A Randomized Trial of Daily Prednisone versus Pulsed Dexamethasone in Treatment-Naïve Adult Patients with Immune Thrombocytopenia: EIS 2002 Study.

Oral prednisone is considered the standard first-line therapy of adult immune thrombocytopenia, but its long-term efficacy is limited. We performed a prospective, randomized, multicenter trial comparing daily prednisone (1-2 mg/kg/day for 2-4 weeks with subsequent dose reduction) with six 3-week cycles of pulsed dexamethasone (0.6 mg/kg/day, days 1-4). The primary endpoint was remission duration. Of 26 patients enrolled, 22 were evaluable for response. Nine were treated with prednisone and 13 with dexamethasone. The median follow-up was 46 months. The initial response rate (PLT ≥50 × 109/l) was 100% in both groups. Long-term remissions were significantly more frequent with pulsed dexamethasone than with daily prednisone (12 months posttreatment: 77 vs. 22%; p = 0.027). The side effects were similar, but patients on dexamethasone suffered significantly more often from insomnia, while patients on prednisone tended to have more infectious complications. Although the cumulative cortisol equivalent dose was comparable during the first 4 weeks of therapy, it was significantly higher in the dexamethasone arm than in the prednisone arm during the ensuing treatment period. We conclude that repeated cycles of pulsed dexamethasone are a good alternative to daily prednisone as a first-line treatment of immune thrombocytopenia. The duration and intensity of glucocorticoid therapy are important determinants of treatment outcome.

Diagnosis and management of chronic ITP: comments from an ICIS expert group.

Immune thrombocytopenia (ITP) is a common disorder in children and adults. In a patient with newly diagnosed ITP, the treatment strategy is relatively well defined. Second-line treatments are more controversial, and the management of chronic ITP is even more so. During the 3rd ICIS Expert Meeting on Consensus and Development of Strategies in ITP, held in Basel on September 3-5, 2009, a group of experts were tasked with reaching a consensus on some frequently asked questions relating to diagnosis and management of children and adults with chronic ITP. The content of this article is designed to provide a practical support to trained haematologists in their care of patients with chronic ITP.

Thrombophilia in cardiac surgery-patients with symptomatic factor V Leiden.

BACKGROUND AND AIM OF THE STUDY: Thrombophilia may cause severe complications in cardiac surgical patients. We analyzed our experience with symptomatic factor V Leiden patients. METHODS: Over an eight-year period, 14 symptomatic patients previously diagnosed with activated protein C resistance,caused by factor V Leiden, underwent a cardiac surgical procedure. We retrospectively reviewed the clinical data, operative and postoperative courses, and the intermediate-term results of these patients. RESULTS: Procedures performed were coronary artery bypass grafting (CABG, 10 patients), aortic valve replacement+ CABG, pulmonary thromboendarterectomy, left ventricular thrombus removal, and aortic valve reconstruction(one patient each). Eleven patients survived; three patients died perioperatively, one from sepsis (25 days after surgery), one from recurrent stroke (28 days after surgery), and one from multiorgan failure following perioperative stroke (31 days after surgery). In one patient, all bypass grafts occluded intraoperatively.Three patients underwent cardiac surgery under continuous anticoagulation with phenprocoumon. In these three patients, no perioperative thromboembolic events occurred. At a mean follow-up of 32 months,three patients had suffered from cerebral stroke, two from graft occlusion, of which one was recurrent. Two more patients had died (one after cerebral stroke and one from cerebral metastases of a renal cell carcinoma). CONCLUSION: In 14 patients with symptomatic factor V Leiden who underwent cardiac surgery, we observed a considerable number of fatal and nonfatal thromboembolic events in the perioperative period and during a 32 months' follow-up. As conducted in three patients, continued anticoagulation with coumarin was safe and prevented perioperative thromboembolic events.

Methods to evaluate the pharmacology of oral antiplatelet drugs.

