Postpartum Hemorrhage
Conditions
Keywords
postpartum hemorrhage, estimated blood loss, coagulation, thromboelastography, tranexamic acid
Brief summary
The aim of this study is to characterize the coagulation changes, using thromboelastography (TEG), after prophylactic tranexamic administration during cesarean delivery. Specifically, TEG values will be compared in patients who receive prophylactic tranexamic acid or placebo before surgery, during elective cesarean delivery, and 2 hours postpartum. Postpartum hemorrhage (PPH) is increasing in incidence in the United States, renewing interest in multimodal approaches to blood conservation during cesarean delivery. Pharmacologic therapy with the antifibrinolytic agent, tranexamic acid (TA), has been shown to reduce estimated blood loss (EBL) during cesarean delivery, but its effect on global coagulation as assessed by TEG, and how this correlates with lowering blood loss, has not been elucidated. This study will be conducted as a randomized, double-blind, controlled trial with two study arms: control (60 patients); and treatment (60 patients). Subjects will be pre-medicated with routine pre-cesarean delivery medications including oral sodium citrate 30 mL and intravenous (IV) metoclopramide 10 mg. A peripheral IV and noninvasive hemoglobin monitor will be placed, and baseline labs sent: type and screen, serum hemoglobin, platelet count, fibrinogen, activated partial thromboplastin time (aPTT), prothrombin time (PT), and baseline TEG values (r time, k time, alpha angle, and maximum amplitude). Patients will have blood pressure, heart rate, and pulse oximetry measured throughout surgery as per standard of care. Patients will all receive IV lactated Ringers' (LR) solution prior to surgery and throughout surgery, with volume recorded and a goal of less than 2 L unless more IV fluid is clinically indicated. All patients will have a spinal anesthetic as per standard of care, with hyperbaric bupivacaine 12 mg, fentanyl 10 μg, and hydromorphone 100 μg. If the anesthetic plan is altered (combined spinal-epidural, general anesthesia conversion, general anesthesia planned), indications and medication doses used will be noted for analysis. Immediately following induction of anesthesia and prior to skin incision, infusion of study solution will be initiated. Study solutions will consist of: 1. Control group: 100 mL 0.9% normal saline (NS). 2. Treatment group: 100 mL 0.9% NS containing 1g tranexamic acid (TA). Study solution will be infused via an infusion pump over 10 minutes. Blood loss will be measured by visual estimate and weight of surgical sponges. Noninvasive hemoglobin will be measured throughout the study. All routine care lab values will be noted. At minimum, one lab panel will be sent one hour after study solution initiation (hemoglobin, fibrinogen, platelet count, aPTT, PT, and TEG).
Interventions
DRUGTranexamic Acid
1 gram IV over 10 minutes
DRUGPlacebo; Normal Saline
0.9% Normal Saline
Sponsors
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* American Society of Anesthesiologists (ASA) class I or II * aged 18-50 years * singleton vertex pregnancy * scheduled elective cesarean delivery (with or without prior labor) with a planned pfannenstiel incision
Exclusion criteria
* allergy to tranexamic acid * history of inherited or acquired thrombophilia * history of deep vein thrombosis or pulmonary embolism, or use of anticoagulant medication. * preeclampsia, hemolysis, elevated liver enzymes, low platelet syndrome * seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| TEG Value- Thromboelastography R-time, Control and Treated Groups | one hour after initiation of study infusion | Blood samples will be collected for evaluation one our after initiation of the study infusion. Whole blood samples are tested in a point-of-care thromboelastography machine and R time, or time to initiation of clot formation, is measured in minutes. |
| Intraoperative Blood Loss | during surgery in the operating room | Blood loss will be measured using the following methods: * visual estimate of blood in the suction canister * weight of surgical sponges * postoperative hemoglobin values |
| Delayed Complications at the 6-Week Postpartum Visit With the Obstetrician. | 6 weeks postpartum | The electronic patient record from each patients' 6-week postpartum visit will be reviewed for the following: * delayed bleeding complications, defined as obstetric bleeding requiring surgical intervention, blood transfusion, or both. * thrombotic complications including: venous thrombus seen on ultrasound, thromboembolic event |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Control, Low Risk PPH Patients at lower risk for postpartum hemorrhage during cesarean delivery, to receive standard of care NOT including tranexamic acid.
Placebo; Normal Saline: 0.9% Normal Saline | 7 |
| Treated, Low Risk PPH Patients at lower risk for postpartum hemorrhage during cesarean delivery, to receive standard of care AND tranexamic acid.
Tranexamic Acid: 1 gram IV over 10 minutes | 13 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treated, Low Risk PPH | Control, Low Risk PPH | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 7 Participants | 20 Participants |
| Age, Continuous | 31.9 years | 35.2 years | 32.9 years |
| Region of Enrollment United States | 13 participants | 7 participants | 20 participants |
| Sex: Female, Male Female | 13 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 13 |
| other Total, other adverse events | 0 / 7 | 0 / 13 |
| serious Total, serious adverse events | 0 / 7 | 0 / 13 |
Outcome results
Primary
Delayed Complications at the 6-Week Postpartum Visit With the Obstetrician.
The electronic patient record from each patients' 6-week postpartum visit will be reviewed for the following: * delayed bleeding complications, defined as obstetric bleeding requiring surgical intervention, blood transfusion, or both. * thrombotic complications including: venous thrombus seen on ultrasound, thromboembolic event
Time frame: 6 weeks postpartum
Population: postpartum Obstetrician evaluation at 6 weeks: obstetric bleeding requiring surgical intervention, blood transfusion, or both; thrombotic complications including: venous thrombus seen on ultrasound, thromboembolic event
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control, Low Risk PPH | Delayed Complications at the 6-Week Postpartum Visit With the Obstetrician. | 0 complications |
| Treated, Low Risk PPH | Delayed Complications at the 6-Week Postpartum Visit With the Obstetrician. | 0 complications |
Primary
Intraoperative Blood Loss
Blood loss will be measured using the following methods: * visual estimate of blood in the suction canister * weight of surgical sponges * postoperative hemoglobin values
Time frame: during surgery in the operating room
Population: weight of surgical sponges
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control, Low Risk PPH | Intraoperative Blood Loss | 637 milliliters | Standard Error 151 |
| Treated, Low Risk PPH | Intraoperative Blood Loss | 685 milliliters | Standard Error 155 |
Primary
TEG Value- Thromboelastography R-time, Control and Treated Groups
Blood samples will be collected for evaluation one our after initiation of the study infusion. Whole blood samples are tested in a point-of-care thromboelastography machine and R time, or time to initiation of clot formation, is measured in minutes.
Time frame: one hour after initiation of study infusion
Population: Thromboelastography R-time
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Control, Low Risk PPH | TEG Value- Thromboelastography R-time, Control and Treated Groups | 5.3 minutes |
| Treated, Low Risk PPH | TEG Value- Thromboelastography R-time, Control and Treated Groups | 4.2 minutes |