Prevention and treatment of adverse effects of corticosteroids in systemic lupus erythematosus

The therapy of deep venous thrombosis consists of several elements and depends on the localization, the age and the extent of the thrombus. This article discusses various types of initial therapy and long-term treatment of venous thromboembolism and also reviews future perspectives of pharmacological treatment. The initial treatment regimens comprise thrombolysis, thrombectomy, inferior vena cava filters and the anticoagulation with either unfractionated heparin or low molecular weight heparins. Various thrombin-inhibitors have been tested for initial treatment of thrombosis, however, further investigations of their efficacy, safety and cost-effectiveness will have to provide firm evidence on their superiority when compared to unfractionated or low molecular weight heparins.     

Influence of various antithrombotic therapy methods on the incidence of subacute coronary stent occlusions, hemorrhagic complications and length of hospitalization

BACKGROUND: The clinical benefit of coronary stenting is reduced by the risk of thrombotic stent occlusion as well as hemorrhagic complications of intensive antithrombotic therapy. We compared the influence of different antithrombotic therapies on the incidence of post-interventional complications and in-hospital stay duration. METHODS: After successful placement of a coronary stent, 334 consecutive patients were given different antithrombotic treatments in addition to aspirin 100 mg/d indefinitely: (1) phenprocoumon for 3 months (n = 47), (2) low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 90), (3) ticlopidine 2 x 250 mg/d and low molecular weight heparin 2 x 100 U/kg/d s.c. for 4 weeks (n = 72) and (4) ticlopidine 2 x 250 mg/d for 4 weeks (n = 125). RESULTS: Major events were subacute stent thrombosis in 17 patients (5%), and severe hemorrhagic complication in 20 patients (5.9%). The incidence of subacute stent thrombosis in groups 1 to 4 was 10.6%, 11%, 1.4% and 0.8% respectively. The use of ticlopidine was associated with a significant lowering of stent occlusions in univariate and multivariate analysis (p = 0.0013). Additional uni- and multivariate predictors were stent placement as a "bail-out" procedure (p = 0.033) and in patients with acute coronary syndrome (p = 0.049). Anticoagulant therapy was associated with a higher incidence of severe hemorrhagic complications (p < 0.01) and a prolonged in-hospital stay (p = 0.01). CONCLUSIONS: These results confirm that anti-thrombotic therapy with aspirin and ticlopidine combines low rates of subacute stent occlusion and hemorrhagic complications. Treatment with phenprocoumon and low molecular weight heparin does not improve the rate of subacute stent occlusion but increases hemorrhagic complications. Very low rates of stent occlusion permit short in-hospital stays with concomitant reduction in cost.     

Increased platelet responsiveness following coronary stenting. Heparin as a possible aetiological factor in stent thrombosis

AIMS: Platelet activation may be a determinant of thrombotic and restenotic complications following intracoronary stenting. In order to measure the effect of stenting on platelet activation antigen expression we used whole blood flow cytometry in 18 patients undergoing Palmaz-Schatz stenting (treated with full anticoagulation) and compared these with a group of 18 patients undergoing elective angioplasty. The effects of low molecular weight heparin and unfractionated heparin on platelet behaviour were also studied, both in vitro and in vivo to determine the contribution of prolonged heparin therapy to platelet activation following stenting. METHODS AND RESULTS: Fibrinogen binding to activated GPIIb-IIIa, and surface expression of P-selectin, GPIb and GPIIb-IIIa antigens were measured in unstimulated peripheral blood samples (rest) and on stimulation with adenosine diphosphate (0.1-10 micromol x 1(-1)) and thrombin (0.02-0.16 U x ml(-1)). No changes were seen in resting samples following angioplasty or stenting. Agonist responsiveness was unaltered after angioplasty, but in stented patients antigen expression in response to thrombin was significantly reduced (P< or =0.04), whilst the adenosine diphosphate response was significantly increased (P=0.01). Similar effects were observed in patients with unstable angina treated with either low molecular weight heparin or unfractionated heparin in vivo. In vitro, both unfractionated and low molecular weight heparin inhibited thrombin-induced platelet activation, but stimulation of adenosine diphosphate responses was more marked with unfractionated than low molecular weight heparin. CONCLUSIONS: There was a significant increase in platelet responsiveness to adenosine diphosphate following intracoronary stenting in patients treated with conventional anticoagulants. This was probably a consequence of treatment with heparin. Activation of platelets by heparin may explain the increased rate of stent thrombosis in patients treated with anticoagulant therapy. Low molecular weight heparins stimulate platelets less than unfractionated heparin.     