Principally, there are two reasons why the pharmacological response to antiplatelet drugs should be measured: on the one hand, an insufficient inhibition of platelet function may result in atherothrombotic complications; on the other hand, an excessive inhibition of platelet function may lead to bleeding complications. The clinical importance to measure the effects of antiplatelet drugs is demonstrated by increasingly growing evidence for an association of resistance to antiplatelet drugs with thromboembolic events. It is often claimed that there is no generally accepted definition of "resistance" and, instead, there is an ongoing semantic discussion about the correct term to be used to describe this phenomenon. From the pharmacological point of view, there is only one acceptable definition of "resistance" to antiplatelet drugs: the term "resistance" should be used when a drug is unable to hit its pharmacological target. Thus, laboratory methods used to evaluate the effects of antiplatelet drugs should be designed to measure the direct pharmacodynamic effect of a drug, rather than the consequences for global platelet function. Based on physiological/pathophysiological, pharmacological, and practical considerations, the authors propose the following assays to be used to measure the effects of oral antiplatelet drugs: for the detection of aspirin actions, thromboxane or arachidonic acid-induced responses (light aggregometry, whole-blood aggregometry) should be measured; for the detection of clopidogrel actions, VASP (vasodilator-stimulated phosphoprotein) phosphorylation (flow cytometry) or ADP-(adenosine diphosphate-)induced responses (light aggregometry, whole-blood aggregometry, possibly also flow cytometry) should be measured.

Thrombophilia in cardiac surgery--patients with protein S deficiency.

BACKGROUND: Thrombophilic diathesis may cause severe problems in cardiac surgical patients. Among these, protein S deficiency is a coagulation disorder associated with recurrent thromboembolic events. We analyzed our experience with 7 patients with protein S deficiency who underwent cardiac surgery. METHODS: We retrospectively reviewed the clinical data, operative and postoperative courses, and the long-term results of 7 patients who were diagnosed to have protein S deficiency. Six of them were operated on using cardiopulmonary bypass, one was operated on with an off-pump procedure. RESULTS: Procedures performed were emergent pulmonary embolectomy (patient 1), aortic valve replacement and coronary artery bypass grafting (CABG, patient 2), re-CABG (patients 3 and 7), and CABG (patients 4, 5, and 6). In patients 1, 2, 3, and 7, the diagnosis was made perioperatively. Patients 4, 5, and 6 were treated with a modified regimen of warfarin or protamine. All of the latter 3 patients had an uneventful perioperative course without thromboembolic complication. At follow-up, all but 1 of the 7 patients were on continuous warfarin, and were well and without any further thromboembolic events. CONCLUSIONS: In patients with a past medical history of thromboembolic events or with a perioperative thromboembolic complication, elaborate laboratory investigation should lead to a definite diagnosis. For instance, patients with protein S deficiency undergoing cardiac surgery belong to a high-risk subgroup. Although rare, this and other coagulation disorders can be a critical issue in cardiac surgery. In such patients, we suggest perioperative warfarin therapy with a target international normalized ratio of 2.0 and incomplete protamine antagonism to minimize the risk of a perioperative thromboembolic event.

Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma, results of a phase II single center study.

The optimum therapy for patients with relapsed or refractory aggressive non-Hodgkin's lymphomas (NHL) not qualifying for platinum-based and/or high-dose chemotherapy is not known. We conducted a prospective phase II study evaluating a regimen consisting of gemcitabine (1 g/m2, days 1 and 8), vinorelbine (30 mg/m2, days 1 and 8) and prednisone (100 mg/day, days 1-8) (GVP) given every 21 days. Fifteen patients with a median age of 68 years and a median of three previous therapies were enrolled. Diagnoses included B lymphoblastic (n=1), diffuse large B cell (n=10), anaplastic large T cell (n=2) and peripheral T-cell NHL (n=2). The median international prognostic index score was 3 (six patients with a score of 4 or 5). Five patients achieved a complete remission and three patients a partial remission. The median overall survival was 13.8 months, and the median time to next treatment was 4.4 months. Haematological toxicities of World Health Organisation grades 3/4 were leucopenia in 58%, thrombocytopenia in 33% and anaemia in 17% of all courses. Three patients had grade 3 infections. There was no treatment-related mortality. GVP shows substantial activity in poor prognosis relapsed or refractory aggressive lymphomas and is generally well tolerated, but haematological toxicity is dose limiting.