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THE MANAGEMENT OF SECONDARY POSTPARTUM HEMORRHAGE K. M. Groom and T. Z. Jacobson

INTRODUCTION ETIOLOGY OF SECONDARY POSTPARTUM HEMORRHAGE Secondary postpartum hemorrhage is defined as excessive vaginal from 24 h after Subinvolution/ delivery up to 6 weeks postpartum1. Unlike The major cause of secondary postpartum primary postpartum hemorrhage, there is no hemorrhage is subinvolution of the uterus. This clear definition for quantity of loss and results in failure of obliteration of blood vessels this can vary from ‘increased lochia’ to massive underlying the placental site, leading to pro- hemorrhage. The diagnosis is therefore subjec- longed bleeding. The two main causes of this tive, which may account for the variation are infection (see Chapter 44) and inflammation in reported incidence. The reported overall (endometritis) and retained placental tissue. incidence of secondary postpartum hemorrhage Endometritis is more common following pro- in the developed world varies from 0.47% to longed rupture of membranes, prolonged labor, 1.44%2,3. emergency Cesarean section or with a retained The etiology of secondary postpartum placenta requiring manual removal. A history of hemorrhage is diverse and management is offensive lochia, maternal pyrexia and uterine dependent on identifying the cause and tailoring tenderness is often present and retained placen- treatment appropriately. The published work tal tissue is more common in women with a pre- on the management of secondary is limited vious history of retained placenta or if there compared with primary postpartum hemor- were concerns at the time of delivery of incom- rhage4. However, with falling maternal mor- plete placenta and/or membranes. It is less likely tality rates, there is increasing interest following delivery by Cesarean section. Differ- and attention to maternal morbidity and the entiation between the two causes is often diffi- important topic of management of secondary cult and both conditions may co-exist. postpartum hemorrhage. The majority of cases of secondary postpartum hemorrhage are asso- ciated with minor morbidities but may still Lower genital tract trauma require re-admission to hospital, use of anti- Missed vaginal lacerations and hematomas may biotics and surgical intervention. In more present as secondary postpartum hemorrhage. extreme cases, major morbidity requiring These are often associated with traumatic hysterectomy, arterial ligation or radiological deliveries or those requiring ventouse or intervention is possible5 and forceps. They usually present within the first may still result from massive secondary post- few days after delivery. Infected suture lines and partum hemorrhage despite the use of all avail- episiotomy sites may lead to wound breakdown able interventions. and result in excessive .

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Placental abnormalities cases reported, this has lead to massive postpartum hemorrhage 2–3 weeks after Placenta accreta, increta and percreta are all Cesarean section and the need for subtotal known causes of massive primary postpartum hysterectomy12. Diagnosis of uterine dehiscence hemorrhage. When managed conservatively post-Cesarean section associated with infection with placental tissue left in situ (with or without has also been made at hysteroscopy13, although methotrexate therapy), they can also be associ- causing less significant postpartum hemorrhage ated with delayed bleeding and the need for and only requiring treatment with antibiotics. hysterectomy6,7 (see Chapter 24).

