Management of Obstetrical Hemorrhage
BS. Nguyễn Hồng Anh
Recognition o obstetrical hemorrhage severity is crucial to its management. However, visual estimates, especially when bloo losses are excessive, are notoriously inaccurate. In many cases, true volume losses are oten two to three times the clinical estimate. Moreover, in obstetrics, part an sometimes even all o the lost bloo may be conceale. Estimation is urther complicate in that peripartum hemorrhage also inclues the pregnancy-augmente bloo volume. Ater pregnancy hypervolemia is lost at elivery, bloo loss can be estimate by calculating 500 mL loss or each 3 volume percent rop in hematocrit. Its nair epens on the spee o resuscitation with intravenous crystallois an bloo proucts. With ongoing blood loss, the real-time hematocrit is at its maximum whenever measured in the delivery, operating, or recovery room. Pruently, i bloo loss is consiere more than average, the hematocrit is etermine, an plans are mae or close observation or potential physiological eterioration. Bloo loss etermination as recommene by the American College o Obstetricians an Gynecologists (2019b) is iscusse in etail in Chapter 42. Urine output measure hourly is one o the most important “vital signs.” Unless diuretic agents are given— and these are seldom indicated with active bleeding—accurately measured urine ow reects renal perusion. Tis in turn reects perusion o other vital organs. Te volume o urine output shoul be ≥30 mL/hr an preerably ≥50 mL/hr
Another important actor to consier with management o hemorrhage is whether there are aequate procoagulants to achieve clot ormation an stability. Many cases o severe obstetrical hemorrhage are urther complicate by isseminate intravascular coagulation (DIC), in which bloo has ysunctional coagulation (p. 775).
MANAGEMENT OF HEMORRHAGE
■ Hypovolemic Shock
Shock rom hemorrhage evolves through several stages (Cannon, 2018). Early, the mean arterial pressure, stroke volume, cariac output, central venous pressure, an pulmonary capillary wege pressure ecline. Greater ierences in arteriovenous oxygen content values reect enhance tissue oxygen extraction, although overall oxygen consumption alls. Bloo ow to capillary bes is controlle by arterioles, which are resistance vessels an partially controlle by the central nervous system (CNS). However, approximately 70 percent o total bloo volume is containe in venules, which are passive resistance vessels controlle by humoral actors. Tus, the catecholamine release uring hemorrhage prompts greater venular tone, an this provies an autotransusion rom this capacitance reservoir. Tis volume boost is accompanie by compensatory rises in heart rate, systemic an pulmonary vascular resistance, an myocarial contractility. At the same time, selective, CNS-meiate arteriolar constriction or relaxation, terme autoregulation, preerentially reistributes cariac output an bloo volume. Tus, more bloo ow is iverte to the heart, brain, an arenal glans, whereas perusion to the kineys, splanchnic bes, muscles, skin, an uterus is relatively iminishe.
When the bloo volume ecit excees approximately 25 percent, compensatory mechanisms usually are inaequate to maintain cariac output an bloo pressure. Importantly, aitional small losses o bloo will now cause rapi clinical eterioration. Following an initial augmente total oxygen extraction by maternal tissue, malistribution o bloo ow results in local tissue hypoxia an metabolic aciosis. Tis creates a vicious cycle o vasoconstriction, organ ischemia, an cellular eath.
Hemorrhage also activates lymphocytes an monocytes, which in turn prompts enothelial cell activation an platelet aggregation (Cannon, 2018). Tis enotheliopathy promotes release o vasoactive meiators that occlue small vessels an urther impair microcirculatory perusion. Comorbi preeclampsia or sepsis also leas to loss o capillary enothelial integrity, aitional loss o intravascular volume into the extracellular space, an platelet aggregation. Tese then can incite DIC.
Te pathophysiological events just escribe create important but oten overlooke extracellular ui an electrolyte shits involve in both the genesis an successul treatment o hypovolemic shock. Tese inclue changes in the cellular transport o various ions such as soium an water into skeletal muscle as well as potassium loss. Replacement o extracellular ui an intravascular volume are both necessary. Patient survival rates are enhance in acute hemorrhagic shock i bloo plus crystalloi solution are given compare with bloo trans- usions alone.
■ Fluid Resuscitation
Whenever excessive bloo loss is suspecte, steps are simultaneously taken to ientiy the bleeing source an to begin resuscitation. Reer to the algorithm or hemorrhage management (Fig. 42-3, p. 735). I the woman is unelivere, restoration o bloo volume benets both mother an etus. It also prepares or emergent elivery. I she is postpartum, immeiately ientiying uterine atony, retaine placental ragments, or genital tract lacerations is essential. One or two large-bore intravenous inusion systems are ieally establishe promptly, crystalloi solutions are rapily inuse, an bloo proucts are orere.
An operating room is reaie, an a surgical an anesthesia team are quickly assemble. Specic management o hemorrhage is urther epenent on its etiology. A neonatal resuscitation team is inclue i imminent elivery is planne.
Serious hemorrhage emans prompt an aequate relling o the intravascular compartment with crystalloi solutions. Tese rapily equilibrate into the extravascular space, an only 20 percent o crystalloi remains intravascular in critically ill patients ater 1 hour (Zuckerbraun, 2010). Because o this, initial uid is inused in a volume two to three times the estimated blood loss.
Crystalloid Versus Colloid Solutions
Resuscitation o hypovolemic shock with colloi versus crystalloi solutions has been ebate. In a Cochrane review o resuscitation o nonpregnant critically ill patients, Lewis an coworkers (2018) oun selection o collois versus crystallois probably makes little or no ierence to mortality rates. Similar results were oun in the Saline versus Albumin Flui Evaluation (SAFE) ranomize trial o almost 7000 nonpregnant patients (Finer, 2004). At Parklan Hospital, acute volume resuscitation is preerably one with crystalloi solutions an bloo.
