Vasoseal hemostasis following coronary interventions with Abciximab

Femoral arteriotomy management using a collagen vascular hemostasis device (VasoSeal) was studied in 50 consecutive patients following interventional coronary procedures performed with Abciximab (ReoPro). Low dose weight adjusted or no heparin was employed. The first 25 patients were permitted to sit up after 6 hours with ambulation the following day. The second 25 patients were allowed to sit up after 1 hour and ambulate after 6 hours. Despite early activity and ambulation, there were no hemorrhagic complications including hematoma, pseudoaneurysm, blood transfusion, or surgical repair. Hemoglobin and platelet counts remained stable overnight prior to discharge. This pilot study demonstrates the potential efficacy of VasoSeal in achieving early sheath removal and ambulation in patients undergoing interventional procedures using ReoPro.     

Sexual orientation and family development: introduction

A new guiding catheter for PTCA is described. In our department, 302 patients (405 lesions) underwent transradial coronary angioplasty using the 6 Fr Kimny guiding catheter since January 1996. The total engagement rate using the Kimny guiding catheter was 91.3% (370/405). The engagement rate after the modified Kimny guiding catheter was introduced in May 1996 increased to 96.0% (243/253). The stent delivery success rate was 98.4%. We had two dislodged stents. PTCA for both left and right coronary arteries in a single procedure with the Kimny guiding catheter was performed via the radial artery in 27 patients. In 24 of these patients (89%) we engaged both coronaries successfully. In the remaining 3 patients we switched to another catheter. Except for 4 patients with non-Q-wave myocardial infarction, no major cardiac complications were encountered. No major entry site-related complications were seen, and no patient required vascular surgery or blood transfusions. In one patient the Kimny guiding catheter tip caused a minor dissection of the LMT, but no ischemic event occurred as a result. In conclusion, the Kimny device is a useful PTCA guiding catheter for routine angioplasty and stenting.     

Randomized, double-blind comparison of hirulog versus heparin in patients receiving streptokinase and aspirin for acute myocardial infarction (HERO). Hirulog Early Reperfusion/Occlusion (HERO) Trial Investigators

BACKGROUND: Thrombolytic therapy improves survival after myocardial infarction through reperfusion of the infarct-related artery. Thrombin generated during thrombolytic administration may reduce the efficacy of thrombolysis. A direct thrombin inhibitor may improve early patency rates. METHODS AND RESULTS: Four hundred twelve patients presenting within 12 hours with ST-segment elevation were given aspirin and streptokinase and randomized in a double-blind manner to receive up to 60 hours of either heparin (5000 U bolus followed by 1000 to 1200 U/h), low-dose hirulog (0.125 mg/kg bolus followed by 0.25 mg x kg(-1) x h(-1) for 12 hours then 0.125 mg x kg(-1) x h(-1)), or high-dose hirulog (0.25 mg/kg bolus followed by 0.5 mg x kg(-1) x h(-1) for 12 hours then 0.25 mg x kg(-1) x h(-1)). The primary outcome was Thrombolysis In Myocardial Infarction trial (TIMI) grade 3 flow of the infarct-related artery at 90 to 120 minutes. TIMI 3 flow was 35% (95% CI, 28% to 44%) with heparin, 46% (95% CI, 38% to 55%) with low-dose hirulog, and 48% (95% CI, 40% to 57%) with high-dose hirulog (heparin versus hirulog, P=.023; heparin versus high-dose hirulog, P=.03). At 48 hours, reocclusion had occurred in 7% of heparin, 5% of low-dose hirulog, and 1% of high-dose hirulog patients (P=NS). By 35 days, death, cardiogenic shock, or reinfarction had occurred in 25 heparin (17.9%), 19 low-dose hirulog (14%), and 17 high-dose hirulog patients (12.5%) (P=NS). Two strokes occurred with heparin, none with low-dose hirulog, and two with high-dose hirulog. Major bleeding (40% from the groin site) occurred in 28% of heparin, 14% of low-dose hirulog, and 19% of high-dose hirulog patients (heparin versus low-dose hirulog, P<.01). CONCLUSIONS: Hirulog was more effective than heparin in producing early patency in patients treated with aspirin and streptokinase without increasing the risk of major bleeding. Direct thrombin inhibition may improve clinical outcome.     

