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2210 Part XII: Hemostasis and Thrombosis Chapter 129: Disseminated Intravascular Coagulation 2211

of heparin to patients with preeclampsia and eclampsia has not resulted fail to thrive and are prone to liver failure and death. LCAD is one of
in convincing benefits. 292 four enzymes taking part in β-oxidation of fatty acids in mitochondria.
When it is deficient, accumulation of medium- and long-chain fatty
HELLP Syndrome acid occurs. One predominant mutation (G1528C) accounts for 65 to
The syndrome of hemolysis (H), elevated liver enzymes (EL), low plate- 90 percent of cases with the deficiency. The precise mechanism by which
let count (LP), and severe epigastric pain is a complication of pregnan- LCAD deficiency in the fetus causes the severe liver disease in the het-
293
cy-induced hypertension. Seventy percent of the cases occur during erozygous mother is unclear. The acute fatty liver disease of pregnancy
the third trimester of pregnancy and 30 percent occur during the post- is characterized by severe liver dysfunction, renal failure, hypertension,
294
partum period. HELLP syndrome occurs more often in whites, mul- and signs of DIC. 304,308 The typical histologic feature is microvesicular
tipara, and women older than 35 years. Liver biopsy findings of fibrin fatty infiltration of the liver. Exceedingly low levels of AT and other lab-
292
deposition in hepatic blood vessels and laboratory tests consistent with oratory signs of DIC were observed in a series of 28 patients, but no def-
DIC in a significant proportion of patients imply that DIC plays a role in inite clinical benefit from AT concentrate infusion was achieved. The
308
the pathogenesis of the syndrome. 294–296 Hepatic imaging in 33 patients primary therapy for these patients is early delivery and supportive care,
revealed subcapsular hematomas in 13 and intraparenchymal hemor- which yield a maternal survival of 90 percent and perinatal survival of
297
rhage in 6. What actually triggers DIC in these cases is not known more than 85 percent. 304,309 Pancreatitis is a potentially lethal complica-
but has been related to endothelial dysfunction. Multiple organ dys- tion of acute fatty liver of pregnancy. 310
292
functions manifested by acute renal failure, ascites, pulmonary edema,
and severe hemorrhage resulting from DIC may develop, leading to sig-
nificant maternal and perinatal mortality rates. Management of patients NEWBORNS
with HELLP syndrome consists of supportive care, careful monitor- Newborns have a limited capacity to cope with triggers of DIC for sev-
ing, and blood component replacement therapy. With few exceptions, eral reasons: (1) their ability to clear soluble fibrin and activated fac-
immediate delivery, not necessarily by cesarian section, is indicