Page 2473 - Hematology_ Basic Principles and Practice ( PDFDrive )

2210 Part XIII Consultative Hematology

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and 7 miscarriages. First trimester loss is the most frequent com- concentrates (Humate-P, Alphanate). Cryoprecipitate can be used on
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plication in patients with PV. Information regarding pregnancy in an emergent basis if vWF-FVIII concentrates are unavailable, but it
primary myelofibrosis is even sparser, with overall fewer than 20 cases is avoided if possible during pregnancy because it poses a small risk
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reported in the literature. However, on the basis of these, fetal loss is of bloodborne infection. Although antifibrinolytic therapy plays a
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common. In women of childbearing age with an MPN, a discus- role in the management of individuals with vWD, it is also generally
sion when the patient is not pregnant should occur, outlining preg- avoided during pregnancy and lactation because of its potential tera-
nancy management and risks. Women should be informed if they are togenicity and effects on newborns. Data concerning the toxicity of
taking a drug with teratogenic potential, and the risk of unplanned antifibrinolytic therapy in pregnancy are limited.
pregnancy should be recognized. Exerting its effect through the type 2 vasopressin receptors,
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Continuing aspirin is considered standard if there is no clear DDAVP rapidly and transiently increases levels of FVIII and vWF.
contraindication, extrapolating from the results of the European It is administered by continuous intravenous infusion over 30 minutes
Collaboration on Low-dose Aspirin in Polycythemia Vera (ECLAP) in the setting of an acute bleeding event. On a prophylactic basis, it
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study, which confirmed the importance of aspirin in the management can be given subcutaneously or inhaled nasally. Although highly
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of MPNs. Certain features may confer a patient at more risk of effective when used in an appropriate clinical context, DDAVP does
maternal or fetal complications during pregnancy. These include have limitations. Patients who have never received DDAVP therapy
cardiovascular risk factors, prior thrombosis, and prior pregnancy- should be tested for responsiveness to the agent during the second
related complications that may have been caused by MPN or for trimester. Because of its potential oxytocic effect, DDAVP is preg-
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which no other cause can be identified. In these settings, cytoreduc- nancy risk category B. Owing to its antidiuretic effect, DDAVP
tive therapy or LMWH can be considered. There are no clear can cause fluid retention and hyponatremia. Finally, DDAVP has
evidence-based management guidelines in these settings, but local uncertain utility in the management of women with type 2 and type
practice is to use LMWH. Six weeks of postpartum LMWH should 3 vWD because of an underlying genetic defect in these individuals.
be considered in the postpartum setting if there is no contraindica- VWF-FVIII concentrate is indicated for these patients.
tion. It is clear that management of these patients requires close Multidisciplinary care by an experienced obstetrician and hema-
collaboration with a hematologist and high-risk obstetrician. tologist should be provided for pregnant women with vWD. This
becomes particularly important as parturition nears. In providing care
for this population of patients, clinicians aim to control the conse-
BLEEDING DISORDERS quences of the disease in pregnant and postpartum mothers. FVIIIc
and vWF:RCo levels, partial thromboplastin time (PTT), type and
von Willebrand Disease crossmatch, and a complete blood count are obtained at the time of
hospital admission. Women with vWD should be monitored for
Affecting approximately 1% of the population, von Willebrand bleeding at the time of delivery, with blood cell products and DDAVP
disease (vWD) is the most common inherited disorder of coagulation available for use as needed. vWF:RCo and FVIIIc levels of 50 IU/dL
(see Chapter 139). By mediating platelet adhesion and functioning generally serve as a target at parturition and in the postpartum period;
as a carrier for circulating factor VIII (FVIII), vWF plays a vital role expert opinion suggests that women with levels below this should
in hemostasis. According to the most widely used classification by receive replacement products. 175
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Sadler, there are three types of vWD: type 1 (partial deficiency of In the management of pregnant women with vWD, the provision
vWF); type 3 (severe deficiency of vWF); and type 2, which includes of regional anesthesia during delivery is an important topic. Some
four subtypes that involve qualitative defects in vWF. FVIIIc, vWF anesthesiologists use epidural anesthesia in patients with mild disease
antigen (vWF:Ag), and the ristocetin cofactor activity (vWF:Rco) are with or without the use of DDAVP. 176,177 For patients with moderate
important components of the laboratory diagnosis. vWD does not to severe disease, an alternative form of analgesia may be considered.
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impair fertility or increase the likelihood of miscarriage. Thus the If epidural analgesia is used in a patient with moderate to severe
management of pregnancy in patients with the condition is an disease, prophylactic factor replacement therapy is indicated. The
important feature of the overall care for these individuals. epidural catheter should be removed soon after delivery because
For pregnant women with vWD, bleeding at parturition and in falling factor levels in the postpartum period increase the bleeding
the postpartum period is of primary concern. Related concerns risk. 173
include the administration of anesthesia, perineal hematoma, episi- The route of delivery is also an important matter in patients with
otomy blood loss and healing, and bleeding at surgical sites. Approxi- vWD. To minimize the risk of neonatal hemorrhage, some obstetri-
mately 75% of women with moderate to severe vWD experience cians recommend cesarean delivery for patients with type 2, type 3,
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significant peripartum bleeding. Overall there is a 20% risk of and clinically moderate type 1 disease. However, neonatal bleeding
postpartum hemorrhage in women with vWD. In a normal preg- occurs in the setting of cesarean delivery as well, and delivery methods
nancy, FVIIIc and vWF levels increase, beginning in the second tri- have not been rigorously compared. 167,176
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mester. They peak as the pregnancy nears term. Among many Prenatal testing is a challenge in women with vWD. The specific
pregnant women with vWD, particularly those with type 1 disease, mutations involved in the pathogenesis of type 1 and type 3 vWD
a similar increase in FVIII and vWF levels is observed. FVIIIc levels are not known. Multiple mutations are involved in the pathogenesis
in pregnant women with vWD peak at 29 to 32 weeks of gestation, of type 2 vWD. Fetal blood vWF levels can be obtained if necessary,
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but vWF:Ag levels peak at approximately 35 weeks of gestation. but inherent risks are associated with the procedure. Expectant
The risk of peripartum bleeding is related to the level of these mothers should be informed of these risks in making decisions about
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factors. In most instances, vWF:Ag, FVIIIc, and vWF:RCo levels prenatal genetic testing.
should be assessed during the first and third trimesters to determine
the bleeding risk for individuals with vWD. However, this may be
less relevant for patients with type 3 vWD, in whom levels tend to HEMOPHILIAS
remain low throughout pregnancy. Patients without a documented
bleeding disorder who have bleeding complications during pregnancy The hemophilias (A and B) are X-linked recessive diseases character-
should be evaluated for vWD because many with the disorder have ized by hemarthrosis and subcutaneous and intramuscular bleeding
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a mild clinical course and remain undiagnosed for a long period. 171 (see Chapter 136). Hemophilia A results from deficient production
As a general rule, therapy can be rendered either in the setting of FVIII, and hemophilia B from deficient production of FIX. As
of a spontaneous bleeding event or in a prophylactic context for X-linked disorders, hemophilia A and B occur most often in men,
the high-risk individual. Mainstays of therapy for pregnant women but they can occur in women under several circumstances, including
with vWD include DDAVP (1-deamino-8-D-arginine-vasopressin; X-chromosome inactivation (lyonization), X hemizygosity, and
desmopressin), a synthetic analogue of vasopressin, and vWF-FVIII double heterozygosity as can occur in the female offspring of an