Either a saline-base or a balance crystalloi solution may be inuse. Te latter inclues Ringer lactate an PlasmaLyte solutions, which have electrolyte compositions similar to plasma. In some stuies, but not in all, balance crystalloi solutions were oun to be superior to saline-base ones (Semler, 2018; Yule, 2020). Excessive saline-base crystalloi solution can theoretically lea to hyperchloremic aciosis. In comparisons, the ifculty lies in separating the eects o the unerlying pathophysiology riving the aciosis.
■ Blood Replacement
Type and Screen Versus Crossmatch
A bloo type an antiboy screen shoul be perorme or any woman at signicant risk or hemorrhage. Because preiction o women at risk or postpartum hemorrhage is poor, we per- orm type an screen in all women upon amission to labor an elivery. Screening involves mixing maternal serum with stanar reagent re cells that carry antigens to which most o the common clinically signicant antiboies react. Instea, crossmatching involves the use o actual onor erythrocytes rather than the stanarize re cells. Tis process is efcient, an only 0.03 to 0.07 percent o patients ientie as having no antiboies are subsequently oun to them (Boral, 1979). Importantly, administration o screened blood rarely results in adverse clinical sequelae.
Transfusion Thresholds
Te hematocrit level or hemoglobin concentration threshol that manates bloo transusion is controversial (Bienstock, 2021). Cariac output oes not substantively rop until the hemoglobin concentration alls to approximately 7 g/L or when the hematocrit approximates 20 volume percent. Military combat trauma units have use a target hematocrit o 21 volume percent, an at this level, most experts recommen consieration o re cell transusion (Carson, 2017; Kogutt, 2019). In general, with ongoing obstetrical hemorrhage, we recommen rapi bloo inusion when the hematocrit is <25 volume percent. Other ecisionmoiying actors are whether the etus is unelivere; surgery is imminent or ongoing operative bloo loss is expecte; or maternal hypoxia, vascular collapse, or other actors are present. Limite ata aress these issues. In a stuy rom the Cana- ian Critical Care rials Group, nonpregnant patients were ranomly assigne to restrictive re cell transusions to maintain hemoglobin concentration >7 g/L or to liberal transusions to maintain the hemoglobin level at 10 to 12 g/L. Te 30-ay mortality rate was similar—19 versus 23 percent—in the restrictive versus liberal groups, respectively (Hébert, 1999). ransusion therapy in nonpregnant patients with septic shock ha similar mortality rates when 7 g/L was compare with 9 g/L as targets or transusions (Holst, 2014). Te number o units transused in a given woman to reach a target hematocrit depends on her body mass and on the expectations o additional blood loss.
Blood Component Products
Te content an eects o transusion o various bloo components are shown in Table 44-1. Because whole bloo is rarely available, most women with obstetrical hemorrhage an ongoing massive bloo loss are given packe re cells, crystalloi solutions, an bloo components. As subsequently iscusse, many institutions use massive transusion protocols (MPs) esigne to anticipate all acets o massive obstetrical hemorrhage. Tese protocols commonly contain plasma, cryoprecipitate, an platelets in various ratios (Cunningham, 2015; Shiels, 2011).
Several stuies have assesse plasma:re cell ratios with MPs use in civilian trauma units an military combat hospitals (Har- in, 2014; Rahouma, 2018). Patients receiving a massive transusion—ene as 10 or more units o bloo—ha much higher survival rates as the ratio o plasma to re cell units neare 1:1.4, that is, one unit o plasma given or each 1.4 units o packe re cells. By way o contrast, the highest mortality group ha a ratio o 1:8.
From the oregoing, when re cell replacement excees ve units or so, evaluation o platelet count, clotting stuies, an plasma brinogen concentration is reasonable (Bienstock, 2021; Pacheco, 2019). In the woman with obstetrical hemorrhage, the platelet count shoul be maintaine >50,000/µL by the inusion o platelet concentrates. A brinogen level <150 mg/L or a sufciently prolonge P or P in a woman with surgical bleeing is an inication or replacement. Fresh-rozen plasma is aministere in oses o 10 to 15 mL/kg, or alternatively, cryoprecipitate is inuse (see able 44-1).
At Parklan Hospital, we use a stanarize response to active hemorrhage. I whole bloo is not available, the ollowing escalation o bloo proucts is applie: 2 units packe re bloo cells, an i continue bleeing, 2 units packe re bloo cells an 2 units resh-rozen plasma are automatically orere. Beyon this, MP is initiate.
Whole Blood and Packed Red Blood Cells
Compatible whole bloo is ieal or management o severe obstetrical hemorrhage. It has a shel lie o 40 ays, an 70 percent o the transuse re cells unction or at least 24 hours ollowing transusion. One unit raises the hematocrit by 3 to 4 volume percent. Important or obstetrical hemorrhage, whole bloo replaces many coagulation actors neee in obstetrics— especially brinogen—an its plasma treats hypovolemia. A collateral erivative is that women with severe hemorrhage are resuscitate with ewer bloo onor exposures than with packe re cells an components.
Experience at Parklan Hospital supports the preerable use o whole bloo or massive hemorrhage (Alexaner, 2009; Hernanez, 2012). O more than 66,000 eliveries, women with obstetrical hemorrhage treate with whole bloo ha signicantly lower inciences o severe maternal morbiity that inclue renal ailure, acute respiratory istress synrome, pulmonary eema, hypobrinogenemia, intensive care unit amissions, or maternal eath compare with those given packe re cells an component therapy. One unit o packe erythrocytes is erive rom one unit o whole bloo to have a hematocrit o 55 to 80 volume percent. One unit will increase the hematocrit by 3 to 4 volume percent epening on the size o the woman.
