Transcript Hematologic management of massive PPH

Hematologic management of
massive PPH
Mehran Karimi
Professor of Pediatric HematologyOncology Shiraz University of
Medical Science
29 Khordad,Shiraz
postpartum hemorrhage (PPH)
• PPH is the loss of 500 ml or more of blood from
the genital tract within 24 hours of the birth of a
baby
• PPH can be minor (500–1000 ml) or major (more
than 1000 ml)
• PPH is the most common cause of maternal
death worldwide
• PPH is responsible for 25% of the deaths of an
estimated 358000 women world-wide each year
WHO guidelines for the management of postpartum haemorrhage and retained placenta, 2009
Severe PPH
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•
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•
Pale, sweating
PR > systolic blood pressure
Blood loss: watery, non clot
Decreased Hb more than 2-4 gr/dl from
baseline (anemia is a risk factor for PPH)
• Decreased HR + decreased BP when blood loss
> 1500 mls
Hematological Changes
in Pregnancy
• Non pregnant: < 1% of her cardiac output flows through
her uterus but at the end of pregnancy uterine blood
flow accounts for 15% of CO
• 40% expansion of blood volume by 30 weeks
• 600 ml/min of blood flows through intervillous space
• Appreciable increase in concentration of Factors I
(fibrinogen), VII, VIII, IX, X
• Plasminogen appreciably increased
• Plasmin activity decreased
• Decreased colloid oncotic pressure secondary to 25%
reduction in serum albumin
Blood Products Utilization
• Local protocols are helpful
• Don’t wait for lab abnormalities if actively
bleeding!
• Massive hemorrhage without replacement of
coagulation factors (FFP) will result in
coagulation abnormalities
Causes and treatment of massive PPH
Causes
• Uterine atony: The most
common cause of PPH that
bleeding leading to
coagulopathy
• Incisions and lacerations
• Hemostatsis defect
Treatment
• Massage, remove clot,
uterotonic agent, uterine
tamponade
• Surgical repaire
• Factor replacement
Early hysterectomy indications : 1- Placenta accreta
2- Uterine rupture
Goals in management of a postpartum hemorrhage
Journal of Thrombosis and Haemostasis, 2011; 9: 1441–1451
Blood components for prevention of massive bleeding
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Whole blood and RBC
Fresh frozen plasma (FFP)
Cryopercipitate
Platelets
Fibrinogen
rFVIIa
Main therapeutic goals of management of massive blood loss
Restore circulating volume
crystalloid ,colloid , blood transfusion
Arrest bleeding
Early surgical or obstetric intervention
Haemoglobin
> 8g/dl
Platelets count
> 75000/µ/
Prothrombin Time (PT)
< 1.5 x mean control
Activated Partial Thromboplastin time
(PTT)
< 1.5 x mean control
Fibrinogen
> 1.5 g/l
Avoid DIC
Treat underlying cause (shock,
hypothermia, acidosis, hypotension)
Blood Product Utilization
Product
Contents
Volume
Effect
500ml
↑ Hct 3%
PRBCs
RBCs, WBCs, few 300ml
plasma proteins
↑ Hct 3%
Platelets
Pooled
concentrate
1 unit = 6 pack
50ml
↑ PLT 5000
30000
FFP
Fibrinogen, ATIII,
clotting factors,
plasma
250ml
↑ fibrinogen 510mg/dl
Cryoprecipitate
Fibrinogen,
Factor VIII, XIII,
vWF
40ml
↑ fibrinogen 510mg/dl
Whole Blood
blood components
• When the blood loss reaches about 4.5 liters (80% of
blood volume) and large volumes of replacement fluids
have been given, there will be clotting factor defects
and blood components should be given
• transfusion of coagulation factors, up to 1 liter of FFP
and 10 units of cryoprecipitate may be prevent
bleeding
• Critical levels of fibrinogen rich after a loss only 140%
of the calculated blood volume
• Critical levels of prothrombin, FV, FVII and PLT rich after
a loss only 200% of the calculated blood volume
Fluid therapy and blood products transfusion
Crystalloid
Up to 2 liters Hartmann's solution
Colloid
Up to 1–2 liters colloid until blood arrives
Blood
Crossmatched. If crossmatched blood is still
unavailable, give uncrossmatched group-specific
blood OR give 'O RhD negative' blood
Fresh frozen plasma
4 units for every 6 units* of red cells or
prothrombin time/activated partial
thromboplastin time >1.5 x normal (12–15 ml/kg
or total 1 litre)
Platelets concentrates
If platelet count <50 x 109
Cryoprecipitate
If fibrinogen <1 g/l
•FFP/RBC ratio mortality: 1/4: 19%,
2/5: 34%,
1/8: 65%
Fibrinogen concentrate
• Acquired hypofibrinogenaemia develops early in relation
to fluid resuscitation, imbalanced transfusion of blood
components and bleeding
• This state of impaired hemostasis also develops in
relation to PPH
• Fibrinogen concentrate is a commercially available drug
produced from human plasma
• It seems that early fibrinogen substitution in cases of PPH
is benefit in prevention PPH
• The FIB-PPH trial is investigator-initiated and aims to
provide an evidence-based platform for the
recommendations of the early use of fibrinogen
concentrate in PPH (Wikkelsoe et al. Trials 2012, 13:110)
• If fibrinogen less than 2 gr/lit
severe PPH
Fluid replacement
• By consensus, total volume of 3.5 liters of clear fluids
(up to 2 liters of warmed Hartmann’s solution as
