- Email: [email protected]
Obstetric haemorrhage
Thrombosis Research (2009) 123 Suppl. 2, S30–S34
intl.elsevierhealth.com/journals/thre
Obstetric haemorrhage Claire McLintock* National Women’s Health, Auckland City Hospital, Grafton Rd, Auckland, New Zealand
Introduction Maternal mortality due to haemorrhage continues to be one of the most important causes of maternal death worldwide. The difference between resource-rich and resource-poor countries is one of scale. The most recent South African Maternal Mortality Report from 2002 2004 reports that obstetric haemorrhage is the third most frequent cause of maternal death accounting for 13% of deaths: 442 deaths 313 due to postpartum haemorrhage [1]. In contrast, in the United Kingdom the most recent report of Confidential Enquiries into Maternal Deaths identified 17 maternal deaths resulting from haemorrhage, nine from postpartum haemorrhage [2]. These figures reveal that maternal mortality rates due to haemorrhage are almost 25 times greater in South Africa than in the UK. A sobering fact is that in both countries, suboptimal or substandard care was a contributing factor in the majority of maternal deaths due to haemorrhage. Obstetric haemorrhage is one of the commonest causes of severe maternal morbidity and there if concern that postpartum haemorrhage rates are increasing. The definition of postpartum haemorrhage as blood loss >500 ml i.e. in excess of the average loss in a normal vaginal delivery [3] is not of major clinical relevance to otherwise healthy pregnant women can easily accommodate this degree of blood loss. Blood loss of >1000 ml is perhaps a more clinically relevant definition of postpartum haemorrhage that is likely to be associated with increased maternal morbidity and occurs in around 2 4% of deliveries. However, women who have a normal haemoglobin before delivery can withstand even this degree of * Correspondence: Tel.: +64 93670000. E-mail address: [email protected] (C. McLintock).
blood loss without major maternal morbidity. Massive blood loss of >1500 ml, with development of haemodynamic compromise is much less common; haemorrhage leading to severe maternal morbidity is reported to occur in as many as 4 in every 1000 deliveries [1]. Placental development in human pregnancies marked by extensive utero-placental invasion has evolved to allow maximal access of the developing fetus to maternal nutrients. In doing so, however, it places the mother at increased risk of haemorrhage during pregnancy and at delivery. Blood flow through the maternal uterine spiral arteries increases from 10 15 ml prepregnancy to 600 800 ml at term and while procoagulant changes in the maternal circulation can modify the haemorrhagic risk to a degree, placental separation from the uterus at the time of following delivery the poses a huge haemostatic challenge. The uterus responds by rapidly contracting to staunch blood flow, and this can be augmented by administration of ecbolics in the third stage of labour reducing the risk of postpartum haemorrhage >1000 ml [4]. Factors that inhibit uterine contraction or lead to retention of adherent placental tissue will obviously prevent this normal physiological response and lead to bleeding. A number of risk factors for postpartum haemorrhage (Figure 1), can be identified in the antenatal period or intrapartum. A recent study of nulliparous women in the Netherlands identified retained placenta and prolonged 3rd stage >30 min as the most important risk factors responsible for 39% of cases of severe postpartum haemorrhage i.e. blood loss of 1000 ml [5]. However, the majority of women who develop PPH have no identifiable risk factors so all pregnant women must be considered to be at risk of haemorrhage and continuous vigilance is essential (Figure 2).
0049-3848/ $ – see front matter © 2009 Elsevier Ltd. All rights reserved.
Obstetric haemorrhage
S31 Uterine atony
Coagulopathy/DIC
previous PPH *
placental abruption
labour >12 h **
preeclampsia *
Induction of labour *
amniotic fluid embolism
prolonged 3rd stage **
sepsis *
retained placenta
massive transfusion
baby >4kg * multiple pregnancy * maternal obesity * sepsis *
inherited bleeding tendency *
Risk Factors for Postpartum Haemorrhage
anticoagulant therapy *
Placental problems
Uterine, cervical or vaginal injury
placenta previa *
instrumental delivery **
placental accreta/increta/percreta *
caesarean section **
Fig. 1. Risk factors for Postpartum Haemorrhage. *Identifiable in antenatal period; **identifiable intrapartum.