Differential interactions of heparin and heparan sulfate glycosaminoglycans with the selectins. Implications for the use of unfractionated and low molecular weight heparins as therapeutic agents

The selectins are calcium-dependent C-type lectins that bind certain sialylated, fucosylated, sulfated glycoprotein ligands. L-selectin also recognizes endothelial proteoglycans in a calcium-dependent manner, via heparan sulfate (HS) glycosaminoglycan chains enriched in unsubstituted glucosamine units. We now show that these HS chains can also bind P-selectin, but not E-selectin. However, while L-selectin binding requires micromolar levels of free calcium, P-selectin recognition is largely divalent cation-independent. Despite this, HS chains bound to P-selectin are eluted by ethylenediamine tetraacetic acid (EDTA), but only at high concentrations. Porcine intestinal mucosal (mast cell-derived) heparin (PIM-heparin) shows similar properties, with no binding to E-selectin, calcium-dependent binding of a subfraction to L-selectin and to P-selectin, and calcium-independent binding of a larger fraction to P-selectin, the latter being disrupted by high EDTA concentrations. Analysis of defined heparin fragment pools shows a size dependence for interaction, with tetradecasaccharides showing easily detectable binding to L- and P-selectin affinity columns. L-selectin binding fragments include more heavily sulfated and epimerized regions and, as with the endothelial HS chains, they are enriched in free amino groups. The P-selectin binding component includes this fraction as well as some less highly modified regions. Thus, endothelium-derived HS chains and mast cell-derived heparins could play a role in modulating the biology of selectins in vivo. Notably, P- and L-selectin binding to sialyl-Lewisx and to HL-60 cells (which are known to carry the native ligand PSGL-1) is inhibited by unfractionated pharmaceutical heparin preparations at concentrations 12-50-fold lower than those recommended for effective anticoagulation in vivo. In contrast, two low molecular weight heparins currently considered as clinical replacements for unfractionated heparin are much poorer inhibitors. Thus, patients undergoing heparin therapy for other reasons may be experiencing clinically significant inhibition of L- and P-selectin function, and the current switchover to low-molecular weight heparins may come at some loss of this effect. Low-dose unfractionated heparin should be investigated as a treatment option for acute and chronic diseases in which P- and L-selectin play pathological roles.     

Treatment of venous thromboembolism

This review provides meta-analytic data of studies aiming at improved treatment of deep vein thrombosis and pulmonary embolism. The introduction of low molecular weight heparin has considerably ameliorated the initial treatment of deep vein thrombosis, and should now be regarded as the treatment of choice for most patients with deep vein thrombosis. Oral anticoagulant treatment is presently considered safe and effective for the long-term treatment of venous thromboembolism, provided that the INR is maintained at 2.0-3.0. However, the optimal duration as well as the optimal intensity of anticoagulation have still to be determined. Patients with submassive pulmonary embolism should presently be treated with adjusted dose unfractionated heparin and coumarins. Studies determining the efficacy and safety of low molecular weight heparin in this condition deserve priority. Thrombolytic therapy should be restricted to patients with massive pulmonary embolism, unless safer methods of thrombolysis have been developed. Surgical embolectomy and catheter fragmentation of emboli seem alternative options but deserve further investigations.     

Low molecular weight heparins. Implications in anesthesia and resuscitation

Low molecular weight heparins are a group of drugs that have only recently been introduced in clinical practice. The are widely used for prophylaxis in thromboembolic disease and are being employed increasingly to treat established venous thrombosis. One way in which these drugs are often used is for prophylaxis in the perioperative period for patients at high risk of developing venous thromboembolism, and the anesthesiologist must therefore be familiar with the main aspects of this application. We review pharmacological characteristics of these drugs as well as the literature on low molecular weight heparins, stressing points of main interest to the anesthesiologist and intensive care recovery unit specialist, namely adverse effects (mainly bleeding) and the implications that use of low molecular weight heparin will have on choice of anesthetic (in particular the dilemma of whether to use local/regional anesthesia).     

