Effect of fingolimod (FTY720) on cerebral blood flow, platelet function and macular thickness in healthy volunteers.

AIM: Fingolimod, a sphingosine 1-phosphate receptor modulator, is the first oral disease modifying therapy approved for the treatment of relapsing multiple sclerosis. The aim of this double-blind, placebo-controlled study was to evaluate the effect of fingolimod on cerebral blood flow, platelet function and macular thickness in healthy volunteers. METHODS: The study included 88 healthy volunteers who received fingolimod 0.5 mg or 1.25 mg or matched placebo over a period of 4 weeks. Transcranial colour coded sonography was performed to measure mean blood flow velocities, the platelet function was measured by the PFA-100® assay using a collagen/epinephrine cartridge and macular thickness was measured using optical coherence tomography. An assessment of non-inferiority of fingolimod vs. placebo was performed against a reference value (20% of the overall baseline value). RESULTS: All 88 randomized participants completed the study. At day 28 compared with baseline value, for 0.5 mg, 1.25 mg and placebo treatments, the mean middle cerebral artery blood flow velocity decreased by 4, 1 and 3.7 cm s(-1), respectively. The platelet function analyzer closure time increase was not significant (7.8, 7.5 and 10.4 s, respectively). The mean percentage change in the central foveal thickness from baseline for both eyes was below 3% for all groups. The safety profile of fingolimod in this study was found consistent with the previous reports. CONCLUSIONS: In healthy volunteers, the changes seen with both fingolimod doses were found to be within normal variability, non-inferior and comparable with those observed with placebo for all the pharmacodynamic parameters assessed.

Fibrinogen and factor XIII A-subunit genotypes interactively influence C-reactive protein levels during inflammation.

OBJECTIVE: Fibrinogen is a target of autoimmune reactions in rheumatoid arthritis (RA). Fibrin(ogen) derivatives are involved in inflammatory processes and the generation of a stable fibrin network is necessary for sufficient inflammation control. As the density and stability of fibrin networks depend on complex interactions between factor XIIIA (F13A) and fibrinogen genotypes, the authors studied whether these genotypes were related to C-reactive protein (CRP) levels during acute-phase reactions. METHODS: Association between α-fibrinogen (FGA), ß-fibrinogen (FGB) and F13A genotypes with CRP levels was tested in two cohorts with longitudinal CRP measurements. Discovery and replication cohorts consisted of 288 RA (913 observations) and 636 non-RA patients (2541 observations), respectively. RESULTS: Genotype FGB -455G>A (rs1800790) was associated with CRP elevations (≥ 10 mg/l) in both cohorts (RA, OR per allele 0.69, p=0.0007/P(adj)<0.015; non-RA, OR 0.70, p=0.0004/p(adj)<0.02; combined, OR 0.69, p<10(-5)/p(adj)=0.001). Genotype F13A 34VV (rs5985) was conditional for the association of FGB -455G>A with CRP as indicated by a clear restriction on F13A 34VV individuals and a highly significant heterogeneity between F13A 34VV and F13A 34L genotypes (p<10(-5), p(adj)=0.001). In both cohorts, mean CRP levels significantly declined with ascending numbers of FGB -455A alleles. Genotype FGA T312A (rs6050) exhibited opposite effects on CRP compared with FGB -455G>A. Again, this relation was dependent on F13A V34L genotype. CONCLUSION: Novel genetic determinants of CRP completely unrelated to previously known CRP regulators were identified. Presumably, these haemostatic gene variants modulate inflammation by influencing fibrin crosslinking. These findings could give new perspectives on the genetic background of inflammation control.

Nutritional status as marker for disease activity and severity predicting mortality in patients with systemic sclerosis.

OBJECTIVE: To assess and analyse nutritional status in patients with systemic sclerosis (SSc) and identify possible associations with clinical symptoms and its prognostic value. METHODS: Body mass index (BMI) and parameters of bioelectrical impedance analysis (BIA) were assessed in 124 patients with SSc and 295 healthy donors and matched for sex, age and BMI for comparisons. In patients with SSc, BMI and BIA values were compared with clinical symptoms in a cross-sectional study. In a prospective open analysis, survival and changes in the nutritional status and energy uptake induced by nutritional treatment were evaluated. RESULTS: Patients with SSc had reduced phase angle (PhA) values, body cell mass (BCM), percentages of cells, increased extracellular mass (ECM) and ECM/BCM values compared with healthy donors. Malnutrition was best reflected by the PhA values. Of the patients with SSc, 69 (55.7%) had malnutrition that was associated with severe disease and activity. As assessed by multivariate analysis, low predicted forced vital capacity and high N-terminal(NT)-proBNP values discriminated best between good and bad nutritional status. Among different clinical parameters, low PhA values were the best predictors for SSc-related mortality. BMI values were not related to disease symptoms or mortality. Fifty per cent of patients with SSc had a lower energy uptake related to their energy requirement, 19.8% related to their basal metabolism. Nutritional treatment improved the patients' nutritional status. CONCLUSIONS: In patients with SSc, malnutrition is common and not identified by BMI. BIA parameters reflect disease severity and provide best predictors for patient survival. Therefore, an assessment of nutritional status should be performed in patients with SSc.

