EXPLORE PAST ISSUES
Maternal Death
Vol. 15 No 1 | Autumn 2013
Feature
Massive haemorrhage in early pregnancy
Dr Martina Mende
DRANZCOG


This article is 7 years old and may no longer reflect current clinical practice.

Massive haemorrhage in early pregnancy is a rare, but potentially life-threatening condition.

In the Centre for Maternal and Child Enquiries (CMACE) report, Saving Mothers’ Lives, five deaths owing to uterine haemorrhage in early pregnancy were reported in the UK, while in Australia ectopic pregnancy was the most common cause of first trimester maternal deaths, accounting for two per cent of maternal deaths from 1997–2005.1,2

Massive haemorrhage in obstetric practice should be regarded as blood loss >1500ml, approximately 25 per cent of the patient’s blood volume in later pregnancy.3 It is associated with a number of serious sequelae including hypovolaemic shock, disseminated intravascular coagulation (DIC), renal failure, hepatic failure, adult respiratory distress syndrome (ARDS), psychological trauma and loss of fertility.3 Recognition of haemorrhage, adequate resuscitation and early surgical management are essential in the safe management of women with early pregnancy haemorrhage.

Physiology in early pregnancy

Uterine placental blood flow increases in a gradual and linear fashion early in pregnancy from 20–50ml/min up to 450–800ml/min at term in singleton pregnancies. This is achieved through a number of mechanisms both uterine and systemic. Uterine changes include an expansion of the uterine vasculature, vasodilatation resulting in reduced vascular tone and the development of the placenta. On a systemic level, maternal cardiac output increases and there is an expansion of maternal vascular volume.4

Maternal cardiovascular changes start as early as four weeks gestation. Red blood cell mass increases from four weeks and plasma volume expansion increases by 10–15 per cent by 12 weeks gestation.5 Cardiac output increases by 30–50 per cent during pregnancy and half of this increase occurs by eight weeks gestation. Systolic and diastolic blood pressure falls early in pregnancy to around 5–100mmHg below baseline and remains lower until the third trimester.6 Young healthy women can often compensate due to these changes until there has been substantial blood loss.

Table 1. Causes of haemorrhage in early pregnancy.

Common Rare
  • Spontaneous miscarriage
  • Retained products of conception
  • Ruptured ectopic pregnancy
  • Molar pregnancy
  • Haemorrhagic ruptured
    corpus luteal cyst
  • Uterine abnormality arteriovenous malformation
  • Complication of dilation and curettage
  • Placenta accreta
  • Spontaneous uterine rupture/ scar rupture
  • Cervical ectopic pregnancy
  • Thrombotic thrombocytopenic purpura

Clinical presentation

Haemorrhage in early pregnancy can present with obvious vaginal bleeding, vague abdominal symptoms or haemoperitoneum, depending on the site of pregnancy (see Table 1).

Spontaneous miscarriage is the most common cause of uterine haemorrhage in early pregnancy, but molar pregnancy should always be considered if unusually heavy bleeding occurs. Arteriovenous malformation can be a cause of haemorrhage at the time of dilation and curettage and rarer causes of vaginal bleeding, such as a cervical ectopic pregnancy, should be considered.7,8

Signs of haemoperitoneum can present with abdominal pain, bloating, vomiting and/or diarrhoea, signs of peritonism or collapse. All women of fertile age should have a pregnancy test, if presenting with these symptoms or undifferentiated abdominal pain, to exclude pregnancy.2 Ruptured ectopic pregnancy is the most likely cause of haemoperitoneum, but there are increasing case reports of uterine rupture in first trimester pregnancy, secondary to accreta or molar pregnancy implanted into a previous scar. Although rare, a history of previous uterine surgery in a woman presenting in early pregnancy with signs of haemoperitoneum may warrant laparoscopy, despite ultrasound confirming an intrauterine pregnancy.9-12

Management

The management of haemorrhage in early pregnancy differs according to the location of the pregnancy and site of haemorrhage. Assessment of the woman needs to determine if she is haemodynamically stable, and whether imaging is appropriate, or if she should be taken directly to theatre for surgical management.

There is little evidence-based literature in regards to management of acute uterine haemorrhage in early pregnancy. The approach to haemorrhage in early pregnancy should be similar to that in postpartum haemorrhage (PPH): determine the cause of the bleeding, assess extent of haemorrhage, examination, resuscitation, medical and surgical management.

Women presenting with heavy vaginal bleeding should have a speculum examination to remove any product from the os; this is an important part of the resuscitation process.13 If heavy bleeding occurs during dilation and curettage, examination of the cervix should be performed in case of cervical damage requiring repair, uterine perforation should be considered and diagnostic laparoscopy may need to be performed to exclude perforation.14,15

The therapeutic aims in massive haemorrhage are to maintain tissue perfusion and oxygenation, stop bleeding and prevent coagulopathy. The first goal in massive haemorrhage is resuscitation and adequate volume expansion. A (airway) B (breathing) C (circulation) is the initial step in resuscitation and often women with haemorrhage are not adequately resuscitated at the outset. Two large-bore cannulas (16g) should be sited and a full blood count (FBC); group and hold; and antibody screening should be sent. Baseline electrolyte, renal function and coagulation screen (including fibrinogen and thrombin time) should also be collected.16 All women should have a blood group test and rhesus-negative women given anti-D at an appropriate time when stable.

