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INTRODUCTION — The approach to treatment of postpartum hemorrhage (PPH) differs somewhat depending on the cause and whether hemorrhage occurs after a vaginal birth or after a cesarean delivery. The approach also depends on the available resources, time for preparation, and whether the bleeding occurs before, during, or after the operation.
This topic will discuss the approach to the patient with hemorrhage associated with cesarean delivery. As with hemorrhage after vaginal delivery, the key to management is to identify the cause of bleeding and to initiate appropriate intervention. Increasingly, hospitals have adopted policies, protocols, and guidelines to deal with massive obstetric hemorrhage. A physician practicing obstetrics should be aware of the existence and content of such protocols.
An overview of issues related to diagnosis and management of PPH and the approach to the patient with PPH after vaginal delivery are reviewed separately:
OVERVIEW — Causes of PPH after cesarean delivery include uterine atony, placenta accreta/increta/percreta, bleeding from the uterine incision or extensions of this incision, retained placenta or placental fragments, bleeding from vaginal or cervical tears or uterine rupture, or an underlying bleeding diathesis.
After delivery of the placenta, the volume and source(s) of bleeding are routinely assessed. Concealed hemorrhage is a major consideration, especially in patients who appear to be developing hypovolemia even though observed bleeding is light. Communication between the surgeon and anesthesia team is crucial in order to detect and appropriately respond to developing hypovolemia. Ongoing bleeding may not be recognized when it is retroperitoneal (including vaginal and vulvar hematomas), hidden under surgical drapes or thick dressing, or confined to the uterine cavity after closure of the hysterotomy; these sites should be actively evaluated when compensated shock is present (normal blood pressure with increasing heart rate).
Atony — Uterine atony can be isolated or associated with one or more of the other causes of hemorrhage. It may be diffuse or localized to an area of uterine muscle. In the latter, the fundal region may be well contracted while the lower uterine segment is dilated and atonic. Because a boggy and dilated uterus may contain a significant amount of blood, the patient may develop hemodynamically significant preload reduction. The diagnosis is made if the uterus does not become firm after uterine massage and administration of uterotonic agents.
Cervical and vaginal lacerations — Cervical and vaginal lacerations typically occur after a long labor with complete or nearly complete dilatation. They can develop spontaneously, during a trial of forceps or vacuum extraction, or during cesarean delivery when the fetal presenting part is extricated from deep in the pelvis. The presence of cervical and lower genital tract lacerations may not be noted until excessive vaginal bleeding postoperatively prompts lower genital tract examination. Ideally, the perineum should be inspected in the operating room to determine if there is active vaginal bleeding and, if bleeding lacerations are present, they should be repaired. Examination of the vulva and vagina for hematoma formation is important in any hemodynamically unstable patient after a cesarean delivery, particularly if there was a failed attempt at operative vaginal delivery or traumatic disimpaction of the fetal head at the time of the cesarean birth.
Uterine lacerations — Serious hemorrhage from the uterine incision is generally caused by lateral extension of the incision, which can result from spontaneous tearing of an edematous lower segment during an otherwise uneventful cesarean delivery after prolonged labor, from an incision made too low or not sufficiently curved on the lower segment, or from delivery of the fetus through an incision that is too small. Bleeding from lateral extension of the uterine incision is readily ascertained by inspection of the incision, lateral pelvic sidewalls, and broad ligament.
Retroperitoneal hemorrhage — Retroperitoneal enlargement or bulging of the broad ligament can be signs of retroperitoneal hemorrhage; the abdomen should not be closed until the possibility of ongoing retroperitoneal bleeding has been excluded.
Defective hemostasis — Coagulation abnormalities may result in PPH during or after delivery. These abnormalities include factor deficiencies and platelet abnormalities (von Willebrand Disease [VWD], vitamin K deficiency, hemophilia carrier status, Bernard-Soulier Disease [BSS], Glanzmann’s thrombasthenia), and disseminated intravascular coagulopathy (DIC) from systemic causes such as amniotic fluid embolism and sepsis.
Retained placenta or placental fragments — Inspection of the endometrial cavity should reveal any retained placental fragments or areas of focal accreta. Placenta accreta should be suspected if the placenta does not separate readily, but can be present even if placental delivery appeared to be complete. Placenta accreta usually manifests as hemorrhage from an implantation site.