Dilutional Coagulopathy
A major rawback o massive hemorrhage treatment with crystalloi solutions an packe re bloo cells is epletion o platelets an clotting actors. Discusse later, this can lea to a ilutional coagulopathy that is clinically inistinguishable rom DIC (Cunningham, 2015; Hossain, 2013). Trombocytopenia is the most requent coagulation eect oun with bloo loss an multiple transusions. In aition, packe re cells have only very small amounts o soluble clotting actors, an store whole bloo is ecient in platelets an in actors V, VIII, an XI. Tus, hypofbrinogenemia an prolongation o the prothrombin (P) an partial thromboplastin times (P) are other sequelae. Because many causes o obstetrical hemorrhage also cause DIC, the istinction between ilutional an consumptive coagulopathy can be conusing. Fortunately, treatment or both is similar.
Platelets
Platelet transusions are consiere with ongoing obstetrical hemorrhage i the platelet count alls below 50,000/µL (Kenny, 2015). In the nonsurgical patient, bleeing is rarely encountere i the platelet count is 10,000/µL or higher (Murphy, 2010). Te preerable source o platelets is one “bag” obtaine by single-onor apheresis. Tis contains the equivalent o one unit each rom six iniviual onors. Depening on maternal size, each single-onor-apheresis, six-unit bag raises the platelet count by approximately 20,000/µL. I these bags are not available, then iniviual-onor platelet units are use, an six to eight such units are generally transuse.
Importantly, the onor plasma in platelet units must be compatible with recipient erythrocytes. Further, because some re bloo cells are invariably transuse along with the platelets, only units rom D-negative onors shoul be given to D-negative recipients.
Fresh-frozen Plasma
Tis component is prepare by separating plasma rom whole bloo an then reezing it. Approximately 30 minutes are require or rozen plasma to thaw. It is a source o all stable an labile clotting actors, incluing brinogen. Tus, it is oten use or treatment o women with consumptive or ilutional coagulopathy. Plasma is not a suitable volume expander in the absence o specifc clotting actor defciencies. It is consiere in a bleeing woman with a brinogen level <150 mg/L or with an abnormal P or P.
An alternative to rozen plasma is liquid plasma (LQP). Tis never-rozen plasma is store at 1 to 60 C or up to 40 ays, an its use compares avorably with resh-rozen plasma (Backholer, 2017). Liqui plasma is not universally available in many centers.
Cryoprecipitate and Fibrinogen Concentrate
Each unit o cryoprecipitate is prepare rom one unit o resh-rozen plasma. Each 10- to 15-mL unit contains at least 200 mg o brinogen along with actor VIII:C, actor VIII:von Willebran actor, actor XIII, an bronectin (American Association o Bloo Banks, 2017). It is usually given as a “pool” or “bag” using an aliquot o brinogen concentrate taken rom 8 to 120 onors. Cryoprecipitate is an ieal source o brinogen when levels are angerously low an surgical incisions show oozing. Because o transit time, the return o cryoprecipitate to transusion services is oten not easible an is consiere wastage i not eploye. Nearly 17 percent o orere cryoprecipitate has been reporte to be waste in labor an elivery units, an this is the most commonly waste prouct (Yee, 2019).
Another alternative is virus-inactivate brinogen concentrate (Ng, 2020). Tese poole brinogen proucts are markete as RiaSAP an Fibryna. Each gram o concentrate raises the plasma brinogen level approximately 40 mg/L. Tese concentrates are use to treat congenital hypobrinogenemia synromes.
Recombinant Activated Factor VII
Tis synthetic vitamin K–epenent protein is available as NovoSeven. Recombinant activate actor VII (rFVIIa) bins to expose tissue actor at the injury site to generate thrombin that activates platelets an the coagulation cascae. Since its introuction, rFVIIa has been use to help control hemorrhage rom surgery, trauma, an obstetrical causes (Goonough, 2016; Murakami, 2015). Many Level I trauma centers inclue it in MPs. Importantly, rFVIIa will not be eective i the plasma brinogen level is <50 mg/L or the platelet count is <30,000/µL.
One concern with rFVIIa is associate arterial—an to a lesser egree—venous thrombosis. In a review o 35 ranomize trials, arterial thromboembolism evelope in 55 percent (Levi, 2010). A secon concern is that it has been oun to have only marginal efcacy (Pacheco, 2019).
Tranexamic Acid
Normally, plasminogen bins with tissue plasminogen activator (tPA) to orm plasmin. Tis bining egraes brin into brinogen–brin egraation proucts an leas to clot lysis. Instea, tranexamic aci (XA) reversibly bins to plasminogen, an thereby blocks plasmin bining to brin. Fibrin strans are not broken, an a clot persists to slow own bleeing.
Ahmazia an coworkers (2021) recently reporte the pharmacoynamics o XA at cesarean elivery using rotational thromboelastometry. XA inhibite tPA-inuce clot lysis in a ose-epenent manner. In the ranomize WOMAN trial o gravias with hemorrhage ollowing vaginal birth or uring cesarean elivery, mortality rates rom obstetrical hemorrhage were 1.2 percent in those given a 1-g intravenous XA ose plus traitional care or bleeing. Tis rate was statistically lower than the 1.7-percent eath rate in women given traitional care alone (WOMAN rial Collaborators, 2017). Te trial was carrie out in eveloping nations an because o the results, the rug is recommene by the Worl Health Organization (2017). In a large ranomize trial o tranexamic aci given or prophylaxis, the rug i not ecrease the rate o postpartum hemorrhage ollowing vaginal elivery (Sentilhes, 2018). In the ranexamic Aci or Preventing Postpartum Hemorrhage Following a Cesarean Delivery—RAAP2 trial—women unergoing cesarean elivery who were given tranexamic aci prophylaxis ha a lower incience o re-cell transusions (Sentilhes, 2021).
