Disseminated intravascular coagulation (DIC) during pregnancy: Management and prognosis

INTRODUCTION — Any patient with disseminated intravascular coagulation (DIC) presents a major management challenge, and this challenge is further complicated when the patient is carrying a fetus at or beyond the limit of viability. For example, delaying delivery to transfuse a pregnant patient with DIC who is bleeding heavily may not be in the best interest of a fetus with a category III heart rate tracing, whereas performing an emergency cesarean delivery on a pregnant patient with DIC may not be in the pregnant patient's best interest. Even in the setting of fetal demise, labor and vaginal delivery of a pregnant patient with DIC carries the potential for catastrophic hemorrhage.

This topic will review the management and prognosis of pregnant women with DIC. Clinical findings, etiology, and diagnosis of DIC in pregnancy are discussed separately (see "Disseminated intravascular coagulation (DIC) during pregnancy: Clinical findings, etiology, and diagnosis"). Broader discussions of the pathogenesis, clinical manifestations, diagnosis, and treatment of DIC can also be found separately. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)

GENERAL PRINCIPLES

●Anticipate acute disseminated intravascular coagulation (DIC) in situations where one of the underlying conditions is present. The most common obstetric disorders that may result in DIC are listed in the table (table 1A). (See "Disseminated intravascular coagulation (DIC) during pregnancy: Clinical findings, etiology, and diagnosis", section on 'Causes'.)

●Identify and treat the underlying condition and provide supportive care.

●Immediately begin efforts to recognize development of overt DIC (monitor coagulation status) and prepare staff and resources (alert staff and blood bank). Maintain fibrinogen levels above 300 mg/dL or treat (with appropriate blood products and/or drugs) latent and/or compensated activation of coagulation to mitigate the onset of overt, uncontrolled DIC.

●In the obstetric setting, most patients with DIC are intrapartum and have severe uterine bleeding. Resuscitation aims to treat the condition that caused the DIC, achieve euvolemia, normalize tissue oxygen delivery, and resolve acidosis and coagulopathy. This is achieved by appropriate fluid therapy and transfusion (using a 1:1:1 ratio of packed red blood cells, plasma, and platelets), warming the patient, and providing appropriate airway and ventilatory management. Multiple techniques for controlling uterine bleeding are available after the fetus has been delivered. (See "Postpartum hemorrhage: Medical and minimally invasive management" and "Postpartum hemorrhage: Management approaches requiring laparotomy".)

●Many interventions are implemented concurrently. They are appropriate in acutely ill patients with suspected DIC even if the diagnostic evaluation is in progress and the diagnosis is uncertain.

INITIAL PREPARATION AND ASSESSMENT OF ALL PATIENTS

Establish intravenous access — Establish intravenous access peripherally with at least two large intravenous catheters (≥18 gauge).  

Assess hemodynamic stability — Make a provisional diagnosis of hemodynamic instability in nonanesthetized pregnant patients with one or more of the following:

●Systolic blood pressure <100 mmHg

●Acute change in heart rate or systolic blood pressure by >15 percent

●Shock Index (SI) (ie, heart rate/systolic blood pressure), which is a predictor of hemodynamic compromise in obstetric patients. It performed better than conventional vital signs alone in one study in which SI ≥1.7 was predictive of blood transfusion ≥4 units [1]. Of note, patients with preeclampsia/eclampsia and PPH tend to have lower mean SI values as compared to non-preeclamptic/eclamptic patients, suggesting that SI may not be a reliable indicator in patients with preeclampsia/eclampsia [2].

●Urine output <30 mL/hour

●Heart rate >100 beats per minute (although the 97^th percentile in normal pregnant people is approximately 115 beats per minute in the third trimester [3])

Other signs and symptoms of hemodynamic instability may be present, such as altered level of consciousness; shortness of breath; cold, clammy skin; and pallor.

Of note, pregnant women display changes in blood pressure and heart rate later than nonpregnant women with similar blood loss.

Assess fetal status — Fetal viability and gestational age significantly impact management of pregnant patients with DIC.

●If a fetal demise is identified or the fetus is clearly under the limit of viability, then the entire focus of management becomes the optimal care of the mother. The limit of viability is defined as the stage of maturity that would ensure a reasonable chance of survival without severe deficits.

Determining the limit of viability is desirable so that futile interventions that are costly and painful can be avoided in a fetus/neonate who does not have the possibility of a reasonably favorable outcome. However, deciding on a threshold of viability is challenging since it remains uncertain which extremely preterm infants, particularly those born at 22, 23, and 24 weeks of gestation, have a reasonable chance of survival without severe deficits. The short- and long-term morbidity from preterm birth, the intensity of care required, and the likelihood of survival at various gestational ages are discussed in detail separately. (See "Preterm birth: Definitions of prematurity, epidemiology, and risk factors for infant mortality" and "Periviable birth (limit of viability)".)

●If the fetus is alive and at a gestational age above the limit of viability, the fetal heart rate typically shows a category III tracing in pregnancies complicated by severe bleeding since maternal hemodynamic instability results in poor placental perfusion and suboptimal fetal oxygenation. In these cases, the maternal and fetal risks and benefits of immediate delivery for fetal indications versus delaying delivery to initiate maternal resuscitation need to be weighed. Involving the neonatology and anesthesia services can help when discussing these issues with the patient or the patient's legal guardian. (See 'Delivery' below.)

