Patient Blood Management for Massive Obstetric Hemorrhage
Patient Blood Management for Massive Obstetric Hemorrhage
Obstetric Hemorrhage continues to be the first cause of maternal morbidity and mortality
 around the world especially in middle to low income countriesThe blood components are high
 value resources; however, its use has been shown to be a risk factor of known complications.
 The aim of the study is to compare two algorithms of coagulation management in massive
 obstetric hemorrhage Methods A randomized prospective trial single center two arms study in
 patients with severe obstetric hemorrhage (PPH > 1000) 2 different transfusion protocols one
 guided by thromboelastometry and hemostatic drugs (protrombine complex concentrate and
 fibrinogen concentrate) and the second guided by standard coagulation test and
 hemocomponents. Sample is calculated to known variance, Analyses are intention-to-treat
 without imputation, with outcomes will be performed between groups using mixed-effects two
 level regression models. For binary outcomes, a logistic model will be used and results
 presented as adjusted odds ratios (ORs) alongside 95% confidence intervals (CIs). Count data
 will be analysed using Poisson multilevel or negative binomial models.

 Primary Outcome Parameter:

 Compare between the two protocols:

 Number of allogeneic blood products transfused intra-op, within 24h after screening and
 in-hospital (RBC, Platelets and FFP; separate and overall)

 Secondary Outcome Parameter:

 Analysis of mortality, lenth of stay admission to the ICU, hysterectomy surgical
 reintervencion, Transfuse associated circulatory overload, Transfusion associated Acute lung
 injury, health associated infection will be measured as secondary outcome.
Introduction Obstetric Hemorrhage continues to be the first cause of maternal morbidity and
 mortality around the world especially in middle to low income countries. Copying trauma
 transfusion therapies now a days algorithms have been developing for 2.1.1 transfusion in
 massive obstetric hemorrhage. Blood products, play an essential role in the management of
 these patients, either during resuscitation or definitive treatment. Early transfusion,
 defined as that required in the first 24 hours after admission, it is required in about 5%
 that enters the hospital and about 3% comes to require massive transfusion. The blood
 components are high value resources; however, its use has been shown to be a risk factor for
 infectious transfusion related immunomodulation, and noninfectious complications (TRALI,
 TACO), development of systemic inflammatory response, multiple organ failure and death. A
 liberal transfusion policy can further introduce the risk of a patient who is already
 committed.

 Patient blood management is an evidence-based, multidisciplinary approach to optimizing the
 care of patients who might need transfusion. PBM encompasses all aspects of patient
 evaluation and clinical management surrounding the transfusion decision-making process,
 including the application of appropriate indications, as well as minimization of blood loss
 and optimization of patient red cell mass.

 The aim of the study is to compare two algorithms of coagulation management in massive
 obstetric hemorrhage Methods A randomized prospective trial single center two arms study in
 patients with severe obstetric hemorrhage (PPH > 1000) 2 different transfusion protocols one
 guided by thromboelastometry and hemostatic drugs (protrombine complex concentrate and
 fibrinogen concentrate) and the second guided by standard coagulation test and
 hemocomponents.

 Randomization for the patients will be made for every obstetric patient that enters the
 obstetric ward for attention of partum, and will be asked to sign consent, and the patients
 will be selected for each group of the study. Only does that have severe PPH will be entering
 the protocol with the algorithm for management previously selected. Demographic
 caracteristics will include Ethnicity, Body weight (KG), body height (CM) and BMI at hospital
 admission, Previous deliveries, Previous Caesarean section, Pre-eclampsia during pregnancy,
 History of obstetric hemorrhage, History of other kind of hemorrhage, Onset of labor
 (spontaneous, induced, no labor) Multiple gestation (singleton, twins, triplet) Reported
 cause of obstetric hemorrhage (placenta previa, placenta accreta, placenta abruption,
 retained placenta, uterine atony, trauma, surgical bleeding Mode of delivery (spontaneous
 vaginal, instrumental vaginal , elective Caesarean section, non-elective Caesarean section)
 Baseline Hb, Hct, Plt count, Fibrinogen (Clauss), PT/INR, PTT (at hospital admission)
 Estimated blood loss at study entry (ML).

 Treatment algorithms are evidence based and the management of coagulopathy is based on treat
 first what kills fist (ATLS proposal)

 Group A:

 THROMBOELASTOMETRY-GUIDED ALGORITHM FIBRINOGEN CONCENTRATE FIBTEM A5 < 12 MM AND EXTEM A5 <
 40 MM FIBTEM A5 = 9-11 MM → 2 G FIBRINOGEN CONC. (25 MG/KG); FIBTEM A5 = 4-8 MM → 4 G
 FIBRINOGEN CONC. (50 MG/KG); FIBTEM A5 < 4 MM → 6 G FIBRINOGEN CONC. (75 MG/KG) GOAL: FIBTEM
 A5: 12-16 MM PLATELETS EXTEM A5 < 40 MM AND FIBTEM A5 ≥ 12 MM EXTEM A5 < 40 MM → 1 PLATELET
 POOL OR APHERESIS; EXTEM A5 < 30 MM → 2 PLATELET POOL OR APHERESIS GOAL: EXTEM A5: 40-50 MM
 PROTROMBIN COMPLEX CONCENTRATE EXTEM CT > 80 SEC AND FIBTEM A5 ≥ 8 MM 4F-PCC 20 IU/KG (F II,
 VII, IX and X) GOAL: EXTEM CT ≤ 80 SEC NO INTERVENTION FIBTEM A5 ≥ 12 MM AND EXTEM A5 ≥ 40 MM
 AND EXTEM CT > 80 SEC NO FIBRINOGEN, CRYO, PLATELETS, 4-PCC, FFP; TRANSFUSE RBC IF Hb < 7
 G/DL GOAL: Hb > 7.5 G/DL

