Improving the PLASMIC score with the use of RDW-SD in the differential diagnosis for thrombotic thrombocytopenic purpura in Chinese patients.

Validation of the Plasmic Score and Development of a Novel Predictive Model for Thrombotic Thrombocytopenic Purpura: Exploring Socioeconomic Disparities and Outcomes

In this issue of TRANSFUSION, Kim and colleagues1 analyze the cost-effectiveness of different strategies for the initial management of patients with suspected thrombotic thrombocytopenic purpura (TTP) using previously published data. They analyzed four hypothetical scenarios: two different rates of reporting ADAMTS13 activity measurements, each with and without the prior use of a clinical prediction score (the PLASMIC score2). Scenarios 1 and 2 evaluated the rates of reporting ADAMTS13 activity: 3 days after the blood was drawn (the test is performed at a distant site, "send-out") or on the same day that blood was drawn (the test is performed "in-hospital"). Scenarios 3 and 4 were the two rates of reporting ADAMTS13 activity combined with the PLASMIC score; the ADAMTS13 test was not performed when the PLASMIC score was less than 4 (maximum score, 7), indicating a low probability of ADAMTS13 activity of less than 10%.2 Kim and colleagues1 conclude that an in-hospital ADAMTS13 test combined with the PLASMIC score provides the most cost-effective management. Even though there is cost required for the implementation of an in-hospital ADAMTS13 test, cost saving would result from avoidance of plasma exchange treatment (TPE) for patients with a low probability of TTP (PLASMIC score of 4 or less ADAMTS13 activity ≥ 10%). Avoidance of TPE would also mean fewer TPE-associated major complications and their cost of extended hospitalization and care.3, 4 The question for readers of TRANSFUSION may be: Why are these data important for clinicians requesting TPE or transfusion medicine specialists providing TPE on a consultative basis? For clinical practice, these data would be applied to the evaluation of patients who have anemia with features of microangiopathic hemolysis and thrombocytopenia, the signs that create initial suspicion for the diagnosis of TTP. Evaluation of these patients leads to one critical decision. Should TPE be requested immediately or is it better to hesitate and to intensify the search for an alternative diagnosis? How do the data of Kim and colleagues1 help this decision? Their conclusion that a rapid report of ADAMTS13 activity together with a PLASMIC score provides the most cost-effective practice may not be the same as providing the most clinically effective practice. However, my interpretation is that these two outcomes, cost-effective and clinically effective, are aligned. My interpretation is that a rapid report of ADAMTS13 activity of less than 10% together with a PLASMIC score of more than 4 should support a decision for urgent initiation of TPE treatment. Alternatively, ADAMTS13 activity of 10% or more or a PLASMIC score of 4 or less may (or may not) support a decision to hesitate requesting TPE and to intensify the search for an alternative diagnosis. These data of Kim and colleagues,1 together with the data that supported the derivation of the PLASMIC score,2 are important for clinicians whenever they evaluate a patient for the possible diagnosis of TTP. The decision to begin TPE, or to hesitate, is urgent because of the risk of death if TTP is not treated5 and the effectiveness of TPE for treatment of TTP.6 The decision to begin TPE is related to the physician's impression that the risks from hesitation are greater than the risks from TPE. This dilemma is evident from our experience. Among 363 patients who have been enrolled in the Oklahoma Registry during the past 20 years because TPE was requested (almost always for suspected TTP), only 78 (21%) had ADAMTS13 activity of less than 10% and also a clinical diagnosis of TTP.4 These data document that physicians in Oklahoma have had a low threshold for ordering TPE when TTP was suspected. Most patients did not have TTP. I assume that physicians in Oklahoma are not different from physicians everywhere. Our experience may be similar to data reporting the frequency of TPE for TTP in Canada7 during the clinical trial comparing plasma infusion with TPE (1982-1988) and after its completion and publication in 1991.6 Even when this clinical trial was still enrolling patients, TPE use for suspected TTP increased, presumably because of increasing awareness of the effectiveness