Gayet-Ageron an coworkers (2018) conucte a metaanalysis with more than 1000 patients with postpartum hemorrhage treate with XA. Tey also analyze ata rom two ranomize trials that inclue more than 40,000 women treate with XA. Tey conclue that treatment must be given soon ater bleeing onset to reuce maternal mortality rates. Shakur an colleagues (2018) perorme a Cochrane atabase review an also conclue that early XA aministration ecreases maternal eaths.
Most o these stuies were conucte in impoverishe countries, an the American College o Obstetricians an Gynecologists (2019a) oes not recommen XA or either prophylaxis or rst-line treatment o obstetrical hemorrhage. I use, aministration within 3 hours o elivery is recommene.
Massive Transfusion Protocols
As note, these protocols are initiate once our to ve units o packe re cells have been given within 2 hours or so. Tese protocols spee bloo prouct elivery to provie early resuscitation an help avoi ilutional coagulopathy. Once activate, packe re cells, plasma, platelets, an brinogen are given set ratios (Table 44-2). Some protocols inclue rFVIIa, XA, or prothrombin complex concentrates (Jackson, 2018).
Te ata supporting the superiority o MPs compare with traitional component replacement to improve survival rates in obstetrical stuies are limite. Most reports escribe nonpregnant trauma victims, but some observational stuies aress obstetrical hemorrhage (Green, 2016; Pacheco, 2016).
Viscoelastic Assays
Tromboelastography (EG) an rotational thromboelastometry (ROEM) are point-o-care tests that assess coagulation in whole bloo uring massive transusions. Tese tests work by analyzing both clot ormation an breakown in a whole bloo sample rom a given patient. esting prouces a prole o coagulation ynamics, an isplaye values inicate the spee an quality o clot ormation (Fig. 44-1). Tese assays provie inormation regaring time to clot ormation, clot strength, an brinolysis (Arnols, 2020). Currently, they guie bloo prouct replacement in trauma, liver transplant, an cariac surgery patients. Stuies o EG an ROEM techniques in pregnant women have conrme the hypercoagulable state o pregnancy an provie reerence ranges or use in this population (Lee, 2021; McNamara, 2019; Pacheco, 2019).
Although promising, they also have several limitations. For example, they are less inormative in a woman with torrential hemorrhage in whom clotting unction woul nee to be measure minute-by-minute. Tey cannot be use to etect isorers o primary hemostasis (Solomon, 2012). A major rawback is the risk o misinterpretation when tests are use by inaequately traine personnel. Although use is gaining avor, we an others recommen urther stuy beore these tests are wiely applie or obstetrical hemorrhage treatment (Amgalan, 2020). We have oun this testing moality to be more applicable ater initial management o hemorrhage an with intensive care recovery than uring acute hemorrhage.
Cell Salvage and Autologous Transfusion
Preoperative patient phlebotomy an autologous blood storage or transusion in obstetrics has been isappointing. Exceptions are women with a rare bloo type or with unusual antiboies (Pacheco, 2013; Sullivan, 2019). Intraoperative blood salvage with reinusion is consiere a sae intervention in obstetrical patients. Tis practice may ai women eclining transusion (Chap. 30, p. 549). Prior concern centere on amnionic ui contamination an embolism (Dhariwal, 2014; Goucher, 2015). o evaluate benets, one trial ranomly assigne 3028 women at risk or hemorrhage an unergoing cesarean elivery either to routine care or to cell salvage. Te rate o nonautologous onor bloo transusion was not signicantly reuce in the cell salvage group—2.5 versus 3.5 percent (Khan, 2017). In another stuy, Sullivan an colleagues (2019) routinely set up most cesarean eliveries or autologous transusions an reporte a lower rate o nonautologous onor transusion. Similar to prior reports, no cases o amnionic ui embolism were reporte in these two stuies.
■ Transfusion Complications
O serious known risks, transusion o an incompatible blood component may result in acute hemolysis. I severe, this can cause DIC, acute kiney injury, an eath. Preventable errors responsible or most o these reactions requently inclue mislabeling o a specimen or incorrectly transusing a patient not slate or those proucts.
Te rate o such errors in the Unite States is estimate to be 1 case in 14,000 units, but these events are likely unerreporte (Lerner, 2010). A transusion reaction is characterize by ever, hypotension, tachycaria, yspnea, chest or back pain, ushing, severe anxiety, an hemoglobinuria. Immeiate supportive measures inclue stopping the transusion, treating hypotension an hyperkalemia, provoking iuresis, an alkalinizing the urine. ransusion-related acute lung injury (RALI) an transusion-associated circulatory overload (ACO) are the most common causes o transusion-relate mortality (Semple, 2019).