Regular observations should be recorded and, ideally, a member of the team should be assigned to the task of scribing to record all observations and medications given. The importance of clear communication between clinicians, team members and pathology (blood bank) as well as accessing early senior-level assistance in maternal haemorrhage has been emphasised in multiple reports into maternal deaths.3,16,17

Volume resuscitation

Delay in attempting to restore circulating volume can result in serious complications and prolonged hypotension; increases morbidity and mortality; and increases the risk of DIC. Crystalloid solution, such as 0.9 per cent normal saline or Hartmann’s solution, should be the first-line therapy in early resuscitation and should be infused as a bolus until systolic blood pressure is restored to 80–100mgHg. The risks of aggressive fluid resuscitation include pulmonary oedema, exacerbation of thrombocytopenia and coagulopathy secondary to haemodilution, and this must be balanced with the need to maintain tissue perfusion with adequate blood pressure.18 It is recommended that crystalloids be used for resuscitation and, in situations where colloids are used, at a maximum volume of 1000–1500ml in 24 hours, as larger volumes affect haemostatic function.3 Hypothermia increases the risk of end-organ damage and, in cases where large volumes of fluid are required, the use of warm air blankets and pre-warmed fluids helps prevent hypothermia and the risk of coagulopathy.16

Blood transfusion

Transfusion of red blood cells (RBCs) should not be used as a volume expander, but to provide oxygenation to tissue and contribute to haemostasis by contributing to platelet function.16 Red cells are usually not indicated with an Hb >100 and are usually always indicated for an Hb <60. In massive haemorrhage where a crossmatch is unavailable, O (Rh) D-negative blood cells can be administered but should be swapped for ABO-specific blood as soon as possible. Each hospital should have a massive transfusion protocol and the suggested criteria for activation of this protocol is in patients who will need four units of RBC in less than four hours (actual or anticipated) and/or are haemodynamically unstable with or without ongoing bleeding.18 Blood should be given through a blood warmer, with regular monitoring of FBC, coagulation studies, ionised calcium and arterial blood gases (see Table 2).18 Coagulopathy is often present early in obstetrics patients and the triad of acidosis, hypothermia and coagulopathy increases the mortality rate.18

Table 2. Parameters in massive blood transfusion: monitor every 30–60 minutes.18

Aim for
Temp >35°
pH >7.2
Base excess <-6
Lactate <4mmol/l
Ca2+ >1.1mmol/l
Platelets >50 x 109/l
Partial thromboplastin time/activated partial thromboplastin time <1.5x normal
International normalised ratio ≤1.5
Fibrinogen >1.0g/l

 

Once four units of RBCs have been administered, other blood components should be considered and administered (see Table 3). Fresh frozen plasma (FFP) should be given to maintain a partial thromboplastin time (PTT) or activated partial thromboplastin time (APTT) ≤1.5 x normal. A suggested regime is four units FFP per four units of RBC and a single adult dose of platelets, with appropriate correction of calcium.19 Thrombocytopaenia will be present when 1.5–2 times blood volume has been transfused due to dilution and increasing consumption. The platelet count should be kept above 50×109/l and should be kept above 80–100×109/l if surgical intervention is required. If the platelet count drops below 50×109/l and bleeding is not under control during massive haemorrhage, then a bolus of FFP followed by 8–12 units of platelets should be rapidly transfused.3 Fibrinogen may not be corrected by FFP alone and cryoprecipitate should be administered if fibrinogen is <1g/l.18 If haemorrhage continues – despite adequate stabilisation, massive transfusion protocol and surgical or radiological management – consideration of Factor VIIa should be made in consultation with a haematologist (see Table 3). Patients who receive Factor VIIa are at high risk of thromboembolism and calf compressors and TEDs should be started immediately with consideration of prophylactic doses of unfractionated or low molecular weight heparin within 24 hours after haemorrhage.19 Early DIC should always be considered in obstetric patients and cryoprecipitate should be administered early and consultation with a haematologist about the role of antithrombin (Thrombotrol-VF) should be considered.18

Medical management

Medical management includes syntocinon, ergometrine and misoprostol or prostaglandin F2α. There is little evidence to support a certain regime or dosing in early pregnancy and generally the doses used are the same as for postpartum haemorrhage.14 Bimanual massage can be used in conjunction with uretotonics; this may be while the patient is being stabilised, is waiting for theatre or during theatre when bleeding continues despite suction dilation and curettage.