Awareness of the risk
Early identification and treatment if it occurs
Obstetric haemorrhage
Identification of risk factors ‐ antenatal, intrapartum
1o prevention ‐ active management 3rd stage of labour Fig. 2. Obstetric haemorrhage: continuous vigilance.
Understanding the physiological changes of pregnancy that predispose women to rapid development of severe, life-threatening haemorrhage and in particular disseminated intravascular coagulation should ensure that all clinicians caring for pregnant women remain alert to the risk of PPH. As recommended previous Confidential Enquiries into Maternal Deaths [6] antenatal identification of women with risk factors for PPH will to allow an appropriate management plan for delivery to be instituted (Table 1). Women with placenta previa who have had previous uterine surgery are at high risk of having placenta accreta i.e. morbid attachment of the placenta to the uterine wall that is associated with a significant risk of massive, rapid haemorrhage and should be delivered by experienced consultant staff. A management plan should be developed by a multidisciplinary team
for women identified antenatally to have placenta accreta, percreta or increta. The increased risk of these placental abnormalities in women with prior caesarean section requires that the site of placental implantation should be determined in all women with this history. Clinical vigilance to ensure that there is rapid recognition of the development of severe postpartum blood loss with prompt restoration of the circulating blood volume, reversal of coagulopathy and correction of surgical bleeding. Table 1 Essential steps in women identified at high risk of postpartum haemorrhage Women should be screened and treated for pre-partum anaemia All elective and emergency surgery should be performed by an experienced team of consultant obstetricians and anaesthetists Adequate intravenous access (two large bore cannulae) should be established before surgery starts At least four units blood should be cross-matched and immediately available If bleeding is excessive the obstetrician should consider embolisation of uterine arteries by an interventional radiologist or further surgical procedures and should call for immediate assistance from a colleague or vascular surgeon if they do not feel competent to perform the required procedure A consultant haematologist should be consulted for advice regarding transfusion requirements in cases of massive transfusion or disseminated intravascular coagulation (DIC) A multidisciplinary massive haemorrhage protocol should be available in all units and updated and rehearsed regularly in conjunction with the blood bank
S32
C. McLintock Identify problem
uterine atony, retained placenta, abruption, amniotic fluid embolism, PPH, sepsis, genital tract trauma etc
Immediate resuscitation
Maintain circulating blood volume and tissue oxygenation
Blood and plasma product replacement
Initial coagulation study: platelets, PR, aPTT, fibrinogen
Definitive clinical intervention
Uterotonic agents and tamponade
crystalloids, packed red cells
Ruesh balloon, B-Lynch suture
Restore normal haemostasis
FFP, cryoprecipitate, platelets
Arterial ligation or embolisation, rFVIIa, hysterectomy
Fig. 3. Goals of management in postpartum haemorrhage.
Management of massive postpartum blood loss If severe obstetric haemorrhage does occur, the main aims of management of postpartum blood loss are the same as in all cases of massive blood loss: (1) restoration and maintenance of circulating blood volume to prevent tissue and organ hypoperfusion and oxygenation and (2) achievement of haemostasis by either correction of surgical cause of blood loss or reversal of coagulopathy by use of appropriate blood and plasma components (Figure 3). Key components in management of postpartum haemorrhage relate to identification and treatment of obstetric causes of bleeding. Manoeuvres include bimanual compression and ecbolics for uterine atony, examination under anaesthesia to remove retained placental tissue, identify genital tract trauma, laparotomy to identify uterine rupture, enable placement of a bracing suture, internal artery ligation or hysterectomy is required. Another important difference with obstetric haemorrhage compared to major bleeding due to other causes is an increased rate of disseminated intravascular coagulation (DIC) that is present prior to effects of massive transfusion. Obstetric DIC can be the result of amniotic fluid embolism, placental abruption, infection, preeclampsia and HELLP syndrome. A coagulation screen taken early in the resuscitation can identify unanticipated DIC and help guide blood product replacement. In addition, the rapid activation of coagulation in obstetric haemorrhage leads to consumption of fibrinogen with brisk falls in the high fibrinogen levels in pregnancy of 6 7 g/L. Activation of coagulation also induces the fibrinolytic pathway. Hyperfibrinolysis in obstetric haemorrhage with production of fibrin(ogen) degradation products directly inhibits coagulation factor activity and uterine contraction, further exacerbating the clinical situation.
Choice of blood and blood products for transfusion Red cells These are most commonly given as resuspended red cell concentrates. The choice of red cell issues will depend on the urgency of transfusion and whether the blood bank has an up-to-date maternal blood group and antibody screen. The urgency of the situation depends on how much blood has been lost, whether the bleeding has been stopped, and if the patient unstable. In obstetric bleeding, the degree of urgency can change rapidly. (1) Immediate transfusion required blood needed “NOW” unstable patient, blood loss >2000 ml, ongoing bleeding issue (i) no group and antibody screen urgent or “desperate” O-negative red cells (ii) group and antibody screen negative group specific red cells can be issued (iii) group and antibody screen positive issue urgent or “desperate” O-negative red cells (2) Blood required within <30 mins blood loss 1000 1500 ml, unstable patient (i) group and antibody screen negative group specific red cells can be issued (ii) group and antibody screen positive full crossmatch required (takes 40 60 issue urgent or “desperate” minutes) O-negative red cells (3) Blood required within 30 60 mins blood loss 1000 1500 ml, stable patient (i) group and antibody screen negative group specific red cells can be issued (ii) group and antibody screen positive await full crossmatch issue compatible blood. Plasma products Fresh frozen plasma: Prior to the introduction of blood component therapy in the 1980s throm-
Obstetric haemorrhage bocytopenia was the most common coagulopathy to develop after transfusion of whole blood with depletion of clotting factors occurring at a later stage. However, the change to using red cell concentrates (RCC) did not lead to a change in transfusion dogma so that most transfusion “recipes” continued advocate RCC to fresh frozen plasma (FFP) ratios of 1:4. Recent data from observational studies in non-pregnant populations requiring massive transfusion i.e. more than 10units in a 24-hour period show improved mortality in patients transfused with 1:1.4 ratios of red cells to FFP [7]. These and other data have lead to recommendations that in massive transfusion a ratio of 1:1 red cells to FFP should be used to avoid coagulopathy [8]. It seems logical to apply the same arguments to massive transfusion in obstetric haemorrhage. The recognition that thawed units of FFP are stable for 24 hours has prompted some centres now keep a small number of thawed units available for use in massive transfusion. Platelets: Thrombocytopenia not uncommonly complicates obstetric haemorrhage given the predisposing disorders that lead to the haemorrhage. Similar arguments to those for FFP have been made for early transfusion of platelets in cases of massive haemorrhage in non-obstetric populations with recommendation to transfuse one “conventional” unit of platelets for each unit of RCC and FFP. An apheresis unit is equivalent to around 5 8 “conventional” units. Cryoprecipitate: Cryoprecipitate is used as a source of fibrinogen replacement and is still frequently used in centres in Australasia but is used less frequently in centres in Europe and North America. Fibrinogen concentrates are available in these areas and are plasma products that have undergone viral inactivation steps. Obstetric haemorrhage is particular among causes of massive haemorrhage in that fibrinogen depletion is an early occurrence. A recent study of coagulation parameters in obstetric haemorrhage revealed significantly lower fibrinogen levels in women who went onto develop severe PPH than those with less severe PPH, 3.3 g/L and 4.4 g/L, respectively [9]. Of note, both fibrinogen levels were within the normal range for pregnancy. All women in the study with fibrinogen levels <2 g/L developed severe PPH. Early replacement of fibrinogen in obstetric haemorrhage may be important in preventing morbidity and be considered until clinical studies are developed to answer this question. Peripartum hysterectomy Peripartum hysterectomy is frequently seen as the definitive procedure to treat life-threatening
S33 obstetric haemorrhage. The UK Obstetric Surveillance System recently reported management and outcomes of peripartum hysterectomy in 229 consultant lead units in the UK between February 2005 and February 2006 [10]. A total of 315 hysterectomies were carried out with uterine atony and placental accreta/increta/percreta the most common associated risk factors in 53% (n = 167) and 38% (n = 121), respectively. Eighty percent of women had delivered by caesarean section, 16% had a spontaneous vaginal delivery and 4% an assistend vaginal delivery. Blood product transfusion rates reflected the severity of blood loss with a median of 10 units of red cells (range 0 116) and four units of FFP (range 0 29) transfused. Bladder damage was reported in 12% of women and almost 20% of women required further surgery. Two women died, but for each of these women more than 150 survived. However, the physical and psychological sequelae for women who undergo peripartum hysterectomy should not be underestimated. The loss of fertility is particularly devastating for women who have not completed their family. Recombinant