The use of activated clotting time (ACT) to optimize heparinization during coronary angioplasty. The nursing personnel of the Hemodynamics Laboratory

BACKGROUND: Suboptimal anticoagulation during coronary angioplasty is reported to be a major risk factor for occlusive complications. AIM: To define an appropriate timing for activated clotting time (ACT) tests in order to optimize anticoagulation with heparin during coronary angioplasty. METHODS: In 50 consecutive procedures of elective angioplasty ACT was measured at baseline, at 30, 60 and 120 min after heparin 10,000 U iv. In a subgroup of 25 patients (SG1) no additional heparin was given until the ACT test at 60 min. In a second subgroup of 25 patients (SG2) heparin 5,000 U was administered 30-45 min after the initial bolus if the ACT at 30 min was < 300 sec. ACT values were analyzed, and the correlation with the biological variables of patients was tested. RESULTS: In 20 patients out of 50 (40%) ACT values at 30 min were < 275 min. Heparin response was correlated with the body surface area but nor with age, neither with baseline ACT. Values at 60 min showed an adequate anticoagulation in only 6 patients (24%) in SG1 vs 21 (84%) in SG2. There were not complications. CONCLUSIONS: ACT testing 30 min after heparin 10,000 U during coronary angioplasty identifies most patients requiring early supplemental heparin. This yields an adequate anticoagulation at 60 min in most patients.     

Growth and congenital heart disease

PURPOSE: To assess the efficacy of heparin in preventing the abrupt closure after coronary angioplasty in low risk patients for this phenomenon. METHODS: In the last 4 years, 525 patients successfully dilated were randomized to receive intravenous heparin (n = 264) or not (n = 261) after the angioplasty. The excluding criteria were contraindications for heparin and risk for abrupt closure (refractory unstable angina, primary coronary angioplasty in acute myocardial infarction, evidence of intracoronary thrombus, intimal tear after the procedure and cases of chronic total occlusions). Both heparin and non heparin groups were similar in respect to female sex (15% x 17%; p = NS), age over 70 years old (7% x 9%; p = NS), previous myocardial infarction (26% x 24%; p = NS), multi-vessel procedures (4% x 7%; p = NS, stable angina (40% x 46%; p = NS), unstable angina (52% x 48%; p = NS) and angioplasty after thrombolytic therapy (8% x 6%; p = NS). RESULTS: The overall incidence of abrupt closure was 2/525 (0.4%), with one case (0.4%) in each group. The in-hospital mortality was 1/525 (0.2%), which occurred in a non-heparin patient, due to a anterior myocardial infarction. Major complications occurred similarly in heparin and non-heparin groups (0.4%). Bleeding complications were observed more frequently in the heparin group (7% x 2%; p = 0.002). All of them were in the catheterization site and none required blood transfusion. Severe systemic bleeding were not observed. CONCLUSION: In patients regarded as low risk for abrupt closure, the incidence of this complication was really low (0.4%) and heparin probably do not prevent it.     

