Thromboelastography to Assess Age-Related Coagulation Differences in Patients Undergoing Cesarean Delivery

• ClinicalTrials.gov Identifier: NCT01416454
• Recruitment Status: Completed
• First Posted: August 15, 2011
• Last Update Posted: March 22, 2013
• Sponsor: Stanford University
• Information provided by (Responsible Party): Stanford University

Study Description

Brief Summary:

The purpose of the study is to assess potential age-related differences on coagulation profile of patients undergoing Cesarean Section, using thromboelastography (TEG). The investigators will compare coagulation data collected from the study to assess potential differences in coagulation parameters for the following age groups: (i) women less than 35 yrs (ii) women 35 yrs or older.

Condition or disease
Thrombophilia

Detailed Description:

The purpose of the study is to assess potential age-related differences on coagulation profile of patients undergoing Cesarean Section, using thromboelastography (TEG). The investigators will compare coagulation data collected from the study to assess potential differences in coagulation parameters for the following age groups: (i) women less than 35 yrs (ii) women 35 yrs or older. This study will allow us to collect more information about differences regarding coagulation profile in patients undergoing cesarean section who are less than 35 y vs. 35y or older. This information will add to current knowledge base about potential risk for thrombotic events according with age.

All obstetric patients presenting for elective Cesarean delivery (CD) will be informed about the study prior to and on admission to the labor and delivery unit. Patients will be informed at parents' education classes (during education sessions by obstetric anesthesiologists who are also members of the research team). Potential participants will be approached by a member of the research team prior to surgery. A study investigator will obtain patient written informed consent.

Pre-operatively, blood sampling will take place by venepuncture for the following analysis:

Hematocrit, Platelet count (which are part of standard of care), TEG, prothrombin time (PT), Partial Thromboplastin Time (PTT), International Normalized Ratio (INR), fibrinogen (for research purposes only, unless they are needed for clinical purposes).

The investigators would prefer to avoid taking blood samples from indwelling peripheral IV lines, as the samples will likely be diluted with intravenous fluid and therefore may significantly affect blood sampling analysis. The volumes of blood necessary for TEG analysis are extremely small (1 ml - less than half of a teaspoon - per TEG analysis; total =3 samples), and therefore will not significantly affect any potential degree of hemorrhage or total blood loss incurred. The volumes of blood for laboratory analysis will also be small (4-5 ml - about 1 teaspoon - for each research sample: total =3 samples), and will not affect overall blood loss. No randomization will be possible. TEG and laboratory samples will be taken at the following time intervals: prior to anesthesia in the preoperative holding unit, post-operative days one and three.

Data will be assessed for normality using normality plots and the Kolmogorov-Smirnov test. Normally and non-normally distributed TEG parameters before and after CD (PACU samples) will be assessed by using the paired t-test and Wilcoxon signed-rank test respectively. The percentage change from baseline for each TEG parameter and Hb before and after CD will also be calculated. Longitudinal analysis of individual changes for each TEG parameter will be performed using mixed effects regression modeling, due to the non-uniformity of time-intervals and to account for correlation among repeated measurements on the same participants. The investigators will examine longitudinal models for individual TEG parameters as a dependent measure, with study group as a fixed factor, and number of previous cesarean section, total blood loss, IV fluids, platelet count and fibrinogen counts as potential covariates (tbc). Separate models will incorporate age as continuous independent variable (as both a fixed and random effect). The investigators will analyze these data using SAS version 9.2 (SAS Institute, Cary, N.C., USA).

Study data will be stored in secured, locked storage boxes which will only be accessed by study investigators. Samples and labels will be identified using a numerical system based allocated prior to the start of the study. Only investigators directly involved in the study will have access to the study data and other related documents.

Study data will be protected as follows:

Hard data will be stored in secure box-files kept in locked file cabinets; databases with study data will be password-protected. Study information will be coded in advance using a numerical coding system not linked to the patients' medical record number or other PHI. Coding will be performed when data is entered into the database. Only study investigators will have access to the coding system for de-identifying data. All codes used to protect study data and confidential information will be used solely by study investigators. All codes used for data- protection will be known only to the study investigators, and software-protection and encryption programs will be used as appropriate.

TEG will be performed by study investigators on the labor and delivery unit. Blood samples will be destroyed after TEG analysis. Other laboratory samples will be analyzed as per normal procedure.

Electronic data will be stored at the Stanford File Management Tool. Only researchers and research staff will be granted password-protected access to identifiable and coded data stored on this server.