FVIIa There are increasing data on the “off-label” use of recombinant FVIIa (Novoseven) in obstetric haemorrhage. Some authors suggest a role for rFVIIa prior to peripartum hysterectomy [11] especially in cases where preservation of fertility is a concern. Clearly there are some situation where early recourse to hysterectomy may the most appropriate first option such as in major placenta accreta/increta/percreta or where the blood loss is rapid and the patient is very unstable. In other situations where the clinical team are considering proceeding to a hysterectomy in the face of ongoing bleeding despite correction of obstetric and surgical causes of bleeding, adequate red cell transfusion and correction of coagulopathy, rFVIIa could be given in an attempt to control bleeding prior to a surgical intervention. Novoseven works rapidly, with any effect on bleeding usually evident within 10 15 minutes after administration. The obstetric team must decide if the clinical situation allows for this intervention in an attempt to prevent recourse to peripartum hysterectomy. Currently there no randomised clinical trials available to inform clinicians whether rFVIIa prevents the need for hysterectomy in obstetric haemorrhage with the most unbiased information relating to its efficacy and safety likely to be that from Registry data that records outcomes from all “off-label” use of rFVIIa [12]. While the
S34 actions of recombinant FVIIa are thought to be localised to the site of vascular injury concerns have been raised regarding the potential for more widespread activation of thrombosis, especially in patients with predisposing risk factors [13]. Summary Postpartum haemorrhage remains an important cause of maternal death in the developed and especially in the developing world. An appreciation of the physiological changes of pregnancy that predispose to rapid development of severe haemorrhage and DIC help maintain a level of vigilance. Although routine antenatal assessment can identify women with factors associated with an increased risk of severe postpartum haemorrhage, a significant proportion of women will develop intrapartum complications that cause severe haemorrhage. Prompt recognition and treatment of women with severe ongoing blood loss is essential to prevent morbidity and mortality. In addition to surgical correction of bleeding, replacement of plasma components to reverse coagulopathy and red cells to maintain tissues oxygenation are the basic aims of management. The haemostatic agent, recombinant Factor VIIa is a potentially useful addition to management of massive, life-threatening obstetric haemorrhage but its safety and efficacy remains untested in clinical trials. Conflicts of interest: I have received honoraria from NovoNordisk for lectures and have acted as an independent medical advisor to the company for submissions relating to use of NovoSeven in Obstetric Haemorrhage. References [1] National Committee into Confidential Enquiries into Maternal Deaths. Saving mothers: Third report on
C. McLintock
[2]
[3] [4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
confidential enquiries into maternal deahts in South Africa; 2006. Confidential Enquiry in Maternal and Child Health. Saving Mothers’ Lives: a report of the confidential enquiry into maternal deaths; 2003 2005. World Health Organisation. Technical working group: care in normal birth: a practical guide. Geneva; 1996. Prendiville WJ, Elbourne D, McDonald S. Active versus expectant management in the third stage of labour. Cochrane Database Syst Rev 2000(3): CD000007. DOI: 10.1002/14651858. Bais JMJ, Eskes M, Pel M, Bonsel GJ, Bleker OP. Postpartum haemorrhage in nulliparous women: incidence and risk factors in low and high risk women. A Dutch population-based cohort study on standard (500ml) and severe (1000ml) postpartum haemorrhage. Eur J Obstet Gynecol Reprod Biol 2004;115:166 72. Confidential Enquiry in Maternal and Child Health. Why mothers die 2000 2002. Report on Confidential enquiries into maternal deaths in the United Kingdom. London: RCOG Press; 2004. Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, et al. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007 Oct;63(4):805 13. Malone DL, Hess JR, Fingerhut A. Massive transfusion practices around the globe and a suggestion for a common massive transfusion protocol. J Trauma 2006 Jun;60(6 Suppl):S91 6. Charbit B, Mandelbrot L, Samain E, Baron G, Haddaoui B, Keita H, et al. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. J Thromb Haemost 2007 Feb;5(2):266 73. Knight M, on behalf of UKOSS. Peripartum hysterectomy in the UK: management and outcomes of the associated haemorrhage. Br J Obstet Gynaecol 2007 Nov;114(11): 1380 7. Welsh A, McLintock C, Gatt S, Somerset D, Popham P, Ogle R. Guidelines for the use of recombinant activated factor VII in massive obstetric haemorrhage. Aust NZ J Obstet Gynaecol 2008 Feb;48(1):12 6. Phillips LE, Isbister J, Dunkley S, McNeil J, Cameron P. The Haemostasis registry: Australian and New Zealand Experience with rFVIIa. J Thromb Haemost 2007; 5(Suppl 2):P-T-001. Roberts HR. Recombinant factor VIIa: a general hemostatic agent? Yes. J Thromb Haemost 2004;2: 1691 4.