Choriocarcinoma Uterine abnormalities The majority of cases of choriocarcinoma after a Fibroids are associated with primary post- non-molar present with secondary partum hemorrhage. They cause uterine postpartum hemorrhage or irregular vaginal enlargement and prevent involution of the bleeding14. In addition, secondary symptoms uterus, therefore leading to prolonged bleeding of metastatic disease may be present. The diag- from the placental bed. More rarely, they can be nosis is made by serum β-human chorionic associated with secondary postpartum hemor- gonadotropin (β-hCG), histological diagnosis rhage. Fibroids have usually been identified by and radiological imaging including ultrasound, ultrasound in the antenatal period. plain film X-ray and computed tomography Abnormalities of uterine vasculature such (CT) scan. as arteriovenous malformations and false aneurysms may also lead to secondary postpartum hemorrhage. Arteriovenous malformations are Bleeding disorders, and due to an abnormal communication between an use of anticoagulants artery and vein with proliferation of each vessel Women with congenital hemorrhagic disorders with interconnecting fistula. It is believed these such as von Willebrand’s disease (quantitative malformations may result from venous sinuses or qualitative deficiency of von Willebrand becoming incorporated in scars within the myo- factor), carriers of hemophilia A (factor VIII metrium after necrosis of the chorionic villi. The deficiency), hemophilia B (factor IX deficiency) majority are acquired after pregnancy and may and factor XI deficiency are at an increased risk result from trophoblastic disease, previous uter- of postpartum hemorrhage. Often, these abnor- 8,9 ine curettage, uterine or cervical malignancy malities of the coagulation system are unde- 10,11 or Cesarean section . Diagnosis is made tected until challenged by trauma, surgery or using ultrasound with color Doppler analysis. and so may be undiagnosed prior to pregnancy. These women are not at increased risk of antepartum hemorrhage15 but at sig- Cesarean section wound dehiscence or nificant risk of both primary and secondary surgical injury postpartum hemorrhage. The risk of secondary Surgical injury to pelvic blood vessels at postpartum hemorrhage may be even greater the time of Cesarean section10 usually presents than primary postpartum hemorrhage as the within 24 h. However, later presentations, in pregnancy-induced rise in maternal clotting fac- particular those causing broad ligament tors falls after delivery. The reported incidence hematomas, have been described5 and should for secondary postpartum hemorrhage in these be considered in women presenting acutely with conditions is 20–28% for von Willebrand’s dis- signs of intra-abdominal hemorrhage. Delayed ease, 11% for hemophilia carriers and 24% in presentation of bleeding from non-union/ factor XI deficiency16–19. Postpartum acquired dehiscence of the Cesarean section uterine scar hemophilia has also been described. This is a has also been described. This is believed to rare condition but can cause severe hemor- be due to local infection at the site of uterine rhage. It is caused by antibodies to factor VIII closure causing erosion of blood vessels. In the which partially or completely suppress factor

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VIII procoagulant activity in women with previ- output should be maintained throughout resus- ously normal levels and activity of factor VIII. citation. Blood and blood products should be Bleeding usually commences within 3 months given according to blood loss, response to initial of delivery but may be delayed for up to 12 fluid administration and hemoglobin and months15. coagulation results. If hemorrhage is life- The use of anticoagulants in the postpartum threatening, transfusion with uncross-matched period may also cause delayed bleeding. In O rhesus-negative or type-specific blood may particular, women using should be need to be considered. Identification of the carefully monitored and informed of the risks of cause of bleeding should then be made and hemorrhage. further management planned accordingly. In cases of less significant hemorrhage, basic resuscitation should be instigated as appropriate MANAGEMENT OF SECONDARY but blood transfusion may be delayed whilst POSTPARTUM HEMORRHAGE establishing a cause for the bleeding. Evidence