Urgent Management of Bleeding in Immune Thrombocytopenia: Towards a Standardized Protocol in the Emergency Department
Authors: Mithoowani Siraj , Cervi Andrea , Shah Nishwa , Ejaz Resham , Barty Rebecca , Li Na , Nazy Ishac , Arnold Donald M. 
Published: October 2019

Abstract
Background
Severe bleeding is a rare but serious complication of immune thrombocytopenia (ITP). A standard approach to treatment is lacking and the delivery of emergency care is often disjointed. The objective of this study was to describe 1) the treatments and outcomes of ITP patients who present to the emergency department (ED) with severe thrombocytopenia and bleeding; and 2) predictors of worsening bleeding or death among ITP patients presenting to the ED.
Methods
We did a retrospective cohort study of all patients with ITP who presented to the ED with severe thrombocytopenia (platelet count <20 x109/L) and bleeding in 4 academic hospitals affiliated with McMaster University in Hamilton, Canada between January 2008 and April 2016. Patients were followed from arrival to the ED until 10 days after hospital admission, discharge or death. We extracted demographic data, bleeding symptoms at presentation, all ITP treatments administered, new or worsening bleeding, thrombosis and mortality. Bleeding was graded using the ITP Bleeding Score. We defined major bleeding as intracranial hemorrhage (ICH), pulmonary bleeding, or gross gastrointestinal bleeding (GIB). We summarized the results descriptively by frequencies (percentage), and medians (interquartile range [IQR]). Ethics approval was obtained from the Hamilton Integrated Research Ethics Board. Funding was provided by the Platelet Disorder Support Association.
Results
We identified 110 patients who presented to the ED (n=139 ED visits) with platelets <20 x109/L and bleeding. Median age was 59 years (IQR: 38-74) and 57% were female. For 63 patients (57%), this was their initial presentation of ITP; for the remaining 47 patients, 36% had previously been treated for ITP and had received a median of 3 (IQR: 2-4) ITP therapies. Twenty-eight patients presented to the ED with major bleeding; the remaining 82 patients had ED visits with minor bleeding only.
There were 31 ED visits with major bleeding at presentation including GIB (n=23 visits), ICH (n=4), pulmonary hemorrhage (n=3) and GIB plus ICH (n=1). Median platelet count among patients with major bleeding was 3 x109/L (IQR: 3-8 x109/L). Patients received a median of 3 ITP therapies (IQR: 2-4) after presentation to the ED, including intravenous immune globulin (IVIG; 90% of visits), corticosteroids (77% of visits), platelet transfusions (74% of visits), and romiplostim (3% of visits). Median time from ED presentation to first treatment was 7.6 (4.5-9.5) hours. Treatment for bleeding was initiated by Internal Medicine or Hematology consultants in 19/31 visits (61%) or Emergency Department physicians in 12/31 visits (39%). One patient developed arterial thrombosis and 2 patients died, both from bleeding. There were 6 patients who initially presented to the ED with minor bleeding but who subsequently developed major bleeding after a median of 2 days (range: 1-7). All 6 patients had oral purpura and 4 had frank hematuria before or coincident with the development of major bleeding.
Conclusions
Management of ITP-associated bleeding in the ED consisted mostly of IVIG, corticosteroids and platelet transfusions. Time to first ITP treatment was greater than 7 hours from ED presentation. Oral purpura and hematuria were associated with the development of new or worsening bleeding. A standardized protocol for the management of ITP bleeding in the ED would help identify patients at risk for new or worsening bleeding, and improve health care delivery by making appropriate treatments available in a timely manner.

Disclosures
Arnold: Amgen: Consultancy, Research Funding; UCB: Consultancy; UCB: Consultancy; Amgen: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb: Research Funding; Novartis: Consultancy, Research Funding.