intl.elsevierhealth.com/journals/thre
Obstetric haemorrhage Claire McLintock* National Women’s Health, Auckland City Hospital, Grafton Rd, Auckland, New Zealand
Introduction Maternal mortality due to haemorrhage continues to be one of the most important causes of maternal death worldwide. The difference between resource-rich and resource-poor countries is one of scale. The most recent South African Maternal Mortality Report from 2002 2004 reports that obstetric haemorrhage is the third most frequent cause of maternal death accounting for 13% of deaths: 442 deaths 313 due to postpartum haemorrhage [1]. In contrast, in the United Kingdom the most recent report of Confidential Enquiries into Maternal Deaths identified 17 maternal deaths resulting from haemorrhage, nine from postpartum haemorrhage [2]. These figures reveal that maternal mortality rates due to haemorrhage are almost 25 times greater in South Africa than in the UK. A sobering fact is that in both countries, suboptimal or substandard care was a contributing factor in the majority of maternal deaths due to haemorrhage. Obstetric haemorrhage is one of the commonest causes of severe maternal morbidity and there if concern that postpartum haemorrhage rates are increasing. The definition of postpartum haemorrhage as blood loss >500 ml i.e. in excess of the average loss in a normal vaginal delivery [3] is not of major clinical relevance to otherwise healthy pregnant women can easily accommodate this degree of blood loss. Blood loss of >1000 ml is perhaps a more clinically relevant definition of postpartum haemorrhage that is likely to be associated with increased maternal morbidity and occurs in around 2 4% of deliveries. However, women who have a normal haemoglobin before delivery can withstand even this degree of * Correspondence: Tel.: +64 93670000. E-mail address: [email protected] (C. McLintock).
blood loss without major maternal morbidity. Massive blood loss of >1500 ml, with development of haemodynamic compromise is much less common; haemorrhage leading to severe maternal morbidity is reported to occur in as many as 4 in every 1000 deliveries [1]. Placental development in human pregnancies marked by extensive utero-placental invasion has evolved to allow maximal access of the developing fetus to maternal nutrients. In doing so, however, it places the mother at increased risk of haemorrhage during pregnancy and at delivery. Blood flow through the maternal uterine spiral arteries increases from 10 15 ml prepregnancy to 600 800 ml at term and while procoagulant changes in the maternal circulation can modify the haemorrhagic risk to a degree, placental separation from the uterus at the time of following delivery the poses a huge haemostatic challenge. The uterus responds by rapidly contracting to staunch blood flow, and this can be augmented by administration of ecbolics in the third stage of labour reducing the risk of postpartum haemorrhage >1000 ml [4]. Factors that inhibit uterine contraction or lead to retention of adherent placental tissue will obviously prevent this normal physiological response and lead to bleeding. A number of risk factors for postpartum haemorrhage (Figure 1), can be identified in the antenatal period or intrapartum. A recent study of nulliparous women in the Netherlands identified retained placenta and prolonged 3rd stage >30 min as the most important risk factors responsible for 39% of cases of severe postpartum haemorrhage i.e. blood loss of 1000 ml [5]. However, the majority of women who develop PPH have no identifiable risk factors so all pregnant women must be considered to be at risk of haemorrhage and continuous vigilance is essential (Figure 2).
