Coagulation Factor Changes Associated With Postpartum Hysterectomies

Condition(s) targeted: Labour; Hemorrhage; Cesarean Section

Intervention: Blood Draw (Procedure)

Phase: N/A

Status: Completed

Sponsored by: Northwestern University

Official(s) and/or principal investigator(s):
Cynthia A Wong, M.D., Principal Investigator, Affiliation: Northwestern University

The purpose of this study is to examine components of the coagulation system in women undergoing postpartum hysterectomy and to compare laboratory parameters of coagulation in these women to women at increased risk for a postpartum hysterectomy, but who do not have postpartum hemorrhage and a postpartum hysterectomy. During normal pregnancy, the hemostatic balance tips toward hypercoagulation. Non-obstetric surgical blood loss is associated with increased coagulation activity. We have observed that women undergoing a postpartum hysterectomy become hypocoagulable secondary to a consumptive coagulopathy and/or excessive fibrinolysis. This coagulopathy may lead to the administration of multiple blood products. Worldwide, postpartum hemorrhage is a leading cause of maternal death. Plasma levels of tissue plasminogen activator, urokinase plasminogen activator and their inhibitors increase during pregnancy. During labor and delivery activation of coagulation occurs with consumption of platelets, coagulation factors and inhibitors. Obstetric complications during delivery can excessively activate the coagulation system and disseminated intravascular coagulation may ensue. Current treatment for postpartum coagulopathy is non-specific and primarily consists of replacing blood components. If specific causes or markers of abnormal coagulation can be identified in women at risk, then it might be possible to target (with specific medications) specific abnormalities early in the process and decrease hemorrhage and the need for blood transfusions.

Official title: Coagulation Factor Changes Associated With Postpartum Hysterectomies

Study design: Screening, Cross-Sectional, Defined Population, Prospective Study

Detailed description: Study design: Observational with cohort control group. Methods: Size of study groups(s): The sample size calculated for this study was based upon a repeated analysis of variance measures design with 1 between factor and 1 within factor that has 2 groups with 12 subjects each for a total of 24 subjects. Each subject is measured 4 times. This design achieves 84% power to test a difference between groups if a Geisser-Greenhouse Corrected F Test is used with a 5% significance level and the actual effect standard deviation is 0. 50 (an effect size of 0. 63), achieves 100% power to test a difference within groups across time if a Geisser-Greenhouse Corrected F Test is used with a 5% significance level and the actual effect standard deviation is 0. 50 (an effect size of 1. 41), and achieves 100% power to test a group by time difference if a Geisser-Greenhouse Corrected F Test is used with a 5% significance level and the actual effect standard deviation is 0. 50 (an effect size of 1. 41). Patient entry, exclusion and dropout criteria: All women scheduled for a Cesarean-hysterectomy will be asked to enroll in the study, as well as the women with the following diagnoses, which puts them at increased risk for Cesarean hysterectomy: placenta previa, placenta accreta, vaginal trial of labor after aa previous Cesarean delivery.

Protocol specific methods: Written, informed consent will be obtained from all subjects. A blood sample will be obtained shortly after admission to the hospital. In women who go on to have a hysterectomy (anticipated N = 12), blood samples will be obtained at predefined time periods (at time of decision to perform hysterectomy, with every clinically indicated blood draw for coagulation tests, 2, 8, 24 and 48 h after delivery (approximately 9 coagulation panels per subject = approximately 70 mL per study subject for study tests). The next patient at risk of Cesarean hysterectomy, but who does not go on to have a hysterectomy, will serve as a cohort control. Blood samples will be drawn at 2, 24 and 48 h after delivery for coagulation testing (4 coagulation panels per subject = 50 mL). Baseline samples from all other study subjects will be discarded and no further blood work will be obtained.

Obtaining blood for coagulation tests: Every patient at risk for hemorrhage has at least one peripheral intravenous cannula inserted upon admission to the Labor & Delivery Unit. A 2nd IV cannula is almost always placed, usually when the decision is made to proceed with a Cesarean delivery. All study subjects will have a 2nd IV cannula placed for drawing blood for study coagulation tests, and any other clinically indicated blood tests. The cannula will be connected to a stopcock with a “heparin lock” (cannula and stopcock are flushed with saline between aspirations) and left in place for 48 hours after delivery.

Coagulation tests: Blood for coagulation tests will be withdrawn from the 16 gauge IV cannula-stopcock, after aspirating a 5 mL blank. The blank blood will be returned to the study subject immediately after the sample blood is withdrawn and the catheter-stopcock will be flushed with saline solution. The following coagulation tests will be performed at each time period: 1) complete blood count (CBC) (4 mL), prothrombin time (PT), and activated partial thromboplastin time (aPTT) (4. 5 mL): NMH laboratories; 2) fibrinogen, d-dimer, antithrombin, thrombin-antithrombin complex, plasminogen, plasminogen-antiplasminogen complex (2 mL): Dr. David Green’s laboratory (NU); and 3) thrombelastography (TEG) (2 mL): Dept. of Anesthesiology. The total amount of blood for each coagulation panel is 12. 5 mL. If blood is withdrawn for clinically indicated coagulation tests, an extra 4 mL will be withdrawn for study tests.

Minimum age: 18 Years. Maximum age: 60 Years. Gender(s): Female.

Criteria:

Inclusion Criteria:

- All women scheduled for a Cesarean-hysterectomy will be asked to enroll in the study,

as well as the women with the following diagnoses, that puts them at increased risk for Cesarean hysterectomy: placenta previa, placenta accreta, vaginal trial of labor after previous Cesarean delivery.

Exclusion Criteria:

- Anyone who does not fit the above criteria.

Northwestern University, Chicago, Illinois 60611, United States

Related publications:

Tuman KJ, Spiess BD, McCarthy RJ, Ivankovich AD. Effects of progressive blood loss on coagulation as measured by thrombelastography. Anesth Analg. 1987 Sep;66(9):856-63.

Hellgren M. Hemostasis during normal pregnancy and puerperium. Semin Thromb Hemost. 2003 Apr;29(2):125-30. Review.

Lanir N, Aharon A, Brenner B. Procoagulant and anticoagulant mechanisms in human placenta. Semin Thromb Hemost. 2003 Apr;29(2):175-84. Review.

Saftlas AF, Olson DR, Atrash HK, Rochat R, Rowley D. National trends in the incidence of abruptio placentae, 1979-1987. Obstet Gynecol. 1991 Dec;78(6):1081-6.

Starting date: December 2003
Ending date: November 2006
Last updated: April 4, 2007