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Bleeding Disorders in Pregnancy
Postpartum hemorrhage (PPH) is a leading cause of maternal death worldwide. Although the majority of PPH occurs as a result of uterine atony or other anatomical defect, the risk is increased when a congenital or acquired hemostatic defect is present. PPH can be categorized as primary, if there is abnormal bleeding during the first 24 hours (>500 or >1000 mL following vaginal or Caesarean delivery, respectively, or results in hemodynamic instability), and secondary, if abnormal bleeding from 24 hours until 6 weeks postpartum. This chapter will review the more common congenital and acquired hemostatic disorders affecting pregnancy.
Congenital Disorders
Preconception and Prenatal Counseling
Management of pregnancy in women with congenital bleeding disorders is best started before conception. Preconception counseling allows for discussion with a hematologist, obstetrician, and genetic counselor regarding risks to the mother and fetus. Strategies to reduce the risks, including prenatal testing, can be reviewed. Ultimately a treatment plan for delivery should be developed by a hematologist and shared with the patient, obstetrician, and anesthesiologist involved in the patient’s care. The location of delivery will depend in part on the severity of the women’s bleeding disorder and the severity of the known or potential bleeding disorder in the fetus.
von Willebrand Disease
During pregnancy, von Willebrand factor (VWF) and factor VIII (FVIII) levels begin to increase in the 6th week, peak between the 29th and 35th weeks of gestation, and return to near baseline within 7–10 days following delivery. Because of this rise, most patients with von Willebrand disease (VWD) will not have significant bleeding during the antepartum period; however, women with more severe disease, who experience little or no increase in their VWF and FVIII levels, may have bleeding complications that require active management (see Chapter 109 ). It is unknown whether women with VWD are more likely to miscarry compared with women without VWD, however, there is observational evidence to suspect this may be the case. In the event of miscarriage, bleeding can be severe and treatment to raise VWF levels is appropriate.
Management of Labor and Delivery
Because FVIII and VWF increase during pregnancy in patients with type 1 and some type 2 VWD, FVIII, ristocetin cofactor activity (VWF:RCo) and VWF antigen (VWF:Ag), levels should be checked at approximately 34–36 weeks of gestation to plan appropriately for delivery. Both the FVIII and VWF:RCo should be ≥50% at the time of delivery and for neuraxial anesthesia. Most patients with mild type 1 disease will have a rise of FVIII and VWF:RCo above this threshold naturally during pregnancy, and treatment can be deferred until after delivery, when levels will begin to return to baseline ( Fig. 117.1 ). In patients with third trimester FVIII and VWF:RCo levels that are <50%, treatment should be initiated before neuraxial anesthesia and delivery. If with treatment, levels ≥50% are achieved, then neuraxial anesthesia can be used safely. Neuraxial anesthesia without normalization of FVIII and VWF:RCo puts the patient at risk of epidural hematoma and irreversible paralysis. In many patients with type 2 and all patients with type 3 VWD, VWF and FVIII levels are not expected to appreciably change during pregnancy; therefore, most pregnant women with types 2 or 3 VWD will need treatment before neuraxial anesthesia and delivery. The best VWF and FVIII levels to target are a matter of debate. Some argue that treatment should mimic the typical supraphysiological levels of pregnancy; however, the benefit of this approach over a VWF/FVIII target of 100% has not been studied in a prospective fashion.
In all patients, treatment should maintain FVIII levels >50% for 3–4 days following vaginal delivery and 4–5 days following Caesarean section, or until abnormal bleeding has ceased. Some centers may be able to monitor their patient’s FVIII and VWF:RCo activity following delivery, allowing therapy to be withheld in patients with FVIII and VWF:RCo activity ≥50% until levels reach <50%; however, many hospitals are not able to perform this type of testing in real time and therefore empiric treatment should be employed. Although peripartum treatment reduces the risk of early PPH, it may occur up to 2–3 weeks after delivery. Accordingly, postpartum treatment plans should include strategies to promote identification and management of delayed bleeding.
Options for treatment to raise VWF levels include desmopressin (1-deamino-8-arginine-vasopressin, DDAVP) or VWF concentrates (see Chapter 41 ). Desmopressin can be given intranasally (1.5 mg/mL, total dose equals 300 μg) or intravenously (0.3 μg/kg). Desmopressin increases FVIII and VWF in most patients with type 1 VWD. Levels typically increase by about threefold, but not all patients respond adequately. Therefore, it is preferable to have confirmed a response to desmopressin at both 1 and 4 hours after administration before its use at the time of a hemostatic challenge. Tachyphylaxis to this drug occurs, so test administration should be done at least several weeks before its intended use. Because hyponatremia is a potential adverse event with desmopressin, fluid intake should be reduced to 75% of normal and drinks with higher NaCl content should replace free water for 24 hours after its use. Desmopressin does not cross the placenta in significant amounts; therefore, direct effects on the fetus are not of concern. There is concern regarding neonatal hyponatremia if the mother develops hyponatremia before delivery. For patients who do not respond or are intolerant to desmopressin, or have disease types where desmopressin is not effective, i.e., type 3 and 2B, VWF concentrates can be used to target trough VWF:RCo and FVIII levels of 40%–50%.
Management of Bleeding and Breastfeeding
Desmopressin is minimally excreted into breast milk and poorly absorbed by infants; therefore, it is thought to be generally safe for use while breastfeeding. Concentrations of tranexamic acid found in the breast milk are low (1% of maternal serum concentrations) and are thought to be a safe alternative for use while breastfeeding. There are no data on excretion of aminocaproic acid in breast milk. VWF concentrates are safe for use while breastfeeding.
Carriers of Hemophilia A or B
In general, no therapy is needed for women with baseline FVIII or factor IX (FIX) levels ≥50%. For those with levels ≤50% at the time of delivery, treatment is necessary before neuraxial anesthesia and delivery. Women with baseline FVIII levels <50% that rise to >50% at the end of pregnancy do not need treatment before neuraxial anesthesia and delivery but will need postpartum treatment as their FVIII levels will decline after deliver and return to baseline ∼1 week postpartum. Treatment should maintain FVIII and FIX levels ≥50% for 3–4 days postpartum after vaginal delivery and 4–5 days postpartum after Caesarean section. Treatment options to raise FVIII levels in women with FVIII deficiency include desmopressin and FVIII products. Treatment of FIX carriers is with FIX products only (see Chapter 41 ). Tranexamic acid can be used as an adjunct to desmopressin and factor replacement therapy.
Mode of Delivery in Carriers of Severe Hemophilia
For women who are pregnant with a child who is known or could possibly have severe hemophilia A, the risk of intracranial hemorrhage (ICH) is approximately 1%–2% when born via vaginal delivery or unscheduled Caesarean section. This increases to up to 8% in women who are not known to be carriers, likely due to use of assistive devices during delivery. The risk of ICH is reduced, though never zero, when an elective Caesarean section is used for delivery. It is important for the patient and obstetrician to discuss the risks and benefits of elective Caesarean section.
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