of TPE. After publication of this trial, TPE use for suspected TTP doubled.7 With the availability of an effective treatment for TTP (and without the availability of the yet to be discovered ADAMTS13 activity measurements to support the diagnosis), the feeling of urgency for beginning TPE for suspected TTP would have been great. The feeling of urgency for beginning TPE for suspected TTP may become even greater with the future approval of caplacizumab for treatment of TTP.8 Caplacizumab effectively blocks formation of platelet–von Willebrand factor (VWF) thrombi and therefore halts the pathogenesis of TTP. The recommendation for caplacizumab will be that it should be given to patients with TTP as soon as possible. And it will certainly be very expensive. Therefore, the prompt availability of ADAMTS13 activity is clearly an important advantage for clinicians, as it is important for cost-effectiveness. TTP is defined by a severe deficiency of ADAMTS13 activity and ADAMTS13 deficiency is responsible for the clinical features of TTP. A recent consensus panel stated that ADAMTS13 activity of less than 10% confirms the diagnosis of TTP.9 Therefore, it is appropriate to begin TPE in a patient with suspected TTP if the ADAMTS13 activity is less than 10%. But the diagnosis of TTP and beginning treatment with TPE cannot be based on the ADAMTS13 activity alone. The clinician's judgment is also critical for the diagnosis of TTP. This additional diagnostic help is the contribution of the PLASMIC score and other prediction models developed from clinical features10, 11 to assist the evaluation of patients with suspected TTP. These scores combine clinical features to provide a numerical value. They quantify clinical judgment. They convert clinical judgment into data. Then these clinical data can be combined with the ADAMTS13 activity data. They can be synergistic. Thrombotic thrombocytopenic purpura provides a perfect example for the essential value of clinical judgment. I accept that ADAMTS13 deficiency is the definition of TTP and that ADAMTS13 deficiency is responsible for the clinical features of TTP. These concepts have been documented for many years.12-14 But my experience documents that measurements of ADAMTS13 activity alone are insufficient for the clinical decision to initiate TPE or to hesitate. Measurements of ADAMTS13 activity may be inconsistent. Patients with TTP may have reported ADAMTS13 activity of 10% or more. Patients who do not have TTP may have reported ADAMTS13 activity of less than 10%. Patients with TTP may have reported ADAMTS13 activity of 10% or more with their initial episode and then ADAMTS13 activity of less than 10% with subsequent episodes. Although these inconsistencies represent only a small minority of patients with TTP, our responsibility as clinicians is to protect minorities. Here are the data for the apparent discrepancies between ADAMTS13 activity and the clinical diagnosis of TTP. For patients in the Oklahoma Registry, ADAMTS13 activity is measured by two methods15: a fluorogenic assay using a VWF732 peptide (FRET method, the common commercial method) and quantitative immunoblotting (IB method, the original method for measuring ADAMTS13 activity12). We report the lower of the two results. Among the 78 patients whom we have diagnosed as having TTP by both ADAMTS13 activity of less than 10% and also clinical features, ADAMTS13 activity was less than 10% by both FRET and IB assays in 60 patients. In 15 patients, the FRET method measured ADAMTS13 activity as less than 10% while the IB method measured ADAMTS13 activity as 10% to 68%. Among these 15 patients, the three with the highest ADAMTS13 activities by IB measurements (35%-68%) have all relapsed, confirming their diagnosis of TTP. At the time of their relapse, the IB measurement was less than 10% in two patients and 18% in the third. In three other patients, the IB method measured ADAMTS13 activity as less than 10% while the FRET assay measured ADAMTS13 activity as 11% to 23%.4 Therefore, it should be considered that patients may still have TTP even when neither the FRET nor the IB measurement of ADAMTS13 activity is less than 10%. When we reviewed the presenting features and clinical course of patients whose lower measurement of ADAMTS13 activity was 10% to 20%, we determined that four of 22 patients had characteristic clinical features supporting a diagnosis of TTP.16 One additional Registry patient had characteristic clinical features of TTP but his initial