Accreta

1. What every clinician should know

Clinical features and incidence

Placenta accreta is defined as the abnormal attachment of all or part of the placenta to the myometrium. It may occur when there is either a primary deficiency of, or secondary damage to, the decidua basalis and Nitabuch’s layer. Three grades of abnormal placental attachment are defined according to the depth of invasion:

Accreta: Chorionic villi attach directly to the myometrium, and are not restricted within the decidua basalis (82% of cases).

Increta: Chorionic villi invade deeply into the myometrium (12% of cases).

Percreta:Chorionic villi invade through the myometrium into extrauterine tissue and organs (6% of cases).

In this document, the general term placenta accreta will refer to all three grades of abnormal placental attachment unless otherwise specified.

Placenta accreta is associated with an increased risk of massive hemorrhage if partial placental delivery occurs or placental removal is attempted. Blood transfusion is frequently necessary, and hysterectomy is commonly required to control the hemorrhage. Even when placenta accreta is prenatally diagnosed and preparations are made for scheduled delivery by cesarean hysterectomy, complications may occur and may include:

• Damage to bowel, bladder, ureters and neurovascular structures in the retroperitoneum and lateral pelvic sidewalls from placental implantation and its removal.

• Post-operative bleeding requiring repeated surgery.

• Amniotic fluid embolism.

• Complications directly related to massive transfusion of blood products, crystalloids and colloidal solutions (e.g. dilutional coagulopathy, consumptive coagulopathy, acute transfusion reactions, transfusion associated lung injury, acute respiratory distress syndrome and electrolyte abnormalities).

• Postoperative thromboembolism, infection, multisystem organ failure, endocrine issues and maternal death.

The exact incidence of maternal mortality related to placenta accreta and its complications is unknown, but has been reported to be as high as 6-7% in case series and surveys.

Risk factors for placenta accreta

The incidence of placenta accreta appears to be increasing from approximately 0.8 per 1,000 deliveries in the 1980s to about 3 per 1,000 deliveries currently. One of the most important risk factors for placenta accreta is thought to be placenta previa in the presence of a uterine scar. Hung et al, reported a multivariable analysis and found that although placenta previa was an independent risk factor for placenta accreta (Odds Ratio (OR) [95% CI] 54 [18-166]), prior uterine surgery without an associated previa was not (OR 1.5 [0.4-5.1]).

However, the number of patients without a placenta previa was small and may have influenced this analysis. The increasing incidence of cesarean section almost certainly contributes to this since the region of abnormal placental invasion is usually in the site of the previous hysterotomy.

The NICHD cesarean section registry study showed that the risk of placenta accreta was less than 1% for women having up to their 5th cesarean delivery, but that this risk increased to 4.7% for those having 6 or more cesarean deliveries. If, however, a placenta previa was present, the risk of placenta accreta was 3% at the first cesarean delivery and increased to over 40% at the 3rd cesarean delivery. Regardless of placental predominance (anterior versus posterior), women with a placenta previa are at increased risk for placenta accreta, but this risk appears to increase when the placenta overlies the uterine scar. When the placenta previa is anterior or central and overlies the scar, the rate of accreta has been reported to be as high as 29%, compared to 6.5% when it is lateral or posterior and does not contact the scar.

The question of whether a low lying or anterior placenta in women with a prior cesarean section scar poses increased risk has been asked. Twickler et al specifically addressed this issue in 653 patients with a previous cesarean section. In their cohort there were 152 patients who had an anterior placenta and 43 with an anterior low lying placenta. None of these patients ultimately had an accreta. However, of the 20 patients with a previous cesarean section scar who were diagnosed with placenta previa, nine had a placenta accreta (45%) and 15 required cesarean hysterectomy for uncontrolled bleeding (75%).

Additional reported risk factors for placenta accreta include maternal age and multiparity, other prior uterine surgery, prior uterine curettage, uterine irradiation, endometrial ablation, Asherman’s syndrome, uterine leiomyomata and uterine anomalies, hypertensive disorders of pregnancy and smoking. While described in case reports and series, the actual contribution to the frequency of placenta accreta of these additional risk factors remains unknown.

