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Postpartum Hemorrhage Bleeding Complications During Pregnancy Keith McCrae, M.D. Cleveland Clinic 4/13/2016 Disclosure I have no relevant personal financial relationship and I have not presented any promotional talks for any pharmaceutical companies within the past 12 months. Outline • Epidemiology and causes of maternal mortality • Placental structure and relation to hematologic disease in pregnancy • Maternal mortality/morbidity due to bleeding • Life threatening bleeding disorders • Von Willebrand disease in pregnancy Maternal Mortality: WHO Analysis Khan et al, Lancet 2006 Pregnancy-Related Death in the United States http://www.cdc.gov/reproductivehealth/MaternalInfantHealth/PMSS.html Placentation and the Maternofetal Circulation Kingdom and Drewlo, Blood 118:4780, 2011 Defective Placentation in Preeclampsia Normal Preeclampsia Kingdom and Drewlo, Blood 118:4780, 2011 Q1: Postpartum Hemorrhage You are called to see a 24 year old woman who has developed severe postpartum hemorrhage following an extended labor and delivery. Her pregnancy had been previously uncomplicated. On further questioning she has had mild epistaxis about once every year or two, usually in the winter. She had previously undergone tonsillectomy as a child and said she bled afterwards but does not recall needing transfusions. She also underwent a laparoscopic appendectomy without excessive bleeding. Her obstetricians want to know whether she has an underlying coagulopathy. Definitions and Causes of Postpartum Hemorrhage Abdul-Kadir et al: Transfusion, 2014 Bateman et al: Anesth Analg, 2010 Risk Factors for Postpartum Hemorrhage Abdul-Kadir et al: Transfusion, 2014 Massive Obstetric Hemorrhage/Disseminated Intravascular Coagulation • Amniotic fluid embolism • Placental abruption • Placenta previa • Placenta accreta • Retained products of conception Causes and Pathogenesis of DIC in Pregnancy Montagna Sem Thromb Hemost 36:404, 2010 ISTH Scoring System for DIC: Relevance to Pregnancy Réger et al; Thromb Res 2013 Taylor FB et al: JTH, 2001 Charbit G; JTH, 2007 Amniotic Fluid Embolism • Misnomer—“anaphylactoid syndrome of pregnancy” • Incidence: 1/40,000 • Risk factors--controversial – No risk factor identified that justifies prospective alterations of clinical practice • Early clinical signs and symptoms – Hypotension – Dyspnea – Cyanosis – Loss of consciousness – Cardiac arrest • Fulminant coagulopathy (DIC)-diffuse bleeding from uterus, incisions, intravenous sites • Consequences – Maternal mortality in 60% if all classic signs and symptoms are present – If cardiac arrest, mortality increases to 90% – Severe fetal morbidity/mortality if not delivered urgently Amniotic Fluid Embolism Kanayama and Tamura J Obstet Gynec Res 40: 1507, 2014 https://www.studyblue.com/notes/note/n/vascular-disorders-_atlas-images/deck/8094977 Amniotic Fluid Procoagulant Activity/DIC Sarig et al; Thromb Res, 2011 Clark SL; Obstet Gynec, 2014 Placental Abruption • Partial or complete separation of normally implanted placenta before delivery • Incidence: 0.4-1.0% of pregnancies – Highest incidence at 24-26 weeks • Risk factors – Advanced maternal age (>35 years) – Smoking – Chronic hypertension – Vaginal bleeding during pregnancy http://umm.edu/health/medical/pregnancy/labor-and- – PROM/chorioamnionitis delivery/placenta-abruptio – Obstetrical history (preeclampsia, C-section, stillbirth, abruption) – Thrombophilia? • Clinical manifestations – Hypovolemic shock, renal failure – Fulminant DIC in severe cases – Neonatal compromise – Maternal mortality < 1% MRI Placental Abruption Masselli et al. Radiology 259:222, 2011 Ananth et al. AJOG 272e2, 2016 Algorithm for Management After Dx of Amniotic Fluid Embolism Balinger et al. Curr Opin Obstet Gynec 27:398, 2015 PPH: French Guidelines Sentilhes et al; EJOG 198:12, 2016 Treatment Algorithm for DIC Management in Obstetric Syndromes Cunningham and Nelson Obstet Gynec 126:999, 2015 Prevention and Management of PPH Abdul-Kadir et al: Transfusion, 2014 Management of Severe Postpartum Hemorrhage • Uterine massage/uterotonics – Syntocinon – Ergometrine/Syntometrine – PGF2 alpha/Misoprostol • Interventional approaches – Uterine tamponade – B-lynch suture – Uterine artery/internal iliac artery embolization – Hysterectomy Su et al: Best Prac Clin Res Obstet Gyn, 2012 • Aggressive transfusion, platelet, coagulation factor replacement • Recombinant factor VIIa (rVIIa) Massive Transfusion in Obstetrical Bleeding Pacheco LD et al: Am J Perinatol, 2013 Burtelow M et al: Transfusion, 2007 rVIIa in Obstetrical Hemorrhage Leighton et al: Anesthesiology, 2011 Kobayashi et al: Int J Hematolol, 2012 Tranexamic Acid in Postpartum Hemorrhage TXA: 4 gm over 1 hour, then 1 gm/hr infusion, IV Ducloy-Bouthors et al: Crit Care, 2011 Tranexamic Acid in Pregnancies at High Risk for PPH Sujata et al IJOG, 2016 Effect of TA on Postpartum Blood Loss: Systematic Analysis Alam and Choi, Transf Med Rev 29:231-241, 2015 Case 2: VWD in Pregnancy • 32 yo woman with VWD • Menorrhagia • Epistaxis, once per year, usually in winter • Lab • PTT 36 sec (< 32 sec) • RCOF 31% (>35%) • CBA 42% (>41%) • VWF ag 44% (>50%) • All multimers reduced • Presents in week 28 of uncomplicated pregnancy Prophylaxis of Women with Inherited Bleeding Disorders Abdul-Kadir et al: Transfusion, 2014 Hemostatic Disorders in Pregnancy:vWD Sadler JE: JTH, 2006 Huq et al: Haemophilia, 2012 Castaman G: Med J Hematol Inf Dis, 2013 Treatment of VWD in Pregnancy James A. Hemophilia 21:81, 2015 Levels of VWF, Rcof and FVIII Postpartum James A, Hemophilia 21:81, 2015 Effect of Treatment on Levels of VWF, RCof and FVIII James A. Hemophilia 21:81, 2015 Management of Type I VWD at Delivery • Most patients achieve normal levels of VWF by mid second trimester • Vaginal or C-section is safe if RCof and FVIII levels are > 50% • DDAVP can be used in pregnancy if invasive procedures needed before increase in VWF • VWF levels begin to drop by day 3 and return to baseline by day 14— mean time at presentation for hemorrhage in VWF patients is 15.7 days • Patient should be counseled to consult physician at any sign of increased bleeding: treatment options include DDAVP, factor concentrates, tranexamic acid Neff and Sidonio. Am Soc Hematol Educ Prog 2014(1): 536-41 Summary • With respect to coagulation, pregnancy is a closely regulated state, disruption of which can cause profound derangement of hemostasis • The most common cause of post-partum bleeding is uterine atony • Placental abruption is a cytokine/SIRS driven process, in which profound DIC follows the initial insult and may lead to life- threatening hemorrhage • The normal increases in VWF during pregnancy in patients with Type I VWD are usually sufficient to enable safe delivery, but bleeding can occur in the post-partum period. .
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