ADAMTS13 activities were 53% by the FRET measurement and 60% by the IB measurement; he subsequently had five relapses. With his last three episodes, both ADAMTS13 measurements reported activities of less than 10%.17 The reverse situation has also occurred. Five patients who were treated with TPE for suspected TTP had ADAMTS13 activity of less than 10% but their subsequent clinical diagnoses were severe systemic infections or malignancy; four died, and two had autopsies with no evidence of TTP. Two of these patients had high serum bilirubin levels (24 and 64 mg/dL), which can interfere with the FRET measurement, causing falsely low ADAMTS13 activity.18 These observations emphasize that the interactions among ADAMTS13, anti-ADAMTS13 autoantibodies, and VWF are complex and measurements of ADAMTS13 activity may be susceptible for falsely high values.19 These observations document the essential role for clinical judgment in the evaluation and management of patients with suspected TTP. Although an individual physician's clinical judgment is essential, an individual physician's experience with patients who have suspected TTP may be limited. Enhancement of an individual physician's experience and clinical judgment is the goal of the quantitative scores, such as the PLASMIC score2 and its predecessors.10, 11 The derivation and validation of the PLASMIC score was an impressive effort.2 Although some of the seven components of the PLASMIC score may not appear to be common diagnostic variables of TTP, they were selected and validated objectively. The value of these scores is that they provide a consistent, quantitative measure. They supplement, but they do not replace, our individual clinical judgment. For example, in my own experience the occurrence of transient focal neurologic abnormalities has a strong association with TTP. Older age (≥70 years) and a long duration of illness or hospitalization preceding the suspicion for TTP appear to be evidence against the diagnosis of TTP.16 These clinical features are not part of the previously published scores for evaluating patients with suspected TTP.2, 10, 11 Individual physician experience can enhance the ability of a standardized clinical score, but the reproducible qualities of the clinical scores provide a quantitative measure that our individual experience cannot match. Now, back to the report by Kim and coworkers.1 They used data from many published sources (see their Table S1) and they used multiple methods of analysis. Their conclusions are clear. The rapid report of ADAMTS13 activity improves cost-effectiveness and the addition of the PLASMIC score provides additional value. Their principal focus is for hospital administration and economic policy, to present data on the value of introducing a new laboratory test that will be used infrequently but may help to control health care cost. This issue is important for population health, but issues of population health may override the needs of exceptional patients. The needs of exceptional TTP patients may be reflected in another result reported by Kim and coworkers.1 If effectiveness is measured only by the number of averted deaths, rather than the cost, then the send-out ADAMTS13 test is the most effective. The interpretation of this result is that TPE for 3 days before the report of ADAMTS13 activity prevents some deaths. This result is consistent with our experience that some patients with TTP have ADAMTS13 activity of 10% or greater and therefore would not have received TPE if the ADAMTS13 value was known immediately. My conclusion is that three things are important for the initial evaluation of a patient with suspected TTP: 1) prompt availability of ADAMTS13 activity; 2) the PLASMIC score or a comparable, quantitative clinical score for predicting the presence of ADAMTS13 activity of less than 10%; and 3) perhaps most importantly, the primary physician's individual clinical judgment, reviewed and supported by experienced transfusion medicine specialists. All three components contribute to the critical, initial decision: Should TPE begin urgently, or should we hesitate while we search for an alternative etiology for the microangiopathic hemolytic anemia and thrombocytopenia? The author has disclosed no conflicts of interest. James N. George, MD e-mail: [email protected] Department of Medicine, College of Medicine Department of Biostatistics and Epidemiology, College of Public Health University of Oklahoma Health Sciences Center Oklahoma City, OK