Measure blood loss — Although not highly accurate, blood loss can be estimated by collection in a volumetric container and by weighing pads/towels used to soak up the blood. In cases of severe abruption with concealed hemorrhage, the magnitude of blood loss can be estimated and monitored using a combination of parameters, including hourly assessment of changes in fundal height, clot volume on ultrasound examination, urine output, and serial hemoglobin/hematocrit assessment. (See "Overview of postpartum hemorrhage", section on 'Quantify blood loss'.)

Identify and address the triggering event — The cornerstone of therapy is to identify the underlying disorder leading to DIC and initiate appropriate treatment for that disorder. Obstetric etiologies of DIC (table 1A) usually are readily identified by history, physical examination, and ultrasound findings.

Delivery is a key component in management of all obstetric etiologies of DIC because termination of pregnancy leads to resolution of the obstetric disorder that initiated DIC.

Rarely, the triggering event may not be directly associated with the pregnancy (table 1B). The same guidance to address the underlying condition applies.

Notify adjunctive services

●Anesthesiology service – Notify the anesthesia staff for assistance with patient management and to provide anesthetic support for delivery if the patient is not already in the operating room. Placement of neuraxial anesthesia is generally contraindicated in patients with disseminated intravascular coagulation (DIC) because of the risk of spinal epidural hematoma. (See "Neuraxial anesthesia/analgesia techniques in the patient receiving anticoagulant or antiplatelet medication", section on 'Spinal epidural hematoma (SEH)'.)

●Transfusion service – Notify the transfusion service or blood bank regarding the potential need for blood products, including a possible need for massive transfusion. A massive transfusion or large volume obstetric transfusion protocol should be initiated, if indicated and available (table 2 and algorithm 1). Pretransfusion testing (crossmatching) is initiated; if necessary, emergency-release blood products can be made available. (See "Pretransfusion testing for red blood cell transfusion".)

●Neonatology service – Notify the neonatology service of the impending birth of a possibly preterm and/or compromised neonate. If time permits, they may counsel the parents about newborn issues, as needed.

MANAGEMENT OF HEMODYNAMICALLY UNSTABLE PATIENTS

Initial management

Resuscitation

●Maternal peripheral oxygen saturation should be ≥95 percent, which is in excess of the oxygen delivery needs of the mother. Intubation and mechanical ventilation may be necessary.

●Crystalloid (with or without colloid) and/or blood products, when available, are infused to support blood pressure (systolic ≥90 mmHg or mean arterial pressure ≥65 mmHg) and achieve/maintain urine output ≥0.5 mL/kg/hour.

The best approach to fluid resuscitation remains controversial. The trauma literature favors the use of blood and blood products as the initial volume expander in cases of massive hemorrhage. The rationale is that large volumes of crystalloid will dilute the red blood cells (RBCs), platelets, and coagulation factors that are present and thereby potentially worsen bleeding. Thus, in a situation of severe postpartum hemorrhage (PPH) with ongoing bleeding, transfusion of type O, D-negative uncrossmatched blood (switching to type-specific or crossmatched RBCs when available) along with platelets and cryoprecipitate (or lyophilized fibrinogen and/or fresh whole blood, if available) may be preferable to infusing a large volume of crystalloid. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)

If blood and blood products are not immediately available, fluid resuscitation to maintain blood pressure and tissue perfusion may be initiated with infusion of Lactated Ringer solution as rapidly as possible until the blood becomes available. (See "Intraoperative fluid management", section on 'Choosing a fluid management strategy'.)

Blood products — Blood is rapidly administered to actively bleeding patients. In massive hemorrhage, rapid transfusion of blood components and avoiding associated hyperkalemia and hypocalcemia are essential for ensuring adequate tissue perfusion and for preventing the combination of acidosis, coagulopathy, hypothermia, and electrolyte abnormalities, which is often lethal ("lethal quad").

Initial approach — In most instances, preparation of fully typed and crossmatched RBCs requires at least 20 minutes. For patients who are actively bleeding, the clinician can begin transfusion immediately using type O, D-negative RBCs, if necessary, and then switch to type-specific or crossmatched RBCs when available. Initially, type AB FFP (or thawed plasma, either D-positive or negative) can be used when plasma transfusion is necessary prior to obtaining type-specific FFP. (See "Pretransfusion testing for red blood cell transfusion", section on 'Emergency release blood for life-threatening anemia or bleeding'.)

Our initial orders are for a minimum of six units packed RBCs (pRBCs) to be typed and crossmatched, six units of FFP, one or two cryoprecipitate pools (each pool is composed of five individual units), and one dose of platelets (either a pool of four to six whole blood-derived platelet concentrates or a single apheresis platelet unit). Many massive transfusion protocols recommend transfusion of FFP, platelets, and RBCs in a ratio of 1:1:1. Evidence to support this approach and additional information regarding massive transfusion are presented in detail separately. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient" and "Intraoperative transfusion and administration of clotting factors" and "Massive blood transfusion".)