The perioperative von Willebrand factor activity and factor VIII levels among alcohol use disorder patients undergoing total knee or hip replacement.

Alcohol use disorder patients have a five-fold higher risk of postoperative bleeding complications. We measured the perioperative von Willebrand factor and factor VIII levels in consecutive patients with alcohol use disorder. In one university hospital, 105 patients scheduled for arthroplasty were screened, and 25 fulfilled inclusion criteria. Postoperatively, we found significantly decreased von Willebrand factor ristocetin cofactor values over time among alcohol use disorder patients and significantly different time courses of factor VIII levels between patients with and without a diagnosed alcohol use disorder. Blood loss was significantly increased among alcohol use disorder patients on their first postoperative day.

Recombinant activated factor VIIa for the treatment of bleeding in major abdominal surgery including vascular and urological surgery: a review and meta-analysis of published data.

BACKGROUND: The purpose of this study was to determine the role of recombinant activated factor VII (rFVIIa) in abdominal, vascular, and urological surgery. METHODS: We conducted meta-analyses of case series and placebo-controlled studies reporting on the treatment or prophylaxis of bleeding with rFVIIa regarding 'reduction or cessation of bleeding', 'mortality', and 'thromboembolism'. RESULTS: All case reports (n = 15 case reports and 17 patients) documented an effect of rFVIIa in the treatment of bleeding. A meta-analysis of 10 case series revealed a reduction or cessation of bleeding in 39 out of 50 patients after administration of rFVIIa (estimated mean effect 73.2%, 95% confidence interval [CI] 51.0% to 95.4%) and a mean probability of survival of 53.0% (95% CI 26.4% to 79.7%). Among the rFVIIa responders, 19 out of 29 patients (66%) survived versus 1 out of 10 rFVIIa nonresponders (P = 0.003). Six out of 36 patients from the case series had a thromboembolic complication (estimated mean probability 16.5%, 95% CI 1.2% to 31.8%). Compared with a meta-analysis of eight placebo-controlled studies, no increased risk of thromboembolism was seen after administration of rFVIIa. CONCLUSION: The meta-analysis of case series showed that, in a mean of 73% patients, rFVIIa achieved at least a reduction of bleeding and that the probability of survival is increased in patients responding to rFVIIa. rFVIIa was not associated with an increased risk of thromboembolism compared with placebo.

The combinations C1 esterase inhibitor with coagulation factor XIII and N-acetylcysteine with tirilazad mesylate reduce the leukocyte adherence in an experimental endotoxemia in rats.

The study's objective was to determine the effects of the administration of combinations of C1 esterase inhibitor (C1-INH) with coagulation factor XIII (F XIII) and N-acetylcysteine (NAC) with tirilazad mesylate (TM) on leukocyte adherence and on intestinal functional capillary density during experimental endotoxemia in rats. In a prospective, randomized, controlled animal study, 40 male Wistar rats were divided into 4 groups. Group 1 (CON group) served as control group. Group 2 (LPS group), group 3 (C1-INH+F XIII group) and group 4 (NAC+TM group) received endotoxin infusions (10 mg/kg/h for 2 h). In C1-INH+F XIII group, 100 U/kg b.w. C1-INH and 50 U/kg b.w. F XIII were administered after the first 30 min of endotoxemia. In the NAC+TM group, 150 mg/kg b.w. N-acetylcysteine and 10 mg/kg b.w. Tirilazad mesylate were administered after 30 min of endotoxemia. Leukocyte adherence at venules of the intestinal submucosal layer and functional capillary density in the villi intestinales and in the longitudinal and circular muscle layers were estimated by intravital fluorescence microscopy (IVM). C1-INH+F XIII reduced the count of firmly adherent leukocytes that was increased after LPS administration in the V3 venules (CON group 69 (17-160)/mm2; LPS group 635 (556-814)/mm2; C1-INH+F XIII group 503 (337-646)/mm2). NAC+TM reduced the firmly adherent leukocytes in the V3 venules (NAC+TM group 403 (309-572)/mm2) and in the V1 venules (CON group 55 (16-131)/mm2; LPS group 368 (306-475)/mm2; NAC+TM group 270 (216-308)/mm2) as well. FCD was not impaired after LPS challenge and there was no influence of both combinations on the FCD. We conclude that both drug combinations can reduce the leukocyte adherence in a sepsis model in rats.