2. Diagnosis and differential diagnosis

Diagnostic criteria

The antepartum diagnosis of placenta accreta/percreta is usually made using ultrasound in the second and third trimesters. Sonographic criteria include: (1) loss of the normal hypoechoic retroplacental myometrial zone (clear space); (2) thinning or disruption of the hyperechoic uterine serosa-bladder interface; (3) blood vessels crossing the regions of interface disruption; (4) myometrial thickness of less than 1mm; (5) presence of vessels bridging the uterine-placental margin; (6) visualization of placental lacunae (defined as multiple linear, irregular vascular spaces) within the placenta which gives the placenta a “Swiss cheese” appearance; (7) focal nodular projections into the bladder beyond the expected uterine-bladder interface; and (8) numerous coherent vessels visualized with 3D power Doppler in the basal view.

Twickler et al stated that the two specific ultrasound criteria most predictive of accreta were: (i) Myometrial thickness less than 1mm and (ii) large intraplacental blood lakes. If both findings were present the positive predictive value (PPV) for a diagnosis of accreta was 72% and negative predictive value (NPV) was 100%. The PPV of these findings for hysterectomy was 92% and NPV was 57%.

Others have suggested that disruption of the placental-uterine wall interface and the presence of vascular connections crossing these areas of disruption are the only two criteria of real predictive value. In an attempt to improve diagnosis, Wong et al tested a composite scoring system for ultrasound criteria and reported an 89% sensitivity and 98% specificity for the accreta. While the most recently described technique using three-dimensional power Doppler has been reported to have a 97% sensitivity and 92% specificity with a PPV of 76%, the number of patients with placenta accreta included in all of these studies is small and currently there is no consensus on which factors are most accurate in the diagnosis of placenta accreta.

Although there are isolated case reports of placenta accreta being diagnosed in the first trimester the PPV of first trimester ultrasound for this diagnosis remains unknown. It is recommended at this time that ultrasound in the first trimester should not be used routinely to establish or exclude the diagnosis of placenta accreta. However, women with a placenta previa or “low-lying placenta” overlying a uterine scar early in pregnancy should undergo follow-up imaging in the second or third trimester because of the association of these conditions with placenta accreta.

Studies evaluating magnetic resonance imaging for confirmation or exclusion of placenta accreta have yielded conflicting results. Currently, there is no evidence that routine MRI scanning of patients with an ultrasound diagnosed/suspected placenta accreta improves pregnancy management or outcomes. MRI (without gadolinium contrast) may be helpful if ultrasound is inconclusive or if there is suspicion that the placenta has invaded the parametrium or surrounding organs. Although some have reported the use of cystoscopy and sigmoidoscopy in the evaluation of selected patients with suspected placenta accreta, their routine use is unnecessary.

Laboratory tests

Abnormally elevated second trimester serum alpha fetoprotein has been associated with placenta percreta and it has been suggested that there is a direct relationship between the extent of invasion and the elevation of this analyte (7). Creatine kinase has also been reported as a marker for increta and percreta. Abnormal trophoblast invasion has been associated with up-regulation of VEGF and angiopoietin-2 and down-regulation of VEGFR and Tie-2. None of these tests are currently deemed as reliable stand alone prediction tests and they are of research interest only at this time.

3. Management

Antepartum Management

Women with a suspected placenta accreta should be scheduled for delivery in an institution with appropriate surgical expertise, equipment and personnel, and a blood bank that can facilitate transfusion of large amounts of the full range of blood products. In the prenatal period supplementation with oral iron is recommended to maximize iron stores and oxygen-carrying capacity. In those cases where significant anemia is present preoperatively, parenteral iron infusion with concurrent erythropoietin administration may be needed. The expected rise in hematocrit levels will be apparent within 2 weeks. Because placenta accreta in and of itself has not been associated with an increased risk of fetal death or intrauterine growth restriction, intensive antenatal fetal surveillance is not necessary unless otherwise clinically indicated.

The optimal timing for scheduled delivery will depend upon clinical circumstances and the extent of placental invasion. When the diagnosis of placenta accreta is suspected pre-delivery, emergent preterm birth is often required because of pregnancy complications. Because of the risks associated with emergent delivery, it is suggested that indicated preterm delivery at 34-35 weeks gestation is advisable.

