The diagnosis of TTP was made based on (i) clinical manifestations characterized by neurological features, renal impairment and fever; (ii) typical laboratory abnormalities including thrombocytopenia, MAHA (anemia, elevated lactate dehydrogenase [LDH], the presence of schistocytes on peripheral smear, and negative Coomb’s test), and normal clotting tests; and (iii) exclusion of Evens syndrome, disseminated intravascular coagulation, HELLP (hemolysis, elevated liver enzymes and low platelets), and eclampsia, hemolytic uremic syndrome (29, 30). The term idiopathic TTP was used to indicate the absence of any of the following identifiable causes: infection, autoimmune disease, exposure to drugs known to cause TTP, surgery, cancer, pregnancy or postpartum period, malignant hypertension, pancreatitis, and stem cell transplantation. Patients with any of the above conditions were considered to have secondary TTP. Eligible patients included adults (16 years and older) with new diagnosed idiopathic TTP, having survived their first episode of the disease and achieved remission following treatment. Patients with congenital TTP or secondary TTP were not included. This retrospective study was approved by the ethics committees of the First Affiliated Hospital of Wenzhou Medical University and the Second Affiliated Hospital of Wenzhou Medical University. The committees waived the patient’s informed consent due to the retrospective nature of this study, but patient confidentiality was protected.

Clinical and laboratory data was retrieved from physical and electronic medical records, including age, gender, initial clinical manifestation, complete blood counts, schistocyte counts on peripheral smears, coagulation tests, serum LDH, serum creatinine, total and indirect bilirubin. The AMC value was determined either by the Sysmex XE-2100 series automated hematology analyzer or manual differential leukocyte counts (in cases the AMC value was flagged as abnormal). In addition, four individual laboratory parameters (platelet count <30 × 10⁹/L, mean corpuscular volume [MCV] < 90 fL, creatinine <176.8 μmol/L, and international normalized ratio [INR] < 1.5), a combined laboratory parameter (evidence for hemolysis based on either reticulocytes >2.5% or indirect bilirubin [IBIL] > 34.2 μmol/L), and two historical features (no active cancer, no history of solid organ or stem-cell transplantation) were collected for calculating the PLASMIC score (31).

Therapeutic plasma exchange and/or plasma infusion was performed in all patients once the diagnosis of TTP was made. Concomitant therapy with glucocorticoids and/or other immunosuppressive drugs was started at the physician’s discretion. Remission was defined as platelet count recovery (> 150 × 10⁹/L) for 2 consecutive days. Relapse was defined as recurrence of an episode of acute TTP beyond 30 days after remission from the first episode of TTP.

The chi-squared test was used to compare categorical data, which were expressed as counts and percentages. Continuous data were compared using the Wilcoxon test (U test) and were presented as mean ± standard deviation. Above all were analyzed by SPSS Statistics 22 software (IBM, Armonk, NY). All tests were two-sided. Kaplan–Meier survival analysis was used to plot relapse-free survival curves for patients, and the Log-rank test was applied to compare survival differences between groups. Cox regression analysis was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) to identify risk factors, with p-values <0.05 considered statistically significant. These data were analyzed using the Stata version 12 software (StataCorp, College Station, TX).

A total of consecutive 81 patients were diagnosed as the first episode of TTP between August 2009 and April 2023 at the First Affiliated Hospital of Wenzhou Medical University and the Second Affiliated Hospital of Wenzhou Medical University. There was no family history of the disease in any of the 81 TTP patients. 21 patients presented with concomitant conditions associated with secondary TTP (five patients with systemic lupus erythematosus [SLE], five with Sjogren’s syndrome, three with the coexistence of SLE and Sjogren’s syndrome, 1 with rheumatoid arthritis, 1 with connective tissue diseases, and six with pregnancy), six refused plasma exchange or plasma infusion after diagnosis, and 17 died from disease progression during the initial treatment with plasma exchange. Thus 37 patients with idiopathic TTP who survived their first episode of the disease and achieved remission following treatment were eligible for the evaluation of risk factors for relapse (Figure 1).

The characteristics of the 37 idiopathic TTP patients are shown in Table 1. The patient cohort consisted predominantly of females (59.5%), with a median age of 51 years. Neurologic symptoms occurred in 78.4% of the patients, and 56.8% had fever. Of the 37 patients with idiopathic TTP, the median hemoglobin concentration and platelet count were 75 g/L and 19 × 10⁹/L, respectively. The schistocyte percentage was obviously increased with a median of 8.3%. The median serum LDH and indirect bilirubin level at admission were 854 IU/L and 25.2 μmol/L. 35 patients had necessary data for calculation of the PLASMIC score. A total of 22 (62.9%) and 13 (37.1%) patients had a PLASMIC score of 5 and 6 or 7, respectively. The time elapsed from the onset of initial symptoms to initiation of therapy ranged from 1 to 64 days, with a median of 13 days. In this series, all patients received plasma exchange, with the exception of one patient who was treated with plasma infusion and the other seven patients who were initially treated with plasma exchange and subsequently treated with plasma infusion. All patients also received glucocorticoids as adjunctive treatment. Other therapies used to achieve remission were rituximab (n = 4), mycophenolate mofetil (n = 17), cyclosporine A (n = 6), and cyclophosphamide (n = 1) in 25 patients. Within our entire cohort, the median time from initiation of therapy to remission was 11 days.

According to the lower (0.12 × 10⁹/L) and upper limits (0.80 × 10⁹/L) of normal AMC value, there were 1 patient (2.7%) with low AMC, 27 patients (73.0%) with normal AMC, and 9 patients (24.3%) with high AMC at admission. Due to only 1 patient with low AMC in our cohort, we further compared the patient characteristics between patients with normal and high AMC at admission (Table 1). Patients with high AMC tended to associate with high WBC count (p = 0.011).

Ten (27.0%) of 37 patients in our cohort subsequently relapsed (1 in the low AMC group and 9 in the normal AMC group), with a median time to relapse of 17.5 months (range: 2.7–87.0 months) from remission. Most relapses (7 patients, 70.0%) occurred within the first years after remission. With a median follow-up duration of 44.3 months (range: 0.7–124.7 months) from the data of remission to the date of the last follow-up visit, the estimated 5-year rate of RFS for the entire cohort was 72.60% (95% confidence interval [95% CI], 47.62–87.09%). No patients died during the follow-up.

Figure 2 compares RFS curves among the three AMC groups of patients. There was a trend of higher RFS rate in patients having increased AMC (log-rank test, p = 0.026). Results of the Cox univariate analysis for risk factors for RFS are reported in Table 2. When AMC was transformed to ordinal variable and ordered as 1 (low AMC), 2 (normal AMC) and 3 (high AMC), increased AMC at admission was significantly associated with higher RFS (hazard ratio [HR] = 0.12, 95% CI: 0.02–0.62, p = 0.011). None of the other parameters analyzed were significant (p > 0.05), so multivariate analysis was not performed.