Use of abciximab during coronary angioplasty

The IIb-IIIa glycoprotein is the platelet receptor of fibrinogen and the final common pathway of platelet activation and aggregation. Abciximab is a Fab fragment of the chimeric monoclonal antibody (c7E3) interfering with the glycoprotein receptor. It is the only anti IIb-IIIa currently available, commercialized under the name of Reopro. Preliminary clinical data has been obtained with its use in high risk coronary angioplasty. The EPIC trial showed a 35% relative reduction of the principal combined criterion of judgement of cardiac morbidity and mortality at 1 month, a benefit even greater in acute coronary syndromes (-72%) than in programmed procedures for complex type C lesions (-10%). The incidence of severe bleeding was high (14%). The results of the CAPTURE trial could widen the indications of abciximab to include the period surrounding angioplasty for unstable angina as the use of Reopro in the 24 hours before the procedure significantly reduced the risk of ischaemic events (10.8% versus 16.4%). In programmed angioplasty, the EPILOG trial investigated the effects of adapting the dose of heparin and an infusion of abciximab to body weight early (4th to 6th hour) withdrawal of the arterial introducer without continuing heparin. Using a 70 IU/Kg dosage modulated to algorithms taking into account the ACT, the incidence of bleeding complications was reduced to 1.8%, the same as the control group, and the benefits with regards to ischaemic events were not only maintained but increased (a 56% reduction at 1 months). Utilization of abciximab would be supported by the Cost saving approach of the EPIC trial 3-years follow-up which showed presentation of the initial benefits.     

Balloon angioplasty for the treatment of vasospasm: results of first 50 cases

OBJECTIVE: To report the results of the first 50 consecutive patients with vasospasm secondary to subarachnoid hemorrhage treated with balloon angioplasty after failure of medical management. METHODS: Retrospective uncontrolled study of 50 consecutive patients treated with balloon angioplasty between February 1988 and July 1992. Forty-six had objective clinical deterioration despite maximal medical therapy, whereas four were treated on the basis of rapidly accelerating transcranial Doppler velocities and decreased regional blood perfusion detected by technetium-99m-exametazime brain single photon emission computed tomography. All patients had evidence of marked vasospasm demonstrated by angiography. Thirty-two (64%) and 46 (92%) patients underwent angioplasty within 12 and 18 hours, respectively. RESULTS: Of the patients with clinical evidence of vasospasm-induced ischemia, 28 (61%) showed sustained neurological improvement within 72 hours of angioplasty. Three (6%) patients deteriorated within 72 hours after angioplasty, with two (4%) patients dying immediately after angioplasty as a result of vessel rupture and the other patient's Glasgow Coma Scale score decreasing by 2. Two additional patients in poor condition with Hunt and Hess Grade V at the time of angioplasty subsequently died during hospitalization. Two other patients died as a result of unclipped aneurysms that subsequently bled 4 and 12 days after angioplasty, respectively. The improvement demonstrated clinically, angiographically, and by transcranial Doppler after angioplasty was sustained, with only one patient requiring subsequent angioplasty of a previously dilated segment (total, 170 vessel segments dilated). Two patients developed vasospasm in previously undilated segments. CONCLUSION: Timely balloon angioplasty can reverse delayed ischemic deficit caused by vasospasm in patients for whom medical therapy has failed.     

Dietary and non-dietary factors associated with iron status in a cohort of Danish adults followed for six years

PURPOSE: Suboptimal distal coronary flow reserve after successful balloon angioplasty has been attributed to angiographically unrecognized inadequate lumen expansion, and adjunct coronary stenting has been shown to improve coronary flow reserve. The aim of this study was to investigate whether myocardial fractional flow reserve (FFRmyo) would increase further after coronary stenting compared with balloon angioplasty alone in the same patient group. METHODS: FFRmyo and quantitative coronary angiography were obtained before and after pre-stent balloon dilation, and again after stent placement in 11 patients (7 left anterior descending artery, 3 right coronary artery and 1 left circumflex artery). FFRmyo was calculated as the ratio of Pd/Pa during intracoronary adenosine 5'-triphosphate (50 micrograms and 20 micrograms in the left and right coronary arteries, respectively)-induced maximum hyperemia, where Pd represents mean distal coronary pressure measured by a 2.1 Fr infusion catheter and Pa represents mean aortic pressure measured by the guiding catheter. RESULTS: Percent diameter stenosis significantly decreased after balloon angioplasty (74% +/- 15% vs 37% +/- 17%, p < 0.001), and decreased further after stent placement (18% +/- 10%, p < 0.001 vs baseline and balloon angioplasty). FFRmyo after coronary stenting (0.85 +/- 0.09) was significantly higher than that at baseline (0.51 +/- 0.16, p < 0.001) and after balloon angioplasty (0.77 +/- 0.11, p < 0.05). There was a significant correlation between angiographic variables and FFRmyo. The increase in lumen dimensions after coronary stenting was followed by a further significant improvement of FFRmyo. CONCLUSION: These results suggest that coronary stenting may provide a more favorable functional status and lumen geometry of residual coronary stenosis compared with balloon angioplasty alone.     

