Prothrombin complex concentrate (Octaplex) in patients requiring immediate reversal of oral anticoagulation.

INTRODUCTION: Rapid reversal of anticoagulant effect from the use of vitamin K antagonists (VKA) is essential when acute bleeding or emergency surgery occurs. Prothrombin complex concentrates (PCCs) produce a more rapid effect with a better clinical outcome, and do not cause volume overload as compared with fresh-frozen plasma (FFP). Octaplex is a modern, double virus safeguarded PCC with balanced content of vitamin K-dependent coagulation factors, which ensures fast onset of action and efficacious treatment, i.e. rapid correction of international normalized ratio (INR). MATERIALS AND METHODS: The main purpose of this study was to demonstrate that Octaplex, when individually dosed, efficiently corrects INR to pre-determined levels in patients under oral anticoagulation who have bleeding complications or are undergoing invasive procedures. To measure the efficacy response, the INR achieved after PCC application per patient was calculated as geometric mean of three measurements within 1 h post-infusion. RESULTS: Sixty patients received a median total Octaplex dose of 41.1 (15.3-83.3) IU/kg body weight (bw). Of 56 patients evaluable in terms of efficacy, 51 (91%) showed a response as pre-defined in the protocol and in 52 (93%) the INR decreased to a value below 1.4 within one hour after dosing. The median INR declined from 2.8 (1.5-9.5) to 1.1 (1.0-1.9) within 10 min. All prothrombin complex coagulation factors recovered in parallel. Three patients had minor adverse drug reactions. One patient showed a non-symptomatic parvovirus B19 seroconversion. No thrombotic side effects were observed. CONCLUSIONS: Octaplex is efficacious and safe in immediate correction of dosage-dependent INR in patients with VKA-related deficiency of prothrombin complex coagulation factors.

Salvage chemotherapy for refractory or relapsed post-transplant lymphoproliferative disorder in patients after solid organ transplantation with a combination of carboplatin and etoposide.

This pilot study assessed the feasibility and efficacy of salvage chemotherapy (carboplatin and etoposide; CE) supported by granulocyte colony-stimulating factor (GCSF) in patients with refractory or relapsed post-transplant lymphoproliferative disorder (PTLD) following solid organ transplantation. Intensified salvage regimens were not feasible for these patients, due to their immunosuppressive conditions and potential organ (especially kidney and bone marrow) malfunctions. Salvage chemotherapy consisted of carboplatin [area under the curve (AUC) 4], on day 1, etoposide (120 mg/m2), on days 1-3 and GCSF (5 microg/kg) starting on day 5. This therapeutic regimen was planned to be repeated every 21 d. Nine patients (seven with refractory, two with relapsed disease) were enrolled. Five patients were heart transplant recipients, three liver transplant recipients and one patient had been a double lung transplant recipient. Five patients achieved a complete remission (CR), with follow-up at 92, 39, 55+, 17 and 9+ months. One patient showed stable disease after two cycles of CE and one patient had progressive disease. Two patients experienced early deaths, after the first and third cycles of chemotherapy respectively. One died of septic complications and one because of a perforated intestine, which had been infiltrated by lymphoma. In respect of the difficulties experienced in treating patients with refractory or relapsed PTLD after solid organ transplantation, the combination of carboplatin and etopoide with GCSF support (filgrastim) proved to be an effective regimen.

Identification of early antigen BZLF1/ZEBRA protein of Epstein-Barr virus can predict the effectiveness of antiviral treatment in patients with post-transplant lymphoproliferative disease.

Epstein-Barr virus (EBV)-associated B-cell lymphoproliferations may arise in solid organ transplant recipients. In these patients, an insufficient control of EBV-infected B cells commonly occurs. Antiviral treatment against EBV may represent a causal, relatively low-toxic treatment option. Treatment with foscarnet, an inhibitor of viral-DNA polymerase, in three patients with EBV-associated post-transplant lymphoproliferative disease (PTLD) after heart (n = 2) and heart/kidney transplantation (n = 1), who did not respond to, or were not eligible for reduction of immunosuppression, resulted in complete remission (48+, 27 and 15 months respectively). Response of PTLD to antiviral treatment correlated with the expression of lytic phase antigen BZLF1/ZEBRA protein, an early antigen of lytic EBV-activity, in the biopsied PTLD specimens.