v. at the time of injury, and s.c. before and after injury would reduce neointimal formation 4 weeks later and would regulate procoagulant activity in vessels with neointima undergoing ballooning a second time.

RESULTS

at the time of injury rabbits received: NAC, unfractionated heparin (HEP) or both (NAC + HEP). Neointimal thickening at 28 days, calculated as the ratio between the intimal and medial area, was attenuated after NAC, HEP and NAC+HEP by 39%, 30% and 47% respectively when compared to untreated injured animals (CONTROLS) (p <0.05). At 28 days, bound thrombin activity and platelet adhesion 1 h after a repeated balloon injury decreased in animals receiving NAC, HEP and NAC+HEP bv 54%, 63% and 64% for thrombin activity (p <0.05 vs CONTROLS), and by 56%, 66% and 75% respectively for 111Indium-platelet deposition (p <0.05 vs CONTROLS).

CONCLUSIONS

NAC in-vivo was effective in reducing neointimal thickening and procoagulant response after balloon injury.

BACKGROUND

Patients with heparin-induced thrombocytopenia type II require an alternative to standard heparin anticoagulation. However, in patients with renal impairment, anticoagulation during cardiopulmonary bypass with agents such as danaparoid sodium or r-hirudin are associated with hemorrhage. Anticoagulation with unfractionated heparins combined with prostacyclin, a potent platelet aggregation inhibitor, is associated with severe hypotension. The authors investigated a new concept using unfractionated heparins after platelet inhibition with the short-acting platelet glycoprotein IIb-IIIa antagonist tirofiban.

METHODS

Ten patients with heparin-induced thrombocytopenia type II and renal impairment were enrolled in the investigation. All had heparin-induced thrombocytopenia type II antibodies present as proved by the heparin-induced platelet aggregation assay, the heparin-platelet factor 4 enzyme-linked immunosorbent assay, or both. In all patients, preoperative anticoagulation to an activated partial thromboplastin time of 40-60 s was performed with r-hirudin. Anticoagulation during cardiopulmonary bypass was achieved with a bolus of 400 IU/kg unfractionated heparins after a bolus of tirofiban 10 microg/kg followed by an infusion of tirofiban at a rate of 0.15 microg x kg(-1) x min(-1) until 1 h before conclusion of cardiopulmonary bypass. Additional unfractionated heparins were only administered if activated clotting time decreased below 480 s. Coagulation was monitored by a abciximab-modified TEG and the adenosine diphosphate-stimulated (20 microm) platelet aggregometry. D-dimer concentrations, as a marker of venous thromboembolism, were measured before and 12, 24, and 48 h after surgery. Postoperative antithrombotic therapy was started immediately with r-hirudin to anticoagulation to an activated partial thromboplastin time of 40-60 s.

RESULTS

The postoperative blood loss ranged from 110 to 520 ml. No patient needed reexploration. In no patient was there clinical evidence of thrombosis or embolism in the postoperative period or of a critical increase of the D-dimer concentrations, suggesting venous thromboembolism. Transfusion of platelets was necessary in only two patients.

CONCLUSIONS

The protocol is easy to perform and no increased postoperative bleeding and no thromboembolic complications occurred. The combination of unfractionated heparins and tirofiban may be an alternative to other anticoagulation strategies in patients with heparin-induced thrombocytopenia.

OBJECTIVE

To perform an evaluation from the societal perspective of the cost of treatment with enoxaparin sodium versus unfractionated heparin (UFH) in patients with unstable angina and non-Q wave myocardial infarction in France.

METHODS

Four complementary cost-minimisation analyses based on the results of the Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q wave Coronary Events (ESSENCE) international trial were conducted. We assessed differences in medical resource consumption and in duration of hospital stay in the whole study population (n = 3171) and for the French patients (n = 133).

RESULTS

Results were consistent for the study group as a whole and for the French subgroup. Among patients treated with enoxaparin sodium, there was a statistically significant reduction in the use of angiography and percutaneous transluminal coronary angioplasty (whole group study: p = 0.024 and 0.006, respectively) and a trend towards shorter lengths of hospital stay. The differences in angiography and angioplasty rates led to estimated average net cost savings with enoxaparin sodium of French Francs (FF)1555 per treated patient (whole study population) and FF9993 (French subgroup) [1996 values]. The analyses based on the duration of hospital stay resulted in estimated net cost savings with enoxaparin sodium of between FF1014 per treated patient (whole study population) and FF2804 (French subgroup).

CONCLUSIONS

Our study confirmed earlier results which show that enoxaparin sodium is cost saving in the treatment of unstable angina.

BACKGROUND

Few reports have addressed how current practice reflects uncertainty as to the optimal management of renal replacement therapy (RRT) in Western countries. Current dialytic practice for 2007 in the northwest of Italy was assessed.

METHODS

A total of 24 nephrology and dialysis centers covering all of the RRT provided in the intensive care units (ICUs) in northwest Italy took part in the survey. Consultant nephrologists of each center reported their own activities throughout the year 2007 by an e-mailed questionnaire.

