Secondary (late) postpartum hemorrhage

INTRODUCTION — Postpartum hemorrhage (PPH) may occur shortly after the birth (primary postpartum hemorrhage, within the first 24 hours) or, less commonly, days to weeks later. This topic will discuss secondary (also called late) PPH. Issues related to primary PPH are reviewed separately:

●(See "Overview of postpartum hemorrhage".)

●(See "Postpartum hemorrhage: Medical and minimally invasive management".)

●(See "Postpartum hemorrhage: Management approaches requiring laparotomy".)

DEFINITION/DIAGNOSIS — Secondary PPH is generally defined as any significant uterine bleeding occurring between 24 hours and 12 weeks postpartum [1,2]. However, definitions vary (eg, between 48 hours and 6 weeks postpartum).

INCIDENCE — Secondary PPH occurs in 0.2 to 2.5 percent of postpartum patients in high-income countries [2-6]. Most studies report that the peak incidence is one to two weeks postpartum [2]. Data for low-income countries are not available.

ETIOLOGY — The most common causes of secondary PPH are [2]:

●Retained products of conception (RPOC), including focal placenta accreta

●Subinvolution of the placental bed

●Infection

Less common and rare causes include [2,7-20]:

●Inherited or acquired bleeding diatheses, including medications that may predispose to bleeding

●Pseudoaneurysm of the uterine artery, internal pudendal artery, vaginal artery, or vulvar labial artery

●Arteriovenous fistula

●Choriocarcinoma

●Undiagnosed carcinoma of the cervix

●Adenomyosis

●Infected polyp or submucosal fibroid

●Uterine diverticulum

●Excessive bleeding with resumption of menses

●Hypoestrogenism

●Dehiscence of a cesarean scar

Sometimes the cause cannot be determined.

RISK FACTORS — A previous history of secondary PPH appears to predispose the patient to a recurrence (odds ratio [OR] 6.0, 95% CI 2.1-16.8 [21]) [21-23]. A history of primary PPH is a risk factor for severe secondary PPH (OR 4.7, 95% CI 1.9-11.6 [21]) [4,21,24].

Risk factors for retained products of conception (RPOC), subinvolution of the placental bed, and infection include placental abnormalities, prolonged labor, and the need for manual removal of the placenta. (See "Retained placenta after vaginal birth" and "Postpartum endometritis" and "Overview of postpartum hemorrhage", section on 'Risk factors for PPH'.)

CLINICAL PRESENTATION — Vaginal bleeding in excess of what is expected is the presenting symptom. Bleeding may be accompanied by pelvic pain, fever, uterine tenderness, and/or an elevated white blood cell count. These clinical findings are nonspecific; moreover, it is normal to have some postpartum bleeding, a mildly elevated white blood cell count, and/or mild discomfort. (See "Overview of the postpartum period: Normal physiology and routine maternal care", section on 'Uterine involution'.)

HEMODYNAMICALLY UNSTABLE PATIENTS — For the patient who has heavy bleeding and is hemodynamically unstable, stabilization with fluids and transfusion of blood products is the priority, followed by diagnostic evaluation. Our approach is described in the algorithm (algorithm 1).

In patients experiencing secondary PPH in the first few weeks after the birth, the uterine cavity may be sufficiently large to admit an intrauterine hemorrhage control device (eg, balloon tamponade device), which may be useful to limit bleeding while the diagnostic evaluation occurs. If the uterine fundus is not palpable abdominally, then the uterine cavity is probably too small to accommodate a commercial uterine tamponade device, but it may still be possible to place a standard bladder catheter with a 10 to 30 mL balloon into the uterine cavity and use this balloon for tamponade. If neither of these interventions is possible, packing the uterus with gauze may limit hemorrhage while the patient is moved to the appropriate location for definitive therapy. An intrauterine vacuum-induced hemorrhage-control device has been used to manage primary postpartum hemorrhage caused by atony, with very limited information in other clinical settings. (See "Postpartum hemorrhage: Use of an intrauterine hemorrhage-control device".)