Effects of coagulation factor XIII on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation in experimental endotoxemia.

INTRODUCTION: The objective of this study was to determine the effects of the administration of the coagulation factor XIII (F XIII) on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia. METHODS: In a prospective, randomized, controlled animal study 42 male Wistar rats were divided into three groups. Group 1 served as the control group. Groups 2 (lipopolysaccharide (LPS) group) and 3 (F XIII group) received endotoxin infusions (2.5 mg/kg/h for 2 hours). In group 3, 50 U/kg body weight F XIII was continuously administered during the first 30 minutes of endotoxemia. F XIII levels were measured in all animals. One half of the animals of each group were studied for intestinal functional capillary density (FCD) and leukocyte adherence on venular endothelium by intravital fluorescence microscopy (IVM). In the other half of each group, mesenteric plasma extravasation (FITC-albumin) was determined by IVM. RESULTS: The F XIII level was significantly increased in the F XIII treatment group. In the LPS group, endotoxemia led to a significant reduction of mucosal FCD (-18.5%; p < 0.01 versus control group). F XIII administration in the F XIII group attenuated the decrease in mucosal FCD (-3.7% compared to control; p < 0.05 versus LPS group). During endotoxemia, a significant increase of leukocyte adherence at the endothelium could be noted in the LPS group compared to the control group. Leukocyte adherence at the endothelium and plasma extravasation in the F XIII group did not differ significantly from the LPS group. CONCLUSION: Factor XIII protected mucosal capillary perfusion against endotoxin-induced impairment in an experimental sepsis model in rats, whereas leukocyte adherence and plasma extravasation remained unchanged.

Thawing procedures and the time course of clotting factor activity in fresh-frozen plasma: a controlled laboratory investigation.

BACKGROUND: In this study, we evaluated the effects of the thawing process of 2 commercially available devices on the activity of clotting factors, inhibitors and activation markers of the hemostatic system in fresh-frozen plasma (FFP). In an experimental procedure, FFP was thawed under running warm water at 42 degrees C. METHODS: Plasma of 20 healthy donors was sampled, separated, and distributed in 3 plasma bags. Within 2 h after sampling plasma bags was frozen at a temperature of -30 degrees C to -40 degrees C and stored for at least 8 wk. After sampling (baseline) as well as immediately and 1, 2, 4, and 6 h after thawing, the activity of FV, FVII, FVIII, fibrinogen, fibrin monomers (FM), d-dimers (DD), alpha2-antiplasmin (alpha2-AP), and protein S (PS) was determined from each plasma bag. RESULTS: From 1 h to 6 h after thawing, no significant differences in the activity of the investigated coagulation markers dependent on the thawing procedure were found. However, immediately after thawing and independent of the thawing procedure, the activity of FVII was significantly decreased (P < 0.01), whereas FM were significantly increased (P = 0.001). CONCLUSION: The thawing procedures studied exhibited no significant influence on activity and stability of the investigated markers of coagulation over the study period. The decreased activity of FVII and the clinical significance of the increase in FM require further research.

Heparin-induced thrombocytopenia type II in an infant with a congenital heart defect--anticoagulation during cardiopulmonary bypass with epoprostenol sodium and heparin.

BACKGROUND: Heparin-induced thrombocytopenia type II (HIT II) is a rare but potentially life-threatening complication of heparin therapy. Hitherto, only few reports on HIT II in infants and children have been published. In particular, infants and children who have to be operated under cardiopulmonary bypass are at risk as an alternative anticoagulation is required. CASE PRESENTATION: We report on an infant with a congenital heart defect who was scheduled for cardiac surgery (Damus Kaye-Stansel procedure) with cardiopulmonary bypass. In the intensive care unit, an HIT II was diagnosed. Before surgery, the infant was pretreated with epoprostenol sodium (incrementally increasing up to a maximum dose of 30 ng/kg/min) before heparin was administered shortly after sternotomy. Mean arterial pressure was kept stable with an infusion of norepinephrine and the course of the cardiopulmonary bypass showed no signs of thrombosis. Drainage loss in the postoperative period was moderate. CONCLUSION: In HIT II infants, pretreatment with epoprostenol sodium before reexposure to heparin may offer a safe and effective anticoagulation for cardiopulmonary bypass.