Aecte women characteristically have severe yspnea, hypoxia, an pulmonary eema that evelop within 6 hours o transusion (Peters, 2015). O the two, ACO is more common, an its incience nears 1 percent. RALI is estimate to complicate at least 1 in 12,000 transusions (Carson, 2017). Although their pathogenesis is incompletely unerstoo, injury to the pulmonary capillaries may arise rom human leukocyte antigen (HLA) antiboies an human neutrophil antiboies (HNA) in onor plasma (McCullough, 2016). Management is supportive an may inclue mechanical ventilation (Chap. 50, p. 885)
Bacterial inection rom transusion o a contaminate bloo component is unusual because organism growth is iscourage by rerigeration. Te most oten implicate contaminants o re cells inclue Yersinia, Pseudomonas, Serratia, Acinetobacter, an Escherichia species. Te more important risk is rom bacterial contamination o platelets, which are store at room temperature. Current estimates are that 1 in 1000 to 2000 platelet units are contaminate. Death rom transusion-relate sepsis is 1 case in 17,000 transuse single-onor platelets an 1 case in 61,000 transuse apheresis-onor packs (Lerner, 2010). Viral inection risks rom transusion have been curtaile. Te estimate risk o human immunoeciency virus (HIV) or o hepatitis C virus inection in screene bloo is 1 case in 1 to 2 million transuse units (Carson, 2017). Te estimate hepatitis B transmission rate is <1 case in 100,000 transuse units (Jackson, 2003). Because o the high prevalence o the virus, cytomegalovirus-inecte leukocytes are oten transuse.
Risks or transmitting West Nile virus, parvovirus B19, human -lymphotropic virus type 1, an toxoplasmosis are slight (American Association o Bloo Banks, 2013; ForoutanRa, 2016). Although rare, Zika virus has emerge as another relevant transusion-transmitte inection (Motta, 2016). Collection o all whole bloo components now inclues testing or Zika virus (Centers or Disease Control an Prevention, 2018). At this time, transmission o SARS-CoV-2 virus rom a COVID-positive onor is hypothetical (Leblanc, 2020).
OBSTETRICAL COAGULOPATHIES
Te terms consumptive coagulopathy, defbrination syndrome, an disseminated intravascular coagulation (DIC) are oten use interchangeably, but istinctions are important. Actual consumption o procoagulants within the intravascular tree results in a consumptive coagulopathy. In contrast, massive loss o procoagulants rom hemorrhage results in a ilutional coagulopathy. Semantics asie, consumptive coagulopathy culminates in a systemic intravascular activation that completely isrupts natural hemostasis. As a result, an ineective balance o natural anticoagulant mechanisms leas to wiesprea brin eposition that can cause multiorgan ailure (Levi, 2016).
■ Pregnancyinduced Coagulation Changes
During normal pregnancy, the balance between coagulation an brinolysis changes to create a procoagulant state. Changes that promote coagulation inclue appreciable elevation in the plasma concentrations o actors I (brinogen), VII, VII, IX, an X. A partial list o these normal values is oun in the Appenix (p. 1228). Concurrently, levels o plasminogen, which lyses brin, rise consierably. However, plasminogen activator inhibitor 1 an 2 (PAI-1 an PAI-2) levels also increase. Tus, plasmin activity usually eclines until ater elivery (Hale, 2012; Hui, 2012). As shown in Figure 4-7, (p. 62), mean platelet count rops by 10 percent uring pregnancy, an platelet activation is enhance (Kenny, 2015; Reese, 2018).
Te net results o these changes inclue greater levels o brinopeptie A, β-thromboglobulin, platelet actor 4, an brinogen–brin egraation proucts, which inclues d-imers. In aition to lower concentrations o the anticoagulant protein S, pregnancy-relate hypercoagulability, an ecrease brinolysis, there is augmente—yet compensate—intravascular coagulation that may unction to maintain the uteroplacental interace.
■ Disseminated Intravascular Coagulation
Because o the many enitions an variable severity, the incience o consumptive coagulopathy in gravias varies an ranges rom 0.03 to 0.35 percent (Erez, 2014; Rattray, 2012). For example, some egree o signicant coagulopathy is oun in virtually all cases o placental abruption an amnionic ui embolism. Other instances in which requently occurring but less recognize egrees o coagulation activation can be oun inclue sepsis; thrombotic microangiopathies; acute kiney injury; acute atty liver; severe preeclampsia; an hemolysis, elevate liver enzyme levels, low platelet count (HELLP) syn- rome (Cunningham, 2015).
When consumptive coagulopathy is severe, the likelihoo o maternal an perinatal morbiity an mortality rises. In one stuy o 49 cases, anteceent causes inclue those liste above, an 59 percent receive bloo transusions, 18 percent unerwent hysterectomy, 6 percent require renal ialysis, an three mothers ie (Rattray, 2012). In this series, the perinatal mortality rate was 30 percent. From 2010 to 2011, DIC was the secon most common severe maternal morbiity inicator (Creanga, 2014). DIC was associate with nearly a ourth o maternal eaths uring this stuy perio. Despite these statistics, consumptive coagulopathy as the sole cause o maternal eath is uncommon an accounts or only 0.2 percent o pregnancy-relate eaths in the Unite States (Creanga, 2015).
■ Activation of Normal Coagulation
Instea o the “waterall” sequential activation o the clotting cascae, a current theory proposes that tissue actor—an integral membrane glycoprotein—serves as the principal initiator o coagulation (Levi, 2016). Coagulation then moves orwar but incorporates a eeback loop. o begin, tissue actor orms complexes with actor VII/VIIa to activate actors IX an X. issue actor is oun in highly vascularize organs such as the brain, lungs, an placenta; in amnionic ui; an in certain other cells (Kuczyski, 2002; Østeru, 2006; Uszyski, 2001). issue actor–actor VIIa complexes ultimately generate activate actor X (Xa) to initiate clotting. Subsequently, the previously labele “intrinsic” pathway amplies this process. Specically, the initial thrombin prouce irectly activates actor XI by proviing a eeback amplication loop (Fig. 44-2). Te en result o this amplie coagulation process is brin ormation. Tis is then counterbalance by the brinolytic system, in which plasminogen is activate. Even this process is tie initially to tissue actor. Te nal prouct is brin egraation proucts, sometimes calle brin split proucts, which inclue d-imers.
