Coagulation Factor Changes Associated With Postpartum Hysterectomies

• Sponsor: Northwestern University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00456547
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Duration (Months): 36
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Obstetric Labor Complications; Hemorrhage; Complications; Cesarean Section	Procedure: Blood Draw

Detailed Description

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 a previous Cesarean delivery.

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, 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 hours after delivery. 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 hours after delivery for coagulation testing. Baseline samples from all other study subjects will be discarded and no further blood work will be obtained. The primary outcome will be the the level of fibrinogen at 2 hours following delivery as a marker of consumptive coagulopathy.

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.

Study Design

• Study Type: Observational
• Actual Enrollment: 24 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Coagulation Factor Changes Associated With Postpartum Hysterectomies
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Dec 1, 2006
• Actual Study Completion Date: Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Postpartum hysterectomy Women that require postpartum hysterectomy for post-delivery bleeding.	Procedure: Blood Draw; Blood was obtained for coagulation studies at 2 hours following hysterectomy or cesarean delivery.; Other Names: postpartum coagulation disorder
Cesarean delivery case controls Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy	Procedure: Blood Draw; Blood was obtained for coagulation studies at 2 hours following hysterectomy or cesarean delivery.; Other Names: postpartum coagulation disorder

Outcome Measures

Primary Outcome Measures

1. Fibrinogen Level at 2 Hours After Delivery [2 hours after delivery]

   Fibrinogen level decrease is a marker of consumptive coagulation which is is a pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases or stimulus. We hypothesized that women with excessive bleeding following delivery who require a hysterectomy are more likely to exhibit lower levels of fibrinogen and a consumptive coagulopathy than women following cesarean delivery who do not bleed.

Secondary Outcome Measures

1. Platelet Counts at 2 Hours After Delivery [2 hours after delivery]

   Platelets are decreased in subjects with consumptive coagulopathies which is a pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases. We hypothesized that women who require hysterectomy for postpartum bleeding are more likely to have decreased platelet counts than matched controls that underwent cesarean delivery.

2. Plasminogen Levels 2 Hours After Delivery [2 hours after delivery]

   Plasminogen is converted to plasmin when the coagulation system is activated. We hypothesized that plasminogen should be decrease more in women with continued bleeding following delivery requiring hysterectomy will demonstrated a greater decrease in plasminogen than following cesarean delivery.

3. Antithrombin III Levels at 2 Hours Post Delivery [2 hours after delivery]

   Antithrombin III is a glycoprotein and is the major inhibitor of thrombin and other activated clotting factors, including factors IX, X, XI, and XII, the cofactor through which heparin exerts its effect. We hypothesized that women with continued bleed following delivery and require a hysterectomy will demonstrate a greater reduction in antithrombin III that women undergoing cesarean delivery.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwestern University	Chicago	Illinois	United States	60611

Sponsors and Collaborators

• Northwestern University

Investigators

• Principal Investigator: Cynthia A Wong, M.D., Northwestern University

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Cynthia Wong, Professor of Anesthesiology, Northwestern University
• ClinicalTrials.gov Identifier: NCT00456547
• Other Study ID Numbers: 0524-020
• First Posted: Apr 5, 2007
• Last Update Posted: Apr 14, 2014
• Last Verified: Mar 1, 2014

• Keywords provided by Cynthia Wong, Professor of Anesthesiology, Northwestern University: Cesarean hysterectomy; Postpartum hemorrhage; Coagulation
• Additional relevant MeSH terms: Obstetric Labor Complications; Hemorrhage

Study Results

Participant Flow

Arm/Group Title	Postpartum Hysterectomy	Cesarean Delivery Case Controls
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.	Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
Period Title: Overall Study
STARTED	12	12
COMPLETED	12	12
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Postpartum Hysterectomy	Cesarean Delivery Case Controls	Total
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.	Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy	Total of all reporting groups
Overall Participants	12	12	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	12 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	12 100%	12 100%	24 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	12 100%	12 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	Fibrinogen Level at 2 Hours After Delivery
Description	Fibrinogen level decrease is a marker of consumptive coagulation which is is a pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases or stimulus. We hypothesized that women with excessive bleeding following delivery who require a hysterectomy are more likely to exhibit lower levels of fibrinogen and a consumptive coagulopathy than women following cesarean delivery who do not bleed.
Time Frame	2 hours after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Postpartum Hysterectomy	Cesarean Delivery Case Controls
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.	Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
Measure Participants	12	12
Mean (Standard Deviation) [mg/dL]	186 (80)	418 (126)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Postpartum Hysterectomy, Cesarean Delivery Case Controls
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Adjusted for 12 comparisons
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Platelet Counts at 2 Hours After Delivery
Description	Platelets are decreased in subjects with consumptive coagulopathies which is a pathological activation of coagulation (blood clotting) mechanisms that happens in response to a variety of diseases. We hypothesized that women who require hysterectomy for postpartum bleeding are more likely to have decreased platelet counts than matched controls that underwent cesarean delivery.
Time Frame	2 hours after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Postpartum Hysterectomy	Cesarean Delivery Case Controls
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.	Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
Measure Participants	12	12
Mean (Standard Deviation) [platelets (*1000 per liter)]	124 (30)	179 (51)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Postpartum Hysterectomy, Cesarean Delivery Case Controls
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Corrected for 12 comparisons.
	Method	t-test, 2 sided
	Comments

3. Secondary Outcome

Title	Plasminogen Levels 2 Hours After Delivery
Description	Plasminogen is converted to plasmin when the coagulation system is activated. We hypothesized that plasminogen should be decrease more in women with continued bleeding following delivery requiring hysterectomy will demonstrated a greater decrease in plasminogen than following cesarean delivery.
Time Frame	2 hours after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Postpartum Hysterectomy	Cesarean Delivery Case Controls
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.	Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
Measure Participants	12	12
Mean (Standard Deviation) [mg/dL]	66 (22)	108 (26)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Postpartum Hysterectomy, Cesarean Delivery Case Controls
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Corrected for 12 comparisons
	Method	t-test, 2 sided
	Comments

4. Secondary Outcome

Title	Antithrombin III Levels at 2 Hours Post Delivery
Description	Antithrombin III is a glycoprotein and is the major inhibitor of thrombin and other activated clotting factors, including factors IX, X, XI, and XII, the cofactor through which heparin exerts its effect. We hypothesized that women with continued bleed following delivery and require a hysterectomy will demonstrate a greater reduction in antithrombin III that women undergoing cesarean delivery.
Time Frame	2 hours after delivery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Postpartum Hysterectomy	Cesarean Delivery Case Controls
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.	Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
Measure Participants	12	12
Mean (Standard Deviation) [percentage of normal antithrombin III]	51 (22)	89 (18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Postpartum Hysterectomy, Cesarean Delivery Case Controls
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.05
	Comments	Corrected for 12 comparisons
	Method	Wilcoxon (Mann-Whitney)
	Comments

Adverse Events

Adverse Event Reporting Description	Adverse events were not collected as part of this study. The study protocol was a blood drawn and no additional follow-up was performed.
Arm/Group Title	Postpartum Hysterectomy		Cesarean Delivery Case Controls
Arm/Group Description	Women that require postpartum hysterectomy for post-delivery bleeding.		Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
All Cause Mortality
	Postpartum Hysterectomy		Cesarean Delivery Case Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Postpartum Hysterectomy		Cesarean Delivery Case Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Postpartum Hysterectomy		Cesarean Delivery Case Controls
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.