Effect of nadroparin, a low-molecular-weight heparin, on clinical and angiographic restenosis after coronary balloon angioplasty: the FACT study. Fraxiparine Angioplastie Coronaire Transluminale

BACKGROUND: Experimental studies suggest that the antiproliferative effect of heparin after arterial injury is maximized by pretreatment. No previous studies of restenosis have used a pretreatment strategy. We designed this study to determine whether treatment with nadroparin, a low-molecular-weight heparin, started 3 days before the procedure and continued for 3 months, affected angiographic restenosis or clinical outcome after coronary angioplasty. METHODS AND RESULTS: In a prospective multicenter, double-blind, randomized trial, elective coronary angioplasty was performed on 354 patients who were treated with daily subcutaneous nadroparin (0.6 mL of 10,250 anti-Xa IU/mL) or placebo injections started 3 days before angioplasty and continued for 3 months. Angiography was performed just before and immediately after angioplasty and at follow-up. The primary study end point was angiographic restenosis, assessed by quantitative coronary angiography 3 months after balloon angioplasty. Clinical follow-up was continued up to 6 months. Clinical and procedural variables and the occurrence of periprocedural complications did not differ between groups. At angiographic follow-up, the mean minimal lumen diameter and the mean residual stenosis in the nadroparin group (1.37+/-0.66 mm, 51.9+/-21.0%) did not differ from the corresponding values in the control group (1.48+/-0.59 mm, 48.8+/-18.9%). Combined major cardiac-related clinical events (death, myocardial infarction, target lesion revascularization) did not differ between groups (30.3% versus 29.6%). CONCLUSIONS: Pretreatment with the low-molecular-weight heparin nadroparin continued for 3 months after balloon angioplasty had no beneficial effect on angiographic restenosis or on adverse clinical outcomes.     

Tirofiban. A review of its use in acute coronary syndromes

Tirofiban is an intravenously administered nonpeptide glycoprotein IIb/IIIa receptor antagonist which specifically inhibits fibrinogen-dependent platelet aggregation and prolongs bleeding times in patients with acute coronary syndromes. Adenosine diphosphate (ADP)-induced platelet aggregation returns to near-baseline levels within 4 to 8 hours after cessation of a tirofiban infusion, a finding consistent with the drug's elimination half-life of approximately 2 hours. Three large clinical trials have shown that, when administered with a standard heparin and aspirin regimen, tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave myocardial infarction (MI) and in patients undergoing percutaneous revascularisation. In PRISM-PLUS, a study involving 1915 patients with unstable angina/non-Q-wave MI, administration of intravenous tirofiban (0.4 microgram/kg/min loading dose for 30 minutes followed by a 0.10 microgram/kg/min infusion) with heparin for at least 48 (mean 71.3) hours reduced the 7-day risk of the composite end-point of MI, death and refractory ischaemia by 32% compared with heparin alone. The between-group risk reduction remained significant at 30 days (22%) and 6 months (19%). Similarly, in high-risk patients undergoing coronary angioplasty in RESTORE, the addition of tirofiban (10 micrograms/kg bolus in the 3 minutes prior to intervention followed by 0.15 microgram/kg/min for 36 hours) to a standard heparin regimen significantly reduced the risk of ischaemic complications by 38% on day 2 and 27% on day 7 compared with heparin alone. Although interim analysis in PRISM-PLUS showed that the use of tirofiban without heparin increased the 7-day risk of death compared with heparin alone, this finding was inconsistent with the effects of tirofiban on the risk of death in PRISM, a study involving 3232 patients with unstable angina/non-Q-wave MI. Tirofiban is generally well tolerated. Bleeding complications were the most commonly reported events associated with tirofiban in clinical trials, but the rate of major bleeding in tirofiban recipients was not significantly different from that reported with heparin. Thrombocytopenia (platelet count < 90,000 cells/microliter) occurred slightly more frequently with tirofiban (with or without heparin) than with heparin alone. CONCLUSIONS: Tirofiban reduces the risk of ischaemic complications in patients with unstable angina/non-Q-wave MI and high-risk patients undergoing revascularisation when used against a background of heparin and aspirin. Furthermore, the drug has an acceptable tolerability profile. Therefore, intravenous tirofiban is likely to be used as an adjunct to heparin and aspirin in patients with acute coronary syndromes including high-risk patients undergoing revascularisation.     

