Fibrinogen, haemostasis and postpartum haemorrhage

Ove KarlssonSahlgrenska University Hospital

Gothenburg, Sweden

No conflict of interests

• Gothenburg, Sweden• 10-11.000 deliveries• 3 labour wards

• 2 normal• 1 special

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100

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700

2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

2016 7.2%

Vaginal deliveries with bleeding >1000 ml, Sahlgrenska University Hospital

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90

100

2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

1500 - 1999

2000 - 2999

3000 - 3999

>4000

Bleeding during operation

2010 20161-2 L 8.1% 4.2%>2 L 1.3% 0.76%

• Better routine• Better cooperation• Better knowledge

of haemostasis

0

100

200

300

400

500

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800

2009 2010 2011 2012 2013 2014 2015 2016

Erytrocyter Plasma Trombocyter

Reduced blood transfusions with 39.5%

8.5 per 100.000 maternities

MBRRACE-UK 2012-2014

In all patients with mortality due to haemorrhage, improvements in care may have made a difference to the outcome (MBRRACE-UK 2009-2012)

Treatment of large postpartum haemorrhage:

1. Prophylaxis against postpartum haemorrhage

2. Initial treatment

3. Pharmacological treatment

4. Surgical treatment

5. Haemostasis

6. Anaesthesia

7. And more

Initial treatment

• Aorta compression• Alt. bimanually uterus compression• Call staff• Lower head and Oxygen 5-10 L/min• Blood pressure and pulse• Intravenous access• Hb, screen• Coagulation screen• Warm fluids

• Crystalloid (avoid excessive use)• Colloid (restricted)• Adverse effects of haemostasis

• Catheter• Keep patient warm• Inj Tranexamic acid 2 g iv

Farmacological therapy of atony

• Inj Oxytocin (Syntocinon®)– Bolus 8,3 ug/ml 1 ml iv under 1 min– Oxytocin 8,3 ug/ml = 5 E/ml– Vid elektivt snitt under 5 minuter– Infusion 66,4 ug/ml 120 ml/t

• Inj Metylergometrin (Methergin®)– 0,2 mg iv alt im, långsamt– Kan upprepas 4 ggr

• Inj Karboprost (Prostinfenem®)– 0,25 mg im– Kan upprepas 8 ggr

• T Misoprostol (Cytotec®)– 200 mg 3 st rektalt

Obstetrical interventions

• Inspection of placenta

• Exploration of uterus

• Inspection of cervix/vagina

• Balloon tamponade

• Compression sutures

• Hysterectomy

Goals during on-going bleeding:

• Hb > 90 g/l• Platelets > 100 x 109/l• PK(INR) < 1.5• APTT normal• Fibrinogen > 2.0-2.5 g/l• Temp > 36.5 °C• pH > 7.2• Ionised Ca2+ >1.0• Point-of-Care devices• Repeat sampling!

• Review• Several randomised studies• Reduced bleeding volume• Large RCT required

• 20.000 patients, 21 countries, 193 hospital• Randomised, double-blind, placebo controlled• Inj Tranexamic acid 1g, a second dose possible• Reduced mortality due to reduced bleeding

Transfusion strategy

Bleeding < ½ blood volume

and bleeding will stop

• Transfusion strategy

– As little as possible

– Goal-directed therapy

– Packed red blood cells, until acceptable Hb

Bleeding > ½ blood volume

and bleeding will continue

• Transfusion strategy

– Blood/plasma/platelets

–4:4:1

Try to assess if the bleeding will:

• The risk for severe PPH was 2.63-fold higher for each 1 g/L decrease of fibrinogen

• Positive predictive value of fibrinogen ≤2 g/L was 100%

• A simple fibrinogen can anticipate the risk of severe bleeding in PPH.

• Multicentre, d-blinded, randomized• Study group vs control group

• EBL 1493 (±489) vs 1426 (±463)• Fib 4.5 (±1.1) vs 4.5 (±1.3)• 2 g fibrinogen or saline• Total EBL 1700 vs 1700

• No difference transfusion or (total) estimated blood loss (EBL)

Study group Control groupBleeding, L 2.5 (2.0-3.7) 0.4 (0.2-0.6)Fibrinogen g/L 3.0 (2.7-3.3) 4.8 (4.6-5.0)

range 1.0-5.0 range 3.6-6.7

• Faster clot initiation• Reduced clot strength• TEG, faster results• Strongest correlation

• Fibrinogen - TEG-MA• EBL - Fibrinogen• EBL – TEG-MA

• Fibrinogen concentration mean 5.3 g/L• Interval 2.9 – 8.8 g/L

r = 0.9

p < 0.0001

r = 0.003

p < 0.9

• Fibrinogen does not decrease during labour• Fibrinogen does not predict severe PPH• Predictors of PPH:

• Exploration of uterus postpartum• Caesarean section• Instrumental delivery• Oxytocin stimulation

• >2.0 g/L, improved coagulation• 2.5 g/L, optimized coagulation• Still not stable to fibrinolysis

• Review about fibrinogen• Plasma contains 1-3 g/L• Fibrinogen concentrate 15-20 g/L• Obstetric haemorrhage 1 g,

median increase of 0.36 g/L

American Journal of Obstetrics & Gynecology 2015

• Urgent treatment• Treat the cause• Give it all at once

• Blood/Plasma/Platelets• Fibrinogen• Tranexamic acid

• Repeat sampling

• Off label use• Case reports, obstetric bleeding• No randomised studies• In some guidelines

• No studies, postpartum haemorrhage• Other studier, no difference in bleeding• Indication profylaxis

• von Willebrand• Hemofili A• Platelet dysfunction

• Risk for water intoxication

Work against:• Hypothermia• Hypocalcaemia• Acidosis

Anaesthesia and obstetric complications

Regional anaesthesia

• Less bleeding

• Less transfusions

• Less mortality

• Less morbidity

• Contraindication– Large on-going bleeding

General anaesthesia

• Increased bleeding

• Increased transfusions

• Increased mortality

• Increased morbidity

• Indication– Large on-going bleeding

• Volatile anaesthetics• Dose dependent relaxation• Uterine muscles

• Change volatile anaesthetics• Propofol infusion• Optimize O2/N2O/fentanyl

Bleeding (median and range)• Study group 1400 mL (400-3000)• Control group 8000 mL (2300-40.000)