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 micromol/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.

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.

Platelet prothrombinase activity, a final pathway platelet procoagulant activity, is overexpressed in type 1 diabetes: no relationship with mean platelet volume or background retinopathy.

There is overwhelming evidence that platelets from diabetic individuals are hyperreactive, not only when microvascular complications are apparent, but already at an early stage of the disease. There is still controversy about the question of whether primary hyperreactive platelets may contribute to the origin or progression of microangiopathy or whether diabetic platelet hyperfunctionality is just a logical consequence of a continuous low-grade activation of platelets by contact with a diseased microvascular wall. As a consequence of platelet activation, the outer layer of its phospholipid membrane is more procoagulant than in the quiescent state, stimulating thrombin formation in plasma. This platelet function is called platelet procoagulant activity. We studied platelet prothrombinase activity (PPA), a final pathway platelet procoagulant activity of type 1 diabetic platelets, and looked for an eventual correlation with microvascular disease (background retinopathy) and mean platelet volume (MPV). Stypven clotting times (SCTs), reflecting PPA expression, and MPV of citrated platelet-rich plasma (PRP), were measured in 21 patients with type 1 diabetes-10 with and 11 without background retinopathy-under clinically acceptable metabolic control and compared them to 20 disease-free voluntary controls. We also compared PPA expression and MPV in diabetic individuals with and without retinopathy. With the SCT, a selective test adapted for studying PPA in PRP, we found hyperexpression of PPA in all diabetic patients. We found no difference in MPV between diabetic and control PRP. Comparing patients with and without background retinopathy we found no significant difference in PPA expression. From these results, we suggest that the phospholipid surface of diabetic platelets, more than the surface of normal control platelets, stimulate the expression of PPA. This diabetic platelet coagulant anomaly was not related to an increased platelet mass (higher MPV) nor to the presence of microangiopathy. We conclude that PPA hyperexpression is associated with patients with type 1 diabetes, already occurring in an early stage of the disease, and not necessarily a consequence of early-stage microvascular disease, because the anomaly is also demonstrable, in the same degree, in patients with diabetes without microangiopathy.

The evolution of platelet procoagulant activity of remnant platelets in stored platelet concentrates prepared by the platelet-rich plasma method and the buffy coat method.

Platelets stored as concentrates are gradually activated (storage lesion), a process associated with changes in the expression of platelet procoagulant activity (PPCA). The aim of the present study was to evaluate the evolution of PPCA and the mean platelet volume (MPV) of stored platelets prepared according to the platelet-rich method (PRM) and the buffy coat method (BCM). Using the platelet factor 3 availability clotting test (PF3AT) on appropriately diluted concentrate samples, we found a decrease in PPCA expression of remnant platelets as a function of storage time (0.025 < p < 0.01 between day 1 and 7) in PRM-derived but not in BCM-derived platelet concentrates. Using the PF3AT reduction test we found a more important clotting time reduction in samples obtained from BCM than in samples obtained from PRM platelet concentrates, suggesting a higher PPCA expression of BCM platelets, not significant after 1 day but highly significant after 3 days (p < 0.0005) and after 7 days (p < 0.0005) of storage, as compared with PRM platelets. For both PRM and BCM concentrates there were no significant MPV changes as a function of storage time, but at any storage day the MPV of BCM concentrates was significantly higher (p < 0.0005) than the MPV of PRM concentrates. We conclude that the decrease of PPCA expression in PRM-derived concentrates as a function of storage time is in agreement with the gradual decrease of the platelet activation status in PRM concentrates during storage. There are probably several factors or variables causing platelets of BCM concentrates to express higher PPCA than those of PRM concentrates. Higher PPCA expression in BCM concentrates may be explained by an intrinsic platelet property, such as a difference in MPV between the two kinds of concentrates, or it may be related to an extrinsic factor such as different storage media, e.g., undiluted autologous plasma in PRM concentrates versus Plasmalyte A-diluted autologous plasma in BCM concentrates. Whether the difference in PPCA expression of remnant platelets in PRM and BCM concentrates is just an in vitro laboratory finding or may have consequences for the therapeutic efficiency of the concentrates is an interesting, still unresolved question.

Elevated plasminogen activator inhibitor levels in cyclosporin-treated renal allograft recipients.

Atherosclerosis and thrombosis, two major causes of morbidity and mortality in renal transplant recipients, share the same clinical risk factors including decreased fibrinolysis and lipid disturbances. In a cross-sectional study we have determined parameters of fibrinolysis in control subjects (n = 23) and stable renal allograft recipients without cyclosporin (CsA) (n = 10) and with CsA (n = 87) in their immunosuppressive treatment. In CsA-treated patients, tissue-type plasminogen activator was moderately increased compared to patients without CsA (8.4+/-3.3 vs 5.5+/-2.8 ng/ml). The plasminogen activator inhibitor (PAI) activity in plasma was clearly increased in CsA-treated patients: 14.5+/-8.8 vs 7.2+/-3.2 in normal controls and 8.5+/-2.4 AU/ml in patients without CsA. Total cholesterol and LDL cholesterol levels were higher in CsA-treated patients (256+/-62 and 169+/-60 mg/dl) than in patients without CsA (209+/-45 and 136+/-44 mg/dl). The two groups did not differ in HDL cholesterol, triglycerides, and lipoprotein(a). Hypercholesterolaemia, obesity, and steroid-induced diabetes could be identified as risk factors for elevated plasma PAI activity in CsA-treated patients. Hypofibrinolysis induced by elevated PAI levels and increased LDL cholesterol may contribute to the increased thrombogenicity and accelerated atherosclerosis observed in cyclosporin-treated patients.