Preoperative consultation with anesthesiology and notification of the blood bank are indicated before scheduled surgery when placenta accreta is diagnosed antenatally. Additional surgical services such as gynecologic oncology, urology, general and/or vascular surgery, may provide additional surgical expertise if needed. Anesthesia considerations include large-bore venous access to allow rapid crystalloid and blood product infusion, availability of high flow rate infusion and suction devices, hemodynamic monitoring capabilities (central venous and peripheral arterial access), compression devices to prevent thromboembolism, padding and positioning to prevent nerve compression, and avoidance and treatment of hypothermia. In addition to the potential for severe intra-operative hemorrhage with cardiovascular instability during surgery and the possible need for access to the upper abdomen is an important consideration when surgery for placenta accreta is anticipated.

Anesthesia considerations

The American Society of Anesthesiologists (ASA) task force on obstetric anesthesia has suggested that neuraxial techniques are preferred to general anesthesia for most cesarean deliveries, but that the decision to use a particular anesthetic technique for cesarean delivery should be individualized. The recent suggestion that some general anesthetic gases may cause damage to the neonatal brain has caused some rethinking of the anesthetic technique used in these cases.

We currently employ a combined regional and general anesthetic technique which allows for epidural anesthesia for the cesarean section and delivery of the baby, and then conversion to general anesthesia for the remainder of the surgery. The epidural also helps with postoperative pain control. It is clear that in some situations general anesthesia may still be the most appropriate choice, especially when severe hemorrhage is present or imminent.

Surgery for placenta accreta is typically prolonged, with recent publications reporting mean operative times of 2-3 hours regardless of whether the diagnosis of placenta accreta is made before or at delivery.

The amounts of blood products needed in this type of surgery (e.g. packed red blood cells, fresh frozen plasma, platelets and cryoprecipitate) are difficult to predict. Women undergoing cesarean hysterectomy under controlled circumstances may not require any blood transfusion, but an intraoperative blood loss of 2,000-5,000 mL has typically been reported. Given that massive blood loss in excess of 10 liters has been reported, preoperative determination of whether the blood bank has the available stores to meet anticipated emergent needs is essential. Most blood banks, even in tertiary care facilities, will still need to make arrangements for adequate blood products at the time of the scheduled surgery, especially if the patient has a rare blood type or antibodies to blood group antigens.

Preoperative considerations

Immediate pre-operative ultrasound visualization of the placental location can assist in determining the optimal approach to the abdominal and uterine incisions to avoid disturbing the placenta before and after the delivery of the fetus.

When prenatal imaging has identified involvement of the lower segment by the placenta accreta, preoperative ureteric stent placement facilitates palpation of the ureterus intra-operatively and reduces ureteral trauma. Preoperative cystoscopy under epidural anesthesia allows for placement of large bore ureteric stents with minimal discomfort to the patient. We leave the patient in the lithotomy position after this and proceed with the surgery.

Preoperative pelvic artery occlusion does not improve outcomes and catheter placement can result in complications, such as insertion site hematoma, abscess, tissue infarction and necrosis. Routine use of this modality is not currently recommended. Intra-operative selective uterine artery embolization prior to hysterectomy has been reported to significantly reduce blood transfusion needs. This technique does result in significantly increased operative time and is not recommended as a routine measure.

An earlier case series described intraoperative arterial embolization after cesarean delivery followed by delayed hysterectomy (10 and 6 weeks). One patient developed pulmonary emboli, and both had significant residual placenta despite methotrexate therapy. While these staged techniques have been successful in some cases, further research regarding the optimal intra-operative approach is needed.

When the need for hysterectomy is anticipated, antibiotic prophylaxis should be administered in the hour before surgery. Prophylactic antibiotics can be repeated if surgery is prolonged (3 hours or more) or if heavy bleeding occurs.

A preoperative summary, or checklist, may be helpful to confirm that needed preparations have been made and to identify the name and contact information for consultants in case they are needed for intra- or peri-operative assistance.

In cases where placenta accreta is diagnosed and childbearing is complete the optimal management will usually be cesarean delivery followed by hysterectomy with no attempt to remove the placenta after the delivery of the baby. The patient should be counseled preoperatively regarding the increased risk of maternal death during and following delivery, the almost certain need for hysterectomy and blood transfusion, and the risk of damage to other organs such as the bladder and ureters, bowel, and ovaries during the surgery. Unilateral oophorectomy is necessary in up to 10% of cases because of persistent bleeding.