Salutary effects of aspirin in coronary artery disease are not limited to its platelet inhibitory effects

Aspirin is widely used in the treatment and prevention of coronary artery disease (CAD). However, other platelet inhibitory agents, which inhibit platelet activation, have not been found to be effective or as effective as aspirin. The discrepancy between the efficacy of these compounds and aspirin suggests that the therapeutic efficacy of aspirin may not be limited to its platelet inhibitory effect. In this review, the basis for a unique place for aspirin in the therapy of patients with CAD is discussed. The author believes that the nonplatelet-mediated effects of aspirin could be more important than the platelet inhibitory effect, or at least may complement the platelet inhibitory effects of aspirin in patients with acute myocardial ischemia and in others undergoing intracoronary procedures.     

Pharmacokinetic optimisation of the treatment of deep vein thrombosis

The current treatment for deep vein thrombosis is a 5- to 10-day course of heparin followed by 3 to 6 months of oral anticoagulants. Both heparin and oral anticoagulants present a high inter- and intra-individual variability and require individualisation and monitoring of their dosage. The pharmacokinetic properties of heparin have been difficult to assess through the radiolabelling procedures typically used for many other drugs. This is partially a result of the heterogeneous nature of heparin. Thus, the pharmacokinetics of heparin are expressed in terms of its pharmacodynamic activity. Improved coagulation test methodology coupled with the incorporation of patient factors such as bodyweight, height, baseline coagulation status, pretreatment heparin sensitivity and heparin concentrations, can be used to improve the accuracy of heparin dosage determination. Computer-based systems are now available to assist clinicians in quantitating dosage requirements, estimating bleeding risks, and storing patient dose-response relationships for future therapy monitoring. Low molecular weight heparin products might improve our ability to control anticoagulant therapy because drug concentration, as well as the effect on the clotting system, will be more predictable in patients receiving these products. In addition, low molecular weight heparins produce a more consistent, predictable anticoagulant response, and clinicians have a new pharmacological tool which may readily lend itself to patient-controlled, home-based anticoagulant pharmacotherapy. Where pharmacokinetics and pharmacodynamics could contribute to the optimisation of warfarin treatment is in the initiation of treatment, the estimation of the dosage required, the methods for drug monitoring, the assessment of unusual responses and the avoidance of drug interactions. Traditional pharmaco kinetic methods have limited applicability to the optimisation of warfarin therapy because there is no direct relationship between drug concentration and therapeutic effect. However, a variety of simple or sophisticated computer-assisted methods have been developed to help clinicians in individualising and monitoring warfarin treatment. New therapeutic approaches, such as direct thrombin inhibitors and thrombolytic agents, could overcome some limitations of the standard heparin plus oral anticoagulation therapy.     

Self-blame and peer victimization in middle school: an attributional analysis

Intravenous heparin followed by warfarin has been the classical anticoagulant therapy of acute venous thromboembolism for the past 30 years. In recent years a number of low-molecular-weight heparins have become available for clinical trials. These agents have a number of advantages over unfractionated heparin and are now being used internationally for the prevention and treatment of venous thromboembolism. Low-molecular-weight heparin will undoubtedly replace intravenous unfractionated heparin not only in the treatment of venous thromboembolism but in other conditions where heparin therapy is indicated. Whether or not the low-molecular-weight heparins can decrease or eliminate some of the complications of unfractionated heparin will depend on the outcome of future clinical trials.     

