Cytokines in childhood hemolytic uremic syndrome and thrombotic thrombocytopenic purpura

Serum and urine cytokines were analyzed in children with hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Interleukin-6 (IL-6) was elevated in the serum of 33 of 35 children with HUS (94%) and in 2 of 2 children with recurrent TTP. Serum IL-6 was higher in children with HUS who developed anuria, extrarenal manifestations during the acute phase of illness and/or chronic renal sequelae. Tumor necrosis factor-alpha (TNF-alpha) was detected in the serum of 7 patients with HUS (20%) and 1 patient with TTP. IL-6 and TNF-alpha were elevated in the urine of 4 of 4 children with HUS and 2 of 2 children with TTP. Urinary levels were higher than serum levels, suggesting local production of cytokines in the urinary tract. Sequential serum and urine samples showed that IL-6 levels varied with disease activity. IL-6 and TNF-alpha were not detected in the serum (n = 25) and urine (n = 15) of healthy children. We conclude that IL-6 in urine may be used to monitor disease activity in HUS and TTP.     

Hepatic veno-occlusive disease in a case of polymyositis associated with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

A 50-year-old woman was treated with prednisolone for polymyositis. During the therapy, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) occurred. Neither plasma infusion nor plasma exchange could relieve the clinical manifestations of TTP/HUS. Moreover, massive ascites appeared and worsened her condition. She died approximately one year after the diagnosis of polymyositis. The autopsy revealed centri-lobular hepatic necrosis and nonthrombotic obliteration of hepatic small veins. The diagnosis of hepatic veno-occlusive disease (VOD) was made. It was suspected that common factors other than cytoreductive therapy had damaged the endothelium and caused TTP/HUS and VOD in a case of polymyositis.     

Treatment of cancer chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome by protein A immunoadsorption of plasma

BACKGROUND: Chemotherapy-associated thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (C-TTP/HUS) is a condition involving thrombocytopenia, microangiopathic hemolytic anemia, and progressive renal dysfunction that develops in 2-10% of patients with a history of malignant neoplasms treated with certain chemotherapeutic agents. Pathogenesis of the disease may depend on the following: (1) generation of endothelial lesions in the kidney microvasculature, resulting from drug toxic effects and/or generation of small soluble circulating immune complexes (CIC), and (2) generation of autoantibodies and/or CIC that trigger aggregation and deposition of platelets around the lesions. METHODS: Extracorporeal immunoadsorption treatment of plasma (PROSORBA columns, IMRE Corporation, Seattle, WA) to remove immunoglobulin G and CIC was evaluated in 55 patients for the potential to induce significant clinical benefits (increase in platelet count, decrease in hemolysis, stabilization of renal function) and longer survival. RESULTS: Response to therapy was achieved in 25 of 55 patients examined. Response was associated with an estimated 1-year survival rate of 61%, as compared with an estimated survival rate of only 22% in those who did not respond (P = 0.0001). Patients whose malignant neoplasms were in complete or partial remission at the time of development of C-TTP/HUS had a significantly higher estimated 1-year survival rate (74%) as compared with a historic control group of patients receiving other treatments (22%, P = 0.0161). Clinical responses were correlated with normalization of serum levels of CIC and complement components C3c and C4. There were no side effects associated with 75% of treatments. Immunoadsorption therapy was associated with generally mild to moderate manageable side effects, such as fever, chills, nausea/vomiting, respiratory symptoms, pain, hypertension, and hypotension, which were reported in 25% of procedures. CONCLUSIONS: This multicenter study establishes protein A immunoadsorption as an effective and safe treatment for cancer chemotherapy-associated TTP/HUS, an otherwise fatal disease.     

Effect of intravenous gammaglobulin infusion on recurrent episodes of thrombotic thrombocytopenic purpura (TTP)

One of the most difficult aspects of leading a discussion and trying to facilitate group problem solving is restraining domineering group members. A group leader who cannot control aggressive, talkative individuals will soon have a group where members are not only angry and frustrated, but also who will make excuses to be excluded or who will leave the group.     