Effect of intravenous heparin infusion on thrombin-antithrombin complex and fibrinopeptide A in unstable angina

BACKGROUND: In unstable angina, the clinical efficacy of heparin is limited in time, and recurrence of adverse events has been reported after discontinuation of the anticoagulant. METHODS: In 21 episodes of unstable angina, we used the plasma level of fibrinopeptide A (FPA) and of thrombin-antithrombin complex (TAT) to evaluate the pattern of thrombin inhibition by heparin and the effect of stopping heparin and initiating aspirin. RESULTS: At admission, the plasma level of FPA was increased: median value 3.7 ng/mL compared with 5.5 ng/mL in a control group of 20 patients with early myocardial infarction (not significant). The following findings were observed during a 4-day course of intravenous heparin infusion: (1) FPA decreased significantly 6 hours after the start of therapy; (2) FPA was lower when activated partial thromboplastic time (aPTT) was >1.5 times baseline; (3) there was a significant negative correlation between aPTT and FPA. Twenty-four hours after heparin was discontinued and aspirin initiated, a significant increase in TAT and FPA in plasma was observed. CONCLUSIONS: The results confirm ongoing fibrin formation in the active phase of unstable angina, indicate incomplete and variable inhibition of thrombin by heparin during continuous infusion, and suggest a risk of re-emergence of thrombosis (in spite of initiating aspirin) 24 hours after withdrawal of heparin. Data demonstrate a better control of thrombin activity when heparin is infused at rates that maintain aPTT at >1.5 times baseline, as currently recommended in unstable angina.     

Thromboembolism complicating surgery for cervical and uterine malignancy: incidence, risk factors, and prophylaxis

Venous thromboembolism is a leading cause of death and morbidity after extended surgery for early malignancies of the cervix and uterus. Two hundred eighty-one patients who underwent such surgery were retrospectively evaluated for associated risk factors, the incidence of clinically significant thromboembolic complications, and prophylactic value of low-dose heparin and antiembolism stockings. Significant thromboemboli were encountered in 7.8% of patients postoperatively and accounted for the only 4 postoperative deaths. Forty-five percent of patients who developed thromboemboli did so after discharge from the hospital. The preoperative risk factors found to be associated with thromboembolism, in order of statistical significance, were weight in excess of 85.5 kg, advanced clinical stage of malignancy, and radiation therapy within 6 weeks of the operative procedure. Low-dose heparin therapy and the use of antiembolism stockings as preventative measures did not appear to reduce the incidence of thromboembolic complications. A prospective study will be necessary to evaluate definitely the effectiveness of various therapeutic modalities on thromboembolism in gynecologic oncology patients.     