Transfusion targets — We transfuse blood products (table 3) to achieve the following minimum levels for delivery:

●Hemoglobin ≥7 g/dL

●Fibrinogen ≥300 mg/dL

●Platelet count ≥50,000/microL

●Prothrombin time and activated partial thromboplastin time less than 1.5 times control

Hemoglobin target — The optimal hemoglobin concentration for pregnant patients who are about to deliver has not been determined and likely depends on patient-specific factors, such as the expected blood loss during delivery, baseline hemoglobin level and rate of fall, and presence of medical comorbidities. The overall risk of mortality increases as the hemoglobin concentration decreases; some experts have suggested a minimum hemoglobin of 7 g/dL for pregnant patients receiving massive transfusion with an overall treatment target of 8 to 10 g/dL in patients with ongoing severe PPH [4,5]. Additional evidence to support transfusion targets in other settings is presented separately. (See "Use of blood products in the critically ill".)

Our goal in massive obstetric hemorrhage is to maintain the hemoglobin ≥7 and as high as 8 to 10 g/dL because pregnant patients with DIC have ongoing blood loss that will further increase at the time of delivery and because equilibration generally results in a fall in hemoglobin. This is likely to require transfusions matched to the estimated blood loss rather than waiting for the results of laboratory testing, depending on the turnaround time for the hemoglobin or hematocrit. A lower hemoglobin level (7 versus 8 to 10 g/dL) is acceptable after the patient has delivered, is no longer actively bleeding, or is hemodynamically stable. In cases of severe, ongoing hemorrhage, we use a 1:1:1 ratio (units of FFP to platelets to RBCs). This is based on data from other populations showing improved outcomes compared with other ratios. Lower ratios of FFP to RBCs may result in a greater risk of dilutional coagulopathy. (See "Initial management of moderate to severe hemorrhage in the adult trauma patient" and "Massive blood transfusion", section on 'Data for specific patient populations'.)

Fibrinogen target — A fibrinogen level <200 mg/dL should trigger fibrinogen replacement in a patient with ongoing bleeding [6]. A fibrinogen level ≥200 mg/dL in a pregnant patient is considered the minimum level necessary for adequate coagulation. This author recommends that attempts be made to elevate the fibrinogen level to >300 mg/dL in those situations where there is active bleeding and resuscitation is being carried out, given the higher normal baseline fibrinogen level in pregnancy and the desire to maintain the fibrinogen level well-above the danger zone in these patients.

●Cryoprecipitate, a source of concentrated fibrinogen, is indicated when large amounts of fibrinogen must be administered in a low-volume product, but it takes time to thaw and prepare for transfusion; hence, clinicians need to order cryoprecipitate with enough advanced planning to allow for this time. Unlike fibrinogen concentrate, cryoprecipitate carries a risk of transfusion-transmissible infections, and for this reason, it is not available in every country. A fibrinogen concentration below 300 mg/dL is generally treated with 10 units (two pools of 5 units) of cryoprecipitate (table 3). (See "Clinical use of plasma components".)

●Lyophilized human fibrinogen concentrate (eg, RiaSTAP, Fibryga [formerly Fibryna]) has similar efficacy as cryoprecipitate in resolving the hypofibrinogenemia [7], but can be reconstituted reasonably rapidly (within a few minutes) for use in correcting low fibrinogen levels. However, it is expensive, has to be injected over 10 minutes, and is more appropriate when other blood products are not needed or there is a need to avoid increased volume, neither of which is likely in DIC [8].

●FFP (or comparable plasma product such as thawed plasma) contains fibrinogen and is generally given to correct hypovolemia and replace fibrinogen and clotting factors in cases of obstetric hemorrhage. However, in established DIC with ongoing bleeding, the low concentration of fibrinogen in a unit of FFP makes it difficult to reverse a very low fibrinogen level, so a concentrated form of replacement fibrinogen (cryoprecipitate or lyophilized human fibrinogen concentrate) is used.

Platelet target — The risk of severe bleeding due to thrombocytopenia only increases substantially with platelet counts below 50,000/microL. For women with platelet counts of 50,000 to 100,000/microL, increased bleeding may occur with invasive procedures, but will not occur spontaneously. For women with platelet counts <50,000 and severe bleeding (bleeding into a closed space, bleeding requiring transfusion, bleeding that will not stop) or bleeding that is expected to become severe, platelet transfusion should be given immediately, regardless of the underlying cause of thrombocytopenia. (See "Thrombocytopenia in pregnancy", section on 'Management decisions'.)

Laboratory monitoring — We draw laboratory studies initially every 30 minutes to guide blood product administration. As the clinical situation is stabilized, the interval for laboratory testing can be extended.

Some centers have found point-of-care tests such as thromboelastography or rotational thromboelastometry useful in the setting of massive hemorrhage as it provides a "rapid global assessment" of hemostatic function [9-11]. Point-of-care testing is becoming more common in labor and delivery suites and may be helpful in rapidly diagnosing coagulopathy and guiding administration of clotting factors. Normal ranges in pregnant/postpartum patients are available [12]; however, they are based on sparse data, with minimal data from postpartum patients and patients with PPH. More research is needed since these tests hold the promise of being able to identify early alterations of coagulation and hyperfibrinolysis [13], which may allow more rapid diagnosis and intervention in patients who are developing DIC [14]. (See "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Viscoelastic testing' and "Intraoperative transfusion and administration of clotting factors", section on 'Point-of-care tests'.)