●On recognition of ongoing bleeding, the anesthesia team should be alerted immediately and vital signs, hemodynamic and respiratory parameters, and hematologic and biochemical indices should be closely monitored. Thromboelastography and thromboelastometry, where available, may be useful for guiding plasma and coagulation product therapy , although there is minimal information on use of these tests in pregnancy [2-5]. Treatment of severe hemorrhage, especially when the patient is unstable, should not be delayed in order to review laboratory data. (See "Management of postpartum hemorrhage at vaginal delivery", section on 'Laboratory tests'.)
●Fluid and blood products, as appropriate, are administered for resuscitation and correction of coagulation and electrolyte abnormalities. Treatment is similar to that for PPH after vaginal delivery and is reviewed in detail separately. (See "Management of postpartum hemorrhage at vaginal delivery", section on 'Fluid resuscitation and transfusion'.)
●Acidosis is corrected using bicarbonate, if necessary.
●Body temperature should be maintained and hypothermia prevented.
●The source of bleeding should be addressed:
•If atony is present or suspected, fundal massage and uterotonic drugs are used to contract the uterus. Appropriate blood product and fluid resuscitation should be instituted to restore circulating blood volume even after the atony has resolved, since the blood contained in the atonic uterus will usually exit the vagina and be lost to the circulation once the uterus contracts. (See "Management of postpartum hemorrhage at vaginal delivery", section on 'Uterotonic drugs' and "Management of postpartum hemorrhage at vaginal delivery", section on 'Fluid resuscitation and transfusion'.)
•Bleeding from a hysterotomy incision can generally be controlled by suture ligation. The angles of a transverse incision should be clearly visualized to ensure that they, and any retracted vessels, are completely ligated. This generally requires exteriorization of the uterus with gentle traction and adequate lateral retraction. Given the proximity of the ureter to the vaginal angle and bladder reflection, the placement of hemostatic sutures laterally to control bleeding from an extension of a hysterotomy laceration should be carried out with extreme caution. If possible, the ipsilateral ureter should be identified before the bleeding is controlled and, once the hemorrhage has been controlled, the integrity of the ureter should be ensured. (See 'Post-laparotomy inspection' below.)
•Specific interventions for control of bleeding from placenta accreta are discussed in detail separately. (See "Clinical features and diagnosis of placenta accreta, increta, and percreta".)
●Baseline electrolyte analysis is important to check ionized calcium and potassium levels since, in the event of multiple units of blood transfusion, these electrolytes can reach critical thresholds very quickly. Aggressive management of electrolyte levels is crucial in modern massive transfusion protocols, and the institution of standardized management protocols is recommended. (See "Management of postpartum hemorrhage at vaginal delivery", section on 'Electrolytes'.)
●Use of specific clotting factor therapies can be useful and have some advantages in cases of intractable hemorrhage and coagulopathy. (See "Management of postpartum hemorrhage at vaginal delivery", section on 'Coagulation factor concentrates'.)
CONSERVATIVE SURGICAL INTERVENTIONS — A variety of surgical interventions are effective for controlling PPH. Clinicians should use their clinical judgment in deciding whether to expend time attempting one or more of these interventions in a patient with severe hemorrhage who may be better served by hysterectomy, such as women with diffuse placenta accreta/increta/percreta or uterine rupture. The following list is not progressive and any, or many, of these procedures may be used simultaneously.
Uterine artery and utero-ovarian artery ligation — Bilateral ligation of the uterine vessels (O'Leary stitch) to control PPH has become a first-line procedure for controlling uterine bleeding at laparotomy [6,7]. It is preferable to internal iliac artery ligation because the uterine arteries are more readily accessible, the procedure is technically easier, and there is less risk to major adjacent vessels and the ureters (see 'Internal iliac artery ligation' below).
Uterine artery ligation is primarily indicated when bleeding is due to laceration of the uterine or utero-ovarian artery branches, but can also temporarily decrease bleeding from other etiologies by reducing perfusion pressure in the uterine tissue. Although it will not control bleeding from uterine atony or placenta accreta, it may decrease blood loss while other interventions are being attempted.
