defibrotide and Purpura--Thrombotic-Thrombocytopenic

Thrombotic thrombocytopenic purpura (TTP) has emerged as one of the main transplant-related complications over the last 15 years. The current study defines the incidence and the risk factors for the occurrence of TTP in 131 consecutive leukemic children who were transplanted between January 1994 and December 1997 at four Italian pediatric centers. Patients with ALL (101), AML (21), MDS (9), underwent an HLA-identical sibling BMT (82) or an HLA-identical unrelated BMT (49), receiving a conditioning regimen consisting of high-dose chemotherapy in 24 patients and of F-TBI combined with high-dose chemotherapy in 107 patients. The diagnosis of TTP was retrospectively evaluated on the basis of parallel criteria. TTP treatment varied according to the protocol of each treatment center. Twenty-eight of 131 patients (21.4%) developed TTP at a median of 46 days (range 21-80) after BMT. Multivariate analysis demonstrated that the risk of TTP was higher in patients who underwent unrelated BMT (P value = 0.02). Acute GVHD, stage of disease at BMT, conditioning with TBI, gender, age, did not appear to be associated with the occurrence of TTP. As to the outcome, TTP resolved in 19 patients while in nine it was the principal cause of death (32.1%). In patients with TTP, LDH peak value was the only statistically significant factor (P = 0.001) related to severe TTP. In conclusion, our experience demonstrates that leukemic children undergoing BMT, especially from an unrelated donor, should be carefully assessed for TTP which appears to be a severe and relatively common transplant-related complication when strict diagnostic criteria are applied.

Topics: Acute Disease; Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Female; Fibrinolytic Agents; Graft vs Host Disease; Humans; Immunosuppressive Agents; Incidence; Infant; L-Lactate Dehydrogenase; Leukemia; Male; Plasma; Plasmapheresis; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Prognosis; Purpura, Thrombotic Thrombocytopenic; Remission Induction; Retrospective Studies; Risk Factors; Transplantation Conditioning; Treatment Outcome

Topics: Adolescent; Adult; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Platelet Aggregation Inhibitors; Polydeoxyribonucleotides; Purpura, Thrombotic Thrombocytopenic; Retrospective Studies

Thrombotic thrombocytopenic purpura (TTP) is a common illness characterized by platelet thrombi within the microvascularization. In its natural course, this disease has had a mortality rate of 90%. Plasma infusion or exchange achieved a survival rate of 70% to 90%. However, 10% to 30% of patients surviving the initial TTP episode relapse at regular intervals. The treatment of recurrent forms of the disease remains a challenge; several approaches have been shown to induce medium to long term remissions. We describe a patient with recurrent TTP whose disease remitted after administration of defibrotide.

Topics: Adult; Humans; Injections, Intravenous; Male; Plasma Exchange; Platelet Aggregation Inhibitors; Platelet Count; Polydeoxyribonucleotides; Purpura, Thrombotic Thrombocytopenic; Recurrence

Topics: Adult; Erythrocyte Count; Female; Fibrinolytic Agents; Hemoglobins; Humans; Infusions, Intravenous; Methylprednisolone; Platelet Count; Polydeoxyribonucleotides; Purpura, Thrombotic Thrombocytopenic

Thrombotic microangiopathy (TMA) can occur whenever pathogenetic events lead to fibrin deposition in the microcirculation. It has been suggested that intravascular coagulation is important in the development of renal as well as cerebral lesions. The mortality rate in adults varies from 50 to 70%; chronic or progressive renal failure occurs in approximately two thirds of children over 2 years of age. Poor success may be due to therapy being initiated too late or to inappropriate use of antagonistic drugs, or both. In the last 2 years we have treated 8 patients with TMA (5 with thrombotic thrombocytopenic purpura; 3 with hemolytic uremic syndrome) with defibrotide, a new antithrombotic agent extracted from mammalian lungs. At admission all patients had severe renal involvement (serum creatinine 5.3-14.9 mg/dl) and coagulation abnormalities (low platelet count; high levels of circulating fibrin degradation products). There were neurological manifestations in 6 patients. Defibrotide administration was followed in 6 patients by recovery of renal function. In all patients, defibrotide therapy induced the disappearance of neurological manifestations and normalization of coagulation abnormalities. Defibrotide caused no side effects. All patients are alive after 7-22 months of follow-up.

Topics: Acute Kidney Injury; Adult; Blood Coagulation Tests; Child; Child, Preschool; Female; Fibrin Fibrinogen Degradation Products; Fibrinolytic Agents; Hemolytic-Uremic Syndrome; Humans; Male; Middle Aged; Polydeoxyribonucleotides; Purpura, Thrombotic Thrombocytopenic; Thrombosis

Topics: Acute Kidney Injury; Adult; Child; Fibrinolytic Agents; Hemolytic-Uremic Syndrome; Humans; Polydeoxyribonucleotides; Purpura, Thrombotic Thrombocytopenic