Assessment of the Plasmic Score Utility for Classification of Pediatric Thrombotic Microangiopathies

It is crucial to differentiate critically ill patients exhibiting thrombocytopenia and hemolytic anemia alongside organ damage to enable rapid identification of thrombotic thrombocytopenic purpura (TTP) and TTP-like syndrome, which allows for targeted emergency interventions such as plasma exchange. This study retrospectively analyzed clinical data from patients with TTP and TTP-like syndrome to further elucidate the potential differences between these conditions. We also established a new predictive model to facilitate early identification and differentiation between TTP and TTP-like syndrome. A new predictive model for diagnosing TTP was developed using five key indicators: reticulocyte percentage, platelet count, schistocyte percentage, LDH/ULN, and indirect bilirubin. The performance of this new model was compared with the traditional PLASMIC score by evaluating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Thirty-five patients were diagnosed with TTP and 42 were diagnosed with TTP-like syndrome. TTP is most commonly associated with autoimmune diseases (n=13, 37.14%), while TTP-like syndrome frequently arises from infections (n=23, 54.76%). The ADAMTS13 activity was significantly lower in the TTP group than in the TTP-like syndrome group (Mean 8.30% vs 46.12%). TTP-like syndrome patients had significantly higher levels of inflammatory markers. The new predictive model was developed for TTP with a predictive ability of 96.9%. Overall, 16 patients (20.77%) died, including 3 (8.57%) in the TTP group and 13 (30.95%) in the TTP-like syndrome group. Kaplan-Meier survival analysis showed significant differences in survival between TTP and TTP-like syndrome patients, with a 180-day overall survival (OS) rate of 90.6% vs 60.9% (p=0.009); and plasma exchange improved 180-day OS rate in the TTP group compared to the TTP-like syndrome group (90.6% vs 65.6%) (p=0.054). This study demonstrates that TTP and TTP-like syndrome are two distinct types of diseases. The new predictive model has shown good efficacy in distinguishing TTP and TTP-like syndrome. Plasma exchange significantly improves survival in TTP patients; however, its effect on TTP-like syndrome is minimal.

The PLASMIC score was recently published to aid in the early identification of thrombotic thrombocytopenic purpura (TTP) patients. This study aims to evaluate whether this score is suitable for Chinese suspected TTP patients and find the utility of patients' other characteristics in predicting severe ADAMTS13 deficiency. We retrospectively studied a Chinese cohort of 38 consecutive hospitalized patients with suspected TTP, ADAMTS13 test results, and other clinical data from September 2016 to May 2018. The predictive power of PLASMIC score in our cohort was evaluated, and patients' other characteristics, especially the high lactate dehydrogenase/the upper limit of normal (LDH/ULN), were studied to determine their distinguishing ability for TTP patients. In this Chinese cohort, 17 patients were diagnosed with TTP according to ADAMTS13 activity results. When dichotomized at intermediate-high risk (scores 5-7) vs low risk (scores 0-4), the PLASMIC score predicted TTP with a sensitivity of 100%, a specificity of 9.52%, and a misdiagnosis rate of 90.48%. And the LDH/ULN alone, or plus platelet count, reticulocyte percentage and indirect bilirubin (IBIL) both had excellent predictive power (area under the curve [AUC] 0.937, 95% confidence interval [CI] 0.863-1.000, P = .000, and AUC 0.994, 95% CI 0.980-1.000, P = .000, respectively). The model including platelet count, reticulocyte percentage, IBIL, and LDH/ULN ratio had a sensitivity of 100%, a specificity of 95.2%, and a misdiagnosis rate of 4.8%. A modified PLASMIC score plus LDH/ULN ratio might be more suitable for identifying ADAMTS13 deficiency patients, especially for making an earlier diagnosis, guiding the immediate and reasonable plasma exchange, and also avoiding unnecessary allocation of plasma.

Embolic stroke of undetermined source in a young woman.

Early thrombotic thrombocytopenic purpura (TTP) recognition is critical as this disease is almost always lethal if not treated promptly with therapeutic plasma exchanges. Currently, as ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity is not widely available in emergency, scores have been developed to help differentiating TTP from other thrombotic microangiopathies (TMAs). The aim of this work was to study the accuracy of these diagnostic scores in the intensive care unit (ICU) setting. Performance of both Coppo and PLASMIC scores was studied in a cohort of adult TMA patients requiring admission to one university hospital ICU from 2006 to 2017. Receiver operating characteristic (ROC) curves were established, and confidence intervals of the area under the curve (AUC) were determined. Multivariate logistic regression analysis was performed to identify parameters specifically associated with TTP, to compare diagnostic scores and to elaborate more accurate diagnostic models. During the study period, 154 TMA patients required ICU admission, including 99 (64.2%) TTP and 55 (35.7%) non-TTP patients. AUC under the ROC curve in predicting TTP was 0.86 (95% confidence interval [CI]: 0.81-0.92) for the Coppo score, 0.67 (95% CI: 0.58-0.76) for the PLASMIC score, and 0.86 (95% CI: 0.81-0.92) for platelet count alone. Platelet count ≤20 G/L, determined as the best cut-off rate for thrombocytopenia, performed similarly to the Coppo score and better than the PLASMIC score to differentiate TTP from non-TTP patients, both using AUC ROC curve and logistic regression. In a monocentric cohort of TMA patients requiring ICU admission, the PLASMIC score had limited performance for the diagnosis of TTP. The performance of the Coppo score was good but similar to a single highly discriminant item: platelet count ≤20 G/L at admission.