The patient also should understand the increased postoperative risks of hypotension related injury (renal, cerebral), infection, thromboembolism, need for reoperation for persistent bleeding and the potential iatrogenic complications from interventional radiology procedures that may be required to stop uncontrolled hemorrhage.

If a patient requests conservative management with attempted uterine preservation, the risks and benefits of this approach and the criteria for abandoning conservative surgery should be discussed and documented. If the diagnosis of placenta accreta is uncertain preoperatively and intraoperatively, a period of observation for placental separation without excessive bleeding is appropriate.

In rare circumstances, removal of the uterus will not be possible or will be deemed too dangerous because of extensive invasion into surrounding pelvic tissues. Case reports and small case series have described successful conservative therapy in which the placenta and uterus are left in-situ, or compressive sutures are applied to the uterus. However, the need for delayed hysterectomy due to recurrent bleeding and/or infection is high. Postoperative methotrexate therapy and selective arterial embolization have been reported in some cases under this circumstance. The safety and efficacy of these interventions are unknown, and serious complications have been reported with conservative management (e.g. severe hemorrhage, septic shock, pulmonary embolism).

Intraoperative considerations

A median or paramedian vertical skin incision is best employed to offer optimal visualization and to improve access for a fundal/posterior uterine wall hysterotomy and for the hysterectomy.

Once the abdomen is entered, the uterine serosa may be distended by dilated vessels over the region of placental insertion. In anterior placenta previa/percreta the lower segment may be significantly distorted and highly unusual vasculature may be visible. It should be remembered that in percreta cases the blood supply to the uterus and placenta may be predominantly through arteries other than the uterine arteries (vesical, infundibulopelvic, rectal). Figure 1 shows a massively enlarged infundibulopelvic vascular bundle with arterial supply directly off the aorta and venous drainage into the left renal vein.

Figure 1.n

The uterine incision should avoid the presumed placental edge by at least 5 cm if at all possible to prevent inadvertently causing placental trauma during the delivery of the baby. If necessary, intraoperative ultrasound, with an ultrasound probe covered by a sterile sleeve, can be used to best determine the location of the uterine incision. In some cases, a posterior uterine wall incision may be required and this will necessitate exteriorization of the uterus with the fetus in-situ.

When the index of suspicion for placenta accreta is low and further childbearing is desired, waiting for spontaneous placental separation, followed by removal if separation occurs, may be acceptable. When cesarean-hysterectomy is performed primarily, the placenta should not be disturbed in any way after the umbilical cord is ligated and cut, and the uterus should be closed to limit bleeding from the incision edges.

When rapid control of the uterine bleeding is needed aortic pressure, in association with pressure on the bleeding area, may allow time to resuscitate the patient adequately to allow continued surgery. It can also allow time to mobilize additional surgical assistance.

If bladder involvement is suspected, cystotomy and digital palpation may be needed to confirm the extent of the trophoblast invasion. This can be preceded by filling the bladder via the urinary catheter to delineate its borders and this knowledge will help in the dissection or resection of the involved area. Attempts to dissect (either bluntly or sharply) densely adherent bladder wall from the uterus should be discouraged because of the risk of significant bleeding and placental disruption. In many instances concerted efforts to dissect the adherent bladder off the uterus not only lead to excessive bleeding but yield damaged and devascularized detrusor muscle that is unsuitable for repair.

Such tissue will increase the risk of wound breakdown and fistula formation. Excision of that piece of involved bladder is often the wiser course. If the trigone is resected ureteric reimplantation will be required. Despite ligation of the uterine arteries, massive hemorrhage can occur from the placenta/bladder interface via collateral blood supply through the bladder.

Subtotal hysterectomy has been reported to be successful in some cases of accreta, but given that most involve placenta previa, such an approach frequently will leave placental tissue in-situ, which will result in persistent bleeding.

In some cases where the majority of the placenta separates spontaneously and is easily removed but small areas of focal accreta are present, the placement of deep myometrial sutures in multiple 3-cm squares bracketing the involved area may achieve hemostasis. Cho and colleagues reported successful use of this technique in 23 cases of refractory bleeding with apparently normal uterine cavities on follow-up evaluation. Successful use of an intrauterine tamponade balloon after persistent bleeding from a localized area of accreta has also been reported.