The effect of early ambulation on hematoma formation and vascular complications following 7 French diagnostic cardiac catheterization

OBJECTIVE: To assess the feasibility and safety of early ambulation 3 to 4 h after diagnostic 7 French cardiac catheterization. DESIGN: Randomized, single-blind assignment to one of 3, 4 or 6 h ambulation postcardiac catheterization groups. SETTING: Tertiary care community hospital in an urban region. PATIENTS: Eight hundred and seventy-four consecutive inpatients and out-patients presenting for routine diagnostic cardiac catheterization. INTERVENTION: Hematoma formation and other vascular complications recorded at the time of discharge and 24 h later. MAIN RESULTS: No significant difference in hematoma formation rates was noted among patients mobilized at 3 h (3.6%), 4 h (4.8%) or 6 h (3.2%). Late hematoma formation occurred in 2.3% of patients. Other vascular complications were very rare. Reported rates of hematoma formation varied significantly (P < 0.05) among physicians, ranging from 0.9% to 8.0%. CONCLUSIONS: Early ambulation of patients 3 to 4 h after routine diagnostic 7 French cardiac catheterization is both safe and feasible. These findings could result in more efficient recovery bed utilization, reduced nursing costs and improved patient compliance with bed rest.     

Paradoxical improvement of residual vision following corpus callosotomy in brain damaged cats

The current study was designed to evaluate tubing sets with either polymeric phospholipids or ionically bound heparin in six bovine experiments (body weight, 70 +/- 5 kg). No heparin was given systemically. Left heart bypass was started with 300 ml of clear priming solution and maintained over 6 hours (50 ml/kg/min). Coagulation studies included platelet counts, activated coagulation time (ACT), thrombin time (TT), fibrinogen (Factor I), antithrombin III (AT III), and fibrinopeptide A (FPA). Normalized platelet levels dropped from 100 +/- 12% before to 86 +/- 13% after 6 hours of left heart bypass for heparin, compared with 100 +/- 46% to 90 +/- 44% for phospholipid coating (NS). The ACT increased from 146 +/- 7 sec at 10 min to 159 +/- 16 sec after 6 hours for heparin, compared with 122 +/- 4 to 126 +/- 5 sec for phospholipid (p < 0.05). Thrombin time changed from 18 +/- 0 sec before to 19 +/- 1 sec after 6 hours for heparin, as compared with 16 +/- 1 sec to 18 +/- 1 sec for phospholipid (NS). Factor I levels decreased from 1.5 +/- 0.3 g/L to 1.3 +/- 0.1 g/L for heparin, compared with 1.5 +/- 0.2 g/L to 1.4 +/- 0.3 g/L for phospholipid. Antithrombin III levels changed from 102 +/- 26% to 91 +/- 7% for heparin, compared with 123 +/- 12% to 118 +/- 12% for phospholipid. Fibrinopeptide A levels changed from 100 +/- 60% to 130 +/- 13% for heparin, compared with 100 +/- 11% to 99 +/- 6% for phospholipid (P < 0.05). No macroscopic red clots were found in either group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quality of life after orthopedic surgery of the lower limbs. A new approach

Heparinization is a routine procedure during angioplasty; however, its consequences on the late vascular response to a severe injury are unclear. The authors' objective was to explore the effect of a single heparin bolus at the time of a severe vascular injury on late intimal proliferation and neointimal thickening. The iliac artery of 57 normolipemic rabbits was overdistended with a balloon catheter. Heparin (250 IU/kg i.v.) was given to 29 rabbits ten minutes before angioplasty, whereas 28 rabbits served as untreated controls. Neointimal thickening was prominent at fourteen days after injury and reached near-maximal values at day 28. The intimal/medial area ratio was reduced by an average 28.3% with heparin (at day 28: 2.19 +/- 0.51 vs 1.57 +/- 0.59, control vs heparin, P = 0.02). Neointimal cells stained positively for HHF-35 antibody, directed against smooth muscle cell antigens. Neointimal proliferation, quantified through the number of cell nuclei peroxidase-stained for PCNA/cyclin antigen, was significantly decreased by 43% and 49% with heparin, respectively, at days 7 and 14 after injury. These data suggest that early exposure even to low doses of heparin accounts for much of its inhibitory effect in vascular response to injury; such an effect might prove important in interpreting results of human trials of interventions against restenosis.     

