Residency · Residency · Anesthesiology

Obstetric Hemorrhage and Massive Transfusion

Epidemiology and Definitions

Postpartum Hemorrhage (PPH)

The traditional definition of postpartum hemorrhage is blood loss exceeding 500 mL after vaginal delivery or 1,000 mL after cesarean delivery. The revised ACOG 2017 definition specifies cumulative blood loss of 1,000 mL or greater, or blood loss accompanied by signs of hypovolemia within 24 hours of delivery. PPH is the leading cause of maternal mortality worldwide and occurs in 3 to 5% of all deliveries.

Risk Factors -- "4 T's"

The causes of PPH are organized by the mnemonic of the four T's. Tone (uterine atony) accounts for approximately 70% of PPH and is the most common cause. Trauma includes lacerations, uterine rupture, and uterine inversion. Tissue refers to retained placenta and placenta accreta spectrum. Thrombin encompasses coagulopathy, DIC, and dilutional causes.

Uterotonic Agents

Oxytocin

Oxytocin is the first-line uterotonic, administered as 3 to 10 units IV slowly as a bolus followed by 20 to 40 units in 1 liter of crystalloid as an infusion. It acts as an oxytocin receptor agonist on uterine smooth muscle. Side effects include hypotension from peripheral vasodilation, tachycardia, water retention through ADH-like effects, and nausea. Rapid bolus of high doses can cause cardiovascular collapse, so the drug should always be diluted and infused slowly.

Methylergonovine (Methergine)

Methylergonovine is an ergot alkaloid that causes direct smooth muscle constriction. The dose is 0.2 mg IM -- it must never be given IV due to the risk of severe hypertension and coronary vasospasm. Onset is 2 to 5 minutes by IM injection. It is contraindicated in hypertension, preeclampsia, and cardiac disease, and side effects include severe hypertension, nausea, and vomiting.

Carboprost (Hemabate, 15-methyl-PGF2alpha)

This prostaglandin F2-alpha analogue is given at 0.25 mg IM or intramyometrially, repeated every 15 to 90 minutes to a maximum of 8 doses. It is contraindicated in asthma because it causes bronchospasm. Other side effects include nausea, diarrhea, fever, and hypertension.

Misoprostol (Cytotec, PGE1)

Misoprostol is a prostaglandin E1 analogue given at 600 to 1,000 mcg rectally, sublingually, or buccally. Its advantages include stability at room temperature, no need for injection, and no contraindication in asthma or hypertension. However, it has a slower onset and is less effective than other uterotonics. Side effects include fever, shivering, and diarrhea.

<image>Pharmacology comparison table of the four uterotonic agents (oxytocin, methylergonovine, carboprost, misoprostol) with columns for mechanism, route, dose, onset, key contraindications, and major side effects. Each agent is color-coded, and contraindications are highlighted in red warning boxes (methylergonovine: hypertension/preeclampsia; carboprost: asthma). The table includes a stepwise treatment algorithm showing progression from first-line (oxytocin) through second and third-line agents.</image>

Tranexamic Acid (TXA)

WOMAN Trial

The WOMAN trial randomized over 20,000 women with PPH to TXA 1 g IV versus placebo. TXA reduced death from bleeding (1.5% vs. 1.9%; relative risk 0.81) when given within 3 hours. There was no effect on overall mortality or hysterectomy rate and no increase in thromboembolic events.

Current Recommendations

TXA at 1 g IV over 10 minutes should be administered as early as possible, within 3 hours of hemorrhage onset, with a repeat dose of 1 g if bleeding continues after 30 minutes. It should be part of all PPH protocols, and the WHO recommends TXA for all women with PPH regardless of cause.

Massive Transfusion Protocol (MTP)

Activation Criteria

MTP should be activated when estimated blood loss exceeds 1,500 mL and is ongoing, when hemodynamic instability persists despite initial resuscitation, or prophylactically for high-risk cases such as placenta accreta or abruption.

Ratio-Based Transfusion

The target is a 1:1:1 ratio of PRBCs to FFP to platelets, based on extrapolation from the PROPPR trial. The first cooler typically contains 6 units PRBCs and 4 units FFP (many protocols use 4:4). One apheresis unit of platelets (equivalent to 6 pooled units) is included per cooler. Cryoprecipitate at 10 units is given if fibrinogen falls below 200 mg/dL, keeping in mind that normal pregnancy fibrinogen is 400 to 600 mg/dL.

Goal-Directed Transfusion

TEG/ROTEM-guided transfusion is increasingly used, with targets including fibrinogen above 200 mg/dL (and consideration of above 300 mg/dL in obstetric hemorrhage given the baseline elevation), platelets above 50,000 to 75,000/mcL, PT/INR below 1.5, and hemoglobin above 7 to 8 g/dL. Fibrinogen concentrate (RiaSTAP) at 2 to 4 g IV is an alternative to cryoprecipitate, offering faster preparation since no thawing is needed.

Complications of Massive Transfusion

Hypothermia is prevented by using fluid warmers for all products. Hypocalcemia occurs because citrate in blood products chelates calcium; ionized calcium should be monitored and replaced with calcium chloride 1 g or calcium gluconate 3 g IV. Hyperkalemia is a concern, especially with older PRBC units. Dilutional coagulopathy results from crystalloid and PRBC transfusion without adequate factor replacement. TRALI causes acute lung injury within 6 hours of transfusion and requires supportive care. TACO involves volume overload and is more common in patients with cardiac disease.