The pathogenesis and treatment of hemolytic uremic syndrome

BACKGROUND: This study evaluated the cost-effectiveness of posttreatment surveillance after radiation therapy for early stage seminoma. METHODS: From 1988-1995, 47 patients with Stage I, and 11 patients with Stage II seminoma (based on the Royal Marsden staging system) received paraaortic and pelvic lymph node radiation after radical orchiectomy. Patient records were reviewed and patients surveyed to determine the tests ordered for posttreatment surveillance. RESULTS: With a median follow-up of 55 months, there were 2 recurrences among the 58 patients. Eight-year actuarial disease free survival was 93%, with 100% overall survival. Information concerning follow-up screening was available for 56 patients. The follow-up tests ordered included 842 physical examinations, 815 chest X-rays, 839 serum markers, 250 computerized tomography scans, and 112 abdominal plain films. The total cost of these examinations according to 1996 private sector charges and 1996 Medicare reimbursement rates, respectively, was $602,673.01 (average $10,762.02 per patient) and $282,746.52 (average $5049.05 per patient). The two patients who experienced recurrence were diagnosed independently of their posttreatment screening program. One patient recurred 7.5 months after his original diagnosis with an isolated spinal cord compression. The second patient had a mediastinum recurrence > 6 years after treatment. At last follow-up, both patients were disease free after salvage treatment. CONCLUSIONS: Patients with early stage seminoma treated with orchiectomy and radiation have excellent disease free survival rates. The cost of the surveillance program studied does not appear to be justifiable.     

Thrombotic thrombocytopenic purpura in a patient with genetic haemochromatosis, liver cirrhosis and an iron-free focus

We report a patient with thrombotic thrombocytopenic purpura and genetic haemochromatosis. The patient was shown by the polymerase chain reaction to be homozygous for the Cys282Tyr mutation of the HFE gene. Liver biopsy showed micronodular cirrhosis and the presence of an iron-free focus which was thought to be pre-neoplastic.     

Treatment of thrombotic thrombocytopenic purpura with high-dose immunoglobulins. Results in 17 patients. Italian Cooperative Group for TTP

BACKGROUND: The experimental observation that plasma from TTP patients sometimes exhibits a protein which can cause platelet agglutination, and that such agglutination can be inhibited in vitro by the use of IgG led some authors to treat plasma exchange-resistant TTP patients with high-dose IgG (HDIgG). METHODS: We report the results obtained with HDIgG treatment in 17 patients retrospectively examined by the Italian Cooperative Group for the study of TTP: 6 males and 11 females, mean age was 31.7 years for the women (range: 20-65) and 44.6 for the men (range: 26-66). In all cases HDIgG administration was combined with other treatment modalities. RESULTS: Of the 17 patients, 7 died from disease progression (41.1%), 2 achieved partial remission (11.7%) and the remaining 8 achieved complete remission (47%). Of the 10 cases (58.8%) with a positive response, only in 4 did the addition of HDIgG seem to produce significant improvement. All efforts made to characterize the subgroup of patients who responded to HDIgG and compare them with the non responders failed. CONCLUSIONS: Although our results do not unquestionably demonstrate the role of HDIgG in the treatment of TTP, they suggest a possible role for HDIgG in the treatment of those rare plasma exchange-resistant TTP cases.     

Thrombotic thrombocytopenic purpura associated with ticlopidine use: a report of 3 cases and review of the literature

Ticlopidine hydrochloride is an antiplatelet agent used for an increasing number of indications, including cerebrovascular disease, unstable angina, coronary artery stenting, and peripheral vascular bypass grafting. It has uncommon but severe hematologic effects, including thrombotic thrombocytopenic purpura. We report 3 new cases of ticlopidine-associated thrombotic thrombocytopenic purpura and review the English-language literature. Of the 13 patients described (10 from published articles), an equal number were women and men. The median age of the women was 50 years, and that of the men was 72 years. Thrombotic thrombocytopenic purpura occurred within 2 to 8 weeks of starting ticlopidine therapy. Survivors received plasma therapy, but of the 4 who died, 3 had received platelet transfusions. With discontinuation of the drug and prompt plasma exchange therapy, mortality was comparable to that seen with idiopathic thrombotic thrombocytopenic purpura, and relapse was uncommon. Physicians and patients should be aware of this potentially fatal but treatable complication of ticlopidine therapy.     

Thrombotic thrombopenic purpura and HIV infection. Apropos of a case

In the past years, more than thirty cases of thrombotic thrombocytopenic purpura (TTP) had been described associated to infection by the human immunodeficiency virus. Some authors have suggested the presence of a causal relationship between both entities, although the common nexus is still unknown. It usually has a fulminant onset, affecting all the risk groups and in any stage of the disease. The clinical manifestations are similar to the classical forms, as well as the evolution and response to treatment. We present a new clinical case, typical in its presentation and its good response to treatment with plasmatic spares associated to PFC and steroid infusion. We believe that the presence of clinical signs suggesting TTP in a patient would necessarily discard the presence of HIV infection and, the other way round, the presence of clinical signs suggesting TTP in a patient with HIV infection would determine the onset of an early and aggressive treatment based on plasmatic spares, given that the prognosis is linked to an early onset of the treatment.     

