Postpartum Hemorrhage – Medications to Treat Uterine Atony
ACOG defines PPH as cumulative blood loss ≥ 1,000 mL or blood loss accompanied by signs or symptoms of hypovolemia within 24 hours after the birth process (including intrapartum) regardless of route of delivery. Unfortunately, postpartum hemorrhage (PPH) is still a leading cause of maternal mortality worldwide. Following this summary, you can find excellent professional resources at the California Maternal Quality Care Collaborative (CMQCC) and ACOG District II Safe Motherhood Initiative sites.
CLINICAL ACTIONS:
In the setting of PPH, consider the 4 ‘T’s
Tone (atony)
Trauma (laceration)
Tissue (retained products)
Thrombin (coagulopathy)
Uterine atony is the single most common cause of PPH (70-80%)
250 micrograms IM (may repeat in q15 – 90 minutes, maximum 8 doses)
OR
Intramyometrial: 250 micrograms
Avoid: Asthma
Caution: Hypertension, Active Hepatic, Pulmonary, Cardiac Disease
Misoprostol (Cytotec)
600 – 1000 micrograms PR, PO or SL
Hypersensitivity to this medication
NOTE: Contraindications include hypersensitivity to the specific medication
More on Tranexamic Acid (TXA)
ACOG Update (2017)
In the WOMAN trial (see Related OBG Topics below) women with PPH received
1 g in 10 mL (100 mg/mL) of tranexamic acid intravenously at a rate of 1 mL per min (i.e., over 10 min)
If bleeding continued after 30 min or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid could be given
Tranexamic acid, administered within 3 hours of birth, has been shown to significantly reduce maternal death due to PPH by approximately 30%
Based on improved outcomes and lack of adverse events including thromboembolism, ACOG has updated the practice bulletin to include the following
Although the generalizability of the WOMAN trial and the degree of effect in the United States is uncertain, given the mortality reduction findings, tranexamic acid should be considered in the setting of obstetric hemorrhage when initial medical therapy fails. (Level B evidence)
World Health Organization Update (2017)
Based on evidence review, WHO also supports the use of tranexamic acid with postpartum hemorrhage
Early use of intravenous tranexamic acid (within 3 hours of birth) in addition to standard care is recommended for women with clinically diagnosed postpartum haemorrhage following vaginal birth or caesarean section (Strong recommendation, moderate quality of evidence)
Administration of TXA should be considered as part of the standard PPH treatment package and be administered as soon as possible after onset of bleeding and within 3 hours of birth
The reference point for the start of the 3-hour window for starting TXA administration is time of birth
If time of birth is unknown, the best estimate of time of birth should be used as the reference point
TXA should be used in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes
CONSIDERATIONS IN COVID POSITIVE PATIENTS
Tranexamic Acid (TXA)
COVID-19 appears to be a hypercoagulable state
TXA can be considered for the treatment of PPH in keeping with guidance for non-COVID-19 patients
However, ACOG states
because of the possible additive effect of the increased risk of thrombosis from COVID-19 infection and the hypercoagulative state of pregnancy, it may be prudent to consider this increased likelihood of clotting before administering TXA for postpartum hemorrhage
Hemabate
While Hemabate is not used in asthma due to risk for bronchospasm, patients with COVID-19 have respiratory symptoms consistent with viral pneumonia
While there is no data specific to COVID-19 and this medication, “Hemabate is not generally withheld” in patients with viral pneumonia
SYNOPSIS:
The key to managing PPH is identifying the severity of the situation early and quantifying estimated blood loss (EBL). A second large bore (16 gauge or larger) should be placed and Ringers Lactate used to replace blood loss at 2:1 while, simultaneously as the team is notified, medications are administered to the patient and massive transfusion protocol is initiated. Initiate fundal massage and place a Foley catheter.
KEY POINTS:
ABCs
Airway: Assess and stabilize
Breathing: Supplemental oxygen, 5-7 L/min by tight face mask
Consider intrauterine balloon tamponade or compression sutures for refractory atony
Surgical Interventions may be a life-saving measure and should not be delayed while waiting to correct coagulopathy
Quantitative measurement of blood loss is more acurate than visual estimation (see ‘Learn More – Primary Sources’ below) and require 2 key elements
Direct measurement of blood loss
Protocols for collecting and reporting a cumulative record of blood loss following delivery
Note: The FDA, the World Health Organization, and other professional bodies have released an alert following drug-error deaths related to TXA | TXA use during cesarean delivery has been associated with fatal accidental intrathecal administration because the ampoules of local anesthetic and tranexamic acid are similar in appearance | TXA should not be stored on or near an anesthetic trolley
How does TXA Measure Up as a Treatment for Menorrhagia?