If the patient cannot be stabilized promptly, transfer to a venue suitable for emergency surgical intervention (operating room or hybrid surgical/interventional radiology suite) where examination under anesthesia and surgical procedures for control of hemorrhage can be performed is important. If the bleeding is controlled with tamponade and the patient is stable, further evaluation for causes can be conducted in a nonsurgical venue (eg, emergency department or ultrasound suite for sonographic examination, or interventional radiology suite). In the past decades, interventional radiology has proven to be a valuable, nonsurgical, minimally invasive, effective, and safe alternative treatment option to control life-threatening uterine hemorrhages. Catheter angiography serves a dual role: it allows for identification of the exact source of bleeding and subsequent super-selective embolization of "leaking" branches of the uterine artery, which has proven to be very effective in controlling excessive bleeding [25-29]. (See "Postpartum hemorrhage: Management approaches requiring laparotomy".)

DIAGNOSTIC EVALUATION

History and physical examination

●What is the past obstetric history (including the recent birth)? If the patient had a previous PPH, recurrent PPH may have the same etiology. Did the most recent pregnancy have risk factors for retained products of conception (RPOC; eg, preterm birth, multiple gestation, retained placenta) or postpartum endometritis? (See "Postpartum endometritis", section on 'Risk factors'.)

What was the route of birth? RPOC are much more likely after vaginal birth than cesarean birth, whereas postpartum endometritis is more likely after cesarean birth. However, RPOC can occur after cesarean birth, even when the obstetrician thinks that the entire placenta was removed. Thus, the diagnosis should not be excluded based on the surgical history.

Uterine vascular abnormalities are rare. Acquired arteriovascular fistulas and pseudoaneurysms generally result from trauma (eg, pregnancy-related dilation and curettage, vaginal and perineal trauma incurred during spontaneous or assisted vaginal birth, cesarean birth). When increased vascularity is seen in the myometrium postpartum, it is almost always due to subinvolution of the placental bed, rather than an arteriovenous fistula [30]. (See 'Subinvolution of the placental site' below.)

●Does the patient have risk factors for a bleeding diathesis, such as von Willebrand disease (VWD)? A history of heavy menstrual bleeding or other personal or family history of excessive or unusual bleeding increases the probability of a bleeding diathesis. In one study of 16 deliveries of patients with unrecognized VWD, the incidence of primary and secondary PPH was 47 and 31 percent, respectively [31].

Basic laboratory screening for a bleeding diathesis includes platelet count, prothrombin time, and activated partial thromboplastin time; however, these tests may be normal in patients with VWD. (See "Approach to the adult with a suspected bleeding disorder", section on 'Laboratory evaluation' and "Approach to the adult with a suspected bleeding disorder".)

●Is the patient taking any medications (prescribed, over-the-counter, diet supplements, or vitamins) that may predispose them to uterine bleeding, such as anticoagulants, platelet inhibitors, and uterine relaxants (table 1)?

●Has the patient been exposed to any industrial toxins or other poisons (eg, snake venom) that may have affected her coagulation status?

●Has a vaginal or cervical, rather than uterine, source of bleeding been ruled out by examination? A traumatic birth, coitus, or insertion of a foreign object could cause vaginal or cervical bleeding.

●Are signs or symptoms of uterine infection present, such as uterine pain or tenderness, fever, tachycardia, or malodorous vaginal discharge? Predisposing factors for infection may include vaginal sex, use of a tampon, or insertion of an intrauterine device soon after birth. (See "Postpartum endometritis".)

Laboratory tests

●Complete blood count.

●Prothrombin time, activated partial thromboplastin time, fibrinogen level, thromboelastogram (if available).

●Human chorionic gonadotropin (hCG) – In patients with bleeding many weeks after delivery, a quantitative pregnancy test is useful for evaluating for choriocarcinoma, RPOC, or even a new pregnancy. Ultrasound examination and serial hCG determinations may be needed to distinguish among these entities when the test is positive. (See 'Management' below.)

Imaging — The first-line imaging modality for secondary PPH is transabdominal and, whenever possible, transvaginal ultrasound, including two-dimensional (2D) and three-dimensional (3D) anatomical imaging techniques as well as color and spectral Doppler. If the ultrasound imaging findings are indeterminate, computed tomography (CT), including contrast-enhanced CT-angiography (CTA) and CT-venography (CTV), or magnetic resonance imaging (MRI), including MR-angiography (MRA) and MR-venography (MRV), may be used. Catheter digital subtraction angiography is an important diagnostic, and possibly therapeutic, tool for the definitive diagnosis of uterine vascular abnormalities [32].

