Patients with previous ST show an impaired response to antiplatelet therapy with ASA compared with controls and volunteers. Additional treatment with clopidogrel is not able to overcome these differences in PA. Acetylsalicylic acid but not clopidogrel resistance appears to be associated with ST.

Intravascular catheters are prone to staphylococcal infections. To study the role in staphylococcal adherence played by fibrinogen or fibrin and fibronectin deposited on inserted catheters, 187 peripheral or central cannulae were prospectively removed from hospitalized patients. Compared with uninserted catheters, which allowed only minimal adherence, previously inserted catheters promoted significant adherence of staphylococcal isolates from patients with intravenous device infections. Adhesion-promoting properties were studied with laboratory strains having well-defined affinities for either fibronectin or fibrinogen:· adherence of Staphylococcus aureus Cowan I, which has the highest affinity for both adhesins, was more strongly promoted (10-to 50-fold) on inserted cannulae than was that of S. aureus Wood 46 (4-to lO-fold) or Staphylococcus epidermidis Rp 12 (2.2-fold), which has no affinity for fibrinogen but does for fibronectin. Although all types of cannulae contained significant amounts of fibrin, which may promote adherence of coagulase-positive staphylococci, results obtained with coagulase-negative isolates suggested that in vivo-deposited fibronectin is also a critical determinant in this process.Infectious complications associated with the use of intravascular (iv) catheters have been reported to occur in 1070-40070 of cases [1][2][3]; these devices are important causes of nosocomial sepsis (1,(3)(4)(5) and candidemia [3,5]. A major contributing factor in iv device-related infection is the transcutaneous cannula wound allowing microorganisms from the patient's skin flora to migrate across the skin barrier. The microbial colonization of the transcutaneous part of the catheter has been identified as a sensitive index of catheter-associated bacteremia [6]. The establishment of a fibrin sheath [1] surrounding the blood-exposed cannula may favor bacterial attachment and promote bacterial replication around the intravascular part of the catheter. The thrombogenicity of plastic materials plays a role in their associ- ation with device-related infections [7]; the risks of phlebitis increase with duration of insertion and severity of underlying diseases [8]. Finally, impaired host mechanisms secondary to the presence of foreign implants might playa role in catheter-associated infections as for other implants [9].Intravenous catheters are most often colonized by staphylococci [6,[10][11][12]. Staphylococcus aureus was initially considered the predominant species in cannula-related septicemia, and Staphylococcus epidermidis has recently been identified as a major pathogen of these infections [13,14]. A number of studies [15][16][17][18][19][20][21][22][23][24] have shown that most coagulasenegative strains of staphylococci infecting intravascular lines produce an extracellular fibrous matrix, designated either as slime [15][16][17][19][20][21][22] or glycocalix [18,23,24]. This material is assumed to help coagulase-negative staphylococci colonize the indwelling devices [15][16][17][18][19][20][21][22][23][24][2...

Clopidogrel alone or in combination with aspirin markedly inhibited adenosine diphosphate (ADP)-mediated platelet aggregation compared with monotherapy with aspirin (24.6 +/- 3.3% or 26.6 +/- 2.7% vs. 44.7 +/- 2.9%; p < 0.001). Combined treatment significantly inhibited collagen-induced aggregation compared with aspirin and clopidogrel (16.4 +/- 2.4%, 36.5 +/- 4.2% and 59.3 +/- 5.1%, respectively;, p < 0.001) and resulted in considerable inhibition of aggregation induced by thrombin receptor agonist peptide (TRAP, p < 0.03). Clopidogrel with or without aspirin significantly suppressed expression of platelet activation markers CD 62p, CD 63 and PAC-1 after stimulation with ADP or thrombin (p < 0.001). In addition, the combined treatment was more effective than either agent alone after activation with low dose thrombin (p < 0.05). Both doses of aspirin equally potentiated the platelet inhibitory effects of clopidogrel. CONCLUSIONS In this prospective clinical ex vivo platelet study, clopidogrel was more effective than aspirin in inhibiting ADP-mediated platelet aggregation and activation. Clopidogrel in combination with aspirin showed synergistic inhibitory effects after stimulation with collagen and thrombin compared with monotherapies. Thus, this dual antiplatelet treatment strategy deserves further evaluation in clinical trials for secondary prevention of acute myocardial infarction or unstable angina.

To explore relevant changes in unexplained intraoperative bleeding, we evaluated elements of the final steps of the coagulation cascade in 226 consecutive patients undergoing elective surgery. Patients were stratified for the occurrence of unexplained intraoperative bleeding according to predefined criteria. Twenty patients (8.8%) developed unexplained bleeding. The median intraoperative blood loss was 1350 mL (bleeders) and 400 mL (nonbleeders) (P < 0.001). Fibrinogen and Factor XIII (F. XIII) were more rapidly consumed in bleeders (P < 0.001). Soluble fibrin formation (fibrin monomer) was increased in bleeders throughout surgery (P < or = 0.014). However, F. XIII availability per unit thrombin generated was significantly decreased in bleeders before, during, and after surgery (P < or = 0.051). Computerized thrombelastography showed a parallel, significant reduction in clot firmness. We suggest that mild preexisting coagulopathy is not rare in surgical patients and probably can result in clinically relevant intraoperative bleeding. This hemostatic disorder shows impaired clot firmness, probably secondary to decreased cross-linking (due to a loss of F. XIII, both in absolute measures and per unit thrombin generated). We suggest that the application of F. XIII might be worthwhile to test in a prospective clinical trial to increase clot firmness in patients at risk for this intraoperative coagulopathy.

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