Outcome Of Thrombotic Thrombocytopenic Purpura Research Articles

Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go from here?

Randomized clinical trials in thrombotic thrombocytopenic purpura: where do we go from here?

Does cryosupernatant plasma improve outcome in thrombotic thrombocytopenic purpura? No answer yet

A randomized prospective trial compared cryosupernatant plasma (CSP) to fresh frozen plasma (FFP) for treatment of thrombotic thrombocytopenic purpura (TTP). A total of 236 patients were required: 28 patients were treated with CSP and 24 with FFP within 30 months. There were no differences in survival at 1 month. By day 9, 17 of 26 patients with CSP and 18 of 24 with FFP had a platelet count >100 x 10(9)/l. At entry, von Willebrand factor (VWF) multimers were normal in all patients (range 1.1-3.95 IU/ml). ADAMTS-13 levels showed large variations ranging from 10% to 100% activity. At entry, no individual had <5% VWF cleaving protease. By day 9 (end of cycle), 89% (FFP) and 67% (CSP) had levels >50% of the controls. At 6 months some patients showed inhibitors to the enzyme in spite of adequate or normal platelet counts. The data from this study do not show an apparent advantage to the use of CSP in TTP. A large number of patients will be required to determine appropriate replacement therapy. We were not able to find a statistically significant relationship between the low level of protease activity at presentation of TTP and response.

Thrombotic thrombocytopenic purpura after allogeneic stem cell transplantation: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

A survey was carried out among the European Group for Blood and Marrow Transplantation (EBMT) centres to determine the incidence, risk factors, treatment and outcome of thrombotic thrombocytopenic purpura (TTP) following allogeneic haematopoietic stem cell transplantation. TTP was defined as the simultaneous occurrence of red cell fragmentation, laboratory findings of haemolysis, red cell transfusion requirement and de novo or persistent thrombocytopenia caused by consumption, in the absence of disseminated intravascular coagulation. Forty-five centres reported all patients (n = 406) transplanted between July and December 1996. Twenty-three patients developed TTP; the risk of developing TTP was 6.7% at 2 years (95% CI: 4.1% to 9.3%). The median time of onset was 44 d (range 13-319) post transplantation. Significant risk factors for the development of TTP were female gender (P = 0.005) and an unrelated donor (P = 0.046). To treat TTP, cyclosporin administration was discontinued in 10 cases, plasma exchanges were performed in five cases and 12 patients received plasma infusions without plasma exchange. TTP resolved in 13 of the 23 patients (57%). The only factor predictive of resolution of TTP was the absence of nephropathy. Seven patients (30%) were alive at follow-up of 38-45 months from the onset of TTP. Sixteen patients died; the causes were multiple, only three patients had TTP as a central factor. The median time to death was 41 d (range 1-762 d) from the onset of TTP. TTP is a relatively frequent complication of allogeneic stem cell transplantation and it is associated with high mortality, though death is usually caused by multiple factors.

The LDH ratio as a marker for response to plasma exchange in HUS/TTP of the adult.

Plasma exchange improved the outcome of thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) of the adult markedly, but a high number of non-responders remain. Identifying these patients at an early stage would help to optimize therapy. determine the value of serologic measures in predicting the response to plasma exchange. We performed a retrospective chart review of 30 patients with HUS/TTP of the adult treated with plasma exchange. According to the treatment protocol, a mean of 42 +/- 8.2 ml plasma per kilogram of body weight was exchanged daily for 3 days and continued every second day thereafter. Prior to each session, clinical status and serologic markers for hemolysis and kidney function were obtained. To assess the early individual response to plasma exchange, the decline of LDH from the first to the third cycle was calculated as: LDH concentration before the third session/LDH concentration before the first session (LDH ratio). During the observation period (median 195, range 6-1500 days), 80% of the patients responded to therapy with plasmapheresis. None of the serologic measures or clinical signs obtained before initiation of plasma exchange showed a significant correlation with the outcome. After 2 sessions of plasma exchange, only LDH and platelet level had improved markedly in responding patients. The LDH ratio was the best predictive marker for the individual response. An LDH ratio < 0.6 predicted a favorable outcome with a sensitivity of 0.96 and a specificity of 0.83. The LDH ratio might be a useful marker for separating patients responding to plasma exchange from those not responding at an early stage.

Thrombotic Thrombocytopenic Purpura and Hemolytic Uremic Syndrome

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are multisystemic disorders that are characterized by thrombocytopenia, microangiopathic hemolytic anemia, and ischemic manifestations, resulting from platelet agglutination in the arterial microvasculature. Until the introduction of plasma-based therapy, TTP was associated with a mortality rate greater than 90%. Current outcomes of TTP and HUS have improved dramatically with the use of plasma exchange, which should be initiated promptly at diagnosis. Recent evidence suggests that deficiency of a specific plasma protease responsible for the physiologic degradation of von Willebrand factor plays a pathogenic role in a substantial proportion of familial and acute idiopathic cases of TTP. Although multiple triggers, such as infection, drugs, cancer, chemotherapy, bone marrow transplantation, and pregnancy, are recognized, knowledge of the pathogenesis of TTP and HUS in relationship to these disorders remains incompletely understood and continues to evolve. While uncommon, TTP and HUS are of considerable clinical importance because of their abrupt onset, fulminant clinical course, and high morbidity and mortality in the absence of early recognition and treatment.