■ Activation of Pathological Coagulation
With DIC, pathological entities prompt tissue actor release rom subenothelial tissue an stimulate monocytes, which in turn provoke cytokine release rom the enothelium. With generalize enothelial activation, iuse activation o coagulation ollows. Tis pathological cycle o coagulation an brinolysis becomes clinically important when coagulation actors an platelets are sufciently eplete to create consumptive coagulopathy.
Purpura ulminans is a severe—oten lethal—orm o consumptive coagulopathy. It is cause by microthrombi in small bloo vessels leaing to skin necrosis an sometimes vasculitis. Debriement o large areas o skin over the extremities an buttocks requently requires treatment in a burn unit. Rarely, our-extremity amputation is require (Bhatti, 2019). Purpura ulminans usually complicates sepsis in women with heterozygous protein C eciencies an low protein C serum levels (Bhatti, 2019; Levi, 2016). Importantly, homozygous protein C or S eciency results in neonatal purpura ulminans, which is atal (Chap. 55, p. 976).
■ Inciting Conditions
Several obstetrical synromes can trigger consumptive coagulopathy. O these, placental abruption is the most common cause o severe consumptive coagulopathy in obstetrics an is iscusse more ully in Chapter 43 (p. 749). With preeclampsia, eclampsia, an HELLP syndrome, enothelial activation is a hallmark. Perhaps 10 percent o HELLP cases have some isseminate coagulation (Haram, 2017). In general, the clinical severity o preeclampsia is irectly correlate with thrombocytopenia an brin egraation proucts (Geik 2017; Kenny, 2015). Tat sai, intravascular coagulation is selom severe enough to be clinically worrisome (Pritchar, 1976). Acute atty liver o pregnancy also causes intravascular coagulation in aition to ecrease procoagulant synthesis (Chap. 58, p. 1034).
Amnionic uid embolism is usually cause by intravenous embolization o meconium-laen amnionic ui. It results in rapi cariorespiratory collapse an prooun consumptive coagulopathy. Te Society or Maternal-Fetal Meicine (2021) has evelope a checklist or the initial management o amnionic ui embolism. It is iscusse in Chapter 42 (p. 745). Sepsis stemming rom various inections can be accompanie by eno-or exotoxin release. Although a eature o sepsis syn- rome inclues activation o coagulation, selom oes sepsis alone cause massive procoagulant consumption. Escherichia coli bacteremia is requently seen with antepartum pyelonephritis an puerperal inections, however, accompanying consumptive coagulopathy is usually not severe. Some notable exceptions are septicemia cause by exotoxins release rom group A Streptococcus pyogenes, Staphylococcus aureus, or Clostridium perringens, C sordellii, or C novyi (Herrera, 2016; Pritchar, 1971). reatment o sepsis an septic shock is iscusse in Chapter 50 (p. 889). Septic abortion—especially associate with these organisms—can incite coagulation an worsen hemorrhage.
Second-trimester induced abortions can stimulate intravascular coagulation even in the absence o sepsis. Ben-Ami an associates (2012) escribe a 1.6-percent incience in 1249 late-secon- trimester pregnancies terminate by ilation an evacuation. wo thirs were one or etal emise, which may have contribute to coagulopathy (Kerns, 2019). Another source o intense coagulation is instillation o hypertonic solutions to eect mitrimester abortions. Tese are not commonly use currently or pregnancy terminations. Te mechanism is thought to initiate coagulation by thromboplastin release into maternal circulation rom the placenta, etus, an eciua by the necrobiotic eect o hypertonic solutions.
Prolonged retention o a dead etus is an unusual cause o consumptive coagulopathy toay. Namely, etal eath can be easily conrme, an highly eective methos or labor inuction are available. Moreover, i the ea etus is unelivere, most women enter spontaneous labor within 2 weeks an gross isruption o maternal coagulation rarely evelops beore 4 weeks (Pritchar, 1959, 1973). Ater 1 month, however, almost a ourth will evelop consumptive coagulopathy.
■ Diagnosis
Bioassay is an excellent metho to etect or suspect clinically signicant coagulopathy. Excessive bleeing at sites o mo- est trauma characterizes eective hemostasis. Examples inclue persistent bleeing rom venipuncture sites, nicks rom preoperative shaving, trauma rom blaer catheterization, an spontaneous bleeing rom the gums, nose, or gastrointestinal tract. Purpura or petechiae at pressure sites such as sphygmomanometer cus or tourniquets suggest signicant thrombocytopenia. Any surgical proceure provies the ultimate bioassay an elicits generalize oozing rom abominal wall layers, the retroperitoneal space, the episiotomy, or incisions an issections or cesarean elivery or hysterectomy.
O laboratory tests, brinogen an d-imer levels can be inormative. In late pregnancy, plasma brinogen levels typically have risen to 300 to 600 mg/L. Tus, even with severe consumptive coagulopathy, levels may sometimes be sufciently high to protect against clinically harmul hypo- brinogenemia. For example, ebrination cause by a placental abruption might lower an initial brinogen level o 600 mg/L to 250 mg/L. Although this woul inicate massive brinogen consumption, levels are still aequate to promote clinical coagulation. Te clinically impactul threshol usually approximates 150 mg/L. Te eects o serious hypo- brinogenemia—less than 50 mg/L—can be illustrate with clinical thrombin clot test. With low brinogen levels, the clot orme rom whole bloo in a glass phlebotomy tube will initially be sot an cannot retract in volume. Instea, uring the next hal hour, platelet-induced clot retraction ensues, an this causes a tighter clot to orm.