Relation between the time to achieve the lower limit of the APTT therapeutic range and recurrent venous thromboembolism during heparin treatment for deep vein thrombosis

BACKGROUND: Randomized trials have demonstrated the importance of achieving adequate heparinization early in the course of therapy. Recently, some authors reported a pooled analysis of selected studies in the literature that suggested that there is no convincing evidence that the risk of recurrent venous thromboembolism is critically dependent on achieving a therapeutic activated partial thromboplastin time result at 24 to 48 hours. METHODS: We provide the analyses of patient groups entered into our series of 3 consecutive double-blind randomized trials evaluating initial heparin therapy for proximal deep venous thrombosis. RESULTS: Logistic regression analysis of the patient groups receiving the less intense initial intravenous heparin dose of 30,000 U/24 h demonstrated that subtherapy for 24 hours predicted the onset of venous thromboembolic events. Failure to achieve a therapeutic activated partial thromboplastin time by 24 hours was associated with a 23.3% frequency of venous thromboembolism vs 4% to 6% for those whose activated partial thromboplastin time exceeded the therapeutic threshold by 24 hours (P=.02). Time-to-event analysis shows the increased frequency of recurrent venous thromboembolic events during the period of study in patients who were subtherapeutic for 24 hours compared with those who were therapeutic (P=.001). CONCLUSIONS: Our findings reaffirm the clinical importance of rapidly achieving therapeutic levels of heparin. Patients who failed to achieve the therapeutic threshold by 24 hours were at an increased risk of subsequent recurrent venous thromboembolism. These findings are independently supported by the results of a randomized trial comparing different intensities of initial heparin treatment by continuous infusion.     

Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection

Four different heparin preparations--sodium and calcium salts of the same batch of heparin (mean molecular weight 15,000), low molecular weight sodium heparin (mean m.w. 9,000) and high molecular weight sodium heparin (mean m.w. 22,000) were injected subcutaneously on different days each into 6 healthy young volunteers in a randomized trial. Plasma heparin levels were measured using the anti-Xa assay at 1 hour, 3-4 hours and 6-7 hours after the injection. The highest anti-Xa potentiating effect was obtained after the injection of the low molecular weight sodium heparin (mean 0.381 i.u./ml) at 3-4 hours after the injection. With sodium heparin (m.w. 15,000) the highest values (0.135 i.u./ml) were found at 1 hour. Significantly lower anti-Xa potentiating effect was obtained 1 hour after the injection of calcium heparin and in particular after the injection of high molecular weight heparin (mean values 0.072 i. u./ml and 0.043 i. u./ml respectively). Both these preparations showed an increase from 1 hour after injection to 3-4 hours after injection (mean values 0.082 i. u./ml and 0.057 i. u./ml at 3-4 hours after injection). These results indicate that the salt and the molecular weight of the preparation may strongly influence the degree of anticoagulation achieved after subcutaneous injection.     

Site-specific intracoronary heparin delivery in humans after balloon angioplasty. A radioisotopic assessment of regional pharmacokinetics

BACKGROUND: Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused gamma-emitting compounds. METHODS AND RESULTS: In 12 patients after balloon angioplasty, 99mTc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a gamma-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99mTc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, define as seven half-lives, were obtained by use of the elimination component after correction for 99mTc decay. Mean peak delivered amount was 45 +/- 44 IU (236 +/- 228 micrograms), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244 +/- 194 IU.h (1.28 +/- 1.01 mg.h). Retention time varied from 12 to 90 hours (mean, 50:33 +/- 22:50 hours:minutes). CONCLUSIONS: Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.     

