Deaths and complications associated with the management of acute immune thrombotic thrombocytopenic purpura

Abstract

BACKGROUND The introduction of therapeutic plasma exchange (TPE) dramatically decreased mortality in patients with immune thrombotic thrombocytopenic purpura (iTTP). However, there are few modern descriptions of residual causes of death from iTTP and complications associated with TPE. STUDY DESIGN AND METHODS This was a retrospective study in a multi‐institutional cohort of 109 patients with iTTP between 2004 and 2017. Complications of TPE were analyzed in a subset of this cohort (74 patients representing 101 treatment courses). RESULTS Death occurred in 8 of 109 patients (7.3%) and in 8 of 219 captured episodes of acute iTTP (mortality rate per episode: 3.7%). Neither the number of TPE treatments nor length of hospitalization predicted mortality. The majority of deaths (5/8) were associated with delay in the diagnosis of iTTP or initiation of TPE or presentation to the hospital in a moribund state. A subset of patients (N = 74) was analyzed for TPE‐related complications. Most patients (56/74; 76%) had at least one minor or major complication of TPE. Seven of 101 (6.9%) discrete treatment courses were associated with one or more severe complications, including anaphylaxis and line‐associated infections and thrombosis. Overall, the most frequent adverse events were mild allergic (urticarial) transfusion reactions, which affected 34 of 101 (34%) treatment courses. One patient died from a TPE‐related complication, line‐associated bacteremia. CONCLUSION Early identification of patients with iTTP and the rapid initiation of TPE are paramount in preventing mortality. While TPE was associated with a high rate of adverse events, the vast majority were treatable and TPE‐related mortality is low.

Diagnostic accuracy of the PLASMIC score in patients with suspected thrombotic thrombocytopenic purpura: A systematic review and meta‐analysis

“…The advent of TPE in the 1980s and 1990s transformed TTP from an almost uniformly fatal condition into a treatable disease with an approximately 90% survival rate 2,27 . Accordingly, clinical practice guidelines recommend immediate initiation of TPE in all patients with suspected TTP 28 .…”

“…Insertion of an apheresis catheter carries a risk of bleeding, infection, and thrombosis. Exposure to plasma may result in allergic reactions or transfusion‐related acute lung injury 27,30 . Moreover, in patients without TTP, effective treatments (eg, anti‐complement therapy for atypical hemolytic‐uremic syndrome) may be delayed while TPE is administered.…”

Case Report of Thrombotic Thrombocytopenic Purpura in a Previously Healthy Adult

“…9 While the introduction of plasmapheresis has dramatically improved survival rates, mortality remains between 7-22% in those who receive standard treatment. [10][11][12] Delayed diagnosis and treatment have been reported to contribute significantly to this mortality rate and to an increased risk of relapse. 10,11 In a small retrospective study examining TTP-related deaths at six institutions, Colling et al reported an association between mortality and a delay in the initiation of plasma exchange for more than 24 hours after presentation, highlighting the urgency for rapid diagnosis and immediate treatment.…”

“…[10][11][12] Delayed diagnosis and treatment have been reported to contribute significantly to this mortality rate and to an increased risk of relapse. 10,11 In a small retrospective study examining TTP-related deaths at six institutions, Colling et al reported an association between mortality and a delay in the initiation of plasma exchange for more than 24 hours after presentation, highlighting the urgency for rapid diagnosis and immediate treatment. 11 However, early diagnosis of iTTP can be challenging, as symptoms are often generalized and overlap with various other forms of thrombotic microangiopathies, and the clinical presentation can vary widely between patients.…”

Assessing the risk of refractory disease in iTTP

“…Notably, while the complete dataset was characterized by a very high mortality rate (24/134, 17·9%), death itself was not included within the definition of refractoriness, thereby limiting the clinical utility of the AHC score. This is relevant in light of prior work suggesting that early deaths are not uncommon in iTTP, 7 and some patients may die before they are able to meet the definition of refractoriness. Additionally, rituximab (RTX) was used in only a subset of refractory patients (28/55) and it is possible that the AHC score may be less predictive in settings where RTX is used as standard of care.…”