BACKGROUND AND PURPOSE:
There are several treatments for heavy menstrual bleeding, with good evidence supporting levonorgestrel intrauterine system as a good management option
Not all women will want an IUD
Important to review safety of TXA due to concerns regarding thromboembolic disease
Bryant-Smith et al. (Cochrane Reviews, 2018) assessed the effectiveness and safety of antifibrinolytic medications, specifically tranexamic acid (TXA), for the treatment of heavy menstrual bleeding (HMB)
METHODS:
Database search of RCTs comparing TXA and precursor (antifibrinolytic) agents versus
Placebo
No treatment
Other medical treatment
Population: Women of reproductive age with menorrhagia
Menstrual blood loss were measured by
Objective assessment of mean blood loss in mL (using alkaline haematin method or similar)
Subjective assessment of blood loss using continuous measures such as Pictorial Blood Assessment Chart (PBAC) scores, where over 100 correlates with heavy bleeding using objective methods
TXA dose
Majority of studies used regular oral dose TXA (3 g/day to 4 g/day) while 4 studies used low-dose TXA (2 g/day to 2.4 g/day)
Primary outcomes
Menstrual blood loss | Improvement in bleeding | Thromboembolic events
Secondary outcomes
Quality of life | Side effects
RESULTS:
13 RCTs were included, totaling 1312 participants
The evidence was very low to moderate quality
When compared with a placebo, antifibrinolytics were associated with
Reduced mean blood loss (Mean Difference (MD) -53.20 mL per cycle, 95% CI -62.70 to -43.70; moderate-quality evidence)
Higher rates of improvement (RR 3.34, 95% CI 1.84 to 6.09; moderate-quality evidence)
Compared to progestogens, antifibrinolytics were associated with
No difference between the groups in mean blood loss (very low-quality evidence)
Higher likelihood of improvement (RR 1.54, 95% CI 1.31 to 1.80; low-quality evidence)
Fewer adverse events (RR 0.66, 95% CI 0.46 to 0.94; low-quality evidence)
Compared to NSAIDs, TXA was associated with
Reduced mean blood loss (MD -73.00 mL per cycle, 95% CI -123.35 to -22.65; low-quality evidence)
Higher likelihood of improvement (RR 1.43, 95% CI 1.18 to 1.74; low-quality evidence)
Compared to herbal medicine (Safoof Habis and Punica granatum), TXA was associated with
Reduced mean PBAC score after three months’ treatment (MD -23.90 pts per cycle, 95% CI -31.92 to -15.88; low-quality evidence)
Inconclusive rates of improvement
Compared to levonorgestrel intrauterine system, TXA was associated with
Higher median PBAC score (median difference 125.5 points; very low quality evidence)
Lower likelihood of improvement (RR 0.43, 95% CI 0.24 to 0.77; very low quality evidence)
CONCLUSION:
Antifibrinolytic treatment appears effective for treating menorrhagia compared to placebo, NSAIDs, oral progestogens or herbal remedies
However, they appeared less effective compared to levonorgestrel IUD
The authors suggest that if 85% of women improve with levonorgestrel IUD, 20% to 65% of women will do so with TXA
Adverse outcomes were hard to quantify due to inadequate amount of data
Results From the Landmark Trial on Tranexamic Acid for Postpartum Hemorrhage
PURPOSE:
Tranexamic acid, an anti-fibrinolytic medication, has been shown in the trauma literature to be highly effective in reducing deaths due to bleeding. The aim of this study by the WOMAN Trial Collaborators (Lancet, 2017) was to determine if early administration of tranexamic acid could likewise be beneficial in the setting of postpartum hemorrhage (PPH).
METHODS:
Randomized, double-blind, placebo-controlled trial – multicentered (193 hospitals/21 countries), conducted between March 2010 and April 2016.
RESULTS:
20,060 women were enrolled and randomized to receive either 1 g (100 mg/mL) of tranexamic acid intravenously at a rate of 1 mL per min or placebo. If bleeding continued after 30 min or stopped and restarted within 24 h of the first dose, a second dose of 1 g of tranexamic acid or placebo could be given. Key findings include:
Death due to bleeding was reduced by approximately 30% in the treatment group (risk ratio 0.69, 95% CI 0.52-0.91; p=0.008) if drug given within 3 hours of birth
There did not appear to be reduction if medication given after 3 hours
Laparotomy to control bleeding was similarly significantly reduced in the treatment group (risk ratio 0.64, 95% CI 0.49 – 0.85; p=0.002)
There was not difference in hysterectomy rates
There was no difference in overall death rates or deaths due to hysterectomies
There was no difference in adverse events, including those related to thromboembolism
SUMMARY:
Reduction in death rates by approximately a third mirrored findings in trauma patients
Strengths of study:
Well designed to answer question
Tranexamic acid is low cost and could potentially save tens of thousands of women’s lives worldwide annually
Authors recommend tranexamic acid be given early in PPH and not after uterotonics have failed
Limitations of study:
Primary issue is generalizability to higher resource regions
Tranexamic acid may have more impact on hysterectomy prevention where hysterectomy is a last resort vs. an early lifesaving intervention
Tranexamic acid may have more impact on overall death rates in countries where other causes of maternal death are lower (e.g., sepsis)
Tranexamic acid in this study was administered by IV which may be limiting in regions with limited maternal health resources
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This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. The planners of this activity do not recommend the use of any agent outside of the labeled indications.
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presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications and/or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.
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