All persons involved in this study will receive appropriate training and abide by confidentiality guidelines to protect the subject's privacy. All HIPAA rules and regulations will be strictly followed.

Study Design

• Study Type: Observational
• Actual Enrollment: 46 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Thromboelastography to Assess Age-Related Coagulation Differences in Patients Undergoing Elective Cesarean Delivery.
• Study Start Date: October 2010
• Actual Primary Completion Date: April 2012
• Actual Study Completion Date: November 2012

Groups and Cohorts

Group/Cohort
Elective Cesarean delivery, age <35 yrs; Women undergoing elective cesarean delivery with a spinal anesthetic who are less than 35 y of age (at the time of delivery).
Elective Cesarean delivery, age =>35 yrs; Women undergoing elective Cesarean delivery with a spinal anesthetic who are => 35 yrs of age (at the time of delivery).

Outcome Measures

Primary Outcome Measures :

1. Thromboelastography parameters [ Time Frame: 3 days ]

   Thromboelastography parameters include:

   Reaction (r) time Clot Formation (k) time Alpha Angle Maximum Amplitude (MA) Time to maximum rate of thrombus generation (Tmax) Maximum rate of thrombus generation (MRTG) Total Thrombus generated (TTG)

Secondary Outcome Measures :

1. laboratory coagulation parameters [ Time Frame: 3 days ]
   • Prothrombin time
   • Activated partial thromboplastin time
   • Fibrinogen level.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes
• Sampling Method: Probability Sample

Study Population

Our study population will be obstetric patients undergoing delivery on the labor and delivery unit at Lucile Packard Children's Hospital (LPCH).

Criteria

Inclusion Criteria:

• All obstetric patients with singleton pregnancies admitted to the labor and delivery unit at LPCH who undergo elective Cesarean delivery with neuraxial anesthesia.
• We will enroll only healthy patients with singleton pregnancies and whose pregnancy is not result of in vitro fertilization.

Exclusion Criteria:

• Patients with underlying coagulation disorders.
• Patients with thrombocytopenia.
• Patients with pregnancy-induced hypertension, pre-eclampsia.
• Patients requiring the following medications prior to surgery: non-steroidal anti-inflammatories, aspirin, anticoagulants.
• Patients requiring non-elective Cesarean delivery.
• Patients with significant obstetric or medical disease.
• No patients <18 years of age will be recruited.

Contacts and Locations

Locations

United States, California

Stanford University School of Medicine

Stanford, California, United States, 94305

Sponsors and Collaborators

Stanford University

Investigators

• Principal Investigator: Alex James Butwick; Stanford University

More Information

Publications:

James AH. Venous thromboembolism in pregnancy. Arterioscler Thromb Vasc Biol. 2009 Mar;29(3):326-31. doi: 10.1161/ATVBAHA.109.184127.

Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J. Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008 Jun;133(6 Suppl):844S-886S. doi: 10.1378/chest.08-0761.

Morris JM, Algert CS, Roberts CL. Incidence and risk factors for pulmonary embolism in the postpartum period. J Thromb Haemost. 2010 May;8(5):998-1003. doi: 10.1111/j.1538-7836.2010.03794.x. Epub 2010 Feb 1.

Sharma SK, Philip J, Wiley J. Thromboelastographic changes in healthy parturients and postpartum women. Anesth Analg. 1997 Jul;85(1):94-8. doi: 10.1097/00000539-199707000-00017.

Saha P, Stott D, Atalla R. Haemostatic changes in the puerperium '6 weeks postpartum' (HIP Study) - implication for maternal thromboembolism. BJOG. 2009 Nov;116(12):1602-12. doi: 10.1111/j.1471-0528.2009.02295.x. Epub 2009 Aug 14.

Ng KF. Changes in thrombelastograph variables associated with aging. Anesth Analg. 2004 Aug;99(2):449-54, table of contents. doi: 10.1213/01.ANE.0000133140.75831.1E.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Butwick A, Gutierrez MC, Hilton G. The impact of advanced maternal age on peripartum thromboelastographic coagulation profiles: a prospective observational exploratory study. Can J Anaesth. 2015 May;62(5):504-12. doi: 10.1007/s12630-014-0300-0. Epub 2014 Dec 31.

• Responsible Party: Stanford University
• ClinicalTrials.gov Identifier: NCT01416454
• Other Study ID Numbers: SU-11192010-7216; 19878 ( Registry Identifier: Stanford University )
• First Posted: August 15, 2011
• Last Update Posted: March 22, 2013
• Last Verified: March 2013

Additional relevant MeSH terms:

Thrombophilia; Hematologic Diseases