Postpartum Hemorrhage: Evaluation, Management and Pearls Annie Siewert, MD MS FACOG South Dakota Perinatal Association Annual Meeting. September 22, 2017

Objectives: Identify stages of postpartum hemorrhage Discuss new treatment techniques for postpartum hemorrhage Management of stages of postpartum hemorrhage

PPH: Who is at Risk? Risk Factors History of PPH Asian or Hispanic ethnicity Overdistended uterus Twins, macrosomnia, polyhydraminos Preeclampsia Prolonged labor Augmented labor Rapid labor Episiotomy Especially mediolateral Operative delivery Chorioamnionitis

Situational Awareness: Assessing the Risk on Admission Low Risk: Type and Screen Recommended; BB Hold (Minimum) No prior uterine incision Singleton <4 Vaginal deliveries No history of PPH No bleeding disorder. Negative Antibody screen on PN lab

Situational Awareness: Assessing the Risk on Admission Prior C/S or uterine surgery Multiple gestations >4 vaginal deliveries H/O PPH Large uterine fibroids EFW> 4k BMI>35 Medium Risk: Type and Screen

Situational Awareness: Assessing the risk on admission High Risk: Type and Cross for 2 U PRBCs Placenta Previa, Low-lying placenta Suspected Accreta/Increta/Percreta Hct<30 AND other RF Plt < 100k Active Bleeding Known Coagulopathy

Situational Awareness: Assessing the Risk Prolonged 2nd stage Prolonged Oxytocin use Active bleeding Chorioamnionitis Magnesium Sulfate treatment On-going Risk Assessment:

Postpartum Hemorrhage Causes Uterine atony Retained Placenta Lacerations Abnormal placentation Other

PPH: Definition Vaginal Delivery Cesarean section Decline in Hct by 500cc Cesarean section 1000cc Decline in Hct by 10% Vital sign changes Tachycardia Hypotension Oliguria

Visual Estimates of PPH UpToDate. 2015. Management of Postpartum Hemorrhage at Vaginal Delivery

PPH: Definition of Unstable VS HR > 110 BP < 85/45 O2 Sat < 95% VS >15% change

Postpartum Hemorrhage Management Prevention Conservative Measures Medications Surgical Measures

PPH Management PREVENTION!

Active Management of the Third Stage After delivery of anterior shoulder Has not been shown to increase retained placenta Oxytocin 30 mU in 500 cc @ 250cc q hr X 2 hrs IV or 10 U IM DO NOT PULL TOO HARD Decreases risk of retained placenta Gentle cord traction/ Controlled Traction (+/-) Cord clamping within 1-3 minutes of delivery. Fundal Massage.

Active Management of the Third Stage 2015 Cochrane Review Defined active management as uterotonic administration, early cord clamping, cord traction. 7 studies, 8247 woman Decreased risk of 1˚ PPH with RR 0.34-0.87 Significant decrease in EBL>500cc, transfusion, use of uterotonics in third stage Also demonstrated decreased birth weight and increases in maternal diastolic BP, vomiting, pain, use of pain meds, Begley, et al. Active versus expectant management for women in third stage of labour. The Cochrane Collaboration. 2015.

Active Management of the Third Stage Controlled Cord Traction 2015 Cochrane Review No difference in amount of blood loss ≥1000cc Decreased risk of manual placental removal Decreased risk of blood loss ≥500cc (10cc!) No change in uterotonic administration, transfusion, morbidity, operative procedures. Duration of Third Stage Secondary analysis of 7,121 women at Washington Univ Mean duration of 3rd stage: 5.46 90%ile: 9 min, 95%ile: 13 min, 99%ile: 28 min 3rd stage > 90%ile had increased risk of PPH: 13.2% vs 8.3% PPH risk increases after 20 min (15.9% vs 8.5%) Hofmeyr, et al. Controlled Cord Traction for the third stage of labor. The Cochrane Collaboration. 2015. Frolova, et al. Duration of Third Stage of Labor and Risk of Postpartum Hemorrhage. Obstet Gynecol. 2016.