Avoiding hypothermia and acidosis — Fluids and blood components should be normothermic to avoid hypothermia, which has been linked to coagulopathy in trauma patients [15,16]. Warming devices (blankets, devices for warming all intravenous fluids, insulation water mattresses, and/or upper- and lower-body forced-air warming devices) are employed to maintain normothermia (temperature ≥35.5°C).

Six units of red blood cells at 4°C will reduce the body temperature of a 70 kg adult by 1°C. This heat loss can be additive with the evaporative heat loss associated with an open abdomen or other body cavity which, by itself, can lead to a 1°C decrease in core temperature in 40 minutes. Thus, 10 units of cold blood products and an hour of surgery can lead to a 3°C drop in core temperature and hypothermic coagulopathy.

Hypothermia results in sympathetic stimulation with increased myocardial oxygen consumption, particularly if shivering occurs, which may lead to myocardial ischemia. Other adverse consequences of hypothermia include coagulopathy, decreased platelet function, and increased mortality. The combination of hypothermia and acidosis increases the risk of clinically significant bleeding despite adequate blood, plasma, and platelet replacement, so acidosis should be corrected using bicarbonate, if necessary.

Managing electrolytes — In any massive transfusion situation in which multiple units of blood are rapidly transfused, electrolytes should be monitored, with prompt treatment of abnormalities. The most common electrolyte abnormalities are hyperkalemia and hypocalcemia. Both electrolyte disturbances can lead to cardiac arrest or significantly depressed cardiac function that precludes optimal resuscitation.

●Ionized calcium – Large amounts of citrate are given with massive blood transfusion, since blood is anticoagulated with sodium citrate and citric acid. Citrate binding of ionized calcium can lead to a clinically significant fall in the plasma free calcium (ionized calcium) concentration. Therefore, ionized calcium should be measured at baseline, then every 15 to 30 minutes during a massive transfusion. An ionized calcium level <1 mmol/L (normal: 1.1 to 1.3 mmol/L) impairs coagulation and places the patient at risk of cardiac arrest. Emergency replacement may be accomplished by infusing 1 g of calcium chloride over two to five minutes via a central line. Alternatively, 1 to 2 g of calcium gluconate can be infused intravenously over two to three minutes empirically for every 4 units of pRBCs transfused [17]. Hypocalcemia has a linear, concentration-dependent relationship more important in predicting hospital mortality than the lowest fibrinogen concentration, the development of acidosis, or the lowest platelet count [18]. (See "Massive blood transfusion", section on 'Hypocalcemia from citrate toxicity'.)

After transfusions have been stopped, ionized calcium should still be measured hourly for the next few hours because of the potential rebound hypercalcemia.

●Potassium (K⁺) – Hyperkalemia may result from the rapid transfusion of multiple units of pRBCs, especially if they are older units. The K⁺ concentration in the supernatant increases from 2 to approximately 45 mEq/L as a unit of blood ages from 2 to 42 days. When a massive transfusion protocol is instituted and large numbers of pRBCs are given at a high rate of infusion (>500 mL/minute, in some cases), dangerously high K⁺ levels (>6 mEq/dL) may result, particularly in patients with renal impairment. (see "Massive blood transfusion", section on 'Hyperkalemia')

Patients undergoing massive transfusion should have electrolyte levels evaluated serially to detect hyperkalemia. When urgent reduction of K⁺ is needed, a 1 percent dextrose water infusion of 500 mL/hour should be given along with intravenous regular insulin (10 units). Repeat bolus doses of regular insulin 10 units may be required. (See "Treatment and prevention of hyperkalemia in adults".)

Other steps that can be considered to minimize the risk of hyperkalemia include:

•Use only red cells collected less than 10 days prior to transfusion, if available.

•Wash the unit of red cells immediately before infusion to remove extracellular potassium, if time permits.

After transfusions have been stopped, potassium should still be measured hourly for the next few hours because of the potential rebound hypercalcemia and hypokalemia.

Other interventions

●Tranexamic acid – We suggest early use of tranexamic acid (TXA) in pregnant and recently pregnant patients with coagulopathy and DIC. There are case reports describing the use of antifibrinolytic agents (eg, TXA or aminocaproic acid) in pregnant patients with coagulopathy, but there are no high-quality studies evaluating the use of these agents in pregnancy-associated DIC. The World Maternal Antifibrinolytic Trial found that TXA (1 gram in 10 minutes IV followed by a second dose of 1 gram in 10 minutes if bleeding is still ongoing after 30 minutes) reduced death due to bleeding by 20 to 30 percent in patients with PPH (especially when administered within three hours of delivery) and was not associated with an increase in adverse effects [19]. Although blockade of the fibrinolytic system may increase the risk of thrombotic complications, TXA may be appropriate in patients in whom severe bleeding is associated with a hyperfibrinolytic state [20].

●rFVIIa and PCCs – There is no proven benefit from use of recombinant activated human factor VII (rFVIIa) or prothrombin complex concentrates (PCCs) for managing bleeding in pregnant/postpartum women related to DIC. In addition, rFVIIa and PCCs increase the risk for thrombosis.

