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Coagulation Factor Changes Associated With Postpartum Hysterectomies

Coagulation Factor Changes Associated With Postpartum Hysterectomies

Status
Completed
Phases
Unknown
Study type
Observational
Source
ClinicalTrials.gov
Registry ID
NCT00456547
Enrollment
24
Registered
2007-04-05
Start date
2003-12-31
Completion date
2006-12-31
Last updated
2014-04-14

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Complications; Cesarean Section, Hemorrhage, Obstetric Labor Complications

Keywords

Cesarean hysterectomy, Postpartum hemorrhage, Coagulation

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.

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.

Interventions

PROCEDUREBlood Draw

Blood was obtained for coagulation studies at 2 hours following hysterectomy or cesarean delivery.

Sponsors

Northwestern University
Lead SponsorOTHER

Study design

Observational model
CASE_CONTROL
Time perspective
PROSPECTIVE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to 60 Years
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.

Design outcomes

Primary

MeasureTime frameDescription
Fibrinogen Level at 2 Hours After Delivery2 hours after deliveryFibrinogen 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

MeasureTime frameDescription
Platelet Counts at 2 Hours After Delivery2 hours after deliveryPlatelets 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.
Plasminogen Levels 2 Hours After Delivery2 hours after deliveryPlasminogen 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.
Antithrombin III Levels at 2 Hours Post Delivery2 hours after deliveryAntithrombin 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
Postpartum Hysterectomy
Women that require postpartum hysterectomy for post-delivery bleeding.
12
Cesarean Delivery Case Controls
Women that deliver by cesarean that presented with risk factors for bleeding but did not require post delivery hysterectomy
12
Total24

Baseline characteristics

CharacteristicPostpartum HysterectomyCesarean Delivery Case ControlsTotal
Age, Categorical
<=18 years
0 Participants0 Participants0 Participants
Age, Categorical
>=65 years
0 Participants0 Participants0 Participants
Age, Categorical
Between 18 and 65 years
12 Participants12 Participants24 Participants
Region of Enrollment
United States
12 participants12 participants24 participants
Sex: Female, Male
Female
12 Participants12 Participants24 Participants
Sex: Female, Male
Male
0 Participants0 Participants0 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 00 / 0
serious
Total, serious adverse events
0 / 00 / 0

Outcome results

Primary

Fibrinogen Level at 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.

Time frame: 2 hours after delivery

ArmMeasureValue (MEAN)Dispersion
Postpartum HysterectomyFibrinogen Level at 2 Hours After Delivery186 mg/dLStandard Deviation 80
Cesarean Delivery Case ControlsFibrinogen Level at 2 Hours After Delivery418 mg/dLStandard Deviation 126
p-value: <0.05t-test, 2 sided
Secondary

Antithrombin III Levels at 2 Hours Post 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.

Time frame: 2 hours after delivery

ArmMeasureValue (MEAN)Dispersion
Postpartum HysterectomyAntithrombin III Levels at 2 Hours Post Delivery51 percentage of normal antithrombin IIIStandard Deviation 22
Cesarean Delivery Case ControlsAntithrombin III Levels at 2 Hours Post Delivery89 percentage of normal antithrombin IIIStandard Deviation 18
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary

Plasminogen Levels 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.

Time frame: 2 hours after delivery

ArmMeasureValue (MEAN)Dispersion
Postpartum HysterectomyPlasminogen Levels 2 Hours After Delivery66 mg/dLStandard Deviation 22
Cesarean Delivery Case ControlsPlasminogen Levels 2 Hours After Delivery108 mg/dLStandard Deviation 26
p-value: <0.05t-test, 2 sided
Secondary

Platelet Counts at 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.

Time frame: 2 hours after delivery

ArmMeasureValue (MEAN)Dispersion
Postpartum HysterectomyPlatelet Counts at 2 Hours After Delivery124 platelets (*1000 per liter)Standard Deviation 30
Cesarean Delivery Case ControlsPlatelet Counts at 2 Hours After Delivery179 platelets (*1000 per liter)Standard Deviation 51
p-value: <0.05t-test, 2 sided

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026