RESULTS

RRT for a total of 7,842 days was provided by 24 dialysis centers in 79 ICUs for 1,118 patients. RRT median duration (5.76 days/patient) increased with the increasing number of hospital ICU beds. Of the RRT cases, 69.9% were due to acute kidney injury, 23.6% for continuation of a treatment in chronic dialysis patients and 4.2% for extrarenal indications. More than 90% of the patients were treated with high permeability membranes, at a median target dosage of 35.0 ml/kg per hour in continuous (39.4%) or extended modality (6-14 hours, 38.5%). Unfractionated heparin was the most common anticoagulant used (67.5%, median 500 IU/hour). In patients at high risk of bleeding, RRT without or with heparin at low-dose + saline flushes was the most commonly adopted line of treatment, followed by citrate (18% of days of dialysis). The decision to start RRT was made by nephrologists alone or in collaboration with intensivists, whereas dose prescriptions were given by nephrologists alone.

CONCLUSIONS

This survey may represent a useful starting point for further research into changes in RRT practice and the adoption of common, shared protocols.

Aerosolized unfractionated heparin GM1060 significantly inhibited allergen-induced eosinophil infiltration into the airways of guinea-pigs (as assessed both histologically and by bronchoalveolar lavage, or BAL) at doses of 160 and 1600 U/ml. Similarly aerosolized unfractionated heparin, Multiparin was effective at reducing eosinophil levels in the BAL fluid at 1000, 2000 and 5000 U/ml, but this reduction was statistically significant only at the highest dose used. Additionally, Fragmin (a low molecular weight heparin) significantly inhibited allergen-induced eosinophil infiltration into BAL fluid at a dose of 500 U/ml, an effect that was lost at the higher doses of 1000 and 2000 U/ml. Allergen-induced eosinophil infiltration was unaffected by dermatan sulphate. However, the glycosaminoglycans chondroitin sulphate A, chondroitin sulphate C and heparan sulphate were able to influence the extent of allergen-induced eosinophil infiltration into BAL fluid. These results suggest that heparin and some related glycosaminoglycans can inhibit allergen-induced eosinophil infiltration when administered directly to the airways.

The aim of this study was to assess the efficacy of enoxaparin for prevention of radial artery (RA) occlusion after transradial access for diagnostic and interventional cardiac procedures. RA occlusion is a potential complication of transradial cardiac catheterization. Conventionally, unfractionated heparin is used for prevention of RA occlusion. Effectiveness of low molecular weight heparins for prevention of this complication has not been tested before. Fifty transradial catheterizations were performed for diagnostic and/or interventional cardiac procedures in 39 patients. All the patients received 60 mg enoxaparin through the radial sheath at the beginning of the procedure for prevention of RA occlusion. RA patency was evaluated by Doppler examination. Patients were assessed for postprocedural RA occlusion at discharge and 5.5 +/- 2.8 days follow-up. RA occlusion was detected after 2 of the 50 transradial accesses, yielding a RA occlusion rate of % 4. In this study we found a low rate of RA occlusion with use of enoxaparin during transradial access. Enoxaparin is safe and effective in transradial procedures with a RA occlusion rate comparable to use of unfractionated heparin.

Here we report results from the analyses by enzymatic digestion and reversed-phase ion-pairing liquid chromatography mass spectrometry (RPIP-LC-MS) of active pharmaceutical ingredient (API) unfractionated heparins (UFHs) from six different manufacturers and one USP standard sample. We employed a reverse phase ion-pairing chromatography method using a C(18) column and hexylamine as the ion-pairing reagent with acetonitrile gradient elution to separate disaccharides generated from the digestion of the heparins by lyase I and III (E.C. 4.2.2.7 and 4.2.2.8) before introduction into an ion-trap mass spectrometer by an electrospray ionization (ESI) interface. Extracted ion chromatograms (EICs) were used to determine the relative abundance of the disaccharides by mass spectrometry. Eight disaccharides were observed and a similar composition profile was observed from digests of 20 UFH samples. The compositional profile determined from these experiments provides a measure of the norm and range of variation in "good" heparin to which future preparations can be compared. Furthermore, the profile obtained in the RPIP-LC-MS assay is sensitive to the presence of the contaminant, oversulfated chondroitin sulfate A (OSCS), in heparin.

An unfractionated heparin (UFH) and a depolymerised derivative of low molecular weight heparin (LMWH) have been compared for their ability to activate platelets suspended in citrated plasma (PRP) or after washing and suspension in hepes buffered tyrode containing fibrinogen. Neither heparin alone induced aggregation of washed platelets, but UFH and to a much lesser extent LMWH, induced aggregation of platelets in PRP. Both heparins caused significant enhancement of a low concentration of ADP-induced activation of PRP and, again, the effect of LMWH was somewhat less than that of UFH. UFH produced a marked potentiation of ADP-induced activation of washed platelets and LMWH was about a third as potent. In addition, UFH induced a potentiation of PAF-induced aggregation and dense-granule release in PRP, a property not shared by LMWH. In PRP, UFH was three times more potent at inhibiting thrombin-induced aggregation and dense-granule release, as might be expected from their specific activities in the KCCT and thrombin time assay. However, with washed platelets, both heparins were equivalent at inhibiting thrombin-induced aggregation, dense-granule release and elevation of cytosolic free calcium ([Ca++]i) as monitored by quin 2 fluorescence. UFH and LMWH alone did not induce a change in [Ca++]i, nor had they any effect on ADP- or PAF-induced elevation of [Ca++]i.