Uhl, Lynne

AbstractBackgroundImmune thrombotic thrombocytopenic purpura (iTTP) is a hematologic disorder characterized by severe acquired deficiency in ADAMTS13, resulting in thrombotic microangiopathy and death if untreated. Plasma exchange (PLEX) is the backbone of iTTP management and has improved survival in this disorder. Guidelines suggest initiation of PLEX within 4–8 h of presentation; however, there is little evidence to guide the precise timing of PLEX, and barriers exist to its timely deployment.Study design and methodsWe examined determinants of time between symptom onset to PLEX initiation (S2P) and hospital presentation to PLEX initiation (door to PLEX, D2P) in a large iTTP research cohort at an academic medical center.ResultsIn 225 cases occurring in 143 unique patients, the median (IQR) S2P time was 4.28 (1.92–7.47) days. In linear mixed effects regression analysis, increased S2P was associated with greater distance from a participating apheresis center (p = .01) and higher presenting platelet count (p = .046), while relapse presentation was associated with shorter S2P (p = .036). The median (IQR) D2P time was 8.4 (5.03–15.63) h. Longer D2P time was associated with a higher presenting platelet count (p = .002) and trended towards association with male sex (p = .057). Increased S2P and D2P times were not associated with hospital length of stay, mortality, or the composite of mortality and ICU stay.ConclusionOur data show that different factors contribute to the interval between symptom onset and presentation versus the time between presentation and initiation of therapy in iTTP.

Abstract Patients treated with antineoplastic therapy often develop thrombocytopenia requiring platelet transfusion, which has potential to exacerbate pulmonary injury. This study tested the hypothesis that amotosalen-UVA pathogen–reduced platelet components (PRPCs) do not potentiate pulmonary dysfunction compared with conventional platelet components (CPCs). A prospective, multicenter, open-label, sequential cohort study evaluated the incidence of treatment-emergent assisted mechanical ventilation initiated for pulmonary dysfunction (TEAMV-PD). The first cohort received CPC. After the CPC cohort, each site enrolled a second cohort transfused with PRPC. Other outcomes included clinically significant pulmonary adverse events (CSPAE) and the incidence of treatment-emergent acute respiratory distress syndrome (TEARDS) diagnosed by blinded expert adjudication. The incidence of TEAMV-PD in all patients (1068 PRPC and 1223 CPC) was less for PRPC (1.7 %) than CPC (3.1%) with a treatment difference of –1.5% (95% confidence interval [CI], –2.7 to –0.2). In patients requiring ≥2 PCs, the incidence of TEAMV-PD was reduced for PRPC recipients compared with CPC recipients (treatment difference, –2.4%; 95% CI, –4.2 to –0.6). CSPAE increased with increasing PC exposure but were not significantly different between the cohorts. For patients receiving ≥2 platelet transfusions, TEARDS occurred in 1.3% PRPC and 2.6% CPC recipients (P = .086). Bayesian analysis demonstrated PRPC may be superior in reducing TEAMV-PD and TEARDS for platelet transfusion recipients compared with CPC recipients, with 99.2% and 88.8% probability, respectively. In this study, PRPC compared with CPC demonstrated high probability of reduced severe pulmonary injury requiring assisted mechanical ventilation in patients with hematology disorders dependent on platelet transfusion. This trial was registered at www.ClinicalTrials.gov as #NCT02549222.

AbstractBackgroundPlatelet transfusion carries risk of transfusion‐transmitted infection (TTI). Pathogen reduction of platelet components (PRPC) is designed to reduce TTI. Pulmonary adverse events (AEs), including transfusion‐related acute lung injury and acute respiratory distress syndrome (ARDS) occur with platelet transfusion.Study designAn open label, sequential cohort study of transfusion‐dependent hematology‐oncology patients was conducted to compare pulmonary safety of PRPC with conventional PC (CPC). The primary outcome was the incidence of treatment‐emergent assisted mechanical ventilation (TEAMV) by non‐inferiority. Secondary outcomes included: time to TEAMV, ARDS, pulmonary AEs, peri‐transfusion AE, hemorrhagic AE, transfusion reactions (TRs), PC and red blood cell (RBC) use, and mortality.ResultsBy modified intent‐to‐treat (mITT), 1068 patients received 5277 PRPC and 1223 patients received 5487 CPC. The cohorts had similar demographics, primary disease, and primary therapy. PRPC were non‐inferior to CPC for TEAMV (treatment difference −1.7%, 95% CI: (−3.3% to −0.1%); odds ratio = 0.53, 95% CI: (0.30, 0.94). The cumulative incidence of TEAMV for PRPC (2.9%) was significantly less than CPC (4.6%, p = .039). The incidence of ARDS was less, but not significantly different, for PRPC (1.0% vs. 1.8%, p = .151; odds ratio = 0.57, 95% CI: (0.27, 1.18). AE, pulmonary AE, and mortality were not different between cohorts. TRs were similar for PRPC and CPC (8.3% vs. 9.7%, p = .256); and allergic TR were significantly less with PRPC (p = .006). PC and RBC use were not increased with PRPC.DiscussionPRPC demonstrated reduced TEAMV with no excess treatment‐related pulmonary morbidity.