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Hematologic management of massive PPH


Hematologic management of massive PPH. MehranKarimi. Professor of Pediatric Hematology- Oncology Shiraz University of Medical Science. 29 Khordad,Shiraz – PowerPoint PPT presentation

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Title: Hematologic management of massive PPH

Hematologic management of massive PPH
  • Mehran Karimi
  • Professor of Pediatric Hematology- Oncology
    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 (5001000 ml) or major (more
    than 1000 ml)
  • PPH is the most common cause of maternal death
  • 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
  • Pale, sweating
  • PR gt 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 gt
    1500 mls

Hematological Changes in Pregnancy
  • Non pregnant lt 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
  • 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
  • Dont wait for lab abnormalities if actively
  • Massive hemorrhage without replacement of
    coagulation factors (FFP) will result in
    coagulation abnormalities

Causes and treatment of massive PPH
  • Causes
  • Treatment
  • Uterine atony The most common cause of PPH that
    bleeding leading to coagulopathy
  • Incisions and lacerations
  • Hemostatsis defect
  • Massage, remove clot, uterotonic agent, uterine
  • Surgical repaire
  • Factor replacement
  • Early hysterectomy indications 1- Placenta

  • 2- Uterine rupture

Goals in management of a postpartum hemorrhage
Journal of Thrombosis and Haemostasis, 2011 9
Blood components for prevention of massive
  • Whole blood and RBC
  • Fresh frozen plasma (FFP)
  • Cryopercipitate
  • Platelets
  • Fibrinogen
  • rFVIIa

Main therapeutic goals of management of massive
blood loss
crystalloid ,colloid , blood transfusion Restore circulating volume
Early surgical or obstetric intervention Arrest bleeding
gt 8g/dl Haemoglobin
gt 75000/µ/ Platelets count
lt 1.5 x mean control Prothrombin Time (PT)
lt 1.5 x mean control Activated Partial Thromboplastin time (PTT)
gt 1.5 g/l Fibrinogen
Treat underlying cause (shock, hypothermia, acidosis, hypotension) Avoid DIC
Blood Product Utilization
Product Contents Volume Effect
Whole Blood 500ml ? Hct 3
PRBCs RBCs, WBCs, few plasma proteins 300ml ? Hct 3
Platelets Pooled concentrate 1 unit 6 pack 50ml ? PLT 5000 30000
FFP Fibrinogen, ATIII, clotting factors, plasma 250ml ? fibrinogen 5-10mg/dl
Cryoprecipitate Fibrinogen, Factor VIII, XIII, vWF 40ml ? fibrinogen 5-10mg/dl
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
  • 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 12 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 gt1.5 x normal (1215 ml/kg or total 1 litre)
Platelets concentrates If platelet count lt50 x 109
Cryoprecipitate If fibrinogen lt1 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, 13110)
  • If fibrinogen less than 2 gr/lit severe

Fluid replacement
  • By consensus, total volume of 3.5 liters of clear
    fluids (up to 2 liters of warmed Hartmanns
    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
  • 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

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

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
  • 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

Ducloy-Bouthers et al 2011
Recombinant activated factor VII (rFVIIa)
  • rFVIIa was developed for the treatment of

  • North European Registry 2000-2004
  • 128 women 33 hysterectomy prior rFVIIa
  • 80 improvement after rFVIIa 13(14) required
  • 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

  • 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 gt 50 and Fibrinogen gt 2gm/l

Grade C-IV evidence
Algorithm approach of rFVIIa in PPH
  • P/E R/O GYN problem
  • If -PLT gt 50000
  • - FIBgt 1 gr/dl
  • - Normal PT
  • - PH 7.2
  • - Temp 35
  • Hematology consult
  • rFVIIa 40-60 µg/kg
  • By MOH

  • 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
  • Coagulopathy
  • Hypothermia rFVIIa
    (max 2 doses)
  • Acidosis and hypocalcemia 90 µg/kg before

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

What is your next evaluation for definite
  1. VWF Ag
  2. Factor IX assay
  3. Factor XI assay
  4. Inhibitor assay

Inhibitor assay
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 PTT51 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?
  1. Hemophilia A
  2. Hemophilia B
  3. Acquired Hemophilia A
  4. VWD

Acquired Hemophilia A
What is treatment of bleeding in this case?
  1. FVIII concentrate
  2. IVIG
  3. Recombinant FVIIa
  4. FEIBA
  5. 3 and 4
  6. All

Recombinant FVIIa FEIBA
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
  • 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 karimim_at_sums.ac.ir
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