Hemostatic Profiles in Pediatric CKD

Evaluation of Thrombelastography vs. Non-Viscoelastic Assays to Predict Hypercoagulability in Pediatric Chronic Kidney Disease: A Pilot Study

This cross-sectional pilot study will examine the blood clotting patterns in children with chronic kidney disease stages 3, 4, and 5. A total of 30 participants will be enrolled with 10 participants for each stage of chronic kidney disease. Blood specimens will be collected from each participant during a routine clinic visit, and will then be processed to evaluate blood clotting characteristics according to thrombelastography and more conventional clotting tests.

Study Overview

• Status: Completed
• Conditions: Renal Insufficiency, Chronic; Kidney Disease, Chronic; Pediatric Kidney Disease; Blood Coagulation Disorders in Children
• Intervention / Treatment: Diagnostic test: phlebotomy

Detailed Description

Chronic kidney disease (CKD) is associated with 5% of all pediatric inpatient venous thromboembolism (VTE) occurrences, but rates of occurrence are likely underreported in current literature. VTE is associated with a 2-fold increase in mortality, and exponentially higher rates of healthcare expenditure. Because VTE is a low-incidence but high-impact complication of CKD, evaluating those at risk presents a unique challenge. The underlying pathophysiology of thrombosis in CKD is poorly understood, but likely involves changes across the hemostatic and fibrinolytic systems. Standard laboratory tests provide a poor representation of in-vivo clot formation, particularly in the complex hemostatic environment of CKD, as these tests undergo centrifugation and much of the cellular debris known to contribute to clot formation is lost. Viscoelastic assays are a reemerging tool that provide a qualitative measure of each hemostatic milestone, from clot formation through degradation, in whole-blood; thereby preserving the cellular debris and additional factors that contribute to clot formation in-vivo.

The purpose of this study is to evaluate the utility of Thrombelastography vs conventional clotting tests to predict onset of hypercoagulability and the relationship to the stage of pediatric Chronic Kidney Disease (CKD). The investigators hypothesize that as kidney function deteriorates, a more pronounced prothrombotic profile is expected to emerge according to TEG and conventional clotting tests. This will be demonstrated by an overall increase in measured values across the coagulation portion of the TEG and a decrease in the measured fibrinolysis. According to conventional clotting tests, it is expected to find increased levels of Factor VIII antigen, Fibrinogen, vWF, Protein C/S, and D-dimer. Depending upon an individual's degree of proteinuria, levels of Antithrombin would be expected to decrease as it is lost in the urine. This urinary loss of Antithrombin would also contribute to an overall prothrombotic profile.

This cross-sectional pilot study will enroll 30 participants between the ages of 6 months and 17 years who have been previously diagnosed with CKD stages 3, 4, or 5. Enrollment will occur during a routine clinic visit wherein the participant was also previously scheduled to receive venipuncture for ongoing monitoring of labs. Study specific lab values, in addition to routine lab values of interest and pertinent past medical history, will be extracted from the EMR.

• Study Type: Observational
• Enrollment (Actual): 8

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta - Egleston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 17 years (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Previously established, and routinely followed, pediatric individuals between the ages of 6 months and 17 years with a non-inflammatory etiology of chronic kidney disease staged as 3, 4, or 5.

Description

Inclusion Criteria:

• Pediatric patients ages 6 months - 17 years
• Currently followed in the CKD clinic at Children's Healthcare of Atlanta (CHOA)
• Diagnosed with Stage 3, Stage 4 or Stage 5 CKD
• Must have routine venous laboratory tests planned as a component of their clinic encounter.

Exclusion Criteria:

• Participants <13.6kg (to allow for safe blood sample volumes).
• History of venous thromboembolism, post solid organ transplant, co-diagnosis of inflammatory disease, and nephritis.
• Personal or family history of inherited thrombophilia conditions
• Hospital admission within the last 30 days.
• Transfusion (PRBC, FFP, Platelets, or Cryoprecipitate) within the last 30 days.
• Those on the following medications: steroids and anti-coagulants.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
CKD stage 3; Between the ages of 6 months and 17 years currently followed within the hospital system's CKD clinic, and diagnosed with CKD 3 from a non-inflammatory etiology.	Diagnostic test: phlebotomy; phlebotomy will be performed to obtain coagulation labs of interest. Specifically, in addition to standard clinical labs, the following will be drawn on study participants: thrombelastography with platelet mapping, antithrombin, DIC panel, factor VIII, vWF antigen, Protein C antigen and activity, Protein S antigen and activity, and ferritin.
CKD stage 4; Between the ages of 6 months and 17 years currently followed within the hospital system's CKD clinic, and diagnosed with CKD 4 from a non-inflammatory etiology.	Diagnostic test: phlebotomy; phlebotomy will be performed to obtain coagulation labs of interest. Specifically, in addition to standard clinical labs, the following will be drawn on study participants: thrombelastography with platelet mapping, antithrombin, DIC panel, factor VIII, vWF antigen, Protein C antigen and activity, Protein S antigen and activity, and ferritin.
CKD stage 5; Between the ages of 6 months and 17 years currently followed within the hospital system's CKD clinic, and diagnosed with CKD 5 from a non-inflammatory etiology.	Diagnostic test: phlebotomy; phlebotomy will be performed to obtain coagulation labs of interest. Specifically, in addition to standard clinical labs, the following will be drawn on study participants: thrombelastography with platelet mapping, antithrombin, DIC panel, factor VIII, vWF antigen, Protein C antigen and activity, Protein S antigen and activity, and ferritin.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of statistically-significant correlation between conventional clotting tests and thrombelastography when determining the degree of hypercoagulability for pediatric patients diagnosed with chronic kidney disease stages 3, 4, and 5	Thrombelastography with platelet mapping, antithrombin, vwF, Factor VIII antigen, DIC panel, Protein C activity and antigen, Protein S activity and antigen, and Ferritin labs will be evaluated in each participant from the 3 CKD groups.	Day 1

Collaborators and Investigators

• Sponsor: Children's Healthcare of Atlanta
• Investigators: Principal Investigator: Christina Calamaro, PhD, Children's Healthcare of Atlanta

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Actual): May 10, 2022
• Study Completion (Actual): May 10, 2022

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 1, 2021

Study Record Updates

• Last Update Posted (Actual): September 21, 2023
• Last Update Submitted That Met QC Criteria: September 19, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: TEG; thromboelastography; viscoelastic assay
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Urologic Diseases; Disease Attributes; Hematologic Diseases; Hemorrhagic Disorders; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Hemostatic Disorders; Blood Coagulation Disorders; Renal Insufficiency
• Other Study ID Numbers: STUDY00000777

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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