Conservative Measures PPH Management Conservative Measures Call for help Examine patient Empty bladder Bimanual massage Manual evacuation of uterus

Bimanual massage

Manual Exam of the Uterus Conservative Measures MEU Manual Exam of the Uterus It’s cheap. It’s effective! It can hurt.

Conservative Measures Population based cohort study patients with PPH due to atony after SVD in 106 hospitals aimed at studying factors contributing to severe PPH Factors independently associated with severe PPH Delay call for help had a 1.6x higher risk for severe PPH Oxytocin started late or not at all in 24.5% with PPH PPH risk 1.4X higher in women when oxytocin was started 10-20 min after PPH diagnosis, and almost 2X higher if started greater than 20 min MEU was late or not done in 33.2 % PPH risk 1.8X higher when MEU performed >20 min after diagnosis Driessen, et al. Postpartum Hemorrhage Resulting from Uterine Atony after Vaginal Delivery. Obstet Gynecol. 2011.

PPH Management Medications Uterotonics Tranexamic acid Recombinant Factor VIIa

PPH Medications: Uterotonics Drug* Dose/Route Frequency Comment Oxytocin (Pitocin) IV: 10–40 units in 1 liter normal saline or lactated Ringer's solution IM: 10 units Continuous Avoid undiluted rapid IV infusion, which causes hypotension. Methylergonovine (Methergine) IM: 0.2 mg Every 2–4 h Avoid if patient is hypertensive. 15-methyl PGF2α (Carboprost) (Hemabate) IM: 0.25 mg Every 15–90 min, 8 doses maximum Avoid in asthmatic patients; relative contraindication if hepatic, renal, and cardiac disease. Diarrhea, fever, tachycardia can occur. Dinoprostone (Prostin E2) Suppository: vaginal or rectal 20 mg Every 2 h Avoid if patient is hypotensive. Fever is common. Stored frozen, it must be thawed to room temperature. Misoprostol (Cytotec, PGE1) 800–1,000 mcg rectally

PPH Medications Tranexamic acid and Factory VIIa

PPH Medications Tranexamic Acid (TXA) Inhibits ability of plasmin to form fibrin degradation productions Inhibition of fibrinolysis Half life: 2 hours Metabolized by kidney TXA

PPH Medications: Tranexamic Acid (TXA) OB hemorrhage results in increased fibrinolytic activity Placental disruption leads to increase in tPA Increased D-dimer levels postpartum increase fibrinolytic activity

PPH Medications: Tranexamic Acid (TXA) Endothelial injury or hypoperfusion secondary to trauma Increased tPA Decreased tPA inhibition by protein C activation from thrombin-thrombomodulin interaction TXA Plasminogen activates plasmin=fibin degradation and bleeding Increased D-dimer and fibrin degradation products Adapted from Pacheco. Obstet Gynecol. 2017

PPH Medications: Tranexamic Acid (TXA) CRASH-2 trial RCT in trauma TXA given within 3 hours of trauma decreased mortality TXA given ≥ 3 hours after event did not improve outcome or survival TXA administration is also standard of care in cardiac surgery and ortho CRASH-2 trial collaborators. Effects of Tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage. (CRASH-2): a randomized placebo controlled trial. Lancet. 2010; 376: 23-32.

