INTRODUCTION — Postpartum hemorrhage (PPH) may occur shortly after the birth or, less commonly, days later. This topic will discuss secondary (also called late) PPH. Issues related to primary or early 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 [2-5]. 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

●Subinvolution of the placental bed

●Infection

Rare causes include [2,6-18]:

●Inherited or acquired bleeding diatheses

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

●Arteriovenous malformations

●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 [19]) [19-21]. A history of primary PPH is a risk factor for severe secondary PPH (OR 4.7, 95% CI 1.9-11.6 [19]) [4,19,22].

CLINICAL PRESENTATION — Vaginal bleeding in excess of what is expected is the presenting symptom in all patients. Bleeding may be accompanied by pelvic pain, fever, and/or uterine tenderness. These clinical findings are nonspecific; moreover, it is normal to have some postpartum bleeding and 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 a balloon tamponade device, which may be useful to limit bleeding while the diagnostic evaluation occurs. If the fundus is not palpable abdominally, 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. (See "Postpartum hemorrhage: Use of intrauterine tamponade to control bleeding".)

If the patient cannot be stabilized promptly, transfer to a venue suitable for emergency surgical intervention (operating room or hybrid 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, imaging suite). (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 (eg, preterm birth, multiple gestation, retained placenta) or postpartum endometritis? (See "Postpartum endometritis", section on 'Risk factors'.)

What was the route of birth? Retained products of conception are much more likely after a vaginal birth than cesarean birth, whereas postpartum endometritis is more likely after cesarean.

Uterine vascular abnormalities are rare. Acquired arteriovascular malformations 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) [23].

●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 [24].

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, retained products of conception, 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 — Ultrasound examination (including color and spectral flow Doppler) of the uterus may identify the cause of bleeding and will help exclude some potential bleeding sources in the differential diagnosis. 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 [25,26]. In both cases, the uterus may be empty or contain gas, echogenic material, and/or fluid (image 1A-B).

In some cases, the radiologist may suggest additional imaging procedures. (See 'Selective testing' below.)

Infection — Ultrasound findings of endometritis are often nonspecific (image 2). 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.

Retained products of conception — Vascularity of echogenic intracavitary material is a key finding as vascularity on color Doppler suggests retained products (image 3A-B) whereas lack of vascularity is consistent with blood clot (image 4), but does not exclude the presence of retained necrotic (avascular) placental tissue. If no intracavitary mass, endometrial fluid, or vascularity is seen and the endometrial thickness is thin, retained products are not likely.

Retained products of conception have a variable and sometimes nonspecific appearance on ultrasound. They often appear as a solid, echogenic intracavitary mass that extends to the endometrium. However, necrotic decidua and blood clots can mimic retained placental fragments. Color and spectral Doppler showing high-velocity, low-resistance arterial flow in the mass differentiates placental tissue from hematoma, but is not always present in the retained tissue. In the absence of a mass, increased vascularity in a thickened postpartum endometrium is also consistent with retained placental tissue. 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 may be suspected when hypoechoic tortuous vessels are seen along the inner third of the myometrium (image 5) [27]. 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. The increased areas of vascularity correlate with the placental implantation site documented by predelivery sonography. However, these findings cannot always be differentiated from congenital or acquired arteriovenous malformations (AVMs, also referred to as congenital or acquired enhanced myometrial vascularity), and retained products of conception may mimic these findings when echogenic tissue is present within the endometrial cavity.

Bleeding diathesis — Both bleeding diathesis and subinvolution 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. 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.

Vascular malformations — AVM and pseudoaneurysm have characteristic features on ultrasound and computed tomographic (CT) angiography. Ultrasound findings of an AVM include multiple hypoechoic or anechoic serpentine spaces concentrated in a small area of myometrium adjacent to the uterine cavity, with turbulent flow on color Doppler and high-velocity (peak systolic velocity [PSV] ≥0.2 m/sec) and low-resistance flow on spectral analysis [28]. 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 [29]. Subtle myometrial heterogeneity, a myometrial or endometrial mass, or prominent parametrial vessels may be observed. (See "Differential diagnosis of genital tract bleeding in women", section on 'Arteriovenous malformation'.)

Ultrasound findings of a uterine artery pseudoaneurysm may include a hypoechoic intrauterine lesion, vascularity on color Doppler, and bidirectional systolic and diastolic flow with aliasing on spectral Doppler.

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 imaging, and laboratory evaluation, then additional testing, such as pelvic CT 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.

●Three-dimensional ultrasound examination and saline infusion sonohysterography can be helpful to rule out a structural anomaly not identified on routine two-dimensional ultrasound examination and to identify potential sources of bleeding other than the endometrium (such as a scar dehiscence).

In almost all cases, ultrasound is sufficient to assess the patient with late PPH. If there is a large amount of retained products with high velocity 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. Magnetic resonance imaging 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 CT may be used to assess for postpartum abscess in a patient with fever, it is not a second-line imaging modality for abnormal 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 or surgically is still a relatively unstudied aspect of the care of these patients. No data from randomized trials are available to guide management [3]. 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 [30]. 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. 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 [25]. 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 [4,31]. 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 [32,33].

Selective arterial embolization has been effective for controlling severe bleeding in high-risk patients, who can be refractory to uterotonic drugs or uterine curettage [2,34,35]. 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 [36-39], Clostridium perfringens [40], and streptococcal or staphylococcal toxic shock syndrome [41-43]. (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 as the source of bleeding [2,34,44].

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 [15]. 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 [45-47]. NASG is discussed in more detail separately. (See "Overview of postpartum hemorrhage".)

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 [48,49].

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, subinvolution of the placental bed, and/or infection. (See 'Etiology' above.)

•Rare causes of secondary PPH include (see 'Etiology' above):

-Inherited or acquired bleeding diatheses

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

-Arteriovenous malformations

-Choriocarcinoma

-Undiagnosed carcinoma of the cervix

-Adenomyosis

-Infected polyp or submucosal fibroid

-Uterine diverticulum

-Excessive bleeding with resumption of menses

-Hypoestrogenism

Sometimes the cause cannot be determined.

●Management

•If the patient is hemodynamically unstable, stabilization is the priority, followed by diagnostic evaluation (algorithm 1). 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.)

•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 may allow identification of a vascular abnormality or pseudoaneurysm that can be concurrently treated with embolization. (See 'Management' above.)

•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.)