In the majority of cases, ultrasound can identify the cause of bleeding and will help narrow the differential diagnosis. Anatomical 2D and 3D ultrasound allows for identification of focal lesions within the myometrium or inside of the endometrial cavity. Color and spectral Doppler US are very useful for determining the vascularity of the identified abnormality, allowing for differentiation between a blood clot (no flow), RPOC (may or may not have flow), and other uterine vascular lesions. The peak systolic velocity should be determined when an abnormal vessel is seen. However, the postpartum uterus has a variable appearance on ultrasound examination, and there is considerable overlap between normal postpartum findings and findings associated with secondary bleeding [33,34]. In both cases, the uterus may be enlarged and the endometrial cavity may contain fluid, gas, and/or debris (image 1A-B). One of the greatest strengths of ultrasound is in its negative predictive value. In one study, no patient with endometrial thickness <10 mm and absence of an endometrial mass required intervention [35].

Familiarity with the strengths and limitations of the various imaging modalities, as well as a close interaction and collaboration between the treating physicians and radiologists, will guide appropriate imaging-based diagnostics and management. (See 'Selective testing' below.)

Infection — Ultrasound findings of endometritis are most often nonspecific (image 2), overlapping with normal postpartum findings. Even an elevated white blood cell count is not a distinguishing feature. The uterus may have a thickened, heterogeneous endometrium or show common normal postpartum findings, such as intracavitary debris, fluid, or gas. Infected retained placental tissue/fetal membranes or a hematoma may also be present. Endometritis is almost always a clinical diagnosis and may be present in association with other findings, such as RPOC. Tenderness during the ultrasound examination and/or an increased amount of fluid and/or gas over time when the patient has two or more examinations is highly associated with endometritis. However, endometrial gas may be seen in postpartum patients without pathology for up to three weeks after birth. Complementary to ultrasound, CT or MRI may show infectious stranding of the perimetria in better detail [36]. In patients who had a cesarean birth, assessment with CT (CTA/CTV) or MRI (MRA/MRV) can be helpful to evaluate for associated abscess or ovarian vein thrombosis.

Retained products of conception (RPOC) — RPOC have a variable and sometimes nonspecific appearance on grayscale ultrasound. The most sensitive finding is a thickened endometrial echo complex (EEC) [37]. A cut-off value of 10 mm has a reported sensitivity of over 80 percent for RPOC; however, the specificity is relatively low (30 percent). On the other hand, the negative predictive value of an EEC less than 10 mm is between 63 and 80 percent for RPOC.

An important additional ultrasound finding is the direct detection of a solid, echogenic intracavitary mass lesion that extends to the endometrium. A sensitivity of up to 79 percent has been reported for this finding. Color Doppler ultrasound further enhances diagnostic confidence and differentiation [38]. Detectable vascularity (low-resistance arterial flow) in an endometrial/intracavitary mass is highly suggestive of RPOC (image 3A-B) while a lack of vascularity is compatible with intrauterine blood clots (image 4), necrotic decidua, detached retained placental fragments, or avascular RPOC. The degree of vascularity in a thickened EEC or mass lesion can be compared with the myometrial vascularity and graded as type 0, 1, 2, or 3 [39]. The degree of vascularity increases the diagnostic confidence for RPOC. In type 0, no detectable vascularity in a thickened EEC or mass lesion indicates a blood clot or an avascular RPOC. Type 0 are rarely associated with severe bleeding. On the other hand, a type 3, characterized by blood flow of 100 cm/sec or higher and a very low-resistance spectral waveform are at risk for severe bleeding when a large vessel becomes unroofed during curettage [39]. In the absence of a mass, increased vascularity in a thickened postpartum endometrium and enhanced myometrial vascularity is still consistent with retained placental tissue. Enhanced myometrial vascularity and increased blood flow result from abnormal involution of the spiral arteries [20].

On CT and MRI, contrast-enhanced sequences typically show variable degrees of enhancement of the mass lesion. Dynamic contrast-enhanced sequences are particularly helpful to grade the vascularity of the lesion and to identify the exact depth of endometrial and myometrial invasion [40,41]. CTA/CTV and MRA/MRV assist in the differentiation from an uterine arteriovenous fistula. Clinical correlation with the serum level of β-hCG is helpful to exclude gestational trophoblastic disease, which may mimic RPOC on imaging [32].