After identification of the ureter, a large curved needle with a #0 polyglycolic acid suture is passed through the lateral aspect of the lower uterine segment as close to the cervix as possible and then back through the broad ligament just lateral to the uterine vessels. If this does not control bleeding, the vessels of the utero-ovarian arcade are similarly ligated just distal to the cornua by passing a suture ligature through the myometrium just medial to the vessels, then back through the broad ligament just lateral to the vessels, and then tying to compress the vessels (figure 1).
Bilateral ligation of the arteries and veins (uterine and utero-ovarian) is successful in controlling hemorrhage in over 90 percent of patients [7,8]. Uterine necrosis and placental insufficiency in a subsequent pregnancy have not been described as complications [8,9]. However, there is a single case report of ovarian failure and development of intrauterine synechiae after postpartum ligation of the uterine, utero-ovarian, and ovarian arteries for PPH related to atony .
Internal iliac artery ligation — Bilateral ligation of the internal iliac arteries (hypogastric arteries) has been used to control uterine hemorrhage by reducing the pulse pressure of blood flowing to the uterus . The technique is challenging even for an experienced pelvic surgeon, especially when there is a large uterus, a transverse lower abdominal incision, ongoing pelvic hemorrhage, or the patient has a high body mass index (BMI). Successful and safe bilateral hypogastric ligation becomes even more difficult when attempted by a surgeon who rarely operates deep in the pelvic retroperitoneal space . For these reasons, uterine compression sutures and, less commonly, uterine artery ligation, have largely replaced this procedure as first-line surgical options. The internal iliac ligation procedure is described separately. (See "Management of hemorrhage in gynecologic surgery".)
Uterine compression sutures — Uterine compression sutures are an effective method for reducing uterine blood loss related to atony. Procedure-related complications, such as uterine necrosis, erosion, and pyometra, have been reported, but are rare [13-18]. Uterine synechiae have been reported on postpartum hysteroscopy or hysterosalpingogram, although some of these women may have had curettage as well . Limited follow-up of women who have had a uterine compression suture suggests that there are no adverse effects on fertility or future pregnancy outcome [20,21].
The specific placement of compression sutures is determined by the operator at the time of laparotomy, and their location requires operator judgment. Generally, longitudinal sutures should be easier to place and should be safer than transverse sutures, but this may not always be the case. If uterine atony persists after administration of uterotonic drugs, compression sutures should be placed promptly, as delaying placement by more than an hour increases the likelihood that hysterectomy will be needed .
The B-Lynch suture is the most common technique for uterine compression; several variations of this technique have been described and no technique has been proven significantly more effective than another .
B-Lynch suture — The B-Lynch suture envelops and compresses the uterus, similar to the result achieved with manual uterine compression . In case reports and small series, it has been highly successful in controlling uterine bleeding from atony when other methods have failed [23-27]. The technique is relatively simple to learn, appears safe, and preserves future reproductive potential. It should only be used in cases of uterine atony; it will not control hemorrhage from placenta accreta.
A large Mayo needle with #1 or #2 chromic catgut is used to enter and exit the uterine cavity laterally in the lower uterine segment (figure 2). A large suture is used to prevent breaking and a rapid absorption is important to prevent a herniation of bowel through a suture loop after the uterus has involuted.
The suture is looped over the fundus and reenters the lower uterine cavity through the posterior wall. The suture then crosses to the other side of the lower uterine segment, exits through the posterior wall, and is looped back over the fundus to enter the anterior lateral lower uterine segment opposite and parallel to the initial bites. The free ends are pulled tightly and tied down securely to compress the uterus, assisted by bimanual compression.
The technique has been used alone and in combination with balloon tamponade. This combination has been called the "uterine sandwich." (See "Intrauterine balloon tamponade for control of postpartum hemorrhage".)