Homozygous and double heterozygous Factor V Leiden and Factor II G20210A genotypes predispose infants to thromboembolism but are not associated with an increase of foetal loss.

Prospective and controlled data about the individual risk profile in asymptomatic children with homozygous or double heterozygous risk genotypes for Factor V Leiden (FVL) and factor II (FII) G20210A are currently unavailable. The systematic and prospective observational study presented here was designed to determine the impact of the homozygous and double heterozygous FVL and FII G20210A genotypes on the prenatal and postnatal risk profiles of affected children. Risk infants and heterozygous controls were identified by screening of 85,304 neonates. Follow-up included the comparison of prenatal and postnatal development, ultrasonography of brain and kidneys, and a panel of independent determinants of thrombophilia. The numbers of identified or expected FVL homozygotes and double heterozygotes did not differ significantly (FVL: 116 versus 91, p=0.08; FVL/FII: 94 versus 76, p=0.17), indicating the absence of a prenatal disadvantage. A prenatal advantage was suggested in FII homozygotes, whose identified number far exceeded the expected (19 versus 4, p=0.002). Clinical and/or imaging abnormalities indicated spontaneous thromboembolic events in 4 of 129 risk infants (3%) but in none of the 178 controls (p=0.02). Physical and neurological development was normal in both groups during the first 2 years of life. The risk genotypes appear to confer a significant predisposition for spontaneous thromboembolic events in infancy without impeding development within the first two years of life. Foetal risk genotypes do not cause an increased foetal loss rate. Moreover, homozygous FII G20210A appears to be associated with a prenatal advantage.

Effects of C1 esterase inhibitor administration on intestinal functional capillary density, leukocyte adherence and mesenteric plasma extravasation during experimental endotoxemia.

OBJECTIVE: To determine the effects of C1 esterase inhibitor (C1-INH) administration on intestinal functional capillary density, leukocyte adherence, and mesenteric plasma extravasation during experimental endotoxemia. DESIGN AND SETTING: Prospective, randomized, controlled animal study in the experimental laboratory of a university. SUBJECTS: 42 male Wistar rats. INTERVENTIONS: The animals were divided into three groups. One half of the animals of each group underwent studies of intestinal functional capillary density and leukocyte adherence on venular endothelium by intravital fluorescence microscopy. In the other half of the animals mesenteric plasma extravasation (FITC albumin) was determined by intravital fluorescence microscopy. Treatment groups received endotoxin infusion of 2.5 mg/kg per hour (group 2 and 3) and 100 U/kg b.w. C1-INH (group 3) during the 2 h of endotoxemia. MEASUREMENTS AND RESULTS: Endotoxemia resulted in a significant decrease in mucosal functional capillary density (18.5% vs. controls), which was reduced by C1-INH administration (9.5%). Treatment with C1-INH also significantly attenuated intestinal leukocyte adherence in submucosal venules (35% vs. endotoxin group) and mesenteric plasma extravasation (44% vs. endotoxin group). CONCLUSIONS: C1-INH administration diminishes endotoxin-induced changes in the intestinal microcirculation during experimental endotoxemia.

Intermittent high permeability hemofiltration in septic patients with acute renal failure.

OBJECTIVE: High permeability hemofiltration (HP-HF) is a new renal replacement modality designed to facilitate the elimination of cytokines in sepsis. Clinical safety data on this new procedure is still lacking. This study investigates the effects of HP-HF on the protein and coagulation status as well as on cardiovascular hemodynamics in patients with septic shock. In addition, the clearance capacity for interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) is analyzed. DESIGN: Prospective, single-center pilot trial. SETTING: University hospital. PATIENTS: Sixteen patients with multiple organ failure (MOF) induced by septic shock were studied. INTERVENTION: Patients were treated by intermittent high permeability hemofiltration (iHP-HF; nominal cut-off point: 60 kilodaltons). Intermittent HP-HF was performed over 5 days for 12 h per day and alternated with conventional hemofiltration. MEASUREMENTS AND RESULTS: Intermittent HP-HF proved to be a safe hemofiltration modality in regard to cardiovascular hemodynamics and its impact on the coagulation status. However, transmembrane protein loss occurred and cumulative 12-h protein loss was 7.60 g (IQR: 6.2-12.0). The filtration capacity for IL-6 was exceptionally high. The IL-6 sieving coefficient approximated 1 throughout the study period. The total plasma IL-6 burden, estimated by area under curve analysis, declined over time ( p<0.001 vs baseline). The TNF-alpha elimination capacity was poor. CONCLUSIONS: High permeability hemofiltration is a new approach in the adjuvant therapy of sepsis that facilitates the elimination of cytokines. HP-HF alternating with conventional hemofiltration is well tolerated. Further studies are needed to analyze whether HP-HF is able to mitigate the course of sepsis.

