ISOC-2

The ISOC-2 study is now complete.

Study hypothesis

Prolongation of PT does not correlate well with an individual’s coagulation potential, bleeding or thrombosis, and the global clotting tests Thrombin Generation (TG) and thromboelastography (TEG/ROTEM) might be better predictors of bleeding and thrombosis.

Studies evaluating the optimal management of coagulopathy in critically ill patients need to be based around better validated tests of haemostasis. Future clinical studies may then evaluate restricted or targeted use of replacement therapies such as FFP or small volume prohaemostatic drugs such as PCCs.

Study design

Prospective cohort observational study. Multicentre cross-sectional observational cohort study.

All patients admitted to the participating Intensive Care Units with a prolonged PT, within the first 48 hours of admission, will have a screening log completed by a trained clinician. The screening log will be completed from the patient’s notes.

If the inclusion criteria are met and no exclusion criteria are met, consent will be sought. Once consent has been given by the patient (or if the patient is unable to consent with agreement from a personal consultee or clinician not directly involved with the study), a registration form will be completed and registration bloods taken as soon as possible and within the first 48 hours of the patient’s ICU admission.

A 48 hour period is allowed so that patients admitted at the weekend may be included in the study; however the blood samples should be taken as soon as practically possible after admission.

The baseline data collected on the registration form will be collected from the patient’s notes and will include age, gender, hospital and ICU admission date, most relevant ICU admission diagnosis, transfusion history, significant co-morbidities and co-interventions including mechanical ventilation, dialysis and cardiovascular support.

The blood samples taken at registration will confirm a prolonged PT is present, and will be tested for a range of haemostatic tests, including traditional markers of coagulopathy and new whole blood measurements of coagulopathy.

At centres where whole blood ROTEM and TEG can be processed this data will be collected. All centres will centrifuge and freeze plasma for central analysis.

Patients on the Intensive Care Unit have their blood sampled daily for standard tests of coagulopathy whether they are in a study or not, and these results will be recorded on a daily Case Report Form.

The daily Case Report Form will also collect data on transfusions and prompts the completion of a bleeding assessment form, should a clinically significant bleed occur. Clinically significant bleeding is defined as either an estimated total cumulative blood loss of > 300ml, or from a critical site such as intracranial.

Further blood samples specifically for this study will only be taken if FFP is transfused. Blood will be taken within two hours before and between one and two hours after the completion of the first FFP transfusion during the study period.

The FFP dose used on the ICUs should be standardised at 15mls/kg in keeping with national guidelines and any variance will be recorded on the daily Case Report Form. Blood will only be sampled around the first FFP transfusion.

An end of study form will be completed and end of study bloods collected, if no pre and post FFP bloods have been taken, at whichever occurs first: discharge from ICU, day 5 of admission, or death. The whole study will end when this occurs for the last patient.

Publications

Simon J. Stanworth, Michael J.R. Desborough, Gemma Simons, Frances Seeney, Gillian Powter, Stephen MacDonald, Stuart McKechnie, Laura Green, Neil Young, Timothy Walsh, and Mike A. Laffan Clinical bleeding and thrombin generation in admissions to critical care with prolonged prothrombin time: an exploratory study Transfusion 2018 First published: 10 April 2018 DOI.org/10.1111/trf.14605