Other techniques — Other techniques have been reported in small case series and represent modifications of the B-Lynch suture [25,28-35]. Hayman described placement of two to four vertical compression sutures from the anterior to posterior uterine wall without hysterotomy (figure 3) [28,29]. A transverse cervicoisthmic suture can also be placed if needed to control bleeding from the lower uterine segment. Pereira described a technique in which a series of transverse and longitudinal sutures of a delayed absorbable multifilament suture are placed around the uterus via a series of bites into the subserosal myometrium, without entering the uterine cavity (figure 4) . Two or three rows of these sutures are placed in each direction to completely envelope and compress the uterus. The longitudinal sutures begin and end tied to the transverse suture nearest the cervix. When the transverse sutures are brought through the broad ligament, care should be taken to avoid damaging blood vessels, ureters, and fallopian tubes. The myometrium should be manually compressed prior to tying down the sutures to facilitate maximal compression. The multiple squares/rectangles technique of Cho is another variation (figure 5) [32,36].
Balloon tamponade — Devices such as the Bakri tamponade balloon, the Belfort-Dildy Tamponade Balloon, and the BT-Cath have been used successfully to tamponade bleeding from the uterine cavity after vaginal or cesarean delivery . For each device, the balloon is filled until bleeding is controlled; continued excessive bleeding indicates that tamponade is not effective. The technique has been used alone and in combination with uterine compression sutures ("uterine sandwich").
Balloon tamponade after cesarean delivery is performed while the surgeon has direct vision of the uterus, and although few published reports have described outcomes , there does not appear to be any increased risk of uterine rupture when used after cesarean delivery. These data and the use of these devices are described separately. (See "Intrauterine balloon tamponade for control of postpartum hemorrhage".)
TEMPORIZING MEASURES — Severe bleeding may occur despite fluid and transfusion therapy and while the surgeon is attempting to perform procedures for treatment of PPH. In these cases, the following measures can be taken to provide additional patient support.
Uterine tourniquet — Tourniquets have been used to control bleeding at myomectomy, and for other types of pelvic hemorrhage, and may be useful as a temporizing measure in PPH . (See "Techniques to reduce blood loss during abdominal or laparoscopic myomectomy", section on 'Tourniquets and clamps'.)
Aortic compression — Severe bleeding may pose a threat of exsanguination within a few minutes. In these cases, the surgeon should palpate the aorta a few centimeters superior to the sacral promontory and compress the aorta just proximal to the bifurcation. This will markedly slow the volume of bleeding and affords a better opportunity for finding and controlling the source of hemorrhage.
Intraoperative selective pelvic arterial embolization — Where available, intraoperative arterial embolization may be helpful. This procedure requires a hybrid operating room or an operating room with a carbon fiber table with a riser that allows the placement of an x-ray plate under the patient and a portable C-arm x-ray machine. The combination of arterial embolization and pelvic packing while the patient remains in the operating room allows time for resuscitation, acid-base, electrolyte and blood product optimization, and warming of the patient, and thus may be life-saving. Hemodynamically unstable patients should never be transferred from an operating room to an interventional radiology suite for arterial embolization.
Intraaortic balloon catheter placement — An intra-aortic balloon catheter has been used to stabilize patients with life-threatening PPH; evidence is limited to case reports [39-41]. In an extreme emergency, an interventional radiologist may be able to place such a balloon and temporarily occlude the aorta above the bifurcation. This will impair perfusion of the lower limbs, but deflating the balloon intermittently and monitoring distal pulses can prevent ischemic limb complications.
Intraoperative cell salvage — Intraoperative blood salvage with a leukocyte filter and autotransfusion is another option, but its use is investigational in the obstetrical setting [42-45]. Although there is a theoretical concern that reinfusing amniotic fluid may cause amniotic fluid embolism, this has been documented only once . Salvaged blood also may be contaminated by fetal erythrocytes. This is not a major concern as Rh(D) alloimmunization in an Rh(D) negative mother can be prevented by administration of anti-D immunoglobulin and ABO incompatibility reactions are unlikely to be serious because the volume of fetal blood contamination is small and A and B antigens/antibodies are not fully developed at birth. In addition, these risks are probably less than or similar to those from allogeneic transfusion.
HYSTERECTOMY — Hysterectomy is generally the last resort for treatment of atony, but should not be delayed in women who require prompt control of uterine hemorrhage to prevent death. By comparison, in women with placenta accreta/increta/percreta or uterine rupture, early resort to hysterectomy is one of the best approaches for controlling hemorrhage. With improving prenatal diagnosis of placental attachment disorders, hysterectomy can often be anticipated and discussed with the patient before cesarean delivery. (See "Peripartum hysterectomy" and "Clinical features and diagnosis of placenta accreta, increta, and percreta" and "Management of placenta accreta, increta, and percreta".)