As epicte in Figure 44-2, brinolysis cleaves brin into various brin egraation proucts, an one o the smaller ones is the d-imer. Several sensitive assays contain monoclonal antiboies specic or d-imers (Johnson, 2019). Assay values are almost always abnormally high with clinically signicant consumptive coagulopathy. At least in obstetrical isorers, quantication oes not correlate with outcomes. Examples o the magnitue o brin split prouct elevations in various obstetrical coagulopathies are shown in Figure 44-3.
Trombocytopenia is likely i petechiae are abunant or i clotte bloo ails to retract within an hour or so. Conrmation is provie by a low platelet count. I severe preeclampsia syn- rome is comorbi, qualitative platelet ysunction may coexist (Chap. 40, p. 696).
Prothrombin time (P) an partial thromboplastin time (P) are stanar coagulation tests. Prolongation may stem rom very low brinogen concentrations, rom appreciably reuce levels o the procoagulants neee to generate thrombin, or rom large amounts o circulating brinogen–brin egraation proucts.
Tromboelastometry an thromboelastography are point-o- care tests use as ajuncts to conventional laboratory stu- ies (McNamara, 2019; Pacheco, 2019). Teir current role may serve to guie bloo prouct replacements as iscusse earlier (p. 774). Using many o these tests, several organizations have attempte to establish a more uniorm enition o DIC. One is the International Society on Trombosis an
Haemostasis (ISH) scoring system. Te score is use only ater a conition known to cause intravascular coagulation is ientie an is calculate using a combination o laboratory tests. Composite ISH-DIC scores <5 suggest nonovert DIC, whereas scores ≥5 are compatible with overt DIC.
A scoring system or nonovert DIC has been evelope by Alhousseini an coworkers (2020). Tese scoring systems have not been applie wiely in obstetrics (Hizkiyahu, 2019; Jonar, 2016; Nelson, 2014).
■ General Management
o halt ongoing ebrination, ientiying an removing the inciting source is a priority. With incisions or extensive lacerations accompanie by severe hemorrhage, rapi replacement o procoagulants is usually inicate. Vigorous restoration an maintenance o the circulation to treat hypovolemia cannot be overemphasize. Aequate perusion restores hepatic an enothelial synthesis o procoagulants an permits prompt removal o activate coagulation actors, brin, an brin egraation proucts by the reticuloenothelial system.
Asie rom these unamental steps, ew other agents have prove sounly eective. Although its use is seemingly counterintuitive, unractionate heparin has now been abanone. Other agents not recommene or rst-line use inclue tranexamic aci or epsilon-aminocaproic aci, both anti- brinolytic agents (American College o Obstetricians an Gynecologists, 2019a; Pacheco, 2017). Tis is because the brinolytic system is necessary or issolution o wiesprea brin thromboses cause by generalize intravascular coagulation (Levi, 2016). Discusse earlier (p. 773), recombinant actor VIIa (rFVIIa) can be use to help control severe obstetrical hemorrhage rom other causes. However, current clinical evience is insufcient to make rm recommenations on its aministration or obstetrical coagulopathies.
SURGICAL MANAGEMENT OF HEMORRHAGE
Several invasive proceures can help to arrest severe postpartum hemorrhage. A report rom the Agency or Healthcare Research an Quality conclue that most stuies aressing these methos are o poor quality (Likis, 2015). In one stuy o 6660 women with postpartum hemorrhage, 4 percent unerwent an invasive proceure, an 1 percent ha a hysterectomy (Kayem, 2016). Te ailure rate o conservative surgical an embolization proceures was 15 percent. O specic methos, use o uterine balloon tamponae or treatment o atony has ouble in the past ecae (Merriam, 2020; Suarez, 2020). It is escribe in Chapter 42 (p. 737). For low-pressure bleeing, topical hemostatic agents can be use to control persistent surgical oozing. Tese were reviewe by Stachowicz an colleagues (2020). Other than or cesarean hysterectomy, these are selom use in obstetrical hemorrhage.
■ Uterine Compression Sutures
Tis surgical technique uses a no. 2 chromic suture to compress the anterior an posterior uterine walls together (B-Lynch, 1997). Because they give the appearance o suspeners, they are also calle braces (Fig. 44-4). Several moications o the B-Lynch technique have been escribe (Gilmanyar, 2019; Matsubara, 2013; Nelson, 2007).
B-Lynch sutures are mainly use to treat atony. Tese may help iminish DIC-associate bleeing, while coagulation is correcte by transusion. Success rates vary by inication. For example, B-Lynch (2005) cite 948 cases with only 7 ailures. Conversely, in other series, overall ailure rates were 20 to 25 percent (Kaya, 2016; Kayem, 2011). Some unique complications can rarely ollow compression sutures (Matsubara, 2013). Most involve variations o uterine ischemic necrosis with peritonitis (Gottlieb, 2008; Joshi, 2004; reloar, 2006). In most cases, subsequent pregnancies are uneventul i compression sutures are use (An, 2013). A ew women with B-Lynch sutures, however, evelope uterine wall eects or uterine cavity synechiae (Akoury, 2008; Alouini, 2011; Ibrahim, 2013).