Cardiology. II. Coronary heart disease, myocardial infarction

Within the last 30 years pharmacotherapy has significantly contributed to an improvement of the prognosis of patients with coronary artery disease. With regard to antianginal drugs beta-blocker therapy has in particular enabled a risk reduction in patients with unstable angina, acute myocardial infarction and following acute myocardial infarction. Antithrombotic therapy has largely been influenced by platelet inhibitors. Acetylsalicylic acid (ASA) has convincingly shown to enable a risk reduction in patients with stable angina, unstable angina, acute myocardial infarction and in the secondary prevention following myocardial infarction. The introduction of thienopyridines has led to a further improvement of antiplatelet therapy. Thus, the combination of ticlopidine + ASA was combined with a significant risk reduction of subacute stent thrombosis and has enabled stent implantation to become a breakthrough technology. Clopidogrel, another thienopyridine has been shown to be superior in comparison to a monotherapy with ASA in patients with atherothrombotic diseases. The introduction of glycoproteine-IIb-IIIa-receptor antagonists has led to a significant risk reduction of periinterventional complications in patients with unstable angina. The combination of heparin + ASA was clearly superior to a monotherapy with ASA in patients with unstable angina. Recently, a further improvement of prognosis with low molecular weight heparin has been reported. Due to somewhat conflicting results, the definite role of direct thrombin inhibitors like hirudin still has to be defined. A possible risk reduction in patients with unstable coronary syndromes has been reported. Reperfusion therapy with fibrinolytic agents has revolutionised the therapy of patients with acute myocardial infarction throughout the last decades. In numerous trials successful fibrinolysis has convincingly shown to improve the prognosis of patients with acute myocardial infarction and thus is still considered to be the gold standard of treatment in acute myocardial infarction.     

Reduced morbidity and mortality rates of the heparin-induced thrombocytopenia syndrome

PURPOSE: We reported a 61% morbidity rate and a 23% mortality rate for the heparin-induced thrombocytopenia (HIT) syndrome in 1983. We subsequently reported in 1987 that with early recognition, immediate cessation of the administration of heparin, and platelet function inhibition, the morbidity rate could be reduced to 23% and the mortality rate to 12%. One hundred recent cases of patients with heparin-associated antiplatelet antibodies (HAAb) have been reviewed to determine whether aggressive screening, early diagnosis, and alternate management could further reduce morbidity and mortality rates. METHODS: The consecutive records of 100 patients with positive platelet aggregation tests were reviewed. Sixty-six patients were male. The patients' ages ranged from 23 days to 92 years. The patients were from vascular (28), cardiothoracic (42), and other (30) services. HIT was suspected in patients who received heparin and had falling platelet counts, platelet counts less than 100,000/mm3, or new thromboembolic or hemorrhagic events. RESULTS: Heparin was not offered to six patients with known HAAb. Twelve patients were successfully treated with antiplatelet therapy and limited reexposure to heparin, and 75 patients were successfully treated with early diagnosis and prompt cessation of heparin. Alternate forms of anticoagulation therapy were used selectively. Seven patients had 11 complications. Three of the seven patients were treated successfully with warfarin anticoagulation and aspirin (2) or with aspirin alone (1). A fourth patient was treated with thrombectomy, hematoma evacuation, and aspirin. A fifth patient underwent thrombolysis and coronary angioplasty in addition to receiving warfarin and aspirin. The sixth patient required two thrombectomies and warfarin. A seventh patient required two thrombectomies and aspirin. HIT was responsible for one of 17 deaths. CONCLUSION: A 7.4% morbidity rate and a 1.1% mortality rate have been achieved in patients with HAAb by aggressive screening, early recognition of HIT, and prompt cessation of the administration of heparin. Platelet function inhibitors and other anticoagulants, including nonreacting low molecular weight heparin, are important adjuncts in the management of the thromboembolic disorders associated with HIT.     

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.     

Puerperal thromboprophylaxis: comparison of the anti-Xa activity of enoxaparin and unfractionated heparin

Low molecular weight heparins are used extensively for thromboprophylaxis. The aim of this study was to compare the activity of the low molecular weight heparin, enoxaparin, 20 mg and 40 mg, given once per day with unfractionated heparin, 7500iu given twice per day, in terms of their anti-Xa activity in puerperal women following caesarean section and with an additional risk factor for venous thromboembolism. Seventeen women were randomised to receive one of the three treatments. The anti-Xa activity associated with each treatment was measured prior to treatment and at 2, 4, 6, 12 and 24 hours. The mean anti-Xa values of the groups receiving enoxaparin, 20 mg and 40 mg, were significantly higher than those of the group receiving unfractionated heparin. There was no difference between the two enoxaparin groups in terms of the anti-Xa activity profiles. This study suggests that the use of enoxaparin is superior to unfractionated heparin in terms of anti-Xa activity.     