●Antithrombin – We do not use antithrombin to treat bleeding in DIC. In two studies, it did not reduce mortality significantly in nonpregnant patients with sepsis-related DIC or in pregnant patients with DIC [21,22]. However, the latter study reported a reduction in hysterectomy (5.3 versus 8.7 percent; absolute risk difference -2.9 percent; 95% CI -4.2 to -1.6) [22]. The British Society for Haematology guidelines for management of DIC also recommend not administering antithrombin concentrate to patients with DIC not receiving heparin [20].

Delivery

Cesarean birth — Cesarean birth is indicated if the mother is hemodynamically unstable from ongoing brisk bleeding and despite vigorous transfusion; in such cases, cesarean is performed as a maternal life-saving measure. Cesarean birth is also indicated if prompt delivery has the potential to reduce neonatal morbidity and mortality or if the mother would be endangered by vaginal birth (eg, previous classical hysterotomy).

●Blood/blood products – It is desirable, but not always possible, to correct or improve the clotting abnormality prior to cesarean birth. A delay in operative intervention could lead to worsening of the coagulopathy, further blood loss, and, potentially, fetal death. On the other hand, immediate operative intervention in a patient with severe hypovolemia and DIC could prove fatal.

•If a cesarean birth must be performed urgently, then red blood cells (RBCs), fresh frozen plasma (FFP), platelets, cryoprecipitate (or other source of fibrinogen such as fibrinogen concentrate [eg, RiaSTAP, Fibryga (formerly Fibryna)]) should be available in the operating room and administered if clinically indicated (eg, for persistent bleeding without clotting from incision and needle sites). FFP and/or cryoprecipitate should be given immediately, without waiting for the results of laboratory studies. (See 'Blood products' above.)

●Personnel – One or more surgeons experienced in cesarean or puerperal hysterectomy, pelvic surgery, and management of pelvic hemorrhage should be involved in the surgical procedure. This may include a gynecologic oncologist, maternal-fetal medicine specialist, obstetrician, and/or general surgeon. If interventional radiology services are available, they should be notified of the possible need for their services as well. The obstetric, anesthesia, and surgical team members should communicate with each other regarding the volume and rate of blood loss, site(s) of bleeding, quality of clot formation, and response to techniques used for control of postpartum hemorrhage (PPH).

●Operating room – It is important to keep the operating room warm (80°F) during resuscitation. Surgery in patients with a very high potential for massive blood loss is best performed in a hybrid delivery-operating room to provide the ability to embolize and/or place an aortic balloon. A bleeding patient should only be removed from the operating room to an interventional radiology suite if the patient has been adequately resuscitated, is hemodynamically stable, and has blood and blood products available to maintain perfusion and reverse coagulopathy.

●Incision – No data from randomized trials or controlled studies are available for basing recommendations about the optimal surgical approach. These decisions are based on individual patient characteristics and the clinical experience of the surgeon. We prefer an infraumbilical vertical midline incision because it is fast, provides excellent exposure of both the upper and lower pelvis, and is less likely than a transverse incision to be complicated by a postpartum rectus sheath (subfascial) hematoma. After delivery of the fetus, we manually extract the placenta to hasten uterine involution. One or more uterotonic drugs (eg, oxytocin, methylergonovine) are given, as needed, and the hysterotomy incision is closed promptly to curtail bleeding.

●Anesthesia – General anesthesia is required because of the risk for spinal epidural hematoma with neuraxial techniques and because of maternal hemodynamic instability. (See "Anesthesia for cesarean delivery".)

Techniques to control bleeding at laparotomy

●Standard techniques – Standard techniques for control of PPH are applied as clinically appropriate. These techniques include utero-ovarian vessel ligation, uterine compression sutures, and placement of device for intrauterine hemorrhage control (eg, balloon tamponade device, vacuum-induced hemorrhage control device). (See "Postpartum hemorrhage: Management approaches requiring laparotomy".)

If uterine bleeding remains brisk and maternal hemodynamic status is deteriorating despite initial surgical interventions and blood component replacement, we use a Penrose drain or urinary catheter as a uterine tourniquet. The drain is placed as low as possible around the lower uterine segment without incorporating the urinary bladder, and then the two ends are pulled in opposite directions and as tightly as possible around the corpus to mechanically occlude the vascular supply. A second or third tourniquet can also be applied, as needed. The tourniquet can be held in place with a clamp (figure 1). This procedure markedly reduces blood loss and allows time for the anesthesia team members to catch up with transfusion requirements. When the patient is hemodynamically stable, the tourniquet is removed, and the surgical procedure is completed. The abdomen is closed in a standard fashion. (See "Techniques to reduce blood loss during abdominal or laparoscopic myomectomy", section on 'Tourniquets'.)

●Pelvic packing – Some patients will continue to bleed despite these measures and can enter a lethal downward spiral characterized by hypothermia, coagulopathy, and metabolic acidosis [23]. Criteria proposed for this "in extremis" state include pH <7.30, temperature <35°C, combined resuscitation and procedural time >90 minutes, nonmechanical bleeding, and transfusion requirement >10 units packed RBCs [24]. To abort the cycle, the pelvic bleeding needs to be acutely controlled. In some cases, this can be achieved by tightly packing the area using a pelvic pressure pack or lap sponges [25]. If the abdomen is packed as a temporizing effort, the abdominal wound, including the fascia, is left open and a pressure dressing is applied. We have also used towel clips to temporarily reapproximate the skin/subcutaneous tissue.

