TY - JOUR
T1 - A prospective quality improvement initiative in adult hemophagocytic lymphohistiocytosis to improve testing and a framework to facilitate trigger identification and mitigate hemorrhage from retrospective analysis
AU - Merrill, Samuel A.
AU - Naik, Rakhi
AU - Streiff, Michael B.
AU - Shanbhag, Satish
AU - Lanzkron, Sophie
AU - Braunstein, Evan M.
AU - Moliterno, Alison M.
AU - Brodsky, Robert A.
N1 - Funding Information:
SAM was supported by National Institutes of Health, National Heart, Lung, and Blood Institute hematology fellowship training grant T32 HL007525. This work was made possible by a generous gift from the Strome Family Foundation. This publication was made possible by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number UL1TR001079 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research.
Funding Information:
The authors acknowledge assistance for clinical data coordination from the Center for Clinical Data Analytics, supported in part by the Johns Hopkins Institute for Clinical and Translational Research (ICTR). We thank Drs. Thomas Kickler, Richard Ambinder, and Michael Borowitz for their helpful discussions. We thank Ximin Li from the ICTR for statistical consultation. We would like to acknowledge support for the Johns Hopkins Institute for Clinical and Translational Research (ICTR)statistical consultation from the National Center for Research Resources and the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health through Grant Number 1UL1TR001079.
Publisher Copyright:
Copyright © 2018 the Author(s). Published by Wolters Kluwer Health, Inc. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal, hyperinflammatory syndrome in adults triggered by an underlying illness in most cases. As such, suspicion of HLH dictates further investigation to identify the HLH trigger and determine treatment. HLH is clinically challenging due to diverse presentations and underlying triggers, provider unfamiliarity, and bleeding complications. Clinically, we observed diagnostic error from incorrect testing and cognitive biases (interleukin-2 confused with soluble interleukin-2 receptor and natural killer cell quantification confused with functional assays). This study reports our single institutional experience with adult HLH with the aim to reduce erroneous testing with a quality improvement (QI) project, and to facilitate trigger discovery and mitigate hemorrhage. Provider education on HLH testing was the prospective intervention, followed by mistaken test removal. HLH triggers and diagnostic utility were determined by retrospective chart review. Risk factors for hemorrhage were determined by multivariable analysis. Erroneous HLH testing was reduced from 74% to 24% of patients (P < .001) by the QI intervention. These changes were projected to save $11,700 yearly. The majority (64%) of patients evaluated for HLH were on non-hematology/oncology services, highlighting the need for vigilance in hematology consultation. Sixty-three patients met classic HLH-2004 criteria for HLH. Malignancy (38%), infection (27%), Epstein-Barr virus (EBV) (14%), or autoimmune disease (8%) triggered most HLH cases. HLH triggers were most commonly identified by serologic testing (27%) and bone marrow biopsy (19%). Biopsy of other affected organs based on PET-CT imaging after unsuccessful initial diagnostic measures was helpful, and focal fluorodeoxyglucose uptake was predictive of an underlying malignancy (likelihood ratio 8.3, P = .004). Major hemorrhage occurred in 41% of patients. On multivariable analysis the odds ratios (OR) for major hemorrhage were increased for patients with intensive care unit level care (OR 10.47, P = .005), and disseminated intravascular coagulation in the first week of admission (OR 10.53, P = .04). These data are incorporated into a framework to encourage early HLH recognition with the HScore, facilitate trigger identification, identify those at risk for hemorrhage, and minimize low-yield or erroneous testing.
AB - Hemophagocytic lymphohistiocytosis (HLH) is a highly fatal, hyperinflammatory syndrome in adults triggered by an underlying illness in most cases. As such, suspicion of HLH dictates further investigation to identify the HLH trigger and determine treatment. HLH is clinically challenging due to diverse presentations and underlying triggers, provider unfamiliarity, and bleeding complications. Clinically, we observed diagnostic error from incorrect testing and cognitive biases (interleukin-2 confused with soluble interleukin-2 receptor and natural killer cell quantification confused with functional assays). This study reports our single institutional experience with adult HLH with the aim to reduce erroneous testing with a quality improvement (QI) project, and to facilitate trigger discovery and mitigate hemorrhage. Provider education on HLH testing was the prospective intervention, followed by mistaken test removal. HLH triggers and diagnostic utility were determined by retrospective chart review. Risk factors for hemorrhage were determined by multivariable analysis. Erroneous HLH testing was reduced from 74% to 24% of patients (P < .001) by the QI intervention. These changes were projected to save $11,700 yearly. The majority (64%) of patients evaluated for HLH were on non-hematology/oncology services, highlighting the need for vigilance in hematology consultation. Sixty-three patients met classic HLH-2004 criteria for HLH. Malignancy (38%), infection (27%), Epstein-Barr virus (EBV) (14%), or autoimmune disease (8%) triggered most HLH cases. HLH triggers were most commonly identified by serologic testing (27%) and bone marrow biopsy (19%). Biopsy of other affected organs based on PET-CT imaging after unsuccessful initial diagnostic measures was helpful, and focal fluorodeoxyglucose uptake was predictive of an underlying malignancy (likelihood ratio 8.3, P = .004). Major hemorrhage occurred in 41% of patients. On multivariable analysis the odds ratios (OR) for major hemorrhage were increased for patients with intensive care unit level care (OR 10.47, P = .005), and disseminated intravascular coagulation in the first week of admission (OR 10.53, P = .04). These data are incorporated into a framework to encourage early HLH recognition with the HScore, facilitate trigger identification, identify those at risk for hemorrhage, and minimize low-yield or erroneous testing.
KW - Diagnostic error
KW - Hemophagocytic lymphohistiocytosis
KW - Quality improvement
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U2 - 10.1097/MD.0000000000011579
DO - 10.1097/MD.0000000000011579
M3 - Article
C2 - 30075527
AN - SCOPUS:85052235962
SN - 0025-7974
VL - 97
JO - Medicine (United States)
JF - Medicine (United States)
IS - 31
M1 - e11579
ER -