regarding the management of second- ary postpartum hemorrhage is limited. A Cochrane review searched and assessed all ran- Clinical presentation domized or quasi-randomized comparisons of Ninety-five percent of women present within drug therapies, surgical therapies and placebo the first month after delivery, 19% within 7 or no treatment for secondary postpartum hem- days, 41% in 8–14 days, 23% in 15–21 days and orrhage. Forty-five papers were identified, but 12% in 22–28 days2. The amount of blood loss none met the inclusion criteria, and the review at presentation varies but most are hemo- concluded there was no evidence from random- dynamically stable. A thorough history will pro- ized trials to show the effects of treatments for vide information relating to cause and should secondary postpartum hemorrhage4. include details regarding parity, labor, mode of The main aims of treatment are to provide delivery, third-stage or puerperal complications basic resuscitation, establish a cause for the and any relevant medical and family history. bleeding, and tailor the treatment (medical Clinical signs and symptoms at the time of pre- and/or surgical) according to the cause. sentation may include offensive lochia, abdomi- nal cramping, uterine tenderness, pyrexia, Resuscitation enlarged uterus and an open cervical os. Normal postpartum loss may continue Approximately 10% of cases of secondary post- beyond 6 weeks in up to 25% of women, espe- partum hemorrhage will present with massive cially if breast-feeding20 and the first period may hemorrhage20 and require immediate attention. be heavy, prolonged and painful as a result of an In these cases, resuscitation should be com- anovulatory cycle. Women should be given this menced prior to establishing a cause and should information during normal to include the involvement of senior staff at the avoid unnecessary concern and presentation for earliest opportunity (see Chapter 20). medical investigation. Restoration of circulating blood volume should be achieved by gaining intravenous access with two large-bore cannulae and admin- Investigations istering intravenous fluids initially with physio- logical saline (up to 2 liters) and then with Baseline blood tests should include full blood plasma expanders until blood is available. Blood count, coagulation studies, C-reactive protein, a should be obtained for full blood count, group and hold specimen and serum β-hCG. coagulation screen and cross-match. High- Vaginal swabs should be taken at the time of concentration oxygen (10–15 liters per minute) examination for aerobic as well as anaerobic should be administered by a tight-fitting mask21. bacterial growth, including swabs from Close observation of vital signs including pulse, episiotomy or vaginal tear sites. In women with blood pressure, oxygen saturation and urine signs of infection, a mid-stream urine specimen

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should be collected and, if maternal tempera- Ta bl e 1 Causes of secondary postpartum hemor- ture is > 38°C, blood cultures should be taken. rhage Ultrasound imaging of the pelvis should be Subinvolution of the uterus – retained placental considered if there are concerns of retained pla- tissue and/or endometritis, fibroid uterus cental tissue. If this is within 7–14 days of deliv- Lower genital tract lacerations/hematoma ery, interpretation may be difficult as remaining Surgical injury blood clots may appear as mixed echogenic Dehiscence of Cesarean section scar material in a similar manner to retained tissue. Vascular abnormality – arteriovenous malformation The use of duplex color Doppler helps to Placental abnormality – placenta accreta, percreta improve diagnostic accuracy in differentiating and increta clot and tissue22, as retained placental tissue will Choriocarcinoma often maintain a blood supply unlike necrotic Coagulapathies, bleeding disorders, use of decidua and clot23. anticoagulants The over-diagnosis of retained placental tissue on ultrasound may lead to unnecessary Ta bl e 2 A proposed standardized system for surgical intervention and its potential complica- reporting postpartum ultrasound scan. Adapted tions. However, ultrasound does have signifi- from Neill et al., 200224 cant benefits, as it has a good negative predictive value and therefore is helpful in excluding a 1. Normal endometrial cavity 2. Endometrial