Bleeding and the Management of Hemorrhagic Disorders in Pregnancy

Introduction

Successful management of bleeding in pregnancy requires an understanding of the various scenarios in pregnancy in which bleeding can arise. In this chapter the discussion is focused on pregnancy-related bleeding, including bleeding due to obstetric, surgical, and systemic causes. Surgical bleeding is bleeding caused by incisions, lacerations, ruptured vessels, or ruptured viscus and includes the bleeding that accompanies birth trauma, cesarean delivery, or a ruptured ectopic pregnancy. Bleeding related to systemic factors may be caused by inadequate platelet function (thrombocytopathy) or platelet number (thrombocytopenia) and/or inadequate clotting factors, which may be inherited or acquired and may evolve acutely or chronically. Obstetric bleeding has not been defined, but for the purposes of this chapter it is considered to be abnormal bleeding originating from the blood vessels within the uterus. An understanding of obstetric bleeding requires a knowledge of normal placentation, separation and expulsion of the placenta at the conclusion of pregnancy, and involution of the uterus after delivery.

Normal Placentation

Humans are supported in utero through a hemochorial placenta. Fetal trophoblast (the cells that comprise the outer layer of the evolving placenta) invade, erode, and dilate maternal blood vessels so that the chorion or outer membranes of the placenta are ultimately in direct contact with maternal blood. This type of placenta is in contrast with an epitheliochorial placental, a superficial placenta characteristic of horses, pigs, sheep, cows, goats, and deer in which the chorion approximates the uterine epithelium, and an endotheliochorial placenta, characteristic of carnivores, which invades more deeply than an epitheliochorial placenta but only approximates without invading the uterine blood vessels. The fetal trophoblast of hemochorial placentas (which are characteristic of rodents, rabbits, and larger primates, including humans) invades and remodels the spiral arteries (terminal branches of the uterine arteries), so that rather than being narrow and muscular, they are wide and flaccid. Consequently, blood actually leaves the maternal spiral arteries to circulate in the extravascular uteroplacental space before returning to the general maternal circulation.

Placental Separation and Expulsion

No matter how advanced the gestation, at the conclusion of pregnancy, the placenta should separate from the wall of the uterus and be expelled. During gestation, the placenta is anchored to the wall of the uterus through a cell–extracellular matrix interaction between the uterus and the placenta. As gestation advances, a fibrin layer is formed (Nitabuch fibrinoid layer) on the surface of the placenta that facilitates detachment of the placenta at term. Before term, the placenta may not separate as easily or completely, and this may be a factor in hemorrhage associated with miscarriage and preterm delivery. Separation of the placenta is associated with exposure of the open spiral arteries and bleeding across the entire surface previously occupied by the placenta. The mechanism by which bleeding from these vessels is controlled is predominantly contraction of the uterus. Contraction of the interlacing muscle fibers of the uterus results in external pressure on the open spiral arteries. Other factors, not well understood, lead to vasoconstriction of these open vessels. For the process to succeed and bleeding to be controlled, the placenta must be expelled by the uterine contractions and the walls of the uterus apposed.

Involution of the Uterus

After delivery and expulsion of the placenta, bleeding gradually ceases depending largely on the length of the preceding pregnancy. The reported median duration of bleeding after delivery ranges from 24 to 36 days. After term delivery, the uterus returns to its prepregnancy size over the course of approximately 6 to 7 weeks.

Obstetric Bleeding

Bleeding is expected after vaginal delivery, with an estimated blood loss of up to 500 mL, and at the time of cesarean delivery, with an estimated blood loss of up to 1000 mL. Bleeding is not expected during pregnancy, nor is bleeding expected in excess of these amounts at delivery or postpartum. When bleeding does occur during pregnancy or is excessive at delivery or postpartum, the most common reason is obstetric bleeding, which includes bleeding associated with most cases of postpartum hemorrhage (PPH) and most cases of miscarriage.

Miscarriage

Miscarriage is variously defined but usually refers to a pregnancy loss, or spontaneous abortion, before 20 weeks' gestation. The definition of a spontaneous abortion is “the spontaneous termination of a pregnancy occurring before 20 completed weeks of gestation by expulsion complete or incomplete of the products of conception from the uterus, by failure of the embryo to develop or by death of the fetus in utero.” In a large population study examining more than 1 million pregnancy outcomes, 11% of pregnancies that were intended to be carried to term ended in spontaneous abortion. In a study that used a sensitive assay to detect pregnancy, 12% of clinically recognized pregnancies ended in spontaneous abortion, but another 22% ended in spontaneous abortion before being recognized. Miscarriage is relatively common and is diagnosed even more frequently when pregnancy is detected earlier with sensitive home-based pregnancy tests.

In a study of bleeding as a risk factor for miscarriage, 4510 women were enrolled prospectively before pregnancy; 1204 (27%) experienced bleeding in the first trimester of pregnancy. Not all women who bled went on to miscarry, but 517 (43%) of those who experienced bleeding ultimately did miscarry. Heavy bleeding (similar to or greater than that of a menstrual period) was strongly predictive of miscarriage, with 3 times the risk compared with no bleeding (odds ratio [OR], 3.0; 95% confidence interval [CI], 1.9 to 4.6), whereas spotting or light bleeding did not increase the risk of miscarriage.

Bleeding that accompanies miscarriage increases with gestational age, as does the case fatality rate from miscarriage. The risk of maternal death in association with spontaneous abortion was eightfold higher with a fetal gestational age of 12 weeks or longer than with a gestational age of less than 12 weeks, which suggests that bleeding complications are much greater with increasing gestation. Spontaneous abortion accounts for 3% of all pregnancy-related deaths in the United States. In a national study in the United States the leading cause of maternal death associated with spontaneous abortion was infection (59%), followed by hemorrhage (18%), embolism (13%), anesthesia complications (5%), and other causes (5%); disseminated intravascular coagulation (DIC) was an associated condition in half of the cases of spontaneous abortion–related maternal death.

After a determination has been made that the pregnancy has ended, either because no embryo or fetus has developed, because the embryo or fetus has died, or because the miscarriage is actually in progress, the obstetrician-gynecologist will surgically evacuate the uterus or await spontaneous expulsion of the products of conception. Historically, obstetrician-gynecologists believed that all miscarriages should be surgically evacuated, but in the past 25 years, the necessity of surgical evacuation in all cases has been questioned, and there have been a number of randomized trials examining surgical evacuation versus expectant management. In a Cochrane review of five trials with 689 participants, the patients managed expectantly were less likely to have infection (relative risk [RR], 0.29; 95% CI, 0.09 to 0.87) but more likely to have an incomplete miscarriage necessitating unplanned surgical treatment. The expectantly managed patients experienced a significantly greater number of days of bleeding (weighted mean difference, 1.59; 95% CI, 0.74 to 2.45) and a significantly greater amount of bleeding according to a scale (weighted mean difference, 1.00; 95% CI, 0.60 to 1.40). Therefore surgical management of spontaneous abortion is preferred in the patient at risk of bleeding due to a preexisting hemostatic abnormality.