Intracranial hemorrhage associated with idiopathic thrombocytopenic purpura: report of seven patients and a meta-analysis

We present the results of a meta-analysis using clinical data obtained from seven of our patients and 24 previously reported patients with idiopathic thrombocytopenic purpura complicated by intracranial hemorrhage. Twenty-four had an intracerebral hemorrhage (ICH) and seven had a subdural hematoma (SDH). Mean age of the patients with ICH was significantly younger than those with SDH. The mortality rate of ICH associated with ITP was similar to that of spontaneous ICH. All seven patients with SDH improved without sequelae.     

Efficacy of high-dose methylprednisolone as a first-line therapy in adult patients with idiopathic thrombocytopenic purpura

Fifty-seven adult patients with idiopathic thrombocytopenic purpura (ITP) were treated with either conventional-dose prednisolone (CDP) (1 mg/kg/d, 36 patients) or high-dose methylprednisolone (HDP) (30 mg/kg/d, 21 patients), as first-line treatment. Patients in the HDP arm responded more rapidly (4.7 v 8.4 d), with a higher response rate (80% v 52.7%), and without severe side-effects. One quarter of the patients (3/12) who were non-responsive to CDP achieved complete remission when they were treated with HDP. The findings suggest that HDP may be a more effective first-line treatment than CDP for adult ITP, and it may also be preferred for life-threatening cases of ITP. However, these results must be confirmed by a randomized study prior to any change in the current practice of employing CDP as first-line treatment for adult ITP.     

Fibrinogen/fibrin degradation products in serum of patients with idiopathic thrombocytopenic purpura: elevated levels during severe thrombocytopenic phase of the disease

Sera from 23 patients with idiopathic thrombocytopenic purpura (ITP), 14 patients with aplastic anemia with severe thrombocytopenia and healthy control subjects were tested for the presence of fibrinogen/fibrin degradation products (FDP), using the tanned red cell hemagglutination inhibition immunoaassay. The concentrations of circulating FDP of ITP patients (mean 12.01 mug/ml) were significantly higher than those of the patients with aplastic anemia (mean 4.01 mug/ml, p less than 0.05) or normal controls (mean 3.10 mug/ml, p less than 0.001). The patients with untreated ITP with very low platelet counts had higher levels of FDP than those of the treated group (p less than 0.01). Serum FDP and a battery of other coagulation-fibrinolysis tests were serially carried out over a period of 10 weeks in two patients with ITP. The initially high FDP promptly decreased as circulating platelets increased in response to steroid in both patients, while plasma fibrinogen, euglobulin lysis time, prothrombin time and partial thromboplastin time remained essentially normal during the course of observation. The exact source of the increased serum FDP in ITP was not established, but a few possible mechanisms responsible for this abnormality were discussed.     

Description of a laparoscopic technique for treating patients with ovarian remnant syndrome

OBJECTIVE: A retroperitoneal approach for laparoscopic treatment of ovarian remnant syndrome was developed. DESIGN: Clinical study. SETTING: Department of Gynecology, Friedrich-Schiller-University Jena. PATIENT(S): During a 29-month period, seven consecutive patients with ovarian remnant syndrome were treated by laparoscopy. Patients were not preselected and preoperative, intraoperative, and postoperative data were registered prospectively. INTERVENTION(S): For removal of remnant ovaries we used a laparoscopic retroperitoneal approach that included complete dissection of the pelvic course of the ureter and coagulation and dissection of the infundibulopelvic ligament and of the uterine vessels. RESULT(S): In the first patient's case, the right ureter was injured during dissection, which was initiated too far distally between ovary and external iliac vessels. Thereafter, we changed our technique to start the dissection of the ureter at the pelvic brim. No subsequent patient had an intraoperative or postoperative complication. All patients reported fewer preoperative complaints and were free of recurrence by sonographic examination. CONCLUSION(S): Using a retroperitoneal approach laparoscopic resection of a remnant ovary may be a safe and effective technique.     

Incidence and prognostic significance of idiopathic thrombocytopenic purpura in patients with Hodgkin's disease in complete hematological remission

Idiopathic thrombocytopenic purpura (ITP) is a frequent and well recognized complication of lymphoproliferative diseases (especially chronic lymphatic leukemia), but it is an unusual and poorly documented disease in the acute phase (1-2%). We report on two female patients with Hodgkin's disease (HD) followed between 1970 and 1995 at the institute of Hematology and Medical Oncology "Seràgnoli" in Bologna, who developed ITP unrelated to bone marrow failure, 26 and 15 months after achievement of complete hematologic remission from HD.