Intraoperative blood product and fluid administration strategies

Frequent assessment of volume status (blood loss, maternal vital signs, urine output) and laboratory parameters (hemoglobin/hematocrit, platelets, coagulation factors and function) is important. Fluid resuscitation and transfusion should be instituted in a timely manner. Prompt and aggressive blood product transfusion is recommended when heavy bleeding is encountered to minimize hypovolemia, acidosis and coagulopathy. Frequent monitoring of serum electrolytes and blood gases can assist in optimizing or evaluating the need for and effectiveness of resuscitative interventions.

Recent battlefield data have modified our approach to massive obstetric hemorrhage and while there are no pregnancy specific data available, we believe that the administration of fresh frozen plasma and platelets in a 1:1 ratio with packed red blood cells will more rapidly correct coagulopathy, decrease the need for packed red blood cell transfusion in the intensive care unit and reduce mortality in our obstetric patients.

It has been reported that the use of recombinant activated Factor VIIa(rFVIIa) may be beneficial in the treatment of uncontrollable obstetrical hemorrhage. Typically, this intervention is more effective in the presence of fibrinogen levels greater than 100 mg/dL. However caution is advised because of the potential for vascular thrombosis and thromboembolic events, including cardiac and cerebral ischemia, with this treatment.

Cell saver auto-transfusion has not been widely used in obstetric practice because of the theoretical concern that fetal cellular debris and amniotic fluid may result in an amniotic fluid embolism syndrome. However, modern systems have filtering technology that obviates this concern, although fetal red blood cells may remain in the final product (range 0.13-4.35%) and increase the risk of alloimmunization. It should be remembered that when cell-saver auto-transfusion is performed, fresh frozen plasma, cryoprecipitate and/or platelet transfusion will still be needed because a proportion of the coagulation factors and platelets are excluded in the reconstitution process.

While the use of intraoperative cell saver technology appears to be appropriate for emergent use during massive obstetric hemorrhage, prospective studies confirming any benefit of this technique are still lacking.

Postoperative care after hysterectomy for placenta accreta

Level III evidence

Cesarean hysterectomy for placenta accreta increases the risk of intraoperative hypotension, acidosis, hypothermia, persistent coagulopathy, anemia and prolonged surgery. Hypoperfusion and organ ischemia can lead to postoperative renal, cardiac and other organ dysfunction. Sheehan’s syndrome (both transient and permanent) has been reported after massive postpartum hemorrhage and hyponatremia may be an early sign. If large volumes of crystalloids and blood products are given intraoperatively, the patient is also at risk for pulmonary edema, transfusion related acute lung injury and/or acute respiratory distress syndrome.

Such patients require close postoperative monitoring in a specific recovery or high acuity care area, with frequent evaluation of vital signs (blood pressure, pulse pressure, heart rate and respiratory rate). Urine output should be measured via an indwelling urinary catheter. Intensive care admission, central venous monitoring, assessment of peripheral oxygenation by pulse oximetry and evaluation of hemodynamic and respiratory function can be helpful in some cases. Ongoing attention to the correction of coagulopathy and severe anemia with blood products is essential.

The patient should be clinically evaluated for potential blood loss from the abdominal incision and vagina, and for recurrent intra-abdominal or retroperitoneal bleeding. There should be a low threshold for re-exploration if recurrent bleeding is suspected. Renal function should be evaluated and serum electrolytes abnormalities should be treated as needed until the patient is stabilized. If there is persistent hematuria or anuria, the possibility of unrecognized urinary tract injury should be considered. Early ambulation and intermittent compression devices for those requiring bed rest can reduce the risk of thromboembolic complications.

4. Complications

The associated potential acute metabolic effects of massive transfusion should also be kept in mind. These include:

Hypothermia: Hypothermia is common, mostly due to loss of thermal regulation that accompanies shock and evaporation from the exposed abdominal contents. This may be compounded by intravascular infusion of cold fluids and a cold environment. Warming of crystalloid solutions may be supplemented with blood warming when blood is rapidly infused through a central line and/or when the infusion rate is faster than 50 ml/kg/hour (60 mL/min in an adult). Acidosis and coagulopathy are most likely to develop secondary to hypoperfusion and hypothermia rather than from the massive blood replacement.