0049-3848/ $ – see front matter © 2009 Elsevier Ltd. All rights reserved.
Obstetric haemorrhage
S31 Uterine atony
Coagulopathy/DIC
previous PPH *
placental abruption
labour >12 h **
preeclampsia *
Induction of labour *
amniotic fluid embolism
prolonged 3rd stage **
sepsis *
retained placenta
massive transfusion
baby >4kg * multiple pregnancy * maternal obesity * sepsis *
inherited bleeding tendency *
Risk Factors for Postpartum Haemorrhage
anticoagulant therapy *
Placental problems
Uterine, cervical or vaginal injury
placenta previa *
instrumental delivery **
placental accreta/increta/percreta *
caesarean section **
Fig. 1. Risk factors for Postpartum Haemorrhage. *Identifiable in antenatal period; **identifiable intrapartum.
Awareness of the risk
Early identification and treatment if it occurs
Obstetric haemorrhage
Identification of risk factors ‐ antenatal, intrapartum
1o prevention ‐ active management 3rd stage of labour Fig. 2. Obstetric haemorrhage: continuous vigilance.
Understanding the physiological changes of pregnancy that predispose women to rapid development of severe, life-threatening haemorrhage and in particular disseminated intravascular coagulation should ensure that all clinicians caring for pregnant women remain alert to the risk of PPH. As recommended previous Confidential Enquiries into Maternal Deaths [6] antenatal identification of women with risk factors for PPH will to allow an appropriate management plan for delivery to be instituted (Table 1). Women with placenta previa who have had previous uterine surgery are at high risk of having placenta accreta i.e. morbid attachment of the placenta to the uterine wall that is associated with a significant risk of massive, rapid haemorrhage and should be delivered by experienced consultant staff. A management plan should be developed by a multidisciplinary team
for women identified antenatally to have placenta accreta, percreta or increta. The increased risk of these placental abnormalities in women with prior caesarean section requires that the site of placental implantation should be determined in all women with this history. Clinical vigilance to ensure that there is rapid recognition of the development of severe postpartum blood loss with prompt restoration of the circulating blood volume, reversal of coagulopathy and correction of surgical bleeding. Table 1 Essential steps in women identified at high risk of postpartum haemorrhage Women should be screened and treated for pre-partum anaemia All elective and emergency surgery should be performed by an experienced team of consultant obstetricians and anaesthetists Adequate intravenous access (two large bore cannulae) should be established before surgery starts At least four units blood should be cross-matched and immediately available If bleeding is excessive the obstetrician should consider embolisation of uterine arteries by an interventional radiologist or further surgical procedures and should call for immediate assistance from a colleague or vascular surgeon if they do not feel competent to perform the required procedure A consultant haematologist should be consulted for advice regarding transfusion requirements in cases of massive transfusion or disseminated intravascular coagulation (DIC) A multidisciplinary massive haemorrhage protocol should be available in all units and updated and rehearsed regularly in conjunction with the blood bank
S32
C. McLintock Identify problem
uterine atony, retained placenta, abruption, amniotic fluid embolism, PPH, sepsis, genital tract trauma etc
Immediate resuscitation
Maintain circulating blood volume and tissue oxygenation
Blood and plasma product replacement
Initial coagulation study: platelets, PR, aPTT, fibrinogen
Definitive clinical intervention
Uterotonic agents and tamponade
crystalloids, packed red cells
Ruesh balloon, B-Lynch suture
Restore normal haemostasis
FFP, cryoprecipitate, platelets
Arterial ligation or embolisation, rFVIIa, hysterectomy
Fig. 3. Goals of management in postpartum haemorrhage.
Management of massive postpartum blood loss If severe obstetric haemorrhage does occur, the main aims of management of postpartum blood loss are the same as in all cases of massive blood loss: (1) restoration and maintenance of circulating blood volume to prevent tissue and organ hypoperfusion and oxygenation and (2) achievement of haemostasis by either correction of surgical cause of blood loss or reversal of coagulopathy by use of appropriate blood and plasma components (Figure 3). Key components in management of postpartum haemorrhage relate to identification and treatment of obstetric causes of bleeding. Manoeuvres include bimanual compression and ecbolics for uterine atony, examination under anaesthesia to remove retained placental tissue, identify genital tract trauma, laparotomy to identify uterine rupture, enable placement of a bracing suture, internal artery ligation or hysterectomy is required. Another important difference with obstetric haemorrhage compared to major bleeding due to other causes is an increased rate of disseminated intravascular coagulation (DIC) that is present prior to effects of massive transfusion. Obstetric DIC can be the result of amniotic fluid embolism, placental abruption, infection, preeclampsia and HELLP syndrome. A coagulation screen taken early in the resuscitation can identify unanticipated DIC and help guide blood product replacement. In addition, the rapid activation of coagulation in obstetric haemorrhage leads to consumption of fibrinogen with brisk falls in the high fibrinogen levels in pregnancy of 6 7 g/L. Activation of coagulation also induces the fibrinolytic pathway. Hyperfibrinolysis in obstetric haemorrhage with production of fibrin(ogen) degradation products directly inhibits coagulation factor activity and uterine contraction, further exacerbating the clinical situation.
Choice of blood and blood products for transfusion Red cells These are most commonly given as resuspended red cell concentrates. The choice of red cell issues will depend on the urgency of transfusion and whether the blood bank has an up-to-date maternal blood group and antibody screen. The urgency of the situation depends on how much blood has been lost, whether the bleeding has been stopped, and if the patient unstable. In obstetric bleeding, the degree of urgency can change rapidly. (1) Immediate transfusion required blood needed “NOW” unstable patient, blood loss >2000 ml, ongoing bleeding issue (i) no group and antibody screen urgent or “desperate” O-negative red cells (ii) group and antibody screen negative group specific red cells can be issued (iii) group and antibody screen positive issue urgent or “desperate” O-negative red cells (2) Blood required within <30 mins blood loss 1000 1500 ml, unstable patient (i) group and antibody screen negative group specific red cells can be issued (ii) group and antibody screen positive full crossmatch required (takes 40 60 issue urgent or “desperate” minutes) O-negative red cells (3) Blood required within 30 60 mins blood loss 1000 1500 ml, stable patient (i) group and antibody screen negative group specific red cells can be issued (ii) group and antibody screen positive await full crossmatch issue compatible blood. Plasma products Fresh frozen plasma: Prior to the introduction of blood component therapy in the 1980s throm-
Obstetric haemorrhage bocytopenia was the most common coagulopathy to develop after transfusion of whole blood with depletion of clotting factors occurring at a later stage. However, the change to using red cell concentrates (RCC) did not lead to a change in transfusion dogma so that most transfusion “recipes” continued advocate RCC to fresh frozen plasma (FFP) ratios of 1:4. Recent data from observational studies in non-pregnant populations requiring massive transfusion i.e. more than 10units in a 24-hour period show improved mortality in patients transfused with 1:1.4 ratios of red cells to FFP [7]. These and other data have lead to recommendations that in massive transfusion a ratio of 1:1 red cells to FFP should be used to avoid coagulopathy [8]. It seems logical to apply the same arguments to massive transfusion in obstetric haemorrhage. The recognition that thawed units of FFP are stable for 24 hours has prompted some centres now keep a small number of thawed units available for use in massive transfusion. Platelets: Thrombocytopenia not uncommonly complicates obstetric haemorrhage given the predisposing disorders that lead to the haemorrhage. Similar arguments to those for FFP have been made for early transfusion of platelets in cases of massive haemorrhage in non-obstetric populations with recommendation to transfuse one “conventional” unit of platelets for each unit of RCC and FFP. An apheresis unit is equivalent to around 5 8 “conventional” units. Cryoprecipitate: Cryoprecipitate is used as a source of fibrinogen replacement and is still frequently used in centres in Australasia but is used less frequently in centres in Europe and North America. Fibrinogen concentrates are available in these areas and are plasma products that have undergone viral inactivation steps. Obstetric haemorrhage is particular among causes of massive haemorrhage in that fibrinogen depletion is an early occurrence. A recent study of coagulation parameters in obstetric haemorrhage revealed significantly lower fibrinogen levels in women who went onto develop severe PPH than those with less severe PPH, 3.3 g/L and 4.4 g/L, respectively [9]. Of note, both fibrinogen levels were within the normal range for pregnancy. All women in the study with fibrinogen levels <2 g/L developed severe PPH. Early replacement of fibrinogen in obstetric haemorrhage may be important in preventing morbidity and be considered until clinical studies are developed to answer this question. Peripartum hysterectomy Peripartum hysterectomy is frequently seen as the definitive procedure to treat life-threatening
S33 obstetric haemorrhage. The UK Obstetric Surveillance System recently reported management and outcomes of peripartum hysterectomy in 229 consultant lead units in the UK between February 2005 and February 2006 [10]. A total of 315 hysterectomies were carried out with uterine atony and placental accreta/increta/percreta the most common associated risk factors in 53% (n = 167) and 38% (n = 121), respectively. Eighty percent of women had delivered by caesarean section, 16% had a spontaneous vaginal delivery and 4% an assistend vaginal delivery. Blood product transfusion rates reflected the severity of blood loss with a median of 10 units of red cells (range 0 116) and four units of FFP (range 0 29) transfused. Bladder damage was reported in 12% of women and almost 20% of women required further surgery. Two women died, but for each of these women more than 150 survived. However, the physical and psychological sequelae for women who undergo peripartum hysterectomy should not be underestimated. The loss of fertility is particularly devastating for women who have not completed their family. Recombinant FVIIa There are increasing data on the “off-label” use of recombinant FVIIa (Novoseven) in obstetric haemorrhage. Some authors suggest a role for rFVIIa prior to peripartum hysterectomy [11] especially in cases where preservation of fertility is a concern. Clearly there are some situation where early recourse to hysterectomy may the most appropriate first option such as in major placenta accreta/increta/percreta or where the blood loss is rapid and the patient is very unstable. In other situations where the clinical team are considering proceeding to a hysterectomy in the face of ongoing bleeding despite correction of obstetric and surgical causes of bleeding, adequate red cell transfusion and correction of coagulopathy, rFVIIa could be given in an attempt to control bleeding prior to a surgical intervention. Novoseven works rapidly, with any effect on bleeding usually evident within 10 15 minutes after administration. The obstetric team must decide if the clinical situation allows for this intervention in an attempt to prevent recourse to peripartum hysterectomy. Currently there no randomised clinical trials available to inform clinicians whether rFVIIa prevents the need for hysterectomy in obstetric haemorrhage with the most unbiased information relating to its efficacy and safety likely to be that from Registry data that records outcomes from all “off-label” use of rFVIIa [12]. While the
S34 actions of recombinant FVIIa are thought to be localised to the site of vascular injury concerns have been raised regarding the potential for more widespread activation of thrombosis, especially in patients with predisposing risk factors [13]. Summary Postpartum haemorrhage remains an important cause of maternal death in the developed and especially in the developing world. An appreciation of the physiological changes of pregnancy that predispose to rapid development of severe haemorrhage and DIC help maintain a level of vigilance. Although routine antenatal assessment can identify women with factors associated with an increased risk of severe postpartum haemorrhage, a significant proportion of women will develop intrapartum complications that cause severe haemorrhage. Prompt recognition and treatment of women with severe ongoing blood loss is essential to prevent morbidity and mortality. In addition to surgical correction of bleeding, replacement of plasma components to reverse coagulopathy and red cells to maintain tissues oxygenation are the basic aims of management. The haemostatic agent, recombinant Factor VIIa is a potentially useful addition to management of massive, life-threatening obstetric haemorrhage but its safety and efficacy remains untested in clinical trials. Conflicts of interest: I have received honoraria from NovoNordisk for lectures and have acted as an independent medical advisor to the company for submissions relating to use of NovoSeven in Obstetric Haemorrhage. References [1] National Committee into Confidential Enquiries into Maternal Deaths. Saving mothers: Third report on
C. McLintock
[2]
[3] [4]
[5]
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
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