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

factor (VWF), fibrinogen, and factors VII, VIII, and X all increase (excluding neural tube defects) revealed improvement in low hemoglo-
markedly, whereas factors II, V, IX, and XII are essentially unchanged bin level in late pregnancy, but had no measurable effect on any substan-
and factor XIII declines. Levels of protein C and antithrombin remain tive measures of pregnancy outcome (Chap. 41). 25
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stable throughout pregnancy whereas total and free protein S fall with Vitamin B (cobalamin) deficiency during pregnancy is rare, in
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increasing gestational age. Fibrinolysis is also impaired by increases part because deficiency of this vitamin leads to infertility. Serum cobal-
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in plasminogen activator inhibitors I and II, the latter a product of the amin levels are known to fall during pregnancy. A shift from the serum
placenta. 13 to tissue stores is proposed to account for the drop in serum B lev-
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els. However, values less than 180 pmol/L usually are not observed in
ANEMIA IN PREGNANCY healthy women, and these low-normal levels are not accompanied by
increased levels of methylmalonic acid, an indicator of cellular defi-
IRON DEFICIENCY ciency of cobalamin (Chap. 41). 27
Worldwide, the contribution of anemia to maternal and fetal morbidity
and mortality is well recognized; in some parts of Africa, more than RED CELL APLASIA
75 percent of pregnant women are anemic, and there is a significant cor- A rare cause of anemia in pregnancy is pure red cell aplasia (Chap. 36).
relation between maternal mortality and anemia. It has been suggested In pure red cell aplasia, anemia tends to occur early in pregnancy and
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that iron deficiency may protect against placental malaria, but epidemio- often resolves within weeks of delivery. The pathogenic mechanism
logic studies have not been conducted to verify this supposition. In preg- leading to red cell aplasia does not appear to be transferred to the fetus,
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nant women, anemia is defined as a hemoglobin concentration of less than but does tend to recur in subsequent pregnancies. 28,29 Conservative
11 g/dL in the first and third trimesters, and less than 10.5 g/dL in the sec- treatment, if feasible, is probably best until delivery; successful prenatal
ond trimester. In both the industrialized and the developing world, treatments with glucocorticoids and with intravenous immunoglobulin
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iron-deficiency anemia (Chap. 43) is the commonest cause of anemia. have been reported. 30,31
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On average approximately 1 g of iron is required during a normal
pregnancy; 300 mg of iron are required by the fetus and the placenta,
whereas expansion of the maternal red cell mass requires 500 mg, and BLEEDING DISORDERS AND CAUSES
200 mg are lost via excretion. These requirements exceed the iron stor-
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age of most young women and in general cannot be met by the diet. OF THROMBOCYTOPENIA
Even in cases of maternal iron deficiency, the fetal requirements for iron Bleeding disorders in pregnancy require consideration of maternal
are always met; thus there is no correlation between the hemoglobin of bleeding and hemorrhagic complications in the newborn. Data on the
the fetus and that of the mother. 18 fetus are often lacking, and the practitioner must base decisions on past
Iron-deficiency anemia during the first two trimesters of preg- experience and the mother’s previous reproductive history.
nancy is associated with a twofold increased risk for preterm delivery
and a threefold increased risk for delivery of a low-birth-weight infant.
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However, a large randomized trial comparing routine iron prophy- DISSEMINATED INTRAVASCULAR
laxis in pregnancy versus iron supplementation given only as needed COAGULATION
demonstrated no significant differences in adverse maternal or fetal
outcomes. As in nonpregnant individuals, iron-deficiency anemia can Life-threatening bleeding is seen with some pregnancy-unique com-
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generally be diagnosed using laboratory values such as serum ferritin, plications, resulting in disseminated intravascular coagulation (DIC).
and transferrin saturation levels (Chap. 43). Pica, the ingestion of non- Because of the changes in coagulation factor levels, D-dimer, and plate-
nutritive substances, is said to be more common among iron-deficient let count during pregnancy, the normal range for tests routinely used to
pregnant women than among other populations with iron deficiency. diagnose DIC in a nonpregnant state cannot be extrapolated directly to
Ice, clay or dirt, and starch are the most frequent substances ingested DIC in pregnancy. Serial measurement of the prothrombin time (PT),
(Chap. 43); to some extent, however, the choice appears to be cultural partial thromboplastin time (PTT), D-dimer, and fibrinogen are likely
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and much more widespread than most practitioners realize. 21 to be more helpful than measuring a single value. The DIC score devel-
oped by the International Society on Thrombosis and Hemostasis has
been modified for pregnancy and this score may be more useful in iden-
FOLATE AND VITAMIN B DEFICIENCY tifying DIC. 33
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Apart from iron deficiency, folate deficiency is the next most frequent Complications of pregnancy that lead to DIC include placental
nutritional deficiency leading to anemia in pregnant women. In the abruption, a retained dead fetus, and amniotic fluid embolism (Chap.
United States, where foodstuffs are supplemented with folate and the 129). Although amniotic fluid embolism is a significant cause of mater-
level of awareness of the association between folate deficiency and nal death in developed countries, the mortality decreased from 86 per-
neural tube defects in the embryo is high, folate deficiency is relatively cent in 1979 to less than 30 percent in 1994 and 1995, perhaps from
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unusual. Folate requirements in pregnancy are roughly twice those in a better supportive therapy. Amniotic fluid embolism is most likely
the nonpregnant state (800 mcg/day vs. 400 mcg/day), and if diet is to occur in older multiparous women whose pregnancies have gone
insufficient may exceed the body’s stores of folate (5–10 mg) relatively beyond the 40th week and during tumultuous labor. Amniotic fluid
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quickly. Anemia related to folate deficiency most often presents in the enters the maternal circulation through tears in the chorioamniotic
third trimester and responds to folate supplementation with reticulocy- membranes, injury to the uterine veins, or uterine rupture. Its onset is
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tosis within 24 to 72 hours. Reports of severe pancytopenia and even heralded by maternal vascular collapse with dyspnea, hypotension, and
states resembling the HELLP (hemolysis, elevated liver enzymes, and cardiac arrhythmias followed by DIC that is manifested by oozing from
low platelet count) syndrome as a result of folate deficiency in preg- intravenous lines, hematuria, hemoptysis, and excessive uterine bleed-
nancy have appeared in the literature. 23,24 Despite these case reports, a ing. Atypical presentations have also been reported in which there is
review of 21 trials measuring the effect of folate supplementation on rapid deterioration of the fetus, followed by maternal respiratory and
biochemical and hematologic parameters and pregnancy outcome cardiovascular deterioration with development of DIC. 35

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