Delays in the Emergent Management of Patients with Immune-Mediated Thrombotic Thrombocytopenic Purpura: A Ten-Year Retrospective Study

Introduction: Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a hematologic emergency with up to 95% mortality if untreated. Emergent plasma exchange (PLEX) is the mainstay therapy in an acute episode. Due to the morbidity and mortality, the British Society of Haematology recommends initiation of PLEX within 4-8 hours, yet there is a limited data on real-world practice and if earlier initiation affects clinical outcomes. We sought to report timing of PLEX initiation in a tertiary hospital, assess for delays, and determine the variables that contribute to delays.

Methods: The Parkland Health and Hospital System electronic medical record system was queried for ADAMTS13 activity over a ten-year period from 7/2011 to 7/2021, identifying 1,371 ordered tests, with 465 ordered in the emergency department, observation status, or inpatient setting. The first ADAMTS13 activity order was used as the initial time of suspected iTTP diagnosis. Time of line placement was obtained from documentation and imaging for internal jugular central venous catheters (CVCs). The time of PLEX initiation was derived from flowsheets maintained by the apheresis nursing staff. Delays in PLEX were defined as ≥8 hours from ADAMTS13 activity order to PLEX initiation (order-to-PLEX). Categorical variables were compared using the chi-square test, while continuous variables were compared using the Wilcox rank sum test.

Results: Seventy-two patients were identified who were planned to undergo emergent PLEX. Two patients died before PLEX initiation-one patient had a CVC placed. Of the 70 patients receiving PLEX, 44% (n= 31) had an order-to-PLEX time ≥8 hours. The order-to-PLEX median (IQR) time (n=70) was 7.5 hours (4.7 - 20.3) with no significant difference between those with a history of iTTP versus those without (no history: 9.3h v history of iTTP: 6.4h, P = 0.10). Delays in PLEX were associated with eventual non-iTTP diagnoses (<8h: 26% v ≥8h: 52%, P = 0.025), higher platelet count (<8h: 18 v ≥8h: 33, P < 0.001), and the originating ADAMTS13 activity ordering department (P = 0.043). There were delays at each phase of PLEX initiation, including CVC placement (<8h: 2.8 hours v ≥8h: 20.7 hours) and PLEX initiation (<8h: 1.4 hours v ≥8h: 2.2).

Discussion: We demonstrate that at a tertiary hospital only 54% of patients receive PLEX for suspected iTTP within 8 hours. Self-identified race or preferred language other than English were not associated with delays in PLEX. Line placement and PLEX initiation can both be significantly delayed and should be considered as potential benchmarks moving forward. Additionally, there is a knowledge gap since some ordering services waited for the ADAMTS13 activity to result prior to initiating emergent PLEX. Thus, we identify three areas for clinical improvement to expedite CVC placement and timely initiation of PLEX for patients with suspected iTTP: 1) improvement in education and workflows to emphasize the emergent nature of iTTP, 2) codifying agreements with procedure services to expedite CVC placement, and 3) arranging apheresis coverage for immediate PLEX.

No relevant conflicts of interest to declare.