It is prudent to place a large bore drain to alert the team to any ongoing massive bleeding, as the abdomen may need to be opened and repacked or some other intervention attempted. The recently pregnant abdomen will never provide sufficient pressure to tamponade a major bleed; thus, this should not be regarded as an option. The procedure for pelvic packing is described separately. (See "Postpartum hemorrhage: Management approaches requiring laparotomy", section on 'Damage control approach for persistent bleeding after hysterectomy'.)

●Advanced techniques – Intermittent aortic occlusion, intermittent common iliac artery occlusion, and internal iliac artery ligation are procedures of last resort (see "Postpartum hemorrhage: Management approaches requiring laparotomy", section on 'Role of embolization'). There is minimal information on aortic balloon occlusion in this setting, but it can be placed without the need for fluoroscopy and has been used successfully to manage massive obstetric hemorrhage [26,27]. (See "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Consider resuscitative endovascular balloon occlusion of the aorta'.)

Immediate post-cesarean monitoring — It is unwise to move an acutely unstable patient with temporarily controlled bleeding, or uncontrolled bleeding, from the operating room. If possible, the patient should be kept on the operating room table under anesthesia with all resources ready for immediate reopening of the abdomen. It is better to monitor these fragile, unstable patients in the operating room for several hours rather than transfer them back to an intensive care unit where surgical facilities are not available.

Role of hysterectomy — Hysterectomy is a last resort in patients who wish to preserve childbearing capacity, but should not be delayed when less aggressive interventions fail to quickly control hemorrhage. Delaying hysterectomy allows ongoing loss of blood and coagulation factors and increases the frequency of serious complications (eg, kidney failure, acute lung injury, neurologic dysfunction). (See 'Prognosis' below and "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Organ dysfunction'.)

Hysterectomy rates in DIC vary. In the series of 49 cases of DIC in pregnant patients, one-fifth required hysterectomy to control bleeding [28]. (See "Peripartum hysterectomy for management of hemorrhage".)

HEMODYNAMICALLY STABLE PATIENTS

Initial management

●Transfusion – Hemodynamically stable patients with DIC are at risk of developing severe bleeding due to depletion of coagulation factors and thrombocytopenia. When an early stage of DIC is suspected, a falling fibrinogen level that is still within the normal range should prompt replacement therapy, typically with fibrinogen concentrate or cryoprecipitate (if available). Although fresh frozen plasma (FFP) may be used, it will require a significantly larger volume (>10 times) to replace fibrinogen compared with fibrinogen concentrate or cryoprecipitate. If the fibrinogen level is <200 mg/dL in a situation where bleeding is not active but anticipated (eg, patients with preeclampsia with severe features or a concealed abruption), the author believes that it is essential to administer fibrinogen concentrate or cryoprecipitate to increase the fibrinogen level to over 300 mg/dL, given the higher normal baseline fibrinogen level in pregnancy and the desire to maintain the fibrinogen level well-above the danger zone in these patients mg/dL. (See 'Fibrinogen target' above.)

Other blood products should be readily available and used as appropriate for the amount of bleeding. Transfusion is usually appropriate in obstetric patients with DIC since they have, or are at high risk for, massive bleeding and they are likely to experience obstetric events associated with bleeding (eg, cesarean birth, episiotomy, genital tract lacerations). Thresholds for transfusion of blood products are listed above. (See 'Blood products' above and 'Transfusion targets' above.)

●Timing of delivery – Decision-making regarding timing of delivery in hemodynamically stable patients depends on the expected course of the underlying cause of DIC. For example, prompt delivery via induction of labor or cesarean birth is indicated in acute obstetric DIC (table 1A) since termination of pregnancy leads to resolution of the obstetric disorder that initiated DIC. In contrast, chronic DIC (eg, in a twin pregnancy with single twin demise) usually does not require prompt delivery and is managed medically, as discussed separately. (See "Twin pregnancy: Management of pregnancy complications", section on 'Death of one twin'.)

In very rare cases where the mother with acute nonobstetric DIC is responding appropriately to resuscitation with blood products and the fetal heart rate (FHR) tracing is normal, there is no compelling need for immediate delivery via induction of labor or cesarean birth. Instead, the clinical focus is on reversing or eliminating the cause of DIC and reducing the risk of maternal bleeding and thrombosis.

Delivery

Viable fetus with reassuring fetal status and no contraindication to vaginal birth — Vaginal birth is the preferred approach to reduce maternal risks from laparotomy.

Viable fetus with nonreassuring fetal status or contraindication to vaginal birth — Cesarean birth is indicated if the mother has contraindications to vaginal birth or if there are standard fetal indications for cesarean birth. (See 'Cesarean birth' above.)

Nonviable fetus — If the fetus is dead or has a very poor prognosis (eg, gestational age less than 22 to 23 weeks of gestation, lethal or life-threatening congenital abnormality, preterminal FHR tracing), the goal is minimizing maternal morbidity and mortality. In many, but not all, cases, this means avoiding cesarean birth because of the risk of uncontrollable hemorrhage from surgical incisions and lacerations.