Rarely, retained placenta can present as a calcified mass that has the appearance of calcified placental tissue. Also rarely, a focal morbidly adherent placenta presents as secondary PPH. Ultrasound findings include a mass that extends into or beyond the myometrium. (See "Overview of the postpartum period: Normal physiology and routine maternal care", section on 'Findings on ultrasound'.)

Subinvolution of the placental site — Subinvolution of the placental site (also known as subinvolution of uteroplacental arteries) is a rare postpartum condition that should be suspected when hypoechoic tortuous vessels are seen along the inner third of the myometrium at the location of the prior placental implantation site (image 5) [42]. Pulsed wave Doppler sonography shows increased peak systolic velocity (PSV; >0.83 m/second; normal 0.22 m/second three days postpartum, falling to 0.10 m/second after six weeks) with a low-resistance waveform along the inner third of the myometrium.

Few reports on the value of CT or MRI for diagnosis of subinvolution exist. Vascular lakes at the posterior endometrial-myometrial interface with an enlarged uterus have been described on contrast-enhanced CT and MRI [32]. Angiography may show hypertrophied uterine arteries and uterine parenchyma that rapidly opacifies and drains into large pelvic veins. No direct communication between the artery and vein should be present [43]. These imaging findings may mimic a uterine arteriovenous fistula [20]; however, even when systolic velocities and diastolic velocities are high and MR shows an early draining vein, subinvolution of the placental site is the more likely diagnosis. This distinction is important since in clinically stable patients, time and uterotonics can lead to resolution of the increased myometrial vascularity, and thus can avoid an interventional procedure. In patients who are clinically unstable, embolization of the uterine arteries can stabilize the patient.

Bleeding diathesis — Both bleeding diathesis and subinvolution of the placental site can be associated with intracavitary hematomas, which can mimic the ultrasound appearance of retained products of conception. Doppler ultrasound helps to distinguish among these disorders.

Hematomas are not vascularized, whereas retained placental tissue may have vascular flow within the mass on Doppler ultrasound. Patients with subinvolution and an intracavitary hematoma may have increased PSV and low-resistance arterial flow within the myometrium at the placental implantation site but not in the mass, and the uterus may be enlarged.

Intracavitary hematomas are typically hyperechoic on ultrasound and may be hypo- or hyperdense on CT and hypo- or hyperintense on T1-weighted MRI depending on the age of the hematoma. Hematomas should not enhance with contrast, if used, and typically present with restricted diffusion characteristics (hyperintensity) on diffusion weighted imaging (DWI).

Vascular lesions — Arteriovenous fistula and uterine artery pseudoaneurysm have characteristic features on ultrasound and CT/CTA or MRI/MRA.

●Arteriovenous fistula – Arteriovenous fistulas are characterized by a high-flow arteriovenous shunting. They may be congenital or acquired. Arteriovenous fistula-related secondary PPH is usually due to an acquired fistula (eg, after a curettage or a cesarean birth). Grayscale ultrasound imaging findings are nonspecific and include multiple hypoechoic or anechoic tubular or serpentine spaces concentrated in a small area of the myometrium adjacent to the uterine cavity. Color and spectral Doppler examinations are essential and will show turbulent or multidirectional blood flow in a complex tangle of vessels with high-velocity (peak systolic velocity [PSV] ≥0.2 m/sec) and low-resistance flow (consistent with arteriovenous shunting) on spectral analysis [44]. A PSV >0.83 m/second in vascular malformations has been associated with a high risk of hemorrhage, a PSV <0.83 m/second has been associated with an intermediate risk, and a PSV <0.39 m/second has been associated with a low risk [45].

CT/CTA and MRI/MRA including dynamic contrast-enhanced sequences may show dilated, feeding arteries and enlarged, tortuous draining veins. Depiction of draining veins in the arterial contrast phase also suggest significant arteriovenous shunting [32]. However, as mentioned above, most patients with increased myometrial vascularity have subinvolution of the placental site rather than an arteriovenous fistula. Subtle myometrial heterogeneity, a myometrial or endometrial mass, or prominent parametrial vessels may be observed.