Recombinant factor VIIa after aortic valve replacement in a patient with osteogenesis imperfecta.

A 26-year-old man with osteogenesis imperfecta and severe aortic regurgitation was scheduled for aortic valve replacement. As previously described by other authors the operation was difficult owing to the friability and weakness of the tissues. Mean blood losses of 153 mL per hour during the first 7 postoperative hours were observed. Despite normal coagulation indicators the bleeding did not stop and recombinant factor VIIa was applied at 40 microg/kg. Bleeding was successfully stopped after this single application.

A practical concept for preoperative management of patients with impaired primary hemostasis.

In a prospective study, 254 of 5649 unselected patients scheduled for surgery at our hospital were identified preoperatively as having either acquired (n=182) or inherited (n=72) impaired primary hemostasis (platelet dysfunction including von Willebrand disease). All patients were initially pretreated with desmopressin (DDAVP). Response to DDAVP or subsequent treatment(s) was defined as correction of any one of the abnormal PFA-100 platelet function tests. The non-responders were additionally treated with tranexamic acid or aprotinin; those with von Willebrand disease (vWD) received factor VIII concentrates with von Willebrand factor (vWF). Those still unresponsive to therapy received conjugated estrogens and, as a last attempt, a platelet transfusion. The administration of DDAVP led to a correction of platelet dysfunction in 229 of the 254 patients treated (90.2%). Tranexamic acid was effective in 12 of 16, aprotinin in 3 of 5, and factor VIII concentrates with vWF in all 4 patients with unresponsive to DDAVP. The remaining 6 patients were pretreated with conjugated estrogens, and 2 of these patients were additionally treated with platelet transfusion. The frequency of blood transfusion was lower, but not statistically significant (9.4% vs. 12.2%: p = 0.202) in preoperatively treated patients with impaired hemostasis than in patients without impaired hemostasis. In a retrospective group, the frequency of blood transfusion was statistically significant higher (89.3% vs. 11.3%: p < 0.001) in patients without preoperative correction of impaired hemostasis than in patients without impaired hemostasis. Preoperative correction of impaired primary hemostasis is possible in nearly all patients affected, and results in a reduction of homologous blood transfusions.

A practical concept for preoperative identification of patients with impaired primary hemostasis.

The findings of a large prospective study designed to identify primary and/or secondary hemostatic disorders before surgical interventions are presented. A total of 5649 unselected adult patients were enrolled to identify impaired hemostasis before surgical interventions. Each patient was asked to answer a standardized questionnaire concerning bleeding history. Activated partial thromboplastin time (aPTT), prothrombin time (PT), and platelet counts (PC) including PFA-100 (platelet function analyzer): collagen-epinephrine (C/E), and collagen-ADP (C/ADP) were routinely done in all patients. Additional tests, bleeding time (BT), and von Willebrand factor (vWF: Ag) were performed only in patients with a positive bleeding history and/or evidence of impaired hemostasis; e.g., drug ingestion. The bleeding history was negative in 5021 patients (88.8%) but positive in the remaining 628 (11.2%). Impaired hemostasis could be verified only in 256 (40.8%) of these patients. The vast majority were identified with PFA-100: C/E (n=250; 97.7%). The other six patients with impaired hemostasis were identifiable solely based on the PT (n=2), PFA-100: C/ADP (n=2), and vWF: Ag (n=2). The PFA-100: C/ADP detected 199 patients (77.7%). The only abnormality found among patients with a negative bleeding history was a prolonged aPTT due to lupus anticoagulant in nine patients (0.2%). The sensitivity of the PFA-100: collagen-epinephrine was the highest (90.8%) in comparison to the other screening tests (BT, aPTT, PT, vWF: Ag). The positive predictive value of the PFA-100: collagen-epinephrine was high (81.8%), but the negative predictive value was higher (93.4%). The use of a standardized questionnaire and, if indicated, the PFA-100: C/E and/or other specific tests not only ensure the detection of impaired hemostasis in almost every case but also a significant reduction of the cost.