<image>Massive transfusion protocol activation and management flowchart for obstetric hemorrhage. The flowchart shows: recognition triggers (EBL > 1500 mL, hemodynamic instability, clinical judgment), MTP activation with first cooler contents (6 PRBC, 4 FFP), blood drawn for TEG/ROTEM and labs, second cooler with platelets added. Parallel tracks show surgical management (uterotonics, bakri balloon, B-Lynch suture, uterine artery ligation, hysterectomy) and laboratory-guided adjustments (fibrinogen, calcium, potassium monitoring). TXA 1g is shown as an early intervention alongside the first cooler.</image>

Surgical and Interventional Management

Conservative Measures (After Uterotonics)

Bimanual uterine compression is the first physical intervention. A uterine tamponade balloon (Bakri balloon) is inflated with 300 to 500 mL of saline and may serve as a bridge to definitive management.

Surgical Interventions

Options include the B-Lynch (uterine compression) suture, bilateral uterine artery ligation, and internal iliac artery ligation (less commonly performed). Hysterectomy is the definitive treatment when all other measures fail and should not be delayed if hemorrhage is life-threatening.

Interventional Radiology

Uterine artery embolization is effective for hemodynamically stable patients with ongoing hemorrhage. Prophylactic balloon occlusion of the internal iliac arteries can be placed preoperatively for anticipated placenta accreta. These approaches require IR availability and hemodynamic stability for transport.

Placenta Accreta Spectrum (PAS)

Classification

Accreta involves placental adherence to the myometrium without intervening decidua. Increta involves invasion into the myometrium. Percreta involves penetration through the myometrium to the serosa, potentially involving the bladder or other organs.

Risk Factors

Risk increases with prior cesarean deliveries (escalating with each successive procedure), placenta previa with a prior cesarean scar, and prior uterine surgery such as myomectomy or curettage.

Anesthetic Management

Management requires multidisciplinary planning involving obstetrics, maternal-fetal medicine, gynecologic oncology, urology, interventional radiology, anesthesiology, and the blood bank. Large-bore IV access with at least two 14 to 16 gauge IVs is essential, along with an arterial line and consideration of central venous access. Blood products should be available in the room before incision. Cell salvage, though controversial in obstetrics due to amniotic fluid contamination, is considered acceptable with leukocyte depletion filters. General anesthesia is often preferred for percreta given the anticipated prolonged surgery, massive hemorrhage, and potential for hemodynamic instability, though neuraxial anesthesia may be used for accreta or increta with a GA backup plan.

Disseminated Intravascular Coagulation (DIC) in Obstetrics

Common Causes

Placental abruption is the most common obstetric cause of DIC. Other causes include amniotic fluid embolism, HELLP syndrome and severe preeclampsia, sepsis, prolonged intrauterine fetal demise, and massive hemorrhage (both consumptive and dilutional).

Diagnosis

Diagnostic findings include fibrinogen below 200 mg/dL (in pregnancy, even 200 to 300 mg/dL is concerning), elevated PT/INR and aPTT, thrombocytopenia, elevated D-dimer and fibrin degradation products, and schistocytes on blood smear.

Management

The primary goal is to treat the underlying cause. Factor replacement includes FFP, cryoprecipitate (targeting fibrinogen above 200 mg/dL), and platelets. TXA is used if there is a hyperfibrinolysis component, and RBC transfusion addresses anemia.

Amniotic Fluid Embolism (AFE)

Presentation

AFE presents as sudden cardiovascular collapse during labor, delivery, or immediately postpartum. The classic triad includes hypoxia, hypotension or cardiac arrest, and DIC. Mortality ranges from 20 to 60% even with aggressive treatment.

Pathophysiology

Despite its name, AFE is not a true embolism but rather an anaphylactoid reaction to amniotic fluid components. It involves complement activation, an inflammatory cascade, pulmonary vasoconstriction, right ventricular failure, and subsequent left ventricular failure.

Management

Immediate CPR is initiated if cardiac arrest occurs. Aggressive hemodynamic support with epinephrine, vasopressors, and inotropes is provided. Intubation and mechanical ventilation are performed. DIC is treated with massive transfusion. Emergent delivery (perimortem cesarean) is performed if the patient has not yet delivered. ECMO may be considered if available and the condition is refractory.

Clinical Pearls

Pregnancy physiology masks blood loss: a healthy parturient may lose 15-20% of blood volume before tachycardia appears due to the expanded blood volume. In obstetric hemorrhage, fibrinogen is the first coagulation factor to become critically low; a fibrinogen < 200 mg/dL in a pregnant patient is a red flag for DIC. Never give methylergonovine IV (risk of severe hypertension and cardiac arrest); always give IM. TXA should be given early (within 3 hours) for maximum benefit; there is no reason to delay it during PPH. Cell salvage is considered safe in cesarean delivery when used with leukocyte depletion filters; the amniotic fluid contamination concern has been addressed by modern filtration. Do not delay hysterectomy when conservative measures are failing in life-threatening hemorrhage; the decision to proceed to hysterectomy should be made early rather than late.

References

• WOMAN Trial Collaborators. Effect of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with post-partum haemorrhage (WOMAN). Lancet. 2017;389(10084):2105-2116.
• Committee on Practice Bulletins -- Obstetrics. ACOG Practice Bulletin No. 183: Postpartum Hemorrhage. Obstetrics and Gynecology. 2017;130(4):e168-e186.
• Collins PW, Cannings-John R, Bruynseels D, et al. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage (OBS2). British Journal of Anaesthesia. 2017;119(3):411-421.
• Holcomb JB, Tilley BC, Baraniuk S, et al. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: the PROPPR randomized clinical trial. JAMA. 2015;313(5):471-482.
• Silver RM, Barbour KD. Placenta accreta spectrum: accreta, increta, and percreta. Obstetrics and Gynecology Clinics of North America. 2015;42(2):381-402.

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