Results of the multicenter natural interferon-alpha treatment for chronic hepatitis C: correlation between total dose, administration periods and efficacy of therapy. Keio Natural IFN-alpha study group

From January 1993 to December 1995, intraarterial catheter guided urokinase infusion was used as an initial approach in the management of 29 episodes of infrainguinal graft thrombosis (12 venous and 17 prosthetic grafts) in 27 patients. The infusion catheter was embedded inside the occluding clot which was infiltrated by 225.000 U urokinase from distal to proximal. Local low-dose urokinase (1.000 U/kg/hr) was continued for a mean of 39 hours. By this regimen, prompt relief of ischaemia was achieved in 69% (20/29) of cases. Complete recanalization was obtained in 79% of cases. In six cases, the graft remained totally (n = 3) or partially (n = 3) occluded. Two of these patients benefited from secondary surgery, two improved clinically by conservative treatment, and two required amputation. In the 23 successful cases, thrombolysis unmasked an underlying flow-limiting stenosis in 83% (19/23), that was subsequently corrected by percutaneous balloon angioplasty (n = 15), by surgery (n = 3), or by a combination of both (n = 4). One early rethrombosis resulted in an amputation. The immediate limb-salvage rate was 89% (26/29). Surgical intervention was avoided in 17 cases (58%). The main hospital stay was 13 days. The short-term follow-up (mean of 17 months) reveals a high early rethrombosis rate (8/23 or 35%) within one year. Four of these repeated graft failures evolved to amputation. At one year, the overall limb salvage rate dropped to 79%. Thrombolytic management of infrainguinal occluded bypass grafts gives excellent initial technical results (79%), minimizing the need for major surgical revision. It is however characterized by a high procedure-related morbidity (21%). These immediate favourable results are not longstanding. Diffuse graft disease, limited outflow and high recurrence rate of anastomotic stenoses after balloon angioplasty explain poor long-term results after thrombolysis of failed grafts.     

Antithrombotic therapy after coronary stent placement

Subacute stent thrombosis and hemorrhagic complications due to intensive anticoagulant therapy limit the clinical benefit of coronary stenting. Antithrombotic therapy after coronary stent placement has not been standardized yet. From January 1994 to December 1995 a total of 338 Palmaz-Schatz stents were implanted in 285 patients. Procedural success rate was 98.8%. In the initial period, after stent placement, patients were treated with acetylsalicylic acid (ASA) and warfarin (135 patients, Group A), while subsequently, according to the results of other studies, patients were treated with ASA plus ticlopidine (146 patients, Group B). Two hours after sheath removal, Group A patients were treated with intravenous heparin until therapeutic INR (2.5-3.5) was reached; warfarin was stopped 3 months later. In Group B patients 2 hours after sheath removal a treatment with subcutaneous heparin 25,000 IU/die plus ticlopidine 500 mg/die was started. Subcutaneous heparin was maintained until hospital discharge, ticlopidine was stopped after 1 month and ASA was maintained indefinitely. There were no significant differences in baseline characteristics between the two groups. Most patients had unstable angina and in the majority of cases the stent was implanted due to intimal dissection after balloon dilation. Eleven patients had subacute thrombosis of the stent (3.9%): 9 patients were in Group A (6%) and 2 patients were in Group B (1.3%; p = 0.04). Seven patients (6 in Group A, 1 in Group B) were treated with emergency coronary angioplasty and 3 (2 in Group A, 1 in Group B) with coronary bypass; nevertheless 7 patients (6 in Group A, 1 in Group B) had an acute myocardial infarction. Eight patients (6 in Group A, 2 in Group B) had major bleeding due to a large groin hematoma requiring blood transfusion or vascular surgery. In conclusion, after coronary stenting antithrombotic therapy with ASA plus ticlopidine, as compared with anticoagulant therapy, reduces the incidence of both cardiac events and hemorrhagic complications.