Post-laparotomy inspection — At the completion of the laparotomy and before closing the abdomen, the operative field should be inspected carefully for hemostasis. Microvascular bleeding usually can be controlled using topic hemostatic agents. (See "Management of hemorrhage in gynecologic surgery".)
The bladder should be inspected and the ureters identified. If there is a possibility of bladder laceration, then 200 mL of saline mixed with 5 mL of indigo carmine can be infused into the bladder through the Foley catheter. Integrity of the bladder is confirmed by failure of the colored fluid to leak through the serosa.
The ureter should generally be identified before abdominal closure either by transillumination through the broad ligament or direct visual identification during retroperitoneal dissection (figure 6 and figure 7). It courses horizontally along the peritoneum 1 to 5 cm dorsal to the ovarian vessels and can be identified readily as it passes ventral to the bifurcation of the common iliac artery. (See "Surgical female pelvic anatomy".)
The ureters should be inspected to confirm that they are not damaged. Their integrity can be assessed by injecting two ampules (10 mL) of indigo carmine intravenously. A ureter that has been severed will release blue urine into the pelvis in 10 to 15 minutes. If a ureter has been ligated, cystoscopy or direct visualization of the ureters through a cystotomy will demonstrate that urine is only passing through one of the two ureteral orifices. Passage of a ureteral stent can also be employed to localize the site of obstruction. (See "Diagnostic cystourethroscopy for gynecologic conditions".)
Persistent bleeding after hysterectomy — Patients with continued severe hemorrhage after hysterectomy can enter a lethal downward spiral characterized by hypothermia, coagulopathy, and metabolic acidosis [47,48]. Criteria proposed for this "in extremis" state include pH <7.30, temperature <35 degrees Celsius, combined resuscitation and procedural time >90 minutes, nonmechanical bleeding, and transfusion requirement >10 units packed RBCs . To abort the cycle, the bleeding area is tightly packed  and the skin is closed to prevent heat and moisture loss (either with large sutures or with towel clamps). Under most circumstances, the patient should remain in the operating room with continuous monitoring, while replacement of appropriate blood products and correction of physiologic derangements ("damage control") occurs. Once stable and safe for transfer, the patient may be transferred to the intensive care unit (ICU) for ongoing management until definitive surgery can be performed. This approach halts the downward spiral and lessens the risk of abdominal compartment syndrome. Compartment syndrome is more difficult to define postpartum since postcesarean intraabdominal pressure appears to be higher than in the general surgical population, especially in women with elevated body mass index and hypertensive disorders . (See "Abdominal compartment syndrome".)
One technique uses a sufficient number of gauze bandages (eg, Kerlix) tied end-to-end to pack the pelvis tightly and tamponade the hemorrhage. The free end of the gauze train is extracorporealized through the main incision. The peritoneum, muscle, and fascia are closed in the usual fashion, but with the gauze protruding from one end of the incision. The subcutaneous and cutaneous layers are left open and packed with additional gauze.
Different surgeons practice slight variations of this procedure [50,52-61]. One variation is to fill a sterile plastic bag (eg, drawstring bag used to cover x-ray film) or cloth container with gauze and place it against the pelvic bleeders. The drawstrings are pulled through the vagina and attached to a weight, which provides traction so that the pack exerts pressure against the pelvic floor. The author has used the Belfort-Dildy Balloon as a pelvic pressure pack after hysterectomy for PPH .
The need for ≥2 units packed RBCs per hour for three hours is a sign of significant ongoing bleeding and need for surgical intervention or arterial embolization by an interventional radiologist. Placement of a large bore drainage catheter (such as a large Jackson-Pratt drain or a chest tube) in the pelvis at the time of temporary closure will allow early recognition of the need for emergency re-laparotomy.
Otherwise, the patient is returned to the operating room to undergo definitive surgical care in 48 hours. Packing should not be removed until coagulation defects have been corrected. If the packing has controlled bleeding, it generally is removed at this time. If it is removed too soon, bleeding will resume, whereas if it is removed too late, pelvic infection or abscess may ensue.
