Page 2471 - Hematology_ Basic Principles and Practice ( PDFDrive )

2208 Part XIII Consultative Hematology

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Because they share many common clinical features, TTP and mechanism. On the contrary, bacterial endotoxin or exotoxin
aHUS are often categorized as a single entity, TTP-HUS. However, mediates sepsis-associated DIC in pregnant women with pyelone-
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the pathophysiologies underlying the two conditions are distinctive. phritis, chorioamnionitis, endometritis, or septic abortion. On rare
TTP is associated with unusually large multimers of circulating von occasions, elective abortions that use hypertonic solution and those
Willebrand factor (vWF), which foster platelet aggregation and complicated by hemorrhage can be associated with DIC. 133
thrombus formation. Under normal circumstances, a vWF-cleaving AFLP, or acute yellow atrophy, occurs in 1 of every 5000 to 10,000
protease referred to as ADAMTS13 (a disintegrin and metallopro- pregnancies, most often in the third trimester of primiparous
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teinase with a thrombospondin type 1 motif, member 13) cleaves women. Maternal and fetal mortality are 5% and 15%, respectively.
these multimers into smaller multimers of normal size. In TTP, func- Although the pathogenesis of AFLP is not clear, microvesicular fatty
tion of the cleaving protease is impaired. ADAMTS13 deficiency infiltration of the liver’s central zone is observed and presumably plays
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characterizes familial TTP. Inhibition of ADAMTS13 protease activ- a central role in the development of this disease. In some cases,
ity by an autoantibody characterizes the acquired form of TTP. An fatty infiltration can be detected by ultrasonography or computed
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inhibitory autoantibody can be found in 70% to 85% of patients tomography (CT). Patients present with a variety of symptoms,
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with TTP. On the other hand, impaired vWF-cleaving protease including malaise, fatigue, right upper quadrant pain, dyspnea, and
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activity does not appear to play a role in the pathogenesis of a HUS. mental status changes. Laboratory findings include abnormal liver
Our understanding of the pathogenesis of atypical HUS has evolved function test results consistent with cholestatic disease, elevated
in recent years as this disorder has been recognized to be associated ammonia, low fibrinogen and antithrombin levels, and elevated
as a complement-mediated disorder. With this dysregulation of prothrombin time, with evidence of DIC. Hepatic dysfunction can
complement, a picture of profound inflammation evolves. In contrast impair gluconeogenesis. Diabetes insipidus may be present. The
to TTP, there is typically more severe renal involvement with less clinical course of AFLP resembles those of HELLP syndrome, TTP,
severe thrombocytopenia. There can be some similarity found and HUS, although the microangiopathy and thrombocytopenia are
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between the features of TTP-HUS and HELLP syndrome. It can be not as severe. With supportive care, the condition typically resolves
difficult to distinguish TTP and HUS from HELLP syndrome within 10 days after delivery.
because they both have signs of microangiopathy. TTP tends to occur
earlier in pregnancy, with a mean onset at 23.5 weeks, although it
can occur at any point from the first trimester through the postpartum LEUKEMIA AND LYMPHOMA
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period. HUS primarily occurs after delivery; 90% of cases occur
in the postpartum period, with a mean onset at 26 days after deliv- The diagnosis of hematologic malignancy during pregnancy can be
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ery. TTP and HUS do not cause hypertension or liver necrosis. incredibly traumatic for a pregnant patient and her family, and it is
Furthermore, TTP and HUS frequently persist after delivery, but a treatment challenge for the physician. Although great strides have
HELLP syndrome typically resolves in the postpartum period. been made in the treatment of this heterogeneous group of diseases,
Treatment of TTP-HUS involves emergent plasmapheresis within the treatment of pregnant patients is limited because of the lack of
24 to 48 hours of diagnosis. The response rate among pregnant research in this area and limited pregnancy safety data. The need to
women treated with plasmapheresis for TTP is approximately 75%. treat the patient and risk to the fetus must both be taken into
By comparison, the overall response rate in patients with TTP is account. Diagnosis can be difficult because many of the nonspecific
approximately 80% to 90%. 122–125 Long-term sequelae in surviving signs that accompany these disorders, including fatigue, anemia, loss
patients include chronic renal failure, hypertension, and recurrence of appetite, and weight loss, can occur at various times during a
of TTP-HUS. TTP-HUS recurs in approximately 50% of subsequent normal pregnancy. Diagnostic imaging is limited mainly to ultraso-
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pregnancies. Infusion of FFP represents an alternative to plasma- nography and magnetic resonance imaging (MRI). Although the
pheresis, although plasmapheresis is the preferred treatment modality. radiation dose from a CT scan is considered low, it is usually avoided.
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The response rate after FFP infusion is 64%. Corticosteroids have Diagnostic procedures such as bone marrow or lymph node biopsy
also been used successfully in the treatment of pregnancy-associated can usually be performed safely during pregnancy.
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TTP-HUS, with a response rate of 26%. Conversely, antiplatelet In terms of treatment, the risk of teratogenicity from treatment
agents such as aspirin do not play a role in the treatment of pregnancy- appears highest during fetal organogenesis, which occurs mainly
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associated TTP-HUS. 128 during the first trimester of pregnancy. Ideal dosing is unknown,
but dosing is usually based on the woman’s prepregnancy weight.
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In the largest study of its kind, Aviles and Neri followed 84
Disseminated Intravascular Coagulation children born to mothers with hematologic malignancies, including
29 women with acute leukemia and 38 who received treatment
DIC in pregnant women can occur in various clinical settings, includ- during the first trimester. Assessing growth and development, hema-
ing HELLP syndrome, TTP-HUS, placental abruption, amniotic tologic parameters, psychological characteristics, and cognitive func-
fluid embolism, uterine rupture, intrauterine fetal demise, sepsis, tion over 19 years, the authors found no significant, long-term,
elective abortion, and acute fatty liver of pregnancy (AFLP). deleterious consequences related to treatment. The risk of childhood
Severe placental abruption sufficient to cause fetal death occurs in malignancies was not increased. In a retrospective report following
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0.12% of all pregnancies. This condition leads to a consumptive the outcome of 54 newborns of women treated with chemotherapy
hypofibrinogenemia, and (when fibrinogen levels fall below 100 to specifically during the first trimester, long-term development was
150 mg/dL) bleeding may ensue. Maintenance of adequate urine found to be normal. However, this is in contrast to general incidence
output and a hematocrit level greater than 30% are important of congenital malformations found by others for treatment given
components of care for women who have had a placental abruption. during this time period.
Either vaginal delivery or cesarean section is appropriate in the
context of severe placental abruption. In a woman undergoing
cesarean section after abruption, the platelet count should be main- Hodgkin Lymphoma
tained at 50,000/µL or above through platelet transfusion and
fibrinogen replaced with FFP or cryoprecipitate. That hematologic malignancies are among the most commonly
Amniotic fluid embolism is a rare but often lethal condition with diagnosed cancers during pregnancy reflects to a large extent the rela-
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a mortality rate of approximately 80%. About 10% to 15% of these tively high incidence of Hodgkin lymphoma in women between the
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patients develop a coagulopathy. DIC in this setting most likely ages of 15 and 24 years. On the basis of results of several retrospec-
follows the release of thromboplastin-rich material into the maternal tive studies, Hodgkin lymphoma diagnosed during pregnancy appears
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circulation. DIC seen in association with uterine rupture and to have no significant effect on pregnancy outcome. A single-
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intrauterine fetal demise presumably occurs through a similar institution experience published by Dilek and colleagues, however,