●Pseudoaneurysm – Uterine artery pseudoaneurysms are rare causes of PPH. They may result from laceration or injury of the wall of the uterine artery branches, often after cesarean birth or curettage. Grayscale ultrasound findings include an anechoic or hypoechoic intrauterine lesion. Color Doppler ultrasound typically shows turbulent, multidirectional (whirlpool) flow inside the pseudoaneurysm, often called the "yin yang" sign. A hematoma usually surrounds the area of turbulent flow.

CT/CTA and MRI/MRA show T2-hypointense signal void in the area of the blood flow, while the surrounding hematoma may show various densities and signal intensities depending on the composition and age of the hematoma. On contrast-enhanced sequences, the pseudoaneurysm usually shows a strong contrast enhancement, including possible leakage of contrast into the uterine cavity [32]. Selective catheter angiography combines diagnostic sensitivity and specificity with the potential to selectively treat the pseudoaneurysm in the same session.

Hypoestrogenism — A normal-appearing uterus with a thin endometrium may be a sign of hypoestrogenism. Patients who are breastfeeding are more likely to have hypoestrogenism than those who are not breastfeeding.

Selective testing — If the diagnosis is uncertain after the history, physical examination, ultrasound, and laboratory evaluation, then additional testing, such as pelvic CT/CTA or MR/MRA as well as digital subtraction angiography, may be warranted.

●Laboratory testing that might be ordered in these cases includes: FSH, LH, TSH, estradiol, and progesterone to rule out a possible hypoestrogenic state and to determine the cause.

●In almost all cases, ultrasound is diagnostic to assess the patient with secondary PPH. If there is a large amount of retained products with high velocity blood flow (greater than 83 cm/second), then the risk of bleeding during a dilation and curettage procedure is greater. In those cases, an interventional radiology procedure to limit flow to the uterus prior to the procedure can be helpful. MRI is reserved for cases where 1) it is unclear if retained products are present, for example, in a patient with fibroids where the endometrium is poorly visualized; or 2) when placenta accreta is suspected and the extent of the myometrial invasion is incompletely assessed with ultrasound. While contrast-enhanced CT or MRI including DWI may be used to assess for postpartum abscess in a patient with fever, it is not the primary imaging modality of choice for abnormal postpartum bleeding.

MANAGEMENT

Management of common causes of secondary PPH

Initial approach — Our initial approach to management is based on the suspected etiology of bleeding and is described in the algorithm (algorithm 1).

Whether to initially manage secondary PPH medically, surgically, or with interventional is still a relatively unstudied aspect of the care of these patients. No data from randomized trials or prospective cohort studies are available to guide management [46]. A retrospective study of 168 patients with secondary PPH compared the outcomes of those initially managed with surgical evacuation of the uterus with those initially managed medically [47]. The suspected causes of PPH in these cases was not discussed. Primary surgical treatment was associated with a higher frequency of negative primary outcomes (blood transfusion, uterine perforation after curettage, use of broad-spectrum antibiotics, hysterectomy) than primary medical treatment (37.5 versus 16.5 percent). Approximately one-quarter of patients who were initially treated medically required secondary surgical evacuation and 15 percent required readmission, whereas 8 percent of those treated surgically had these outcomes. In addition, primary surgical treatment was associated with a trend toward fewer future deliveries and an increased rate of secondary infertility. This study suggests that a conservative medical approach may be superior to primary surgical treatment, but is limited by selection bias and inability to analyze the data by etiology of bleeding.

Retained products of conception — Surgical procedures (dilation and curettage, suction curettage) are directed at evacuation of retained products of conception, which are more common after vaginal than cesarean birth and when a vascularized endometrial mass is noted on color Doppler ultrasound. It should be noted that retained products can be present, even without flow. In these cases, it is the size of the mass that typically guides decision-making. Curettage is probably the best approach when a significant amount of tissue is present, whereas observation or pharmacotherapy of subinvolution is reasonable when there is no or minimal tissue.

Ideally, curettage is performed under ultrasound guidance. This is likely to reduce the rate of perforation, allow identification of placental tissue, and confirm that this tissue has been evacuated [33]. Suction curettage should be employed when bleeding is over 500 mL and is not controlled by medical measures. The size of the suction cannula is determined by the size of the uterus. The diameter of the cannula is usually chosen according to the uterine size by gestational age (eg, a 12 mm cannula for a uterus of 12 weeks size) with a minimum diameter of 10 mm and a maximum diameter of 16 mm.