Comparative Analysis of Clinical Prediction Scores in Acquired Thrombotic Thrombocytopenic Purpura: The Superiority of Plasmic Score

Can Machine Learning Supplant the Plasmic Score in Improving the Early Diagnosis of Thrombotic Thrombocytopenic Purpura?

The PLASMIC score was developed for distinguishing thrombotic thrombocytopenic purpura (TTP) from other types of thrombotic microangiopathy. However, two components of the PLASMIC score, mean corpuscular volume (MCV) and international normalized ratio (INR), showed non-significant differences between TTP and non-TTP patients in previous validations. Here, we validate the PLASMIC score and aim to modify it by adjusting the criteria of MCV and INR. A retrospective validation of suspected TTP patients was performed by reviewing electronic medical records from two medical centers in Taiwan. The performance of different modified types of the PLASMIC score was carried out. Among 50 patients included in the final analysis, 12 were diagnosed with TTP based on deficiency of ADAMTS13 activity and clinical judgement. When stratified by high (score ≥ 6) and low-intermediate risk (score < 6), the positive predictive value (PPV) of the PLASMIC score to predict TTP was 0.45 (95% confidence interval [CI]: 0.29-0.61). The area under curve (AUC) was 0.70 (95% CI: 0.56-0.82). When adjusting the criteria of the PLASMIC score from MCV < 90 fL to MCV ≥ 90 fL, the PPV increased to 0.57 (95% CI: 0.37-0.75). The AUC was 0.75 (95% CI: 0.61-0.87). When adjusting the INR from >1.5 to >1.1, the PPV increased to 0.56 (95% CI: 0.39-0.71). The AUC was 0.81 (95% CI: 0.68-0.90). MCV ≥ 90 fL and/or INR > 1.1 might be suitable modifications for PLASMIC score but should be validated in a larger sample size.