●Support – The mother is supported, as needed, with crystalloid (with or without colloid), supplemental oxygen, and blood products, as appropriate (see 'Management of hemodynamically unstable patients' above).

●Cervical ripening – If the cervix is unfavorable, we use both a mechanical method of cervical ripening (balloon catheter or hygroscopic dilator) and a pharmacologic method of labor induction (oxytocin or misoprostol). (See "Induction of labor with oxytocin" and "Induction of labor: Techniques for preinduction cervical ripening".)

●Anesthesia – Neuraxial anesthesia is contraindicated in patients with DIC because of the risk of spinal epidural hematoma. (See "Adverse effects of neuraxial analgesia and anesthesia for obstetrics", section on 'Spinal epidural hematoma'.)

●Delivery/extraction

•Delivery is initiated, as removal of the products of conception removes the trigger for DIC in many obstetric cases and causes the myometrium to contract (uterine involution), thus addressing both the major source and the major site of hemorrhage. In the second trimester, dilation and extraction is a good option for rapid uterine evacuation if the clinician is skilled in this procedure. Otherwise, and in the third trimester, labor should be induced if it has not already ensued or should be augmented if it is not progressing rapidly.

•In some cases of attempted induction of labor in patients with DIC complicating abruption, uterotonic agents appear to be less effective at initiating and sustaining labor. If the fetus is dead and in a cephalic presentation, the cervix is sufficiently dilated to allow access to the fetal head, and an experienced operator is available, then attachment of Willett forceps (or a specifically designed cephalic perforator such as the Groote Schuur Hospital perforator) enables traction on the decompressed fetal head and vaginal delivery [29,30]. This is a safer option than performing a cesarean on a patient in fulminant DIC.

●Anticipate PPH – In abruption-related DIC, care should be taken to anticipate postpartum uterine atony, regardless of route of birth. Appropriate drugs, blood products, and devices should be readily available, and surgical and anesthesia services should be prepared to deal with massive hemorrhage. (See "Postpartum hemorrhage: Medical and minimally invasive management" and "Postpartum hemorrhage: Management approaches requiring laparotomy".)

POSTPARTUM PROPHYLAXIS AGAINST THROMBOSIS FOLLOWING PPH — Data from controlled trials are lacking regarding whether prophylactic pharmacologic anticoagulation is beneficial in women recovering from disseminated intravascular coagulation (DIC) after postpartum hemorrhage (PPH).

●It is reasonable to use intra- and postoperative sequential compression devices for thrombosis prophylaxis in all patients who have had DIC following PPH, and in our hospital, this is standard during the recovery phase.

●Given that PPH, blood transfusion, and prolonged surgery are all risk factors for venous thromboembolism, in a stable patient with normal coagulation tests and who is not at high risk for reoperation, adding prophylactic heparin (or equivalent) 24 hours after surgery is also a reasonable option. (See "Venous thromboembolism in pregnancy: Prevention".)

PROGNOSIS

Maternal

●Mortality – Disseminated intravascular coagulation (DIC) is a major contributor to maternal mortality. Rates of DIC-related maternal mortality vary widely and recent figures are not available [28,31,32]. In the United States, approximately 20 to 25 percent of maternal deaths are related to hemorrhage, amniotic fluid embolism, or hypertensive disorders of pregnancy, all of which can be associated with coagulopathy [33]. As in nonpregnant individuals, mortality depends on the ability to reverse the underlying cause as rapidly as possible.

●Morbidity – DIC in a pregnant patient often leads to severe obstetric hemorrhage and its sequelae (see "Overview of postpartum hemorrhage", section on 'Outcome'). However, most patients with DIC due to pregnancy-related complications rapidly improve with delivery and treatment of coagulopathy. In cases complicated by severe liver dysfunction, however, resolution of DIC can take as long as four to five days postpartum because the liver is the source of most coagulation factors and the site for clearance of D-dimer [34].

●Risk of recurrence – The risk of DIC recurrence in subsequent pregnancies is unknown and depends on the underlying cause (eg, the risk of recurrent abruption is 5 to 15 percent). Uterine-sparing surgical interventions for management of hemorrhage do not appear to adversely affect fertility.

Fetus/neonate — Fetal/neonatal survival depends on the stage of pregnancy and placental function. In a series of 91 cases of DIC in which 80 pregnancies were ≥28 weeks, there were 40 fetal/neonatal deaths (44 percent); 28 occurred antepartum, 3 intrapartum, and 9 postpartum [35].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Obstetric hemorrhage".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topic (see "Patient education: Disseminated intravascular coagulation (The Basics)")

SUMMARY AND RECOMMENDATIONS

●Overview – Acute disseminated intravascular coagulation (DIC) should be anticipated in pregnant patients who have a disorder potentially causing DIC (table 1A-B). Early recognition and treatment (table 4) of these underlying conditions may prevent progression to overt, uncontrolled DIC. (See 'General principles' above.)

●Management of hemodynamically unstable patients (algorithm 2)

•Key elements – The key elements in managing the hemodynamically unstable pregnant patient with DIC are to maintain oxygenation and perfusion, administer blood products, frequently monitor hematologic parameters and electrolytes to guide therapy, and avoid hypothermia, acidosis, and electrolyte abnormalities (potassium and calcium), which can be lethal. (See 'Management of hemodynamically unstable patients' above.)

