J. J. Michiels

Among inflammation and coagulation markers, PAI-1 is a true component of the metabolic syndrome

Objective:To investigate whether leukocyte count, fibrinogen, von Willebrand factor (vWF) and plasminogen activator inhibitor-1 activity (PAI-1) are increased in subjects with the metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) and the World Health Organisation (WHO).Design:Cross-sectional study.Subjects:A total of 520 overweight and obese subjects: 379 women and 141 men, visiting the weight management clinic of a University Hospital.Subjects and measurements:Waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose were determined, and the presence or absence of the metabolic syndrome according to the NCEP-ATPIII criteria was assessed. In 349 subjects, data on the waist-to-hip ratio (WHR) and albumin excretion rate were available and the WHO criteria were applied. Insulin resistance was defined using the HOMA-IR index.Results:Subjects with the metabolic syndrome according to the NCEP-ATPIII criteria had significantly higher levels of leukocyte count (P<0.001) and PAI-1 (P<0.001), while no significant differences were found for fibrinogen or vWF (P>0.05). Using the WHO criteria, similar results were found except for vWF, where higher levels were found in subjects with the metabolic syndrome. When subjects were classified according to the number of components of the metabolic syndrome, levels of leukocyte count, vWF and PAI-1 activity were significantly different (P<0.05). In logistic regression analysis PAI-1, gender and leukocyte count were independent determinants of the metabolic syndrome (P<0.001).Conclusion:Evidence for being a true component of the metabolic syndrome is strong for PAI-1, less for leukocyte count and weak for vWF and fibrinogen.

Distal deep venous thrombosis in a hemophilia A patient with inhibitor and severe infectious disease, 18 days after recombinant activated factor VII transfusion.

We describe a 38 year old hemophilia A patient with a factor VIII inhibitor who was admitted to our Hematology Department in January 2001 with a seriously infected and bleeding perianal ulcer. To treat infection and bleeding the patient received broad spectrum antibiotics and recombinant activated factor VII (rFVIIa) (Novoseven(R)) for about 1 month (see detailed time of administration and dosing schedule of rFVIIa further in text). Eighteen days after his last rVIIa infusion the patient developed an ultrasound proven right calf vein thrombosis. In the whole period of admission, preceding the thrombotic event the patient biologically showed a picture of severe systemic inflammatory disease as indicated by persistent increased levels of D-dimer and fibrinogen (table). It is an interesting point of discussion whether the calf thrombosis was provoked as a consequence of rFVIIa infusion (with symptoms 18 days after the last infusion) or as a consequence of long-standing immobilization and severe inflammatory disease immobilization and severe infection are conditions well known for promoting venous thromboembolic disease.

Comparison of antiplatelet effect of loading dose of clopidogrel versus abciximab during coronary intervention.

Randomized clinical trials have evidently shown that the addition of thienopyridines or abciximab to standard aspirin results in a significant reduction of ischaemic complications after coronary stent implantation. A head-to-head comparison of these antithrombotic drug regimens during coronary intervention is, however, lacking, and this was the main aim of the present study. Thirty-nine patients with angina pectoris who were scheduled for coronary stent implantation were assigned to either group 1 (160 mg aspirin + 500 mg ticlopidine post-stent), group 2 (160 mg aspirin + abciximab + 500 mg ticlopidine post-stent) or group 3 (160 mg aspirin + loading dose (375/450 mg) clopidogrel pre-stent and 75 mg clopidogrel post-stent). A loading dose of 450 mg clopidogrel was found to be more effective than the standard loading dose of 375 mg. Platelet aggregation induced by 4 μmol/l adenosine diphosphate (ADP) was assessed in samples collected before intervention and 10 min, 4 h and 20 h after intervention. Before intervention, a moderate antiplatelet effect because of aspirin intake was observed (ADP aggregation level, ± 50%) in all study groups. After intervention, platelet aggregation tended to be enhanced in group 1 while it was strongly inhibited in the groups pre-treated with clopidogrel or abciximab: ADP induced an aggregation level early after intervention of 60 ± 12% in group 1 (ticlopidine post-stenting) versus 30 ± 10% in group 3 (loading dose clopidogrel) versus 3 ± 6% in group 2 (abciximab). Abciximab achieved a more complete inhibition of aggregation than clopidogrel (P = 0.007). The overall complication rate was low with only one major bleeding and one death due to side-branch occlusion with re-infarction occurring, both in the abciximab group. Platelet aggregation during coronary intervention is strongly inhibited by both abciximab and by high loading dose of clopidogrel. Although abciximab showed a stronger antiplatelet effect than clopidogrel, it remains to be established whether this ex vivo superiority of abciximab also translates into an overall clinical benefit in patients with elective stent implantation.

Diagnosis of deep vein thrombosis: How many tests do we need?

Abstract The requirement for a safe diagnostic strategy should be based on an overall post-test incidence of venous thromboembolism (VTE) of less than 1% during 3 month follow-up. Compression ultrasonography (CUS) has a negative predictive value (NPV) of 97 to 98% indicating a post-CUS incidence of deep vein thrombosis (DVT) of 2 to 3%. A post-CUS DVT incidence of 3% implicates that 90 to 120 DVTs per 1 million inhabitants will be overlooked each year indicating the need to improve the diagnostic work-up of DVT as much as possible. The qualitative D-dimer test (SimpliRed) has a sensitivity of 82 to 89% and a negative predictive value of 94 to 95% indicating a 5 to 6% post-test incidence of DVT, which is not sensitive enough for venous thrombosis exclusion. The post-test DVT incidence could be reduced from 3.2% to 0.6% in one study and from 11% to 2% in another study by the combination of a normal CUS and low clinical score and from 4,5% to 1.6% by the combination of low clinical score and a negative SimpliRed test in one study. The combination of a negative CUS and a negative SimpliRed test reduced the post-test incidence of DVT from 2.6% to < 1% or even < 1%o in two management studies without the need of a repeated CUS on the basis of which anticoagulant therapy can safely be withheld. The rapid quantitative turbidimetric D-dimer assay (Tinaquant) has a sensitivity and a negative predictive value (NPV) of 97.7% with a 2.3% post-test incidence of DVT. The combination of a normal Tinaquant D-Dimer test result plus a low to moderate clinical score reduces the post-test incidence of DVT from 2.3 to 0,6% without the need of CUS testing in 29% of patients with suspected DVT. The rapid ELISA VIDAS D-dimer assay has a sensitivity and NPV of 98,6 and 99.5% in two management studies for the exclusion of DVT irrespective of clinical score. The combination of a normal ELISA VIDAS D-Dimer test with clinical score assessment will reduce the post-test DVT incidence of less than 0.5% and the need for CUS testing by 40 to 50%. It is concluded that the sequential use of a rapid quantitative D-dimer test, clinical score and CUS appears to be safe and the most cost-effective diagnostic work-up of DVT.