Thrombotic Thrombocytopenic Purpura (TTP) is caused by reduced activity of von Willebrand factor (VWF) cleaving protease ADAMTS13 which causes the formation of blood clots in small blood vessels throughout the body.1 TTP presents as a microangiopathic haemolytic anaemia and thrombocytopenia. TTP can also present with renal insufficiency, neurologic symptoms, gastrointestinal symptoms and cardiac symptoms such as chest pain and heart failure. Acquired TTP is a rare condition reported in approximately three cases per one million adults per year.2 Diagnosis of TTP is based on reduced (<10) levels of ADAMTS13 activity taken together with the clinical context. Diagnosis of TTP can be made by clinical judgement as well as PLASMIC score, which is based on seven components, to determine risk of TTP and a score of 6–7 is highly predictive of ADAMTS13 activity of ≤10%, with a sensitivity of approximately 91%.3 Identifying and initiating treatment early is critical as TTP is associated with a 90% mortality rate in 10 days if left untreated.4 Standard of care treatment for TTP consists of rituximab, plasma exchange and steroids. Refractory TTP is described as platelet counts not doubling in four to seven days after initiation of treatment. Caplacizumab, an anti-VWF bivalent variable-domain-only immunoglobulin fragment that inhibits interaction between VWF multimers and platelets, was approved for treatment of refractory TTP recently, in February 2019.5 Caplacizumab is the first targeted therapy that blocks the formation of blood clots,6 and this therapy has been demonstrated to reduce time to resolution of thrombocytopenia in refractory TTP cases. Here we describe the case of a 39-year-old female with a medical history of asthma, depression, hyperlipidemia and discoid lupus who presented with the complaint of one week of weakness and headache. She was found to be severely thrombocytopenic with a platelet count of up to 3 × 109/l, anaemic with a haemoglobin level of 70 g/l and hyperbilirubinaemia; manual review of the peripheral smear showed 2+ schistocytes. Microangiopathic haemolytic anaemia was confirmed by elevated lactate dehydrogenase (LDH), undetectable haptoglobin and a negative direct antiglobulin test. Laboratory results were also notable for acute kidney injury with creatinine 1·2 mg/dl (baseline creatinine 0·8 mg/dl) (Fig 1). There was a high suspicion for TTP given the laboratory findings of thrombotic microangiopathy with significant non-immune haemolytic anaemia. This patient had a PLASMIC score of 6. She was immediately started on urgent plasma exchange. After one week of daily plasma exchange at one plasma volume and prednisone 1 mg/kg, the patient's platelet count did not improve (remained at 3 × 109/l). The patient was then started on four doses of weekly rituximab (375 mg/m2). After the first dose of rituximab, her platelet count did not respond appropriately (platelets 5 × 109/l). The diagnosis of TTP was confirmed eight days later when pretreatment ADAMTS13 activity level showed severe deficiency at <5% and a detectable ADAMTS13 inhibitor was present at 1·4 Bethesda units (normal <0·4) in serum. Her clinical course was complicated by worsening renal function (creatinine increased to 1·47 mg/dl), headaches and neurologic symptoms. She developed worsening headache with weakness in the left arm, and became increasingly encephalopathic and menorrhagic. Because her clinical status worsened and the hrombocytopenia was refractory despite treatment with standard therapies for TTP, treatment with daily caplacizumab was initiated. The first dose of 11 mg intravenous (IV) caplacizumab was administered prior to plasma exchange and then another dose of caplacizumab, 11 mg subcutaneous, was administered post plasma exchange. On subsequent days, she was continued on 11 mg subcutaneous daily caplacizumab. After three days of treatment with caplacizumab, the patient had an appropriate response with an increase in platelets to 38 × 109/l. After a total of five days on caplacizumab, she had a substantial increase in platelets to 115 × 109/l. Creatinine also improved to 1·17 mg/dl and LDH improved to 827 U/l. The patient was ultimately treated with plasma exchange (1·5 × plasma volume) daily for one month and then every third day for two weeks. Daily caplacizumab was continued until 30 days after the last plasma exchange session. She also received four doses of weekly rituximab (375 mg/m2 weekly) and a prolonged steroid taper for 13 weeks. Repeat ADAMST13 inhibitor level was obtained after one week of treatment with caplacizumab, ADAMTS13 inhibitor level was <0·4 and ADAMTS13 activity level was 76% indicating that her TTP had resolved. Caplacizumab interferes with VWF and platelet interactions, thereby preventing the consumption of platelets into microthrombosis and consequently preventing progression of tissue ischaemia.7 The mortality associated with TTP is highest in the acute phase due to microthrombotic complications. Thus, initiating timely and effective therapies is imperative. Plasmapheresis is standard of care treatment and should be initiated immediately once there is concern for TTP. Despite great improvement in outcomes with the use of plasma exchange, the mortality among patients with acquired TTP remains 10–20%.8 In this patient there was an insufficient platelet response as well as new neurologic symptoms consistent with refractory TTP. In refractory TTP patients are at highest risk for end organ complications and escalating effective therapies as rapidly as possible is critical given the increased risk of morbidity and mortality. In the HERCULES phase 3 trial, treatment with caplacizumab in patients with TTP has been shown to normalize platelets with a median time of 2·69 days [95% confidence interval (CI), 1·89–2·83] vs. placebo 2·88 days (95% CI, 2·68–3·56; P = 0·01) and patients who received caplacizumab were 1·55 times as likely to have a normalization of the platelet count as those who received placebo. In addition, treatment with caplacizumab prevented the development of refractory TTP.7 Thus, caplacizumab results in a more rapid resolution of TTP episodes, rapidly improves thrombocytopenia, and prevents increased morbidity and mortality by decreasing the formation of microthrombosis. Possible side effects of caplacizumab including haemorrhage, epistaxis, headaches and cost of the medication may be a possible barrier to hospitals carrying this therapy in their pharmacy. Our case exemplifies the benefit of caplacizumab in refractory TTP when standard therapies did not help. Thus, when refractory TTP is recognized caplacizumab should be initiated to prevent increased risk of mortality. *Primary Author