PPH Medications: Tranexamic Acid (TXA) WOMAN trial Effects of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with postpartum hemorrhage (WOMAN): an international, randomized, double-blind, placebo controlled trial. Lancet May 2017. 20,060 woman with diagnosed PPH enrolled from 193 hospitals in 21 countries Significant decrease in death due to bleeding Hysterectomy rates did not change Death from all causes did not decrease No increase in adverse outcomes with TXA (ie VTE) WOMAN trial collaborators. Effects of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with postpartum hemorrhage (WOMAN): an international, randomized, double-blind, placebo controlled trial. Lancet May 2017

PPH Medications: TXA Tranexamic Acid for the Management of Obstetric Hemorrhage. Current Commentary. Obstet. Gynecology. PAP 2017. Diagnosed PPH TXA 1g IV within 3 hours of delivery If continued bleeding, administer second dose within 24 hours Dose not to exceed 2g in 24 hours Risk of renal cortical necrosis Seizure PPH Prophylaxis May be prior to delivery given to patients with hemophilia, vWD and platelet disorders. Can also be given postpartum to prevent bleeding 1g po TID Insufficient evidence to give for primary prevention Does cross placenta and is found in breast milk, but no adverse neonatal outcomes have been demonstrated. Pacheco et al. Tranexamic Acid for the Management of Obstetric Hemorrhage. Current Commentary. Obstet. Gynecology. PAP Sept 15 2017.

PPH Medications: Recombinant Factor VIIa Vitamin K-dependent glycoprotein, promotes hemostasis by activating the extrinsic pathway of the coagulation cascade. It replaces deficient activated coagulation factor VII allowing conversion of Factor X When complexed with other factors, coagulation factor Xa converts prothrombin to thrombin, a key step in the formation of a fibrin-platelet hemostatic plug

PPH Medications: Recombinant Factor VIIa Administration can cause improvement in up to 80% PPH patients Low risk of adverse outcomes Quality evidence is still lacking Very expensive! Cost between 9,000-18,000 depending on patient’s weight and how many doses needed Alfirevic et al. Use of Recombinant Activated Factor VII in Primary Postpartum Hemorrhage. Obstet. Gynecol. 2007; 110: 1270-8.

PPH Management Surgical Measures D&C Bakri balloon Uterine Artery Embolization Exploratory laparotomy B-Lynch suture O’Leary stitch Hysterectomy

Ultrasound diagnosis of Retained POCs

Surgical Measures: Bakri Balloon Fill to 300-500cc Sterile Saline Antibiotics Leave in 12-24 hours No need for slow release of pressure

Surgical Management: Uterine Artery Embolization Case review study demonstrated UAE successful in 89.6% of patients Adverse outcomes Fertility rate 70-80% No increased risk of IUGR Higher risk of abnormal placentation Patient MUST be stable! Labarta et al. Eur J of Obstet Gynecol and Reprod Bio. 206; Nov 2016. 12-21. Soro et al. Eur Radiol. 2017 Feb; 27(2): 749-762.

PPH: Surgical Measures

B-Lynch Suture

Blood Component Therapy PPH Management Blood Component Therapy

Blood Component Therapy Product Volume (mL) Contents Effect (per unit) Packed red cells 240 Red blood cells, white blood cells, plasma Increase HCT 3%, Hb by 1 g/dL Platelets 50 Platelets, red blood cells, white blood cells, plasma Increase platelet count 5,000–10,000/mm3 per unit Fresh frozen plasma 250 Fibrinogen, antithrombin III, factors V and VIII Increase fibrinogen by 10 mg/dL Cryoprecipitate 40 Fibrinogen, factors VIII and XIII, von Willebrand factor

Massive Transfusion Protocols Purpose: Structured system-wide process for early and efficient delivery of specific ratios of blood product, 4 U PRBCs/4U FFP/ 1 Aphoresis pack PLT

PPH Management Stages of PPH Stage 1 Stage 2 Stage 3

PPH Stages Stage 1 EBL>500cc vaginal or > 1000cc cs Stage 2 Continued bleeding or Unstable VS or EBL > 1500 cc Stage 3 EBL>1500cc, > 2U PRBCs given, unstable vs or Suspect DIC

STAGE I Hemorrhage: EBL>500cc vaginal or > 1000cc cs IV access On-going assessment: ARE VS UNSTABLE?? Calculating blood loss TYPE and CROSS (if BB Hold, will delay 20-30 minutes) Keep patient warm and oxygenated Place a foley Nursing interventions Find cause for bleeding MANUAL EXAM OF UTERUS: if you cannot reach the fundus, CALL LABORIST Give medications TYPE and CROSS ARE VS UNSTABLE???: MD/CNMW

Stage I Hemorrhage: Medications Methergine 0.2 mg IM Usually first line—onset action within 5 minutes Contraindicated with HTN Little or no response to 1st dose then MOVE ON Hemeabate 0.25 mg IM Usually works within 2 doses Contraindicated in ASTHMA/HTN** No response after the 2nd dose then MOVE ON Cytotec 800-1000 mcg pr Onset of action usually 30-60 minutes PR SL dose 400mcg-600mcg onset within 11 minutes

STAGE 2: Continued bleeding or Unstable VS or EBL > 1500 cc D&C, Laceration repair Bakri Balloon Interventional radiology Vaginal Delivery B-Lynch O’Leary stitches Uterine/internal iliac ligation Bakri Balloon placement Cesarean Section

STAGE 2: Continued bleeding or Unstable VS or EBL > 1500 cc Request Laborist/OB consult if not present Move patient to OR Notify Anesthesia Nursing interventions Move to OR Continued uterotonic use Request anesthesia 1500 CC EBL with ongoing bleeding---Start transfusing (do not wait for lab results) MD/CNM interventions

Stage 3: EBL>1500cc, > 2U PRBCs given, unstable VS or Suspect DIC Continued monitoring of EBL SUGGEST MTP activation Manage activation of MTP Nursing interventions: Consider CVP or Art line Manage Blood products Anesthesia interventions

Stage 3: EBL>1500cc, > 2U PRBCs given, unstable VS or Suspect DIC MTP activation Call in back-up OR Gyn Onc Transfuse 2 U FFP Keep transfusion ration 4:4:1 (PRBCS:FFP:PLT) Laparotomy/Gyn Onc B-Lynch Uterine/ internal iliac artery ligation Hysterectomy OB MD interventions

Resources UpToDate. 2015. Management of Postpartum Hemorrhage at Vaginal Delivery Begley, et al. Active versus expectant management for women in third stage of labour. The Cochrane Collaboration. 2015. Hofmeyr, et al. Controlled Cord Traction for the third stage of labor. The Cochrane Collaboration. 2015. Frolova, et al. Duration of Third Stage of Labor and Risk of Postpartum Hemorrhage. Obstet Gynecol. 2016 Driessen, et al. Postpartum Hemorrhage Resulting from Uterine Atony after Vaginal Delivery. Obstet Gynecol. 2011. CRASH-2 trial collaborators. Effects of Tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant hemorrhage. (CRASH-2): a randomized placebo controlled trial. Lancet. 2010; 376: 23-32. WOMAN trial collaborators. Effects of early tranexamic acid administration on mortality, hysterectomy, and other morbidities in women with postpartum hemorrhage (WOMAN): an international, randomized, double-blind, placebo controlled trial. Lancet May 2017 Pacheco et al. Tranexamic Acid for the Management of Obstetric Hemorrhage. Current Commentary. Obstet. Gynecology. PAP Sept 15 2017. Alfirevic et al. Use of Recombinant Activated Factor VII in Primary Postpartum Hemorrhage. Obstet. Gynecol. 2007; 110: 1270-8. Labarta et al. Eur J of Obstet Gynecol and Reprod Bio. 206; Nov 2016. 12-21. Soro et al. Eur Radiol. 2017 Feb; 27(2): 749-762. California Maternal Quality Care Collaborative ACOG Practice Bulletin No. 76 Postpartum Hemorrhage

PPH: Definition Primary Secondary or Delayed Occurring within first 24 hours Atony Retained placenta Coagulation problems Uterine inversion Secondary or Delayed Occurring >24 hours Subinvolution Retained POCs Infection Inherited coagulation defects