Page 146 - Williams Hematology ( PDFDrive )

120 Part III: Epochal Hematology Chapter 8: Hematology during Pregnancy 121

In amniotic fluid embolism, DIC appears to involve an abnormal should be tested at the first visit during pregnancy and again in the
host response to exposure to various foreign antigens with the subse- third trimester, but it should be noted that factor IX levels generally
47
quent release of endogenous mediators which drive the clinical mani- do not rise during the course of the pregnancy. The sex of the fetus
36
festations. Treatment is not significantly different than in other cases should be determined to guide the obstetrician at delivery. With the
of DIC with bleeding (Chap. 129); however, there are some reports of recognition that maternal serum contains cell free fetal DNA, genomic
successful management with uterine artery embolization. 37 strategies have been developed to determine fetal gender as early as 7
Placental abruption has also led to development of DIC, and the weeks of gestation. Similarly, strategies to determine whether a male
spectrum of hemostatic failure is broad and appears to be related to fetus is affected by hemophilia based on testing of maternal blood have
the degree of placental separation. Volume resuscitation, delivery of the now been developed and will doubtless enter the clinical arena in the
38
49
fetus, and infusion of blood products to correct the maternal coagula- near future. Cranial hemorrhage is the commonest site of bleeding
tion defect are indicated. Regional anesthesia is contraindicated because in newborns with severe hemophilia, and has the highest potential for
of the risk of bleeding in the epidural space and of the pooling of blood long-term serious sequelae. Risk factors for cranial hemorrhage include
48
in the lower limb vascular bed, which could worsen hypovolemia. prolonged labor and use of instruments during delivery. To protect
38
Fetal trophoblast cells have distinct properties which may activate coag- a potentially affected or known hemophiliac fetus, vacuum extraction
ulation including expression of tissue factor, suppression of fibrinoly- should be avoided at delivery and forceps should be used only with cau-
sis, and exposure of anionic phospholipids. Finally, intrauterine fetal tion. All intramuscular injections should be withheld from the newborn
39
death can also lead to DIC. Thromboplastic substances and specifically until hemophilia testing is completed. If an infant’s hemophilia status
tissue factor released from dead fetal tissues into the maternal circula- is not known, testing should be done on cord blood to avoid poten-
48
tion are thought to trigger DIC; however, this is not usually detectable tial bleeding or bruising after a blood draw. The mother’s factor level
by laboratory tests until 3 or 4 weeks after fetal demise. Overt DIC is should be followed for a few days after delivery and menstrual bleeding
present in approximately 50 percent of women who retain a dead fetus should be monitored to ensure adequate hemostasis.
for 5 weeks or longer. 40 There is also an association between pregnancy and acquired
hemophilia caused by factor VIII autoantibodies (Chap. 127). This con-
VON WILLEBRAND DISEASE dition usually appears 1 to 4 months postpartum, but emerges during
50
Although von Willebrand disease (VWD) is transmitted in an autoso- pregnancy in up to 14 percent of patients. In general, the Bethesda titer
of the inhibitor is low and in most cases the inhibitor disappears sponta-
mal dominant fashion, women appear to be disproportionately affected neously. Inhibitors can recur in subsequent pregnancies. 51
with bleeding symptoms, primarily menorrhagia and postpartum hem- Rarely, pregnant women with factor deficiencies other than factors
orrhage (Chap. 126). In normal women and in types 1 and 2 (but not VIII and IX may be identified. The most important of these to recog-
type 3) VWD patients, levels of factor VIII and VWF rise during preg- nize is deficiency of factor XIII, which is associated with habitual hem-
nancy, with the most pronounced increase in the third trimester. As orrhagic abortions and postpartum hemorrhage. In rare pregnancies
39
a result, prophylactic administration of VWF-containing factor con- reaching term, bleeding complications, including intracranial hemor-
centrates at delivery is often unnecessary in type 1 and type 2 VWD rhage in the infant, have been observed. 52,53 Treatment of this deficiency
patients; however, the risk of postpartum hemorrhage is significant with fresh-frozen plasma, cryoprecipitate, or plasma-derived factor XIII
(13–29 percent) as levels fall rapidly after birth. Thus in type 1 patients, concentrates (now available in the United States) prevents abortion in
41
factor VIII levels should be tested not only late in the third trimester, women, although there are no controlled studies. Most authorities rec-
54
but also for 1 to 2 weeks postpartum. These patients should be moni- ommend more frequent prophylactic therapy during pregnancy (every
tored for increases in menstrual blood flow for at least 1 month. Risk of 3 weeks vs. every 5–6 weeks) with booster doses during labor or before
bleeding appears to be minimal when factor VIII levels are greater than cesarean section to ensure a level of 5 percent or greater. Although
55
50 U/dL. There are several reports of severe thrombocytopenia devel- rare, congenital afibrinogenemia, hypofibrinogenemia, and dysfibrino-
oping late in pregnancy in patients with type 2B VWD, 42,43 and at least genemia (Chap. 125) can cause hemorrhagic and thrombotic pregnancy
one of these patients developed a pulmonary embolus while receiving complications. Most experts recommend fibrinogen replacement (using
cryoprecipitate for postpartum hemorrhage. Despite the possible risk cryoprecipitate or fibrinogen concentrate) to maintain a level of 60 to
of thrombosis, these patients may require treatment with plasma-de- 100 mg/dL during pregnancy and for 6 weeks postpartum. 56
rived VWF-containing concentrates at delivery or postpartum if there is
abnormal bleeding, and with platelets if thrombocytopenic bleeding is
not controlled with infusion of VWF concentrate. Type 3 VWD patients CAUSES OF THROMBOCYTOPENIA
require infusion of a plasma-derived VWF-containing concentrate at Thrombocytopenia in pregnancy is relatively common, with up to
delivery, typically 40 to 80 IU/kg, followed by doses of 20 to 40 IU/kg 5 percent of all pregnant women exhibiting asymptomatic thrombo-
daily for a week then tapered over the next few weeks. Use of des- cytopenia. Many causes of thrombocytopenia in pregnancy are iden-
44
57
mopressin acetate (DDAVP) antepartum is controversial because of the tical to those seen in the nonpregnant state, with some predisposing
theoretical risk of vasoconstriction and placental insufficiency and the to bleeding whereas others predispose to clotting. However, there are
risk of maternal hyponatremia. Guidelines for management of VWD at several conditions leading to thrombocytopenia that are unique to preg-
delivery and during the puerperium have been published and are also nancy, including gestational thrombocytopenia, preeclampsia/HELLP
reviewed in Chap. 126. 45,46 syndrome/eclampsia, and acute fatty liver of pregnancy.

COAGULATION FACTOR DEFICIENCIES Gestational and Immune Thrombocytopenia
Carriers of hemophilia A and B generally have factor levels approxi- Gestational thrombocytopenia and idiopathic thrombocytopenic pur-
mately 50 percent of normal; however, a wide range of values have pura (ITP) are best discussed together as they can be difficult to dif-
been reported as a result of random inactivation of the X chromosome ferentiate and, in fact, may be two extremes of a spectrum of disease.
(Chaps. 10 and 123). 47,48 Ideally, carriers are identified before preg- In general, gestational thrombocytopenia is asymptomatic and is said
nancy when prenatal counseling can be offered. Baseline factor levels to occur later in pregnancy and be less severe than ITP. Most sources

Kaushansky_chapter 08_p0119-0128.indd 121 17/09/15 6:13 pm