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.

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.

We describe a type-III von Willebrand patient who was admitted to the hospital with severe deformity and functional deficit of the left knee joint due to recurrent hemarthrosis. Orthopedic intervention was necessary. To prevent bleeding episodes, von Willebrand factor (vWF) replacement therapy was given during and after surgery. APTT, plasma FVIII activity (FVIIIc), vWF antigen (vWF Ag), and vWF ristocetin cofactor (vWF Rco) were measured. Primary hemostasis was monitored using the PFA-100. This "Platelet Function Analyzer" is designed to measure platelet adhesion and aggregation capacities. Whole blood is aspirated through a capillary and is forced to flow through the central hole of a membrane coated with collagen and epinephrine (COL/EPI) or ADP (COL/ADP) as platelet activators. Irreversible platelet aggregation results in the formation of a stable platelet plug, closing the central hole. The result is expressed as "closure time" (CT), i.e., time necessary to stop the blood flow, and is a measure of platelet hemostasis capacity. Laboratory investigations during substitution therapy revealed no shortening of closure times with both COL/EPI and COL/ADP cartridges despite normalization of plasma vWF Ag, vWF Rco, and FVIIIc levels. These observations suggest that intraplatelet vWF, which is totally absent in type-III von Willebrand disease, plays an important function in the adhesion of platelets to the collagen-coated membrane of the PFA-100 system, simulating an injured vessel wall. Consequently, we conclude that the PFA-100 may not be suitable for monitoring the therapeutic efficacy of von Willebrand concentrate in type-III von Willebrand patients during substitution therapy.

In the studied patients scheduled for elective coronary stenting and pre-treated with aspirin and a loading dose of clopidogrel, further inhibition of platelet aggregation by abciximab does not afford additional cardioprotection. Our data suggest that distal athero-embolization rather than thrombo-embolization is involved in the phenomenon of myonecrosis post-elective stenting.

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