The clinical features, risk factors and outcome of thrombotic thrombocytopenic purpura occurring after bone marrow transplantation.

In this study, we retrospectively analysed the clinical features, risk factors and outcome of 22 patients with thrombotic thrombocytopenic purpura (TTP) occurring after allogeneic stem cell transplantation. All but two of these patients received stem cells from unrelated donors (UDs), two-thirds were female, three-quarters were adults and leukaemia was the major reason for transplant. The incidence of TTP was 20 out of 332 patients (6%) with UD transplants and two out of 104 recipients (2%) of matched sibling allografts (P = 0.16). In order to ascertain basic demographic risk factors for the development of TTP, we compared the 22 patients with 434 patients who did not develop TTP. Compared with patients who did not develop TTP, patients with TTP were nearly three times older (P < 0.001) and were more than twice as likely to be female (P = 0.001). Because > 90% of patients were recipients of UD marrow, we then compared the 20 UD-bone marrow transplantation (BMT) patients with 60 randomly selected UD-BMT patients who did not develop TTP. On univariate analysis, age and female gender were again significant risk factors, as was grade II-IV acute graft-versus-host disease (GvHD) (P = 0.002), and there was a trend towards an association with chronic GvHD (P = 0.083). However, after logistic regression analysis, only age and sex remained significant (P < 0.001 and 0.009 respectively). We report an 86% mortality with only three survivors out of 22 patients, and one of these remains thrombocytopenic and red cell transfusion dependent, possibly in part because of graft hypoplasia. Six out of 17 patients responded to plasmapheresis, but the majority of them ultimately succumbed because of TTP, often in association with GvHD or fungal infection.

Thrombotic thrombocytopenic purpura in a patient with a diffuse form of systemic sclerosis

This paper presents a patient with a rapidly progressive diffuse form of systemic sclerosis, in whom a clinical course thrombotic thrombocytopenic purpura (TTP) also developed. In spite of treatment with plasmapheresis, predonisolone, aspirin and vincristine, she died of pulmonary bleeding. From the analysis of four other reported cases of scleroderma with TTP and this case, the outcome of TTP seems to be closely related to clinical manifestations. It is suggested that a diffuse form of scleroderma with interstitional manifestations would develop a worse outcome; on the other hand, a limited form without interstitional manifestations has a successful outcome.

Thrombotic thrombocytopenic purpura in a patient with a diffuse form of systemic sclerosis

This paper presents a patient with a rapidly progressive diffuse form of systemic sclerosis, in whom a clinical course thrombotic thrombocytopenic purpura (TTP) also developed. In spite of treatment with plasmapheresis, predonisolone, aspirin and vincristine, she died of pulmonary bleeding. From the analysis of four other reported cases of scleroderma with TTP and this case, the outcome of TTP seems to be closely related to clinical manifestations. It is suggested that a diffuse form of scleroderma with interstitional manifestations would develop a worse outcome; on the other hand, a limited form without interstitional manifestations has a successful outcome.

Outcome of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan.

We examined 159 patients with thrombotic thrombocytopenic purpura and hemolytic uremic syndrome in Japan. The subjects were divided in three groups; 90 patients with thrombotic thrombocytopenic purpura, 51 patients with verotoxin-induced hemolytic uremic syndrome, and 18 patients with drug-induced hemolytic uremic syndrome. Eighty-two percent of the patients with thrombotic thrombocytopenic purpura had associated neurological disorders and 78% of drug-induced hemolytic uremic syndrome associated with pulmonary edema. Renal insufficiency was noted in the 69% cases with both hemolytic uremic syndrome groups. Seventeen patients with thrombotic thrombocytopenic purpura had systemic lupus erythematosus and 6 were pregnant. Autoantibody were positive in 53% of thrombotic thrombocytopenic purpura. Seventy-seven percent of patients with thrombotic thrombocytopenic purpura received plasma exchange at 4,000 mL/day three times a week, 71% antithrombotic agents, and 78% steroid administration, respectively. However, 27% of the patients with hemolytic uremic syndrome were treated by hemodialysis in addition to antithrombotic agents. When drug-induced hemolytic uremic syndrome was diagnosed, the drug was immediately discontinued and the patients were treated with antiplatelet agents. Seventy-four percent of the patients with thrombotic thrombocytopenic purpura were alive at 26 weeks compared with 95% of those with hemolytic uremic syndrome. As thrombotic thrombocytopenic purpura had a high mortality rate in Japan, we should carry out early diagnosis and early treatment.

The blood counts and lactate dehydrogenase levels in thrombotic thrombocytopenic purpura (TTP).

The blood counts and lactic dehydrogenase values of eight patients with thrombotic thrombocytopenic purpura (TTP) were reviewed in relation to the clinical course. Three of the eight patients died. In these patients, the hemoglobin was significantly lower and the LDH higher at the time of presentation than that of the patients responding to treatment. The height of the absolute reticulocyte count and platelet count did not correlate as well with outcome as did the degree of anemia and LDH elevation. Microangiopathic changes were noted in all eight patients. A differential count showed that the total microangiopathic changes varied from 0.8 to 54%. The more severe microangiopathic changes occurred in the fatal cases. The observations indicate that the degree of anemia, elevation of LDH, and severity of microangiopathic changes at the time of presentation correlate with the outcome in TTP and provide useful parameters in the assessment of response to therapy.