Under general anesthesia, the wound is opened and the gauze is removed with gentle traction. The pelvis is irrigated with saline to clear loose clots and other debris, but aggressive exploration of the pelvis is not performed if no pooling of blood is noted. The wound is then reapproximated in the usual manner.
MANAGEMENT OF HEMORRHAGE FIRST RECOGNIZED AFTER THE PATIENT HAS LEFT THE OPERATING ROOM — Hemorrhage may not be appreciated before the abdomen has been closed or before the patient has been moved out of the operating room. It may manifest as excessive vaginal bleeding or as hypotension, tachycardia, and/or low urine output from hypovolemia.
If excessive vaginal bleeding is present, the cervix and vagina should be inspected and lacerations repaired under adequate anesthesia.
If the uterus is boggy, the diagnosis of uterine atony is made. The initial management of uterine atony after cesarean delivery is similar to that after vaginal delivery and consists of:
●Uterine massage to contract the uterus.
●Administration of uterotonic drugs.
●Fluid resuscitation and transfusion.
●Laboratory tests to evaluate blood loss and coagulopathy and type and cross for multiple units of packed red blood cells.
If excessive bleeding persists, uterine artery embolization is an option for stable patients in whom volume status can be maintained until the procedure can be completed (approximately two hours). Many clinicians use both balloon tamponade and uterine artery embolization in this situation. These procedures are discussed in detail separately. (See "Management of postpartum hemorrhage at vaginal delivery", section on 'Uterine tamponade' and "Management of postpartum hemorrhage at vaginal delivery", section on 'Arterial embolization'.)
Laparotomy is indicated in patients with massive bleeding and those who are unstable since it is unlikely that replacement of blood products will match blood loss in these patients.
PPH more than 24 hours postpartum is termed secondary PPH. Causes and management are discussed separately. (See "Overview of postpartum hemorrhage", section on 'Secondary postpartum hemorrhage'.)
MENSTRUAL AND FERTILITY OUTCOME — Uterine-sparing surgical interventions for management of postpartum hemorrhage generally do not impair subsequent fertility. In a systematic review including 17 studies (675 women) on fertility outcomes after uterine artery embolization, 5 studies (195 women) on fertility outcomes after uterine devascularization, and 6 studies (125 women) on fertility outcomes following uterine compression sutures, 91 percent of women resumed menstruation within 6 months of delivery and 78 percent women who desired another pregnancy achieved conception . Reports of complications related to individual procedures are described above in the section on the procedure.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, “The Basics” and “Beyond the Basics.” The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on “patient info” and the keyword(s) of interest.)
●Basics topic (see "Patient information: Postpartum hemorrhage (The Basics)")
SUMMARY AND RECOMMENDATIONS
●The initial management of postpartum hemorrhage (PPH) at cesarean delivery includes: fundal massage and uterotonic drugs for treatment of uterine atony, fluid resuscitation and transfusion, laboratory tests to evaluate blood loss and coagulopathy, and inspection for and repair of lacerations and incisional bleeding. Placenta attachment abnormalities require additional interventions. (See 'Initial management' above and "Clinical features and diagnosis of placenta accreta, increta, and percreta".)
●If these measures do not control hemorrhage, we suggest uterine artery ligation as the first-line surgical approach (Grade 2C). (See 'Uterine artery and utero-ovarian artery ligation' above.)
●Early resort to hysterectomy is appropriate in women with severe bleeding due to diffuse placenta accreta/increta/percreta or a large uterine rupture. Hysterectomy is generally a last resort in patients with atony, but should not be delayed in those who have disseminated intravascular coagulation and require prompt control of uterine hemorrhage to prevent death. (See 'Hysterectomy' above.)
●Patients with persistent severe hemorrhage can enter a lethal downward spiral characterized by hypothermia, coagulopathy, and metabolic acidosis. To abort the cycle, the bleeding area is tightly packed and the wound dressed, but left open, and the patient is transferred to an intensive care unit for continuous monitoring, replacement of appropriate blood products, and correction of physiologic derangements. (See 'Persistent bleeding after hysterectomy' above.)
ACKNOWLEDGMENT — The author and UpToDate would like to acknowledge Dr. Allan J Jacobs, who contributed to earlier versions of this topic review.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.