cavity containing fluid only diagnosis of retained placental tissue. Neill 3. Endometrial cavity enlarged (anteroposterior and colleagues assessed 53 women undergoing (AP) depth > 1 cm). Maximum AP dimensions ultrasound for secondary postpartum hemor- noted rhage. Definitive diagnosis of retained placental 4. Endometrial cavity containing echogenic foci. tissue was either made histologically or, in Dimensions of largest foci noted. Doppler those women managed conservatively, absence evaluation of blood flow in foci of retained tissue was assumed if bleeding diminished within 1 week. They demonstrated Ta bl e 3 The management of secondary the diagnostic value of ultrasound assessment to postpartum hemorrhage have a positive predictive value of 46% (95% confidence interval (CI) 31–70%), a negative Medical Surgical predictive value of 96% (95% CI 88–100%), Oxytocics Uterine evacuation with a sensitivity of 93% (95% CI 80–100%) Prostaglandins Uterine tamponade balloon and a specificity of 62% (95% CI 48–79%)24. Antibiotics Uterine compression sutures This study also suggested that a standardized Tranexamic acid Hysterectomy approach to reporting an ultrasound investiga- Vasopressin Pelvic arterial ligation tion of secondary postpartum hemorrhage Clotting factor concentrates would be helpful. This is shown in Table 2. Chemotherapy Radiological Additional imaging should also be consid- Oral contraceptive Selective arterial ered for specific causes of secondary postpartum pill embolization hemorrhage such as plain chest film and CT scanning for metastases in cases of chorio- carcinoma, magnetic resonance imaging (MRI) should include resuscitation as discussed above, for placenta accreta25,26 and angiography for the use of uterotonic agents, administration intractable bleeding of unknown origin10. of antibiotics and consideration of surgical evacuation of the uterus. Treatment Uterotonic agents The majority of cases of secondary postpartum hemorrhage are due to subinvolution of the Syntocinon can be administered as an intra- uterus caused by uterine infection and/or venous or intramuscular bolus (10 units) or in retained placental tissue. Initial management combination with ergometrine (Syntometrine®)

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1 ampoule as an intramuscular injection. This hemorrhage in one study, despite only 36% can be followed by a syntocinon infusion (40 having proven histological evidence of retained units in 500 ml normal saline at an infusion rate tissue3. This study was unable to find any clear ® of 125 ml/h). Prostaglandin F2α (Haemabate / association with presence or absence of retained Carboprost) can be given by intramuscular tissue at the time of evacuation and day of onset injection at a dose of 250 µg every 15 min, up to of bleeding or morbidity at the time of second- a total of 2 mg (i.e. 8 doses). Misoprostol can ary postpartum hemorrhage. However, retained also be given as an alternative prostaglandin tissue was more likely if membranes were (400–800 µg orally or rectally). incomplete at delivery, primary postpartum hemorrhage had occurred or if secondary post- partum hemorrhage was judged to be heavy or Antibiotics moderate (compared with light) in volume3.The Endometritis is likely to play a significant role in use of ultrasound prior to surgical evacuation of many cases of secondary postpartum hemor- the uterus does not appear to significantly alter rhage and the majority of women are prescribed the chances of histological diagnosis confirming antibiotics. In a 3-year study of almost 20 000 retained tissue. In one study, 33% of those with women, 132 women (0.69%) had a secondary no preoperative scan had retained placental postpartum hemorrhage and 97% of these were tissue compared to 37% following a scan2. treated with antibiotics2. However, only three- Retained placental tissue is likely to be quarters of these women had microbiological associated with infection and, therefore, broad- specimens collected and a positive culture was spectrum intravenous antibiotics should be obtained in only 13.5%. In a similar observa- given in conjunction with surgical evacuation. tional study of 83 women with secondary As serum concentrations of most antibiotics postpartum hemorrhage, 45% presented with peak 1 h after intravenous administration, these pyrexia, and 64 had bacteriological swabs taken, should