Experimental kallikrein gene therapy in hypertension, cardiovascular and renal diseases

Argatroban, a direct thrombin inhibitor, is used clinically because of its safe and effective antithrombotic action. This drug of low molecular weight shows reversible inhibition of thrombin irrespective of whether thrombin is fibrin-bound or soluble. Optimal anticoagulant effects can easily be attained by monitoring with the activated partial thromboplastin time or whole-blood activated clotting time when a therapeutic range of argatroban equivalent to that of heparin is used. The antithrombotic action is simply detected with a chromogenic substrate assay. The clinical use of the drug in Japan was approved for the treatment of chronic peripheral arterial obstructive disease and acute ischemic stroke. For coronary artery disease in patients with deficiency of antithrombin activities attributable to either antithrombin III or heparin cofactor II deficiency, argatroban is effective as an anticoagulant. Acute coronary occlusion during and after percutaneous transluminal coronary angioplasty can be treated by argatroban as an alternative to heparin. The presence of platelets activated by a trace amount of thrombin is evidenced by modified methods of platelet aggregometry in acute ischemic stroke. Therefore, argatroban can render the platelets insensitive against the platelet hyperaggregation enhanced by thrombin.     

Current aspects of thrombolytic therapy in unstable angina pectoris

In the last years, several studies addressed the role of the different antithrombotic therapeutics in unstable angina pectoris. Acetylsalicylic acid still is the standard treatment reducing the rate of death and myocardial infarction by 50% in the first six months. Ticlopidin has no clinical effect in the first six days and therefore is not suited for treatment in the acute phase. Unfractionated heparin has an additional favourable effect when added to aspirin. Low molecular weight-heparin is at least as effective as UF-heparin. Direct thrombin-inhibitors (hirudin, hirudin-analoga) seem to be comparable to UF-heparin. Plasminogen-activators should not be given in unstable angina, as they show a tendency to worsen the clinical outcome. GP IIb/IIIa-antagonists (antibodies, synthetic antagonists) significantly improve the clinical effects of aspirin. When combined with a reduced dose of heparin, their favourable effect remains unchanged, while bleeding complications are reduced to a minimum.     

Comparative effects of L-NOARG and L-NAME on basal blood flow and ACh-induced vasodilatation in rat diaphragmatic microcirculation

Anticoagulants are widely used in the prevention of thromboembolic disease (particularly during the postoperative period) and in the curative treatment of deep vein thromboses. Two classes of anticoagulants are currently available: heparins (standard heparin, low molecular weight heparin) and coumarin anticoagulants. The choice of anticoagulant must take into account the clinical context (preventive or curative treatment), as well as the pharmacological and pharmacokinetic properties of the anticoagulant. This treatment requires laboratory monitoring adopted to the anticoagulant selected.     

Therapy for acute myocardial infarction in older persons

OBJECTIVE: To review the early management of acute myocardial infarction (AMI) in older adults. METHODS: Recently published studies relevant to the early management of AMI were systematically reviewed. When possible, the impact of older age on complication rates and clinical outcomes was evaluated. RESULTS: In general, AMI therapies that are effective in younger patients are also effective in older patients. Conversely, older age is associated with an increased risk of complications from therapy, implying that careful patient selection is required to optimize outcomes while minimizing risks. The principal limitation of currently available data is that relatively few patients older than the age of 80 have been enrolled in prospective randomized clinical trials. CONCLUSIONS: Thrombolysis and primary angioplasty are effective in establishing reperfusion and improving clinical outcomes in older patients with AMI. In the absence of contraindications, aspirin and beta blockers should be considered standard therapy in AMI patients of all ages, whereas heparin, nitrates, and angiotensin converting enzyme inhibitors are indicated in selected subgroups. At the present time, calcium channel blockers, magnesium, and antiarrhythmic agents are not recommended for routine use in the AMI setting, and the role of glycoprotein IIb/IIIa inhibitors, low molecular weight heparin, and other newer agents await the results of ongoing clinical trials.     