Uterine perforation and formation of intrauterine adhesions are the major complications of surgery. In the series described above, perforation occurred in 3 percent of cases [4]. (See "Intrauterine adhesions: Clinical manifestation and diagnosis".)

Subinvolution of the placental site — If subinvolution of the placental site is suspected, uterotonic agents are administered. Options include:

●Methylergonovine (0.2 mg intramuscularly, repeated every two to four hours up to three doses), or

●Carboprost tromethamine (Hemabate, 250 mcg intramuscularly; up to eight doses at intervals at least 15 minutes apart), and/or

●Oxytocin infusion

These agents will likely not be useful if the uterus is firm, but given that the subinvolution may be focal in some cases, a trial of uterotonic agents may still be useful even if the uterus is not atonic. Persisting in their use when the uterus is firm is not usually helpful.

Surgical procedures (dilation and curettage, suction curettage) are often effective when medical management fails, even if retained placental or membrane fragments cannot be identified sonographically [4,48]. As an example, a study of 132 consecutive patients with secondary PPH reported 75 (57 percent) were initially treated with surgical evacuation, which was successful in 67 (90 percent) [4]. Of the 57 patients initially managed medically, treatment was successful in 41 (72 percent); 16 patients had continuing symptoms, of whom 12 subsequently underwent surgical evacuation. Tissue specimens were obtained at surgery in only 38 patients, and just one-third of these had histological confirmation of placental tissue. The histologic diagnosis of placental subinvolution is based on dilated myometrial arteries with hyaline material replacing the medial layer, partial occlusion by thrombi of variable age, and extravillous trophoblast in and around the placental bed vessels [49,50].

Selective arterial embolization has been effective for controlling severe bleeding in high-risk patients, who can be refractory to uterotonic drugs or uterine curettage [2,51,52]. If percutaneous therapy fails, hysterectomy may be required.

Endometritis — If bleeding is not massive and fever, uterine tenderness, and/or a malodorous discharge are present, then endometritis should be suspected. Under these circumstances, we prescribe broad-spectrum antibiotic therapy (table 2). However, some clinicians administer antibiotics to all patients with secondary PPH, including those without obvious signs of infection. (See "Postpartum endometritis", section on 'Diagnosis' and "Postpartum endometritis", section on 'Treatment'.)

Rare, but potentially lethal causes of endometritis include Clostridium sordellii [53-56], Clostridium perfringens [57], and streptococcal or staphylococcal toxic shock syndrome [58-60]. (See "Postpartum endometritis", section on 'Endometritis with toxic shock syndrome'.)

Management of uncommon and rare causes of secondary PPH

Vascular lesions — Selective arterial embolization is the preferred approach for patients with radiographic diagnosis of a vascular lesion (eg, arteriovenous fistula, pseudoaneurysm) as the source of bleeding [2,51,61].

Bleeding diathesis — Patients in whom a bleeding diathesis has been documented should be treated as appropriate for the underlying disorder (refer to the relevant topic review for the specific disorder). Consultation with a hematologist is advised.

Neoplasia — Management of patients with neoplasia depends on the specific disorder:

●Gestational trophoblastic disease (image 6 and image 7) (see "Gestational trophoblastic neoplasia: Epidemiology, clinical features, diagnosis, staging, and risk stratification")

●Cervical cancer (see "Invasive cervical cancer: Epidemiology, risk factors, clinical manifestations, and diagnosis" and "Management of early-stage cervical cancer")

●Endometrial polyp (see "Endometrial polyps")

●Adenomyosis (see "Uterine adenomyosis")

●Fibroid (see "Uterine fibroids (leiomyomas): Treatment overview")

Uterine diverticulum — A case report described severe vaginal bleeding on the 47^th day after a cesarean birth [16]. Transvaginal ultrasound examination, which showed a thickened heteroechoic endometrium with an isolated isthmic heteroechoic cystic lesion, was not diagnostic and curettage did not control bleeding. Because of severe bleeding, emergency laparotomy was performed and the diagnosis of a diverticulum in the lateral wall of the uterine isthmus was made. Obliteration of the diverticulum by sutures controlled the hemorrhage.