Plasmic Score in Thrombotic Microangiopathy May Not be Discriminatory in Many Instances

Comparing the characteristics of thrombotic thrombocytopenic purpura (TTP) and TTP-like syndrome patients at admission will allow early differentiation of TTP from TTP-like syndrome and help tailor initial treatment. The medical records of 78 patients with suspected TTP in the Emergency Department of Peking University People's Hospital in the past 5years were retrospectively analyzed and divided into TTP and TTP-like syndrome groups based on ADAMTS13 activity and ADAMTS13 antibody titer. There were 25 and 53 patients in the TTP group and the TTP-like syndrome group, respectively. The neutrophil-to-lymphocyte ratio (P = 0.025) was tremendously higher, and albumin (P = 0.002) was lower in the TTP-like syndrome group, indicating a more severe inflammation. Compared with the TTP-like syndrome group, the TTP group had an approximately two-fold to three-fold higher prevalence of central nervous system dysfunction (P < 0.001). Also, hemolysis was more substantial in the TTP group as evidenced by higher schistocytes (P < 0.001), reticulocyte (P < 0.001), total bilirubin (P = 0.002), indirect bilirubin (P < 0.001), lactate dehydrogenase (P = 0.007) and cell-free hemoglobin (P < 0.001), simultaneously lower platelet (P < 0.001), haptoglobin (P = 0.044), and ADAMTS13 activity (P < 0.001). The Kaplan-Meier survival analysis showed that the TTP group significantly predicted poor prognosis (log-rank test: X2 = 5.368, P = 0.021). TTP and TTP-like syndrome are two kinds of distinct phenotypes with different hemolysis statuses and illustrated differentiated inflammatory reactions, target organ damage (TOD), and the clinical outcome.

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening occlusive disease of the microcirculation characterized by systemic platelet plugs, organ ischemia, deep thrombocytopenia, and fragmentation of erythrocytes. One of the widely used scoring system to determine the clinical probability of TTP is the PLASMIC scoring system. This study aimed to evaluate the contribution of PLASMIC score modifications to sensitivity and specificity in patients with microangiopathic hemolytic anemia (MAHA) undergoing plasma exchange with a prediagnosis of TTP at our center. The data of patients who were hospitalized with a previous diagnosis of MAHA and TTP and underwent plasma exchange at Bursa Uludag University, Faculty of Medicine, Department of Hematology between January 2000 and January 2022 were retrospectively analyzed. Overall, 33 patients (including 15 and 18 with and without TTP, respectively) were included in this study. Receiver operating characteristic (ROC) analysis revealed that the area under the curve (AUC) for the original PLASMIC score was 0.985 (95% confidence interval [95% CI]: 0.955-1.000), and AUC for the PLASMIC score without mean corpuscular volume (MCV) was 0.967 (95% CI: 0.910-1.000), which is close to the original AUC. With the removal of MCV from the scoring system, the sensitivity decreased from 100% to 93%, whereas the specificity increased from 33% to 78%. Based on the results of this validation study, removing MCV from the PLASMIC score led to the categorization of eight non-TTP cases in the low-risk category, and this could avoid unnecessary plasma exchange. However, in our study increasing the specificity was at the expense of the sensitivity by missing one patient with this new scoring system without MCV. Further multicenter studies with large sample sizes are required owing to the fact that different parameters may be effective in TTP prediction among different populations.

PEX can significantly improve the survival rate of TTP patients. PLASMIC score can easily and quickly predict the possibility of ADAMTS13 activity reduction, which is beneficial to the early diagnosis of TTP and PEX treatment. NLR can reflect the systemic inflammatory process, but its significance in TTP needs further study.