Management of intracoronary thrombosis complicating percutaneous transluminal coronary angioplasty

With technological advances in equipment and increased experience of operators, the success rates of percutaneous transluminal coronary angioplasty (PTCA) now exceed 90%. However, acute periprocural occlusion continues to complicate approximately 6% of all procedures, and many of these occlusions are due to intracoronary (IC) thrombus. Patients at highest risk for this complication include those with acute ischemic syndromes or with angiographically apparent thrombus. These individuals may be candidates for the use of prolonged heparin infusions prior to dilatation, intracoronary thrombolytic therapy, or monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor. All patients undergoing PTCA should receive adequate antiplatelet therapy, including aspirin, and heparin with dosing monitored by activated clotting times (ACT). In addition, some recommend the use of ionic contrast material. When IC thrombus accumulates following intervention, initial therapy should include IC nitroglycerin followed by a combination of redilatation and IC urokinase infusion. Prolonged balloon inflations may be useful, particularly with the use of autoperfusion catheters. Platelet glycoprotein IIb/IIIa receptor antagonists may prove to be beneficial in this situation as well. If the patient's clinical status deteriorates in spite of these measures, emergency coronary artery bypass graft surgery may be required.     

Observations of the treatment of women in the United States with myocardial infarction: a report from the National Registry of Myocardial Infarction-I

BACKGROUND: To determine whether there are sex differences in the demographics, treatment, and outcome of patients with acute myocardial infarction in the United States, data from the National Registry of Myocardial Infarction-I from September 1990 to September 1994 were examined. METHODS: The National Registry of Myocardial Infarction-I is a national observational database consisting of 1234 US hospitals in which each hospital submits data from each patient with acute myocardial infarction to a central data collection center. For these analyses, the following variables were examined in 354 435 patients with acute myocardial infarction: demographics; use of medical therapy including thrombolytic agents; use of procedures including cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery; length of hospital stay; adverse events (stroke, major bleeding, or recurrent myocardial infarction); and causes of death. RESULTS: In comparison with men, women experiencing acute myocardial infarction in the United States are older, with 55.7% older than 70 years. Women have a higher mortality rate than men even when controlled for age and die less often from arrhythmia but more often from cardiac rupture whether or not thrombolytic therapy is used. Treatment with aspirin, heparin, or beta-blockers is less frequent in women. When thrombolytic therapy is used, women are treated an average of almost 14 minutes later than men and experience a greater incidence of major bleeding. Cardiac catheterization, percutaneous transluminal coronary angioplasty, and coronary artery bypass surgery are used less often in women. CONCLUSIONS: Observations from the National Registry of Myocardial Infarction-I document important sex differences in demographics, treatment, and outcome of patients with acute myocardial infarction in the United States.     

Administration of abciximab during percutaneous coronary intervention reduces both ex vivo platelet thrombus formation and fibrin deposition: implications for a potential anticoagulant effect of abciximab

Abciximab (c7E3 Fab, ReoPro), a platelet glycoprotein (GP) IIb/IIIa inhibitor, decreases acute ischemic complications after percutaneous coronary interventions. Recently, abciximab was shown to decrease thrombin generation in vitro in a static system. To assess whether abciximab can decrease fibrin formation in blood from patients, we quantified both platelet thrombi and fibrin deposition by using an ex vivo flow chamber model. We prospectively studied 18 consecutive patients who underwent percutaneous interventions for unstable coronary syndromes. Blood was perfused directly from the patient through an ex vivo perfusion chamber at a high shear rate, thus mimicking mildly stenosed coronary arteries. Perfusion chamber studies were performed when patients were being treated with heparin plus aspirin before the procedure (baseline) and then repeated after the procedure, when patients were on either aspirin plus heparin alone (group 1, no abciximab, control) or aspirin plus heparin plus abciximab (group 2, abciximab treated). Each patient served as his or her own control. Specimens were stained with combined Masson's trichrome-elastin and antibodies specific for fibrinogen, fibrin, and platelet GP IIIa. Total thrombus area and areas occupied by platelet aggregates and fibrin layers were quantified by planimetry. Group 1 demonstrated no significant change in thrombus area before versus after the procedure; in contrast, treatment with abciximab reduced total thrombus area by 48% in group 2 (after the procedure versus baseline, P=0.01). This decline was due to significant reductions in both platelet aggregates (55%, P=0.005) and fibrin layers (45%, P=0.03). The addition of abciximab to heparin and aspirin in patients undergoing coronary interventions significantly decreases ex vivo thrombus formation on an injured vascular surface. Treatment with abciximab appears to reduce both the platelet and the fibrin thrombus components. This finding supports a potential role for GP IIb/IIIa receptor blockade in decreasing fibrin formation in addition to inhibition of platelet aggregation. Thus, potent inhibitors of GP IIb/IIIa may also act as anticoagulants.