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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

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Hematologic management of massive PPH

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  1. Hematologic management of massive PPH MehranKarimi Professor of Pediatric Hematology- Oncology Shiraz University of Medical Science 29 Khordad,Shiraz

  2. 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

  3. Severe PPH • 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

  4. Hematological Changesin 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

  5. 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

  6. Causes and treatment of massive PPH Causes Treatment Massage, remove clot, uterotonic agent, uterine tamponade Surgical repaire Factor replacement • Uterine atony: The most common cause of PPH that bleeding leading to coagulopathy • Incisions and lacerations • Hemostatsis defect • Early hysterectomy indications : 1- Placenta accreta • 2- Uterine rupture

  7. Goals in management of a postpartum hemorrhage Journal of Thrombosis and Haemostasis, 2011; 9: 1441–1451

  8. Blood components for prevention of massive bleeding • Whole blood and RBC • Fresh frozen plasma (FFP) • Cryopercipitate • Platelets • Fibrinogen • rFVIIa

  9. Main therapeutic goals of management of massive blood loss

  10. Blood Product Utilization

  11. 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

  12. Fluid therapy and blood products transfusion • FFP/RBC ratio mortality: 1/4: 19%, 2/5: 34%,1/8: 65%

  13. 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

  14. 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

  15. 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

  16. 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 GynecolObstet 2012 Oct 13 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

  17. 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

  18. 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

  19. Recombinant activated factor VII (rFVIIa) • rFVIIawas developed for the treatment of haemophilia

  20. 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

  21. 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

  22. 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

  23. 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: • Coagulopathy • Hypothermia rFVIIa (max: 2 doses) • Acidosis and hypocalcemia90 µg/kg before HST

  24. 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)

  25. What is your next evaluation for definite diagnosis? • VWF Ag • Factor IX assay • Factor XI assay • Inhibitor assay Inhibitor assay

  26. 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

  27. What is your definite diagnosis in this case? • Hemophilia A • Hemophilia B • Acquired Hemophilia A • VWD Acquired Hemophilia A

  28. What is treatment of bleeding in this case? • FVIII concentrate • IVIG • Recombinant FVIIa • FEIBA • 3 and 4 • All Recombinant FVIIa & FEIBA

  29. 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

  30. 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

  31. Thank you karimim@sums.ac.ir

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