be administered just prior to surgery20; of which only 12.5% were positive. Organisms however, in women who are hemodynamically identified included group B streptococcus, stable, it may be appropriate to give 12–24 h bacteroides, E. coli, Clostridium perfringens and of antibiotic cover prior to consideration of Lancefield group D streptococcus. Despite the surgery1. At the time of surgery, uterotonic lack of evidence to support the presence of a agents such as syntocinon, ergometrine and specific bacterial pathogen, 92% of the women prostaglandins may be given to aid uterine received antibiotics3. Recommended choices contractility and control hemorrhage. of antibiotic treatment include amoxycillin There is no clear evidence to support which with clavulanic acid (Augmentin®)27 and a method of evacuation should be used. Manual combination of amoxycillin, metronidazole and removal of tissue, use of a suction catheter and gentamicin3. Endometritis is a major contribu- sharp curettage with a metal curette have all tor to subinvolution of the uterus. Although been described2. The risk of uterine perforation infection may not be confirmed in a large popu- is much higher in uterine evacuation post- lation of cases, we recommend that antibiotics partum and may be even further increased if are always given for secondary postpartum associated with endometritis. Hoveyda and hemorrhage (see Chapter 44). colleagues describe uterine perforation in three of 85 women undergoing the procedure for secondary postpartum hemorrhage. These were Uterine evacuation performed from 4 days to 28 days after delivery Examination under anesthetic and surgical with both a suction and metal curette. In all evacuation of the uterus should be considered if cases, the procedures were performed by senior retained placental tissue is suspected clinically medical staff. One woman went on to require a or after ultrasound examination. This has good hysterectomy, but the other two were managed reported success rates, with bleeding stopping conservatively2. Perforation after Cesarean sec- promptly in all 72 women undergoing evacua- tion is more likely and, as these women have a tion of the uterus for secondary postpartum lower risk of retained placental tissue, surgical

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evacuation in these cases should be very Within an Australian population with an carefully considered. overall incidence of secondary postpartum hem- Additional complications include the risk orrhage of 1.44% over 15 years, only nine cases of Asherman’s syndrome. There is limited required hysterectomy (0.9%)3. However, in a evidence to ascertain if this risk is increased subgroup of women with massive intractable for postpartum uterine evacuation; however, obstetric hemorrhage, two out of seven with in a large study of intrauterine adhesions, secondary postpartum hemorrhage required 21.5% of cases had a postpartum curettage hysterectomy. In one of these cases, hysterec- as a preceding event28. The need for a second tomy was performed 7 days after delivery due to procedure due to incomplete evacuation of intractable bleeding from lower genital tract lac- retained tissue may also occur2. Hysterectomy eration but maternal death still resulted. The may be required to control bleeding in up to 5% second case had further morbidity following her of cases20. hysterectomy for secondary postpartum hemor- In view of these significant complications, rhage with bleeding from wound disunion and women should always be fully counselled of the sepsis and required bilateral hypogastric artery risks and informed consent obtained prior to ligation 14 days after delivery5. Hysterectomy in the procedure. Surgery should be performed by such situations carries significant risks but can experienced senior medical staff. be life-saving and should be considered early in cases of massive hemorrhage, whether primary or secondary. Other surgical procedures Pelvic artery ligation may also be considered In the event of a large secondary postpartum for cases of massive secondary postpartum hem- hemorrhage, other surgical procedures may orrhage uncontrolled by medical and simple need to be considered. This includes cases of surgical measures. Lédée and colleagues report bleeding from an infected placental bed or the use of bilateral hypogastric artery ligation in placental abnormality such as placenta accreta, 49 of 61 cases of intractable hemorrhage; this bleeding from retained placental tissue not includes four out of seven cases of secondary controlled with uterine evacuation, non-union/ postpartum hemorrhage, all of which were suc- dehiscence of Cesarean section scar, bleeding cessful at arresting bleeding5 (see Chapter 32). from a surgical injury or uncontrolled bleeding As with primary postpartum hemorrhage, arte- from a lower genital tract laceration. rial ligation should be performed by an experi- Insertion of an intrauterine tamponade enced surgeon and his/her involvement should balloon, such as the Bakri29 or Rüsch balloon30, be considered whilst planning a laparotomy in has been successfully described for treatment of such cases. primary postpartum hemorrhage and may be considered in cases of secondary postpartum Selective arterial embolization hemorrhage due to uterine subinvolution/atony once retained placental tissue has been excluded Pelvic angiography to assess the internal iliac (see Chapters 28 and 29). Laparotomy may also artery, uterine artery and its vaginal branches be required which allows further investigation is a helpful tool in the assessment of ongoing into the cause of bleeding and treatment by the hemorrhage (Figure 1). It also allows the use of surgical compression sutures, hysterec- introduction of embolization agents to arrest tomy and pelvic arterial ligation as appropriate. bleeding (see Chapter 30). The B-Lynch brace suture is well described Pelage and colleagues studied 14 women for the treatment of primary postpartum hemor- presenting with uncontrollable secondary post- rhage31 and has now been reported in 72 cases partum hemorrhage at a mean of 16 days after of secondary postpartum hemorrhage (B-Lynch delivery. Six women (43%) had delivered by C, personal communication, August 2005). Cesarean section and the remainder by sponta- The use of a surgical compression suture may neous vaginal delivery. Eight women had evi- avoid the need for hysterectomy in women dence of endometritis (57%), with four of those wishing to conserve fertility. associated with histologically proven retained

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Figure 1 Angiogram demonstrating brisk Figure 2 Angiogram after embolization hemorrhage from false aneurysm prior to embolization anterior division of the left internal iliac artery was identified (Figure 1). The vessels were embolized with four coils. There was immediate placental tissue; a further four women had geni- cessation of bleeding and the patient’s vital tal tract lacerations, and the remaining two had signs normalized (Figure 2). The patient made no obvious cause for bleeding. Basic resuscita- a good recovery despite needing 24 units of tion with use of medical treatments and/or uter- blood during the postpartum hemorrhage. Sub- ine curettage were performed. Angiography sequent histology of the uterus showed acute found no extravasation in eight women, active inflammation and subinvolution of the placental bleeding in three women from uterine and bed. vaginal vessels, a false uterine artery aneurysm in two women, and evidence of an arteriovenous fistula in one woman. Pledgets of absorbable Other measures gelatin sponge were introduced to embolize both uterine arteries in 12 women. Unilateral In cases of massive hemorrhage unsuccessfully embolization of a false aneurysm and an treated with surgical measures, the use of intra- 32 arteriovenous fistula were performed for the venous tranexamic acid , recombinant factor 33 34 other two women. External bleeding disap- VIIa and local vasopressin have been peared immediately, and hemodynamic stability reported for primary postpartum hemorrhage. and correction of were obtained There are no reports of their use in secondary for all cases. There were no general or local postpartum hemorrhage but, if available, it may complications10. be appropriate to consider their use in combina- One of the authors (T.J.) recently managed a tion with other therapies and resuscitative case of massive secondary postpartum hemor- support. rhage presenting 4 days after a Cesarean sec- tion. An emergency subtotal hysterectomy was Chemotherapy performed with good initial results. Two hours later, vaginal bleeding restarted. There was The mainstay of treatment for choriocarcinoma no evidence of significant coagulopathy. Pelvic is chemotherapy. A low-risk chemotherapy angiography was performed and a bleed from a regimen includes the use of methotrexate false aneurysm related to a middle branch of the with folinic acid rescue on a 2-weekly cycle35.

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Medium- and high-risk regimens include the research in the form of a randomized controlled use of etopside, methotrexate, actinomycin, trial difficult. However, particularly for the vincristine, cyclophosphomide and 6-mercapto- treatment of hemorrhage due to uterine infec- purine36,37. Women with choriocarcinoma are tion and/or retained placental tissue, this should most appropriately treated through specialist be achievable and would provide valuable trophoblastic disease referral centers14. information to further our understanding of the management of secondary postpartum hemorrhage. Coagulopathies Women with inherited coagulation disorders such as von Willebrand’s disease and carriers of References hemophilia A and B are likely to bleed post- 1. Thompson W, Harper MA. Postpartum partum if maternal clotting factors are low haemorrhage and abnormalities of the third (< 50 IU/dl). Prophylactic administration of stage of labour. In Chamberlain G, Steer P, desmopressin (DDAVP) and clotting factor eds. Turnbull’s , 3rd edn. Edinburgh: concentrates may prevent postpartum hemor- Churchill Livingstone, 2001;619–33 rhage15. The aim is to raise factor levels above 2. Hoveyda F, MacKenzie IZ. Secondary post- 50 IU/dl during labor and delivery and maintain partum haemorrhage: incidence, morbidity and these for up to 5 days after delivery. In the event current management. Br J Obstet Gynaecol 2001; of postpartum hemorrhage15, replacement of 108:927–30 deficient clotting factors should be made and 3. King PA, Duthie SJ, Dong ZG, et al. Secondary identification and treatment of the cause be postpartum haemorrhage. Aust NZ J Obstet instigated. Management should be in close Gynaecol 1989;29:394–8 4. Alexander J, Thomas P, Sanghera J. Treatments liaison with hematologists and specialist hemo- for secondary postpartum haemorrhage. The philia centers as available. In cases of prolonged Cochrane Database of Systematic Review 2002 or intermittent secondary postpartum hemor- Issue 1, Art. No: CD002867. DOI: 10.1002/ rhage15, the use of tranexamic acid (a fibrino- 14651858.CD002867 lytic inhibitor)38 or combined oral contraceptive 5. Lédée N, Ville Y, Musset D, et al. Management pill has been reported15. in intractable obstetric haemorrhage: an audit Hemorrhage from postpartum acquired study on 61 cases. Eur J Obstet Gynecol 2001; hemophilia is treated acutely with factor VIII 94:189–96 (either human, porcine) or recombinant factor 6. Matthews NM, McCowan LME, Patten P. Pla- VIIa15. Immunosuppressive drugs such as centa praevia accreta with delayed hysterectomy. corticosteroids, cyclophosphamide and aza- Aust NZ J Obstet Gynaecol 1996;36:476–9 7. Jaffe R, DuBeshter B, Sherer DM, et al. Failure thioprine may be used to accelerate the dis- of methotrexate treatment for term placenta appearance of factor VIII inhibitors, although percreta. Am J Obstet Gynecol 1994;171:558–9 complete remission is likely to occur spontane- 8. Ggosh H. Arteriovenous malformation of the ously with time. uterus and pelvis. Obstet Gynecol 1986; Reversal of bleeding due to anticoagulants 68(Suppl):40–3 should follow normal protocols. Vitamin K 9. Gaylis H, Levine E, van Dongen L, et al. Arterio- should be considered in women with uncon- venous fistula after gynaecologic operations. Surg trolled bleeding secondary to warfarin use and Gynecol Obstet 1973;137:655–8 protamine sulfate may be considered if hemor- 10. Pelage J-P, Soyer P, Repiquet D, et al. Secondary rhage results from the use of heparin, although postpartum haemorrhage: treatment with selec- this has a much shorter half-life. tive arterial embolization. Radiology 1999;212: 385–9 Secondary postpartum hemorrhage is an 11. Kelly SM, Belli AM, Campbell S. Arteriovenous important cause of maternal morbidity and malformation of the uterus associated with mortality. Basic resuscitation followed by inves- secondary postpartum haemorrhage. Ultrasound tigation and treatment of the specific cause of Obstet Gynecol 2003;21:602–5 hemorrhage are essential. The diverse nature of 12. Nanda S, Singhal S, Sharma D, et al. Nonunion its etiology and often acute presentation make of uterine incision: a rare cause of secondary

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postpartum haemorrhage: a report of 2 cases. 27. Fernandez H, Claquin C, Guibert M, et al. Sus- Aust NZ J Obstet Gynaecol 1997;37:475–6 pected postpartum endometritis: a controlled 13. Paraskevaides E, Stuart B, Gardeil F. Secondary clinical trial of single-agent antibiotic therapy postpartum haemorrhage from non-dehisced with Amox-CA (Augmentin®) vs ampicillin- lower scar: a case for hystero- metronidazole ± amnioglycoside. Eur J Obstet scopy. Aust NZ J Obstet Gynaecol 1993;33:427 Gynecol 1990;36:69–74 14. Tidy JA, Rustin GJS, Newlands ES, et al. Presen- 28. Schenker JG, Margalioth SJ. Intrauterine adhe- tation and management of choriocarcinoma after sions: an update appraisal. Fertil Steril 1982;37: non-. Br J Obstet Gynaecol 1995; 593–610 102:715–19 29. Bakri YN. Amri A, Abdul-Jabar F. Tamponade- 15. Economides DL, Kadir RA. Inherited bleeding balloon for obstetrical bleeding. Int J Gynaecol disorders in obstetrics and gynaecology. Br J Obstet 2001;74:139–42 Obstet Gynaecol 1999;106:5–13 30. Johanson R, Kumar M, Obhrai M, et al. Man- 16. Kadir RA, Economides DL, Braithwaite J, et al. agement of massive postpartum haemorrhage: The obstetric experience of carriers of haemo- use of a hydrostatic balloon catheter to avoid philia. Br J Obstet Gynaecol 1997;104:803–10 laparotomy. Br J Obstet Gynaecol 2001;108: 17. Greer IA, Lowe GDO, Walker JJ, et al. Haemor- 420–2 rhagic problems in obstetrics and gynaecology 31. B-Lynch C, Coker A, Adegboyega HL, et al. The in patients with congenital coagulopathies. Br J B-Lynch surgical technique for the control of Obstet Gynaecol 1991;98:909–18 massive postpartum haemorrhage: an alternative 18. Ramsahoye BH, Davies SH, Dasani H, et al. to hysterectomy? Five cases reported. Br J Obstet Obstetric management in von Willebrand’s dis- Gynaecol 1997;104:372–5 ease: a report of 24 and a review of 32. Alok K, Hagen P, Webb JB. Tranexamic acid in the literature. 1995;1:140–4 the management of postpartum haemorrhage. Br 19. Kadir RA, Lee CA, Sabin CA, et al. Pregnancy in J Obstet Gynaecol 1996;103:1250–1 von Willebrand’s disease or factor XI deficiency. 33. Boehlen F, Morales MA, Fontana P, et al. Br J Obstet Gynaecol 1998;105:314–21 Prolonged treatment of massive postpartum 20. Neill A, Thornton S. Secondary postpartum haemorrhage with recombinant factor VIIa: case haemorrhage. J Obstet Gynaecol 2002;22:119–22 report and review of the literature. Br J Obstet 21. Johanson R, Cox C, Grady K, et al. Massive Gynaecol 2004;111:284–7 obstetric haemorrhage. In Managing Obstetric 34. Lurie S, Appelman Z, Katz Z. Subendometrial Emergencies and Trauma – The MOET Course vasopressin to control intractable placental Manual. London: RCOG Press, 2003;16: bleeding. Lancet 1997;349:698 151–63 35. Bagshawe KD, Dent J, Newlands SL, et al. The 22. Achiron R, Goldenberg M, Lipitz S, et al. role of low dose methotrexate and folinic acid in Transvaginal duplex Doppler ultrasonography in gestational trophoblastic tumours. Br J Obstet bleeding patients suspected of having residual Gynaecol 1989;96:795–802 trophoblastic tissue. Obstet Gynecol 1993;81: 36. Newlands ES, Bagshawe KD, Begent RH, et al. 507–11 Results with EMA/CO (etopside, methotrexate, 23. Zuckerman J, Levine D, McNicholas MM, et al. actinomycin D, cyclophosphamide, vincristine) Imaging of pelvic postpartum complications. Am regimen in high risk gestational trophoblastic J Roentgenol 1997;168:663–8 tumours, 1979–1989. Br J Obstet Gynaecol 1991; 24. Neill AC, Nixon RM, Thornton S. A compari- 98:550–7 son of clinical assessment with ultrasound in the 37. Rustin GJS, Newlands ES, Bergent HJ, et al. management of secondary postpartum haemor- Weekly alternating chemotherapy (EMA/CO) rhage. Eur J Obstet Gynecol 2002;104:113–15 for treatment of central nervous system 25. Thorp JM, Wells SR, Wiest HH, et al. First- metastases of choriocarcinoma. J Clin Oncol trimester diagnosis of percreta 1989;7:900–3 by magnetic resonance imaging. Am J Obstet 38. Bonnar J, Guillebrand J, Kasonde JM, et al. Gynecol 1998;178:616–18 Clinical applications of fibrinolytic inhibition 26. Levine D, Barnes PD, Edelman RR. Obstetric in gynaecology. J Clin Pathol 1980;33(Suppl) MR imaging. Radiology 1999;211:609–17 14:55–9

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