Platelet Reactivity in Septic Shock

Impaired Platelet Reactivity as an Early Biomarker for Sepsis-related Thrombocytopenia

Coagulation disorders and thrombocytopenia are common in patients with septic shock. Despite the clinical relevance of sepsis-induced thrombocytopenia, few studies have focused on the prediction of thrombocytopenia in this setting. The aim of this study was to evaluate whether platelets aggregometry and markers of platelets activation, such as mean platelet volume or platelet volume distribution width, could predict sepsis-induced thrombocytopenia in patients with septic shock and normal platelet count on the day of diagnosis.

Study Overview

• Status: Completed
• Conditions: Sepsis; Septic Shock; Thrombocytopenia; Platelet Aggregation; Disseminated Intravascular Coagulation
• Intervention / Treatment: Diagnostic test: platelet responsiveness evaluation

• Study Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

Study Locations

• Italy
  • Ferrara, Italy, 44121
    • Università di Ferrara

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Patients in intensive care unit

Description

Inclusion Criteria:

• diagnosis of septic shock
• platelet count >150*103/mcL.

Exclusion Criteria:

• age <18 years
• history of any hematologic disorder
• chronic liver failure
• previous chemotherapy
• transfusion of platelet during the previous 4 weeks
• renal replacement therapy before ICU admission
• history of antiplatelet therapy during the 8 days before inclusion
• history of heparin-induced thrombocytopenia (HIT) or other acquired or induced thrombocytopenia
• occurrence of HIT (defined as HIT score over 3)
• active bleeding

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

septic shock patients; Inclusion criteria of the study were diagnosis of septic shock and a platelet count >150*103/mcL.

Diagnostic test: platelet responsiveness evaluation; Blood samples were anticoagulated with 0.129 mmol/L of sodium citrate and then centrifugated for 10 min at 200 rpm; platelets aggregation was assessed with an AggRAM Advanced Modular System light transmittance aggregometer (Helena Laboratories, Beaumont, Texas, USA). Low-molecular-weight heparin (LMWH) was given at least 8 hours before any blood aggregation sample. Agonist used to initiate aggregation test were: -Adenosine diphosphate (ADP) to assess P2Y12-dependent platelet aggregation; (20 ng) - Arachidonic acid (AA) to assess cyclooxygenase-dependent platelet Adenosine diphosphate aggregation (1 mcg) - thrombin receptor-activating peptide-6 (TRAP-6) to assess protease-activated receptor 1-dependent platelet aggregation. Max aggregation reached (Aggmax), the slope of the curve (slope) and the latency time (lat) were analyzed for each agonist.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurence of sepsis-induced thrombocytopenia	Occurence of platelet count <150 *103/μL	5 days after study inclusion

Secondary Outcome Measures

Outcome Measure	Time Frame
life-threatening bleeding	After 28 days from study inclusion
90-day mortality	after 90 days from study enrollment
number of Red blood cells (RBC) packs transfused during ICU stay	After 28 days from study inclusion

Collaborators and Investigators

• Sponsor: Università degli Studi di Ferrara

Publications and helpful links

General Publications

• Campo G, Valgimigli M, Gemmati D, Percoco G, Tognazzo S, Cicchitelli G, Catozzi L, Malagutti P, Anselmi M, Vassanelli C, Scapoli G, Ferrari R. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY Study. J Am Coll Cardiol. 2006 Dec 5;48(11):2178-85. doi: 10.1016/j.jacc.2005.12.085. Epub 2006 Nov 13.
• Dewitte A, Lepreux S, Villeneuve J, Rigothier C, Combe C, Ouattara A, Ripoche J. Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critically [corrected] ill patients? Ann Intensive Care. 2017 Dec 1;7(1):115. doi: 10.1186/s13613-017-0337-7. Erratum In: Ann Intensive Care. 2018 Feb 28;8(1):32.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2017
• Primary Completion (ACTUAL): May 30, 2018
• Study Completion (ACTUAL): August 30, 2018

Study Registration Dates

• First Submitted: October 17, 2018
• First Submitted That Met QC Criteria: October 19, 2018
• First Posted (ACTUAL): October 23, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 23, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Hematologic Diseases; Hemorrhagic Disorders; Shock; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombophilia; Sepsis; Shock, Septic; Thrombocytopenia; Disseminated Intravascular Coagulation
• Other Study ID Numbers: Sepsisplt

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No