Introduction: Idiopathic thrombotic thrombocytopenic purpura (TTP) is a rare hematological disorder caused by deficiency of ADAMTS13 activity and subsequent development of vWF-platelets-rich microthrombi leading to tissue ischemia and organ dysfunction. Standard treatment consists of daily plasma exchange (PEX) to remove the autoantibodies and replenishes ADAMTS13 activity and immunosuppressive therapy for patients with autoimmune process. Recent publication showed that caplacizumab, an anti-vWF humanized nanobody which inhibits the interaction between vWF multimers and platelets, can be used together with PEX to reduce time to platelet normalization but not risk of relapse when compared to placebo. However, incorporate caplacizumab with PEX in high risk TTP patients maybe even more important to reduce long-term organ damage. Therefore, we performed a retrospective single center analysis of TTP patients to identify the incidence and risk factors associated with end-organ damage.
Method: Sixteen adult patients with idiopathic TTP were identified from January 2005 through December 2015. Idiopathic TTP was defined as thrombotic microangiopathy with an ADAMTS13 ≤10%. Cardiac involvement was defined as an increased Troponin I (TnI) level >0.1µg L-1. Renal involvement was defined as serum creatinine >1.30mg/dL. Of note, all the 16 patients had normal baseline renal function. Neurological involvement was defined as documentation of confusion, headaches, seizure, aphasia and syncope. The time to a platelet response was defined as a platelet count that was ≥150,000/mm3 for at least 48 hours. All patients were treated with PEX, corticosteroids, ± rituximab.
Results: The mean (range) age was 48 (23 to 78) and the female: male ratio was 12:4. All (16) patients had end-organ involvements: 16 (100%) neurological, 6 (37.5%) renal, and 4 (25%) cardiac. Seven patients (43.75%) had single organ involvement (Group one), 9 patients (56.25%) had two or three organ involvement (Group two). The mean age for Group one was 44 as compared to 51 for Group two. The mean LDH level on admission was 987 IU/L (range: 417-1,289 IU/L) for Group one as compared to 1,715 IU/L (range: 336-4,455 IU/L) for Group two (p value: 0.06). The mean platelet count on admission was 20 k/µL for Group one as compared to 18 k/µL for Group two. The mean hemoglobin level on admission was 7.5g/dL (range: 5.3-8.6g/dL) for Group one as compared to 8.78g/dL (range: 8.1-10.5g/dL) for Group two. The median time to a platelet response was 5 days in this study population.
Conclusions: Our study showed that more than 50% of TTP patients presented with multi-organ involvement. Very high LDH at initial presentation prior to PEX was identified as a probable single risk factor associated with multi-organ involvement. Prompt arrest of vWF-mediated platelet aggregation with agents such as calpalacizumab in TTP patients could prevent or minimize early irreversible end-organ damage due to tissue ischemia. Identifying risk factors for severe end-organ involvement will be important to study the potential benefit of incorporating calpalacizumab into TTP treatment. Further study on the risk factors for end-organ involvements in TTP patients and their long-term outcome at a multi-center level and with a larger patient population is warranted.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