Hypoestrogenism — If a hypoestrogenic state is identified, the aim is to stimulate rapid endometrial growth with estrogen as long as there are no contraindications to hormonal therapy. The choice of whether to administer estrogen orally or intravenously should be based on severity of bleeding and hemodynamic status.

One option would be to use intravenous conjugated equine estrogen (20 to 40 mg) every four hours (not to exceed a total dose of 300 mg/24 hours). Once the bleeding is controlled, add 5 mg medroxyprogesterone acetate orally, administer one final dose of estrogen intravenously, and begin an estrogen-progestin contraceptive pill with 35 mcg ethinyl estradiol twice a day for 4 to 5 days, tapering to one pill daily.

Alternatively, instead of initiating intravenous conjugated equine estrogen, an oral contraceptive pill with 35 mcg ethinyl estradiol is administered every six hours until the bleeding is controlled, then tapered on consecutive days to 35 mcg every eight hours, every 12 hours, and then daily.

SPECIAL POPULATIONS

Severe PPH outside of the hospital setting — If PPH is severe and does not occur while the patient is hospitalized, emergency responders can administer tranexamic acid and rapidly transport the patient to a hospital where diagnostic evaluation and definitive therapy can be performed. In those desperate cases in which the patient is critically unstable, the use of a nonpneumatic anti-shock garment (NASG) may be helpful for reversing hypovolemic shock and decreasing obstetric hemorrhage while the patient is being transported [62-64]. NASG is discussed in more detail separately. (See "Overview of postpartum hemorrhage", section on 'Recognize alarm findings and intervene early'.)

The abdominal aortic tourniquet (external aortic compression device [EACD]) is a corset like device that provides external aortic compression. Its use reduced morbidity and mortality from PPH in studies from Egypt [65,66].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obstetric hemorrhage".)

SUMMARY AND RECOMMENDATIONS

●Definition – Secondary or late postpartum hemorrhage (PPH) is generally defined as any significant uterine bleeding occurring between 24 hours and 12 weeks postpartum. (See 'Definition/diagnosis' above.)

●Etiology – The most common causes of secondary PPH are retained products of conception (including focal placenta accreta), subinvolution of the placental bed, and/or infection. (See 'Etiology' above.)

•Less common and rare causes of secondary PPH include (see 'Etiology' above):

-Inherited or acquired bleeding diatheses, including medications that may predispose to bleeding

-Pseudoaneurysm of the uterine artery, internal pudendal artery, vaginal artery, or vulvar labial artery

-Arteriovenous fistula

-Choriocarcinoma

-Undiagnosed carcinoma of the cervix

-Adenomyosis

-Infected polyp or submucosal fibroid

-Uterine diverticulum

-Excessive bleeding with resumption of menses

-Hypoestrogenism

-Dehiscence of a cesarean scar

Sometimes the cause cannot be determined.

●Management

•Stabilize the patient – If the patient is hemodynamically unstable, stabilization is the priority. Such patients should be evaluated in a venue suitable for surgical intervention until sufficiently stable for transfer to a lower acuity setting.

In patients experiencing secondary PPH in the first few weeks after the birth, the uterine cavity may be large enough to admit a balloon tamponade device, which may be useful to limit bleeding while diagnostic evaluation occurs. (See 'Hemodynamically unstable patients' above.)

•Determine and treat the cause of bleeding – Diagnostic evaluation to determine the cause is the priority in stable patients. Management is guided by the cause of bleeding (algorithm 1). In those cases where the source of bleeding is difficult to discern, pelvic computed tomographic angiography (CTA) or magnetic resonance angiography (MR/MRA) may allow identification of a vascular abnormality that can be concurrently treated with embolization or covered stenting. (See 'Management' above.)

•Role of surgery – Surgical procedures (dilation and curettage, suction curettage) are often effective when medical management fails, even if retained placental or membrane fragments cannot be identified sonographically. Arterial embolization is another option. It should be noted that, because of the rich vascular supply of the pelvis and perineum in pregnancy, embolization of a single vaginal or vulval supply artery or pseudoaneurysm is unlikely to result in vaginal or perineal ischemia or necrosis. (See 'Subinvolution of the placental site' above.)