Measurement and reversal of prophylactic and therapeutic peak levels of rivaroxaban: an in vitro study.

BACKGROUND: Rivaroxaban (Xarelto, Bayer HealthCare, Leverkusen, Germany) is a new oral anticoagulant drug. Anticoagulants may cause bleeding, thereby requiring reliable monitoring and efficient therapy. We investigated thromboelastometry versus routine coagulation tests to measure prophylactic and therapeutic concentrations of rivaroxaban and their reversal with prothrombin complex concentrate (PCC) and activated recombinant factor VII (rFVIIa) in vitro. METHODS: Rivaroxaban was solubilized, and PCC and rFVIIa were added in 2 concentrations to the rivaroxaban-spiked blood samples, and thromboelastometry and measurements were performed. RESULTS: Rivaroxaban increased tissue factor-activated clotting time (CT(ExTEM)) dose dependently. Activated partial prothrombin time (aPTT), prothrombin time ratio (PTR), and prothrombin time (PT) were changed significantly in both concentrations. Reversal with PCC in both dosages caused no significant change in the measured parameters. For prophylactic rivaroxaban dosage, rFVIIa changed the PT significantly but not CT(ExTEM), aPTT, and PTR. For therapeutic rivaroxaban dosage, the CT(ExTEM) was significantly reduced. The other parameters remained unaffected. CONCLUSIONS: Thromboelastometry can detect rivaroxaban effects. In vitro rFVIIa seems highly effective for reversal in contrast to PCC.

Thrombolysis to treat thrombi of the aortic arch.

Thoracic mobile aortic mural thrombus (TAMT) of the aortic arch is a rare condition. We report 3 cases of symptomatic TAMT treated with systemic alteplase (tissue plasminogen activator [t-PA]) thrombolysis. The first patient was symptomatic with repetitive thromboembolism to the left brachial artery. She was treated with repetitive thrombolysis after surgical embolectomy of the brachial artery. The second patient was symptomatic with splenic infarction and mesenteric ischemia. She was treated with a single cycle of systemic thrombolysis followed by ileocoecal resection. The third patient presented with a TAMT obstructing the left common carotid artery, causing ischemic stroke. After systemic thrombolysis, a reduction in thrombus size was documented; however, the patient died later, of acute heart failure, during the clinical course. On follow-up 6 months after the incidences, the 2 surviving patients were in good condition and free of thromboembolic events. We show that systemic thrombolytic therapy can be performed successfully in patients with TAMT.

Sustained enhancement of residual platelet reactivity after coronary stenting in patients with myocardial infarction compared to elective patients.

INTRODUCTION: Elevated platelet reactivity despite antiplatelet therapy is associated with an increased cardiovascular risk after percutaneous coronary interventions. Current guidelines recommend uniform antiplatelet maintenance regimen after percutaneous coronary interventions for patients with myocardial infarction and elective patients. We sought to demonstrate that there is a persistent enhancement of residual platelet reactivity after myocardial infarction, requiring an intensified antiplatelet maintenance therapy. MATERIALS AND METHODS: A total of 66 patients after coronary stenting for myocardial infarction (n=36) or elective coronary stenting (n=30) were included in this prospective, controlled study. Platelet reactivity to adenosine-5-diphosphate and arachidonic acid under treatment with clopidogrel (75 mg) and acetyl salicylic acid (100mg) were assessed 48 hours and 30 days after coronary stenting using light transmission aggregometry and multiple electrode platelet aggregometry (Multiplate analyzer) simultaneously. RESULTS: Fourty-eight hours after coronary stenting all measures of residual platelet reactivity were significantly elevated in the infarction group. After a mean follow up of 37 days, residual platelet reactivity to adenosine-5-diphosphate was still consistently elevated, albeit statistically not significant. Contrarily, residual platelet reactivity to arachidonic acid significantly decreased and returned to normal by the time of follow up. Regression analyses revealed myocardial infarction, C-reactive protein and fibrinogen as predictors of enhanced platelet reactivity 48 hours after coronary stenting. CONCLUSIONS: Patients undergoing coronary stenting for acute myocardial infarction exhibit an enhancement of residual platelet reactivity sustaining for at least 48 hours following coronary stenting. This finding provides a rationale for a continued intensified antiplatelet therapy after myocardial infarction.