■ Artery Ligation
Ligation o arterial bloo ow to the uterus can halt or iminish obstetrical hemorrhage. Common inications inclue uterine hysterotomy incision laceration, uterine atony, an abnormal placentation. Uterine artery ligation may be unilateral or bilateral an is use mainly or lacerations at the lateral part o a hysterotomy incision (Fig. 44-5). In our experiences, this proceure is less helpul or other hemorrhage etiologies. In rare cases with torrential hemorrhage rom placenta accreta synrome, a tourniquet wrappe aroun the lower uterine segment may slow bleeing sufciently while resuscitation ensues an issection or hysterectomy is perorme.
Internal iliac artery ligation may also be unilateral or bilateral. For years, ligation has been use to reuce pelvic hemorrhage. However, the proceure may be technically ifcult an is successul in only hal o cases (American College o Obstetricians an Gynecologists, 2019a; Bienstock, 2021). Wei an colleagues (2019) reporte it to be successul or improve hemostasis with placenta previa. It is not particularly helpul or abating hemorrhage with postpartum atony (Clark, 1985).
For internal iliac ligation, aequate exposure is obtaine by opening the peritoneum over the common iliac artery an issecting own to the biurcation o the external an internal iliac arteries (Fig. 44-6). Branches istal to the external iliac arteries are palpate to veriy pulsations at or below the inguinal area. Ligation o the internal iliac artery at a point 5 cm istal to the common iliac biurcation will usually avoi the internal iliac artery's posterior ivision branches (Bleich, 2007). Te areolar sheath o the artery is incise longituinally, an a right-angle clamp is careully passe just beneath the artery rom lateral to meial. Care must be taken not to perorate contiguous large veins, especially the internal iliac vein. Suture—usually nonabsorbable—is passe uner the artery with a clamp, an the vessel is then securely ligate.
Te most important mechanism o action with internal iliac artery ligation is an 85- percent reuction in pulse pressure in those arteries istal to the ligation (Burchell, 1968). Tis converts an arterial pressure system into one with pressures approaching those in the venous circulation. Tis creates vessels more amenable to hemostasis via pressure an clot ormation. Even bilateral internal iliac artery ligation oes not appear to interere with subsequent repro- uction. Nizar an colleagues (2003) reporte subsequent pregnancy in 17 such women. From a total o 21 pregnancies, 13 were normal, 3 ene with miscarriage, 3 were terminate, an 2 were ectopic.
■ Angiographic Embolization
Tis moality is now use or many causes o intractable hemorrhage when surgical access is ifcult. Its use has increase remarkably in the past ecae (Merriam, 2020). In more than 500 pregnancy-relate cases, embolization was eective in 90 percent (Grönvall, 2014; Lee, 2012; Poujae, 2011; Zhang, 2015). Ater his review, Rouse (2013) conclue that embolization can be use to arrest reractory postpartum hemorrhage. Other reports have been less enthusiastic. Fertility is not impaire, an many subsequent successul pregnancies have been reporte (Fiori, 2009; Kolomeyevskaya, 2009). An important caveat or these procedures is that women with hemodynamic instability related to active bleeding should not be removed rom the operating room.
Complications are relatively uncommon but can be severe. Case reports etail instances o iatrogenic iliac artery rupture, uterine ischemic necrosis, an uterine inection (Grönvall, 2014; Katakam, 2009; Nakash, 2012). A rare case o massive buttock necrosis an paraplegia ollowe bilateral internal iliac artery embolization (Al-Tunyun, 2012). A myometrial eect in subsequent pregnancy also has been reporte (Choo, 2019).
In a ew instances, massive bloo loss an ifcult surgical issection is anticipate. Te use o balloon-tippe catheters preoperatively inserte into the iliac or uterine arteries is escribe in management o placenta accreta spectrum (Chap. 43, p. 759).
■ Aortic Compression
Prophylactic use o an aortic balloon occlusion evice has been reporte to reuce bloo loss an the nee or hysterectomy (Chen, 2019). Also known as resuscitative endovascular balloon occlusion o the aorta (REBOA), such occlusion lowers the perusion pressure istally, increases cariac aterloa, an reistributes bloo volume to the heart an brain (Cannon, 2018). Prolonge occlusion can result in lower limb ischemia requiring amputation. Whittington an colleagues (2020) escribe its successul prophylactic use in 11 women with placenta accreta spectrum isorers. Instea, manual compression o the aorta above the sacral promontory can be use in cases in which pelvic hemorrhage is torrential. I the abomen is close, pressure place above the umbilicus reuces bloo pressure istally (Barbieri, 2018).
■ Pelvic Packing
I hysterectomy ails to curtail hemorrhage, then pelvic packing with gauze an termination o the operation may be consiere (Pacheo, 2018; ouhami, 2018). Rolls o gauze are packe to provie constant local pressure. In some cases, this may serve as a temporizing step prior to interventional embolization. In other cases, packing alone may be let or 48 to 72 hours. I the patient is stable an bleeing appears to have stoppe, packing is remove. In one review o 104 cases, the success rate was 79 percent. Packing aile in 24 patients, an 13 o these women ie, yieling an overall mortality rate o 13 percent (ouhami, 2018).
Te umbrella or parachute pack uses a similar concept (Logothetopulos, 1926). Although selom use toay, it can be liesaving i all other measures have aile, especially in low-resource areas (Dily, 2006; ouhami, 2018). Te pack is constructe o a stury sterile plastic bag that is lle with gauze rolls that are unwoun an knotte together. Sufcient rolls are use to provie aequate volume in the bag to ll the pelvis. Te pack is introuce transabominally with the stalk exiting the vagina. Mil traction is applie by tying the stalk to a 1-liter ui bag, which is hung over the oot o the be. Te umbrella pack is remove vaginally ater 24 hours.
Nhận xét
Đăng nhận xét