Citrate toxicity: By chelating calcium, citrate prevents clotting in blood products during storage. During massive transfusion, the dose of citrate infused is influenced primarily by the type of blood component and by the rate of administration. The infused citrate is rapidly metabolized and excreted by the liver and kidneys respectively, with bicarbonate being the end product. Citrate toxicity can be manifested by hypocalcemia, and by neuromuscular or cardiac abnormalities. Laboratory evaluations for acid-base status and ionized calcium are strongly recommended prior to initiation of pharmacological therapy, as calcium overtreatment is associated with significant morbidity and mortality.

Hyperkalemia: Potassium leaks out of the red cell during storage (contents of 4-8-mEq content of potassium per red cell unit in a 250-300mL volume). This extracellular potassium load is only a transient effect, because once infused, potassium is taken up by the red cell and/or eliminated by urinary excretion secondary to the bicarbonate production of the citrate metabolism. More often than not recipients of massive transfusion actually become hypokalemic and may require potassium supplementation.

Persistent pelvic bleeding is not uncommonly seen after hysterectomy in patients who have had a hysterectomy associated with massive transfusion. Methods used to manage such hemorrhage include:

Pelvic Artery Embolization

Intraoperative prophylactic ligation of the hypogastric arteries has been recommended as a method of reducing pulse pressure in the uterus during hysterectomy. However, Eller et al did not show benefit from preemptive hypogastric artery ligation at the time of cesarean hysterectomy. Recent reports suggest that X-ray guided pelvic artery embolization is appropriate for persistent but non-catastrophic obstetric bleeding, and such intraoperative embolization during surgery in a hybrid operating room may be helpful. However, transportation from the operating room for staged intraoperative arterial embolization is not advisable for the acutely unstable patient.

Pelvic Pressure Packing

In some circumstances there will be persistent diffuse non-arterial bleeding that is not amenable to surgical control. In such cases, placement of pelvic pressure packing (e.g. laporatomy sponges or a gauze bandage) or tamponade balloon devices, may be considered as a temporizing step to allow time for hemodynamic stabilization, correction of coagulopathy and eventual completion of surgery. Wide bore negative pressure pelvic drains may be helpful to warn of significant persistent or recurrent bleeding in this circumstance.

Aortic compression

Temporary compression of the infrarenal abdominal aorta can be employed to decrease blood flow to the pelvis and allow time for resuscitation with blood products. Temporary balloon occlusion of the aorta and counterpulsation have been reported to be of benefit in extreme cases. If aortic compression, or balloon occlusion or clamping is thought to be necessary, the potential for distal thrombosis and ischemia is high and a vascular surgeon should be consulted.

5. Prognosis and outcome

Mortality associated with placenta accreta is significantly elevated and is believed to be in the range of 6-7% although these data are somewhat dated. The increased antenatal recognition of placenta accreta, the adoption of team management and the development of standard procedures and processes may help in the reduction of variation in management and the improvement of outcomes.

6. What is the evidence for specific management and treatment recommendations

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Franchini, M, Franchi, M, Bergamini, V, Salvagno, GL, Montagnana, M, Lippi, G. “A critical review on the use of recombinant factor VIIa in life-threatening obstetric postpartum hemorrhage”. Semin Thromb Hemost. vol. 34. 2008. pp. 104-12.

Uchiyama, D, Koganemaru, M, Abe, T, Hori, D, Hayabuchi, N. “Arterial catheterization and embolization for management of emergent or anticipated massive obstetrical hemorrhage”. Radiat Med. vol. 26. 2008. pp. 188-97.

Dildy, GA, Scott, JR, Saffer, CS, Belfort, MA. “An effective pressure pack for severe pelvic hemorrhage”. Obstet Gynecol. vol. 108. 2006. pp. 1222-6.

Vrachnis, N, Iavazzo, C, Salakos, N, Papamargaritis, E, Boutas, I. “Uterine tamponade balloon for the management of massive hemorrhage during cesarean section due to placenta previa/increta”. Clin Exp Obstet Gynecol. vol. 39. 2012. pp. 255-7. (Reports successful use of an intrauterine tamponade balloon after persistent bleeding from a localized area of accreta.)

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