Myometrial oxytocin receptors are present at low levels up until week 17 when they increase dramatically until term, with maximal receptors being found in the myometrium during labour.20 A small randomised controlled trial study of 64 women undergoing suction curettage at ≥9 weeks gestation showed that 1ml intravenous syntocinon resulted in a statistically significant reduction in blood loss, although not a clinically significant reduction in loss as both groups of women lost <100ml during the procedure, demonstrating there is some response to syntocinon despite low levels of myometrial receptors being present in early pregnancy.21

Surgical management

Much of the literature concerning surgical techniques for control of haemorrhage in early pregnancy is case studies. Suction dilation and curettage is first-line surgical management for uterine haemorrhage and, again, surgical techniques are aligned closely with clinical practice for PPH (see Table 4). The use of a balloon catheter to tamponade bleeding in PPH is well documented and appears to have increasing evidence in the treatment of bleeding owing to post-abortion haemorrhage, arteriovenous malformations and first and second trimester haemorrhage.22,23 This method is effective and also available in all settings (especially rurally with limited resources) as a Foley’s catheter can be used, volumes of balloon catheter varied in studies from 30ml to 150ml.

Radiological intervention (uterine artery embolisation – UAE) is associated with less morbidity and mortality then laparotomy and hysterectomy, but is not available in all centres. It has been used successfully in arteriovenous malformations, post-abortion haemorrhage and PPH.22,24 UAE has also been used in conjunction with laparoscopy and laparotomy to control bleeding while repair of uterine perforation is performed.14 UAE is also fertility preserving in women wishing to have future pregnancies.

If bleeding continues despite full medical management and the preceding surgical/radiological techniques, laparotomy may need to be performed. Haemostatic sutures, such as the B-Lynch suture, have been reported in the literature and it is reasonable to attempt this before hysterectomy, which is definitive treatment for bleeding.25

Table 4. Surgical management of uterine haemorrhage in early pregnancy.

Suction dilation and curettage
Packing uterus
Balloon catheter
Radiological intervention – embolisation uterine artery
Laparotomy – uterine or internal iliac arty ligation, haemostatic suture (B-Lynch suture)
Hysterectomy

Grief/trauma counselling

Management for haemorrhage can be a traumatic and distressing experience for the woman and her family. In addition to this, they are also dealing with a pregnancy loss and it is important, as clinicians, we recognise both the experience of a life-threatening event and also the loss of a pregnancy and offer debriefing and counselling as appropriate.26

Table 3. Blood components in massive haemorrhage and indications in massive transfusion.27

Therapy Indication and dosing
Red cells
  • Massive transfusion protocol indicated if ≥ 4 units RBC in 4 hours (actual or anticipated) + haemodynamically unstable +/- ongoing bleeding
  • Uncrossmatched group O, RH (D) negative red cells if group unknown; change to group-specific blood when crossmatch available
  • To avoid hypothermia, give through blood warmer
Fresh frozen plasma
  • Give FFP to maintain PT & APTT ≤ 1.5x normal
  • Recommend 4 units fresh frozen plasma for every 4 units red blood cells
  • Usual dose 15ml/kg
  • If blood group unknown – give AB fresh frozen plasma
  • 30 minutes thawing time
Platelets
  • Normal adult dose (1 bag)
  • Recommend 1 bag per 4 units red blood cells and 4 units fresh frozen plasma
  • Aim to keep platelet count >50×109/l and 80–100×109/l if surgery indicated
  • Thrombocytopaenia (<50×109/l) can be expected at 1.5–2x blood volume replacement
Cryoprecipitate
  • If Fibrinogen <1g/l despite FFP replacement cryoprecipitate is indicated
  • Early use of cryoprecipitate is indicated in DIC
  • Dose 3–4g of fibrinogen (consult with transfusion lab)
  • 30 minutes thawing time
Recombinant factor VIIa
  • Ongoing haemorrhage despite:
    • blood component therapy with adequate coagulopathy correction
    • failed surgical or radiological intervention to control bleeding
    • pH >7.2 and temp >34°
    • Consult with haematologist
    • 90µg/kg (rounded to nearest vial) as a single bolus over 3–5 min
  • Check dose at 20 mins and optimise calcium, pH, temp, platelets and fibrinogen, if no response administer second dose19
Calcium correction19
  • Correct calcium as appropriate
  • Optimise temperature and acidaemia
Cell salvage
  • Consider use where appropriate where anticipated blood loss > 1500ml
  • May be appropriate for patients who refuse allogenic blood transfusion (eg. Jehovah’s Witness patients)28

Conclusion

In the report, Maternal Deaths in Australia 2003–05, no deaths from massive uterine haemorrhage in early pregnancy were identified, but massive haemorrhage can occur suddenly and be life threatening, therefore anyone treating women in early pregnancy should be prepared. Management follows the basic principles of postpartum haemorrhage, but often occurs in settings not used to dealing with significant haemorrhage. Recognition of haemorrhage, early help and adequate resuscitation should be implemented as well as early medical and surgical management.

References

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