•Blood products – For patients with heavy bleeding, we order a minimum of 6 units of packed red blood cells (pRBCs), 6 units of fresh frozen plasma (FFP), 1 dose of platelets (either 4 to 6 whole blood-derived platelet units or 1 platelet apheresis), and 10 bags of cryoprecipitate (two pools of 5 units), and begin transfusion of blood products prior to receiving initial laboratory results. We transfuse pRBCs, FFP, and platelets in a ratio of 1:1:1 in cases of severe hemorrhage. This ratio is expected to reduce the risk of dilutional coagulopathy. (See 'Management of hemodynamically unstable patients' above and 'Transfusion targets' above.)

-Fibrinogen – In a pregnant patient with active bleeding and a fibrinogen level <300 mg/dL, fibrinogen is replaced to achieve a level ≥300 mg/dL, which is considered the minimum level necessary to safely ensure adequate coagulation in pregnancy. (See 'Fibrinogen target' above.)

The concentration of fibrinogen in a unit of FFP is low, and successful reversal of a very low fibrinogen level is unlikely unless a concentrated form of replacement fibrinogen is used. A fibrinogen concentration below 300 mg/dL would require 10 units (two pools of 5 units) of cryoprecipitate. Cryoprecipitate takes time to thaw and prepare for transfusion; lyophilized human fibrinogen concentrate is a rapidly available alternative.

•Laboratory studies/targets – Laboratory studies are monitored every 30 minutes to guide blood product replacement, and we transfuse blood products to achieve the following minimum levels (see 'Transfusion targets' above):

-Hemoglobin ≥7 g/dL

-Fibrinogen >300 mg/dL

-Platelet count ≥50,000/microL

-Prothrombin time and activated partial thromboplastin time less than 1.5 times control

•Route of birth – Cesarean birth is required if the mother is hemodynamically unstable despite vigorous transfusion. It is desirable, but not always possible, to correct or improve the clotting abnormality prior to cesarean birth. If a cesarean birth must be performed urgently, pRBCs, FFP, platelets, and cryoprecipitate should be available in the operating room and administered as indicated. (See 'Delivery' above.)

●Management of hemodynamically stable patients (algorithm 2)

•Key elements – Hemodynamically stable patients with DIC are at risk of severe bleeding due to depletion of coagulation factors and thrombocytopenia. Although it is not possible to reliably predict which patients will have massive bleeding, blood products should be readily available and used as is appropriate for the amount of bleeding. Transfusion is usually appropriate in obstetric patients since they have, or are at high risk for, massive bleeding and they are likely to require an invasive procedure. (See 'Hemodynamically stable patients' above.)

If the fibrinogen level is <200 mg/dL in a situation where bleeding is not active but anticipated (eg, patients with preeclampsia with severe features or a concealed abruption), it is essential to administer fibrinogen concentrate or cryoprecipitate to increase the fibrinogen level to over 300 mg/dL. (See 'Fibrinogen target' above.)

•Route of birth – If the fetus is viable, cesarean birth is performed for standard indications, otherwise a vaginal birth is preferable. (See 'Viable fetus with nonreassuring fetal status or contraindication to vaginal birth' above and 'Viable fetus with reassuring fetal status and no contraindication to vaginal birth' above.)

If the fetus is nonviable, the goal is minimizing maternal morbidity and mortality. In the second trimester, we suggest dilation and extraction (D&E), rather than induction, if clinicians skilled in performing D&E are available (Grade 2C). Otherwise, and in most third-trimester cases, we favor supporting the mother with crystalloid (with or without colloid) and blood products and inducing or augmenting labor. In experienced hands, a destructive procedure that reduces the diameter of the fetal head may expedite vaginal delivery and avoid need for a hysterotomy. (See 'Nonviable fetus' above.)

●Management of uterine hemorrhage after placental extraction at cesarean birth

•Uterine tourniquet – For uterine bleeding after placental extraction that persists despite standard measures, we suggest using a Penrose drain or urinary catheter as a uterine tourniquet (Grade 2C). This procedure markedly reduces blood loss and allows time to catch up with transfusion requirements. (See 'Delivery' above.)

•Role of hysterectomy – Even though hysterectomy is considered a last resort in patients who wish to preserve childbearing capacity, it should be performed promptly if continued bleeding persists despite other preventive measures. These patients can enter a lethal downward spiral characterized by hypothermia, coagulopathy, and metabolic acidosis. (See 'Role of hysterectomy' above.)

•Maternal stabilization – If hysterectomy is not performed immediately because the patient is too unstable, the bleeding area should be tightly packed and the abdomen temporarily closed to reduce ongoing blood loss to a level where blood products can be transfused at a higher rate than the loss. Once the patient is resuscitated and euvolemic with a stable blood pressure, attempts to complete whatever surgery is needed may continue.

The patient should not be removed from the operating room in an unstable condition and should stay there until such time as the patient is stable, bleeding has stopped, and coagulopathy is reversed. The patient should be continuously monitored while resuscitation continues, blood products are administered as appropriate, and any physiologic derangements are corrected. When the patient is stable, definitive surgical interventions can be performed. (See 'Techniques to control bleeding at laparotomy' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Kirk D Ramin, MD, and Susan Ramin, MD, who contributed to earlier versions of this topic review.