Refaai, Majed A.

A 75-year-old male was admitted with worsening anemia and spontaneous bruising in the left abdominal wall and paraspinal region. Laboratory workup revealed low factor XIII (FXIII) activity levels. Cryoprecipitate transfusions raised his FXIII level, but still fluctuated drastically, ranging from 4 to 43% was discharged 3 days later once his bleeding was managed. Three days later, he was readmitted for severe pain and new bruising in his latissimus dorsi and lateral right thigh. CT-scan revealed hemothorax and arterial bleeding requiring an urgent angiogram with embolization. Chromogenic and functional FXIII assays were unable to elucidate an inhibitor at this time. Management included FXIII concentrate, rituximab, and prednisone; the patient was discharged 12 days later with FXIII levels of 50%. After prednisone tapering, FXIII levels decreased drastically. This case exemplified that higher levels of FXIII are required to prevent bleeding diatheses rather than the previously reported minimum of 5% activity. Despite the diagnostic uncertainty of laboratory testing, the shortened half-life of FXIII activity following replacement therapy and favorable response to immunotherapy indicates that the bleeding diathesis was caused by an acquired inhibitor.

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.

SummaryIntroductionThe performance of factor XI activity (FXI) by laboratories in the North American Specialized Coagulation Laboratory Association proficiency testing program was analyzed.MethodsOver 10 years (2003–2013), 80 samples were distributed; 33–55 laboratories participated per exercise providing 3833 total responses. Analysis was performed on numeric results and qualitative classification of results.ResultsThe sample FXI levels ranged from 3.8 to 154.0 IU/dL. The overall interlaboratory average coefficient of variation (CV%) was 17.5%; the CV was higher for a sample with low (3.8 IU/dL) FXI. Results were correctly classified as abnormal (100%) for a sample with 3.8 IU/dL FXI and normal/borderline normal (97.7%) for 45 samples with 80 to < 140 IU/dL FXI. The classification was heterogeneous for samples with FXI of 50 to < 80 IU/dL. Six specimens were repeat‐tested from 2007 to 2013. The mean FXI was not significantly different in laboratories using the same method on both exercises, suggesting good intralaboratory precision over time. Univariate analysis of data from 2011 to 2012 did not find a consistent significant difference among the activators, analyzers, calibrators, and FXI‐deficient plasmas.ConclusionLaboratories generally performed well in assessment of FXI based on interlaboratory precision when FXI >30 IU/dL and on classification of samples with very low or normal FXI.