A major adverse effect of recombinant human erythropoietin (r-HuEPO) in hemodialyzed patients are thrombotic events. Several reports on platelet function during r-HuEPO treatment have been published but less is known about fibrinolysis. In the present study, the fibrinolytic capacity was studied in 20 patients on maintenance hemodialysis and treated with r-HuEPO. The patients were randomized into two groups and investigated in a crossover design. r-HuEPO was administred intravenously and subcutaneously in each group and was given for 3 months, respectively. Plasma tissue plasminogen activator (t-PA) and released t-PA remained unaffected by r-HuEPO in both groups throughout the study. Tissue plasminogen activator inhibitor (PAI) increased in a cyclic way reaching peak values 4-6 weeks after the start of investigation and again 4-6 weeks after changing therapy. The increase in PAI was significant in the two groups (0.025 > p > 0.01). Tissue plasminogen antigen was low in the uremic patients. The influence of r-HuEPO on this parameter was not investigated. Compensatory changes in plasma levels of factor XII procoagulant activity, activated protein C and of α₂-antiplasmin were not observed. Thrombotic events occurred in 4 patients at peak values of PAI. Six patients required an increase in heparin dose simultaneously with the increase in PAI. Thus, r-HuEPO seemed to affect the fibrinolytic capacity of uremic patients.

Three cases of salmonella bacteremia in renal transplant recipients are reported. Two patients had prolonged salmonella infections with recurring bacteremia. The longest interval between bacteremic relapses was 15 years. 27 cases from the literature of salmonella bacteremia in renal transplant recipients are reviewed. The courses of salmonellosis in renal transplant recipients are more serious than in other non-compromised patients, being complicated by bacteremia in 70% of the cases. Renal transplant recipients have prolonged carrier states and frequent relapses or recurrences of salmonellosis. 45% of the salmonella bacteremias in renal transplant recipients are seen after a high dose methylprednisolone treatment for graft rejection episodes.

In a 51-year-old man, coronary artery bypass surgery for severe angina pectoris was followed by protracted mediastinal infection. After recovery the patient had several haemoptyses. Angiography revealed aneurysm of a graft near its distal anastomosis. Upper left lobectomy and ligation of the graft were necessitated by bleeding from the aneurysm into a segmental bronchus. Angina pectoris recurred but was successfully treated with verapamil.

Reports on the effect of recombinant human erythropoietin (r-HUEPO) on the platelet activity are conflicting. In the present study platelet function and coagulation factors were investigated in 20 patients with end-stage renal failure on maintenance hemodialysis. The patients were randomized into two groups and, in a crossover design, investigated during intravenous and subcutaneous administration of rHUEPO. The two groups started with a different administration form (intravenously in group 1 and subcutaneously in group 2), and each mode of treatment was given for 3 months. At entrance into the study the platelets were hyperaggregable to exogenous stimulation with collagen (COL) in both groups. Group 1 developed increasing platelet sensitivity to adenosine diphosphate (ADP; 0.01 < p < 0.025) during intravenous treatment. Concomitantly, three episodes of arteriovenous fistula thrombosis occurred. In group 2 one event of fistula thrombosis occurred despite there being no change in platelet reactivity to ADP. After 3 months on r-HUEPO, the platelet reactivity to ADP decreased significantly in both groups, but also the reactivity to COL declined significantly: 0.01 < p < 0.025 (group 1) versus 0.001 < p < 0.005 (group 2). The platelet reactivity to ristocetin remained unchanged in group 1 but decreased significantly in group 2. In group 1 fibrinogen was increased significantly (0.001 < p < 0.005) at the time of the clotting events. The factor VIIL·coagulant activity increased, but antithrombin III, activated factors X and XIII, activated protein C, activated thromboplastin time, and partial prothrombin time remained unchanged. Furthermore, 4 patients in group 1 and 2 patients in group 2 required an increased dose of heparin after 2-3 months of investigation. Thus, r-HUEPO seemed to influence platelet function. Enhanced activity was observed during intravenous administration. Eventually, platelet reactivity to ex vivo stimulation decreased in both groups. Thus, intravascular hemostatic activation seemed to occur following r-HUEPO administration. An increase in hematocrit is probably of importance, but according to the present data, transient platelet activation may also be a contributory factor.

A comparative crossover study of intravenously (i.v.) and subcutaneously (s.c.) administered recombinant human erythropoietin (r-HuEPO) was conducted in 20 patients with end-stage renal disease on maintenance hemodialysis. The patients were randomized into two groups. Group 1 received r-HuEPO i.v. thrice weekly and group II r-HuEPO s.c. twice weekly for 12 weeks, then the therapy was crossed over for another 12-week period. The initial dose was 50 U/kg/i.v. dose and 40 U/kg/s.c. dose. In all but 1 patient an adequate hematologic response was obtained. In group 1 the mean hemoglobin (Hb) level increased from 4.8 (Hbo) to 6.0 after 12 weeks (HbΠ) and further to 6.5 mmol/l after 24 weeks (Hb24) throughout the study (0.025 < p < 0.05). In group II it increased from 4.6 (Hb₀) to 7.1 (Hbι₂) to 6.9 mmol/l (Hb₂₄) (0.01 < p < 0.025). There was a significant difference between the two groups (p < 0.05). The rise in Hb in group II during the first 12 weeks of the study was achieved by only half the cumulative dose of r-HuEPO (11,820 U) per kilogram compared to the consumption in group I (24,575 U). In the last 12 weeks of the study the requirement of r-HuEPO to maintain Hb level was equal in the two groups. In group I serum erythropoietin (EPO) level increased slowly throughout the study. In group II an increment was followed by a decrease beyond prestudy level. This happened at an erythropoietic response with mean hematocrit (Hct) about 35%. In group I a mean Hct > 35% was never reached. This might indicate the existence of an EPO-Hct feedback mechanism. In conclusion, s.c. administration is significantly more effective than i.v. administration as induction therapy, requiring only half the dose of r-HuEPO. Also it can be administered twice weekly, and a start dose of 40 U/kg/dose is suggested aiming at a Hct not exceeding 35%.