rapidly as possible, followed by up to a further 1.5
liters of warmed colloid if blood still not available)
comprises the maximum that should be infused while
awaiting compatible blood
• The choice of fluid to be infused is controversial but of
greater importance is rapid administration and
warming of the infusion
• The woman needs to be kept warm using appropriate
measures
Blood transfusion
• If fully cross-matched blood is unavailable by
the time that 3.5 liters of clear fluid have been
infused, the best available alternative should
be given to restore oxygen-carrying capacity
• Group O RhD-negative blood may be the
safest way to avoid a mismatched transfusion
in an acute emergency
Antifibrinolytic agents
(Tranexamic acid)
• Treatment with TXA is effective in reducing blood
loss in patients undergoing CS
• Although the study was not adequately powered
to address safety issues, the observed side effects
were mild and transient
• TXA given in the dose of 0.5 to 1 g intravenously
was effective in reducing postpartum
haemorrhage after vaginal birth and caesarean
section with minimal side effects
Arch Gynecol Obstet 2012 Oct 13
2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Tranexamic acid
TA and Pregnancy & Post-partum – Systematic review
6 RCT, 7 Observational studies
Peitsidis et al 2011
• Reduction of amount of blood loss
• TXA seems to be safe and effective
• Lack of prospective trial
Tranexamic acid
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•
•
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Ducloy-Bouthers et al 2011
Blood loss – significantly less
Duration of bleeding less
BT – significantly less
Less interventions required to stop
the bleeding
• Loading 4 gr over 1 hr then infusion
of 1 gr/hr over 6 hrs
Recombinant activated factor VII (rFVIIa)
• rFVIIa was developed for the treatment of
haemophilia
rFVIIa
North European Registry – 2000-2004
• 128 women – 33 hysterectomy prior rFVIIa
• 80% improvement after rFVIIa – 13(14%) required
hysterectomy
• 4 cases of VTE + one myocardial infarction
• Death – 5 cases - none due to VTE
Australian and New Zealand Registry – 2002-2008
• 110 cases - 78% of cases single dose (median dose 92 µg/kg
• 76% positive response
• Hysterectomy 41% before rFVIIa
• 21% required hysterectomy after rFVIIa
• 2 cases of VTE
• Death – 9 cases - none related directly to rFVIIa
rFVIIa
rVIIa – should be considered in management of
massive PPH
• Timing ?
Prior to hysterectomy – unless bleeding surgical
• Optimal dose ?
– 90mcg/Kg – two doses 15-30 minutes apart
Ensure
Platelet > 50 and Fibrinogen > 2gm/l
Grade C-IV evidence
Algorithm approach of rFVIIa in PPH
P/E: R/O GYN problem
If : -PLT > 50000
- FIB> 1 gr/dl
- Normal PT
- PH ≥ 7.2
- Temp ≥35
Hematology consult :
rFVIIa: 40-60 μg/kg
*By: MOH
Conclusion
• Severe bleeding because of placenta accreta or
uterine rupture cause early hysterectomy (HST)
• Before early hysterectomy: compression suture or
balloon tomponade is indicated
• Uterine Atony: bleeding persist in spite of
correction:
I. Coagulopathy
II. Hypothermia
rFVIIa (max: 2 doses)
III. Acidosis and hypocalcemia
90 µg/kg before HST
Case presentation
• The patient was a 37 years old
women
• She had normal first vaginal
delivery without history of
coagulation disorders
• Three months after second
normal vaginal delivery she
developed severe skin
ecchymosis and bleeding of right
upper and lower extremities
(compartment syndrome)
What is your next evaluation for definite
diagnosis?
VWF Ag
Factor IX assay
Factor XI assay
Inhibitor assay
Inhibitor assay
.1
.2
.3
.4
Case presentation
• Many works up was done to
finding the cause of her bleeding
tendency
• Coagulation tests were:
 PT: 13 sec, INR: 1
 PTT: 55 sec (mixing PTT:51 sec)
 Serum FVIII level: 0.14%
 Serum FVIII inhibitor level: 145 BU
 Serum FIX inhibitor level: normal
 Serum FX inhibitor level: normal
 ANA: neg
 dsDNA: neg
What is your definite diagnosis in this case?
Hemophilia A
Hemophilia B
Acquired
Hemophilia
A
Acquired
Hemophilia
A
VWD
.1
.2
.3
.4
What is treatment of bleeding in this case?
1.
2.
3.
4.
5.
6.
FVIII concentrate
IVIG
Recombinant
FVIIa
Recombinant
FVIIa
&
FEIBA
FEIBA
3 and 4
All
Case presentation (treatment)
• The patient admitted in the hospital and the recombinant FVII 90
u/kg (every 4 hrs for three times) with partial response
• So the frequency was changed to every 2 hrs for 24 hrs with
complete response and then every 4-6 hours for the second day
• The plasmapheresis was also done without any response
• Immune suppressive treatment was started with prednisolon 1
mg/kg/d and cyclophosphamide 2 mg/kg/d at the same time.
• The coagulation tests resulted to normalization after completion of
treatment
Case presentation (follow up)
• The bleeding symptom was stopped after
2 days of acute treatment
 FVIII level: 30%
 FVIII inhibitor: 40 BU
 PTT: 45 sec
• The patient was discharged with continue
prednisolone and cyclophosphamide for a
period of 6 weeks with complete response
Thank you
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