Clinical experience in treatment of thrombotic thrombocytopenic purpura--hemolytic uremic syndrome with 28 patients.

BACKGROUND: Neither optimal treatment nor significance of ADAMTS13 (A Desintegrin And Metalloprotease with ThromboSpondin type 1 repeats) activity for diagnosis and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS) have not been defined yet. The aim of the report is to analyze response to different volumes of plasma exchange (PE), and relationship to ADAMTS13. DESIGN AND METHODS: 28 patients clinically diagnosed with idiopathic TTP (n = 18), secondary TTP (n = 4), atypical HUS (n = 3) and typical HUS (n = 3) manifested 31 acute episodes. Patients were treated with PE in 26, and with plasma transfusion in 5 episodes with additional different therapies. RESULTS: PE volumes were as follows: 1 in 7, 1.5 in 3, 2 in 14, and intensifying schedule (1 to 1.5) in 2 episodes. Procedure number was lower in patients treated with 2 and 1.5 (p = 0.019) than in those treated with 1 volume exchange and PE intensifying, respectively (p = 0.010). PE response rate was 25/26 (96.15%). Exacerbation frequency was higher in idiopathic TTP patients (3/19) treated with 1 compared with patients treated with > 1 volume exchange (p = 0.003). Survival rate was 25/28 (89.29%). ADAMTS13 activity was reduced in 22 with severe deficiency in 14 patients. CONCLUSION: Patients responded to different treatments regardless of ADAMTS13 activity, requiring less PEs with larger volume exchanges.

Diagnostic relevance of ADAMTS13 activity: evaluation of 28 patients with thrombotic thrombocytopenic purpura - hemolytic uremic syndrome clinical diagnosis.

INTRODUCTION: The significance of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin motif-13) activity for diagnosis and therapy of thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) is still a controversial issue. OBJECTIVE: The aim of this report was to analyze the value of ADAMTS13 measurements in the diagnosis of TTP and HUS. METHODS: At presentation, we analyzed patients with idiopathic TTP (n = 18), secondary TTP (n = 4), diarrhea positive HUS (n = 3) and diarrhea negative HUS (n = 3) treated in Belgrade, Serbia from 2004 to 2010. ADAMTS13 activity from acute phase samples was measured using the residual collagen binding activity assay at the Haemophilia and Thrombosis Centre, Milan, Italy. RESULTS: There was a significant correlation between reduced ADAMTS13 activity and idiopathic TTP diagnosis (p = 0.000) as well as between lower ADAMTS13 activities and higher reticulocytes (p = 0.017) and lactate dehydrogenase levels (p = 0.027). Significant correlation was also found between higher protease activity and diagnosis of HUS (p = 0.000). There was a statistically significant correlation between higher ADAMTS13 activities and higher platelets count (p = 0.002), blood urea nitrogen (p = 0.000), and creatinine level (p = 0.000). CONCLUSION: Severe ADAMTS13 deficiency points at the diagnosis of idiopathic TTP and it is present in the secondary TTP but not in HUS.

[Treatment of 36 cases of thrombotic thrombocytopenic purpura]. / Rezultati lecenja trombozne trombocitopenijske purpure na 36 bolesnika.

Thirty-six patients (pts.) with thrombotic thrombocytopenic purpura (TTP) were treated between May 1990 and May 2003. There were 31 women and 5 men; the average age was 37 years. Twenty-five cases were idiopathic and 11 secondary (3 infection--related, 5 occurred during pregnancy and 3 were drug--associated). The mean lag period between the first symptoms and the diagnosis was 8.5 days (in 14 pts. < or = 5; in 22 > 5). On diagnosis neurological symptoms were present in 31, bleeding in 33, fever in 21 and renal impairment in 27 patients. The mean hemoglobin was 67.5 g/L, the mean platelet count was 10 x 10(9)/L, and the mean reticulocytosis was 17%. The mean serum LDH was 1457 IU. Treatment included plasma exchange (PE) in 24 pts. and only plasma infusions in 12 pts. There were 24 complete responders (20 on PE) and 12 deaths (4 on PE); PE significantly improved survival (p < 0.01). There were 5 treatment-related complications due to the infection and bleeding, 17 exacerbations and 4 relapses. The mean time delay before the onset of symptoms and the treatment initiation lasted for 9 days suggesting the poor disease recognition; the mean time delay from diagnosis to PE institution was 6 days, indicating postponed PE. The mean treatment duration in all patients was 18 days; the mean number of PE cycles needed for the platelet count stabilization was 9. Good prognostic indicators of survival were: the longer prodromal period (> 5 days), the secondary form of TTP and the absence of coma at presentation. The use of PE significantly improved survival. TTP is a severe disorder requiring early recognition and diagnosis in general medical care facilities, which should lead to the timely treatment with PE.