 Group B RATIO / STANDRAD LAB TEST-GUIDED ALGORITHM CRYOPRECIPITATE FIBRINOGEN (CLAUSS) < 250
 MG/DL FIB 200-250 MG/DL → CRYOS, PACK OF 10 (25 MG/KG); FIB 100-200 MG/DL → CRYOS, PACK OF 20
 (50 MG/KG); FIB < 100 MG/DL → CRYOS, PACK OF 30 (75 MG/KG) GOAL: FIB > 250 MG/DL PLATELETS
 PLATELET COUNT < 100/µL PLT < 100/µL → 1 PLATELET POOL OR APHERESIS; PLT > 50/µL → 2 PLATELET
 POOL OR APHERESIS GOAL: PLT COUNT > 100/µL FRESH FROZEN PLASMA TP AND/OR TTP PATHOLOGICAL
 INR, 2.0-4.0 → FFP 20 ML/KG GOAL: TP AND TTP NORMAL AND INR < 2.0 NO LAB RESULTS AVAILABLE
 TRANSFUSE RED BLOOD CELLS IF Hb < 7 G/DL; GIVE 1 UNIT FFP EVERY 2 UNITS OF RBC TRANSFUSED
 GOAL: Hb > 7.5 G/DL Statistical analysis Sample is calculated to known variance. The
 investigators calculated that 100 women will be needed to provide 80% power at the two-sided
 5% level to detect a difference of total allogeneic units between groups. With a total of 100
 patients 50 in each arm, with a first revision of results after recruiting 50 patients (25 in
 each arm). Analyses are intention-to-treat without imputation, with outcomes will be
 performed between groups using mixed-effects two level regression models. For binary
 outcomes, a logistic model will be used and results presented as adjusted odds ratios (ORs)
 alongside 95% confidence intervals (CIs). For continuous outcomes, a linear regression model
 will be performed and results presented as difference in adjusted means (arm A vs arm B)
 alongside 95% CIs. Count data will be analysed using Poisson multilevel or negative binomial
 models if over-dispersion is evident and presented as incident rate ratios (IRRs).

 Objectives

 Primary Outcome Parameter:

 Compare between the two protocols:

 Number of allogeneic blood products transfused intra-op, within 24h after screening and
 in-hospital (RBC, Platelets and FFP; separate and overall)

 Secondary Outcome Parameter:

 Compare between the two arms Number of packs of Cryo (pack of 5 ~ 1 G Fibrinogen), Fibrinogen
 Concentrate (G), and PCC (500 UI) administered intra-op, within 24h after screening and
 in-hospital Incidence ≥ 5 U RBC transfused (first 24h after screening) Incidence ≥ 10 U RBC
 transfused (first 24h after screening) Incidence of RBC, Platelets, FFP, Cryo, Fibrinogen
 Concentrate, and PCC transfusion/administration (intra-op, first 24h and in-hospital) Total
 volume of blood products and coagulation factor concentrates transfused/administered
 (intra-op, first 24h and in-hospital) Infusion: Crystalloid (ML) and Colloids (Type; ML)
 intra-op and within 24h after screening Overall estimated blood loss (EBL, ML) Time to
 bleeding control (time from study entry to last hemostatic intervention/transfusion)
 Incidence of coagulopathy (detected by thromboelastometry or standard coagulation laboratory
 tests) Incidence of hysterectomy Incidence of re-surgery Incidence of TACO Incidence of TRALI
 Incidence of surgical site infection or sepsis Incidence of ICU admission Length of stay
 (LOS) at ICU and hospital In-hospital mortality First post-op Hb, Hct, Plt count, Fibrinogen
 (Clauss), PT, INR, PTT (recovery room or ICU) Last Hb, Hct, Plt count, Fibrinogen (Clauss),
 PT, INR, PTT before discharge from hospital Total acquisition costs of allogeneic blood
 products and coagulation factor concentrates HYPOTHESIS. The algorithm guided by ROTEM plus
 the use of hemostatic drugs, are more efficient for the reversion of coagulopathy due to
 obstetric hemorrhage, than the standard treatment group, decrases the risk of development
 known complications, decreases the need of blood transfusions, decreases morbidity and
 mortality associated to PPH, length of stay, admissions to the intensive care unit and days
 of mechanical ventilation. Without a significant increase in costs.

 RELEVANCE AND EXPECTATIONS To offer a safe alternative in the treatment of severe obstetric
 hemorrhage, which reduces the risk of transfusion associated complications,
Inclusion Criteria:

 Patients with severe obstetric hemorrhage of any cause

 Exclusion Criteria:

 obstetric hemorrhage patients derived from other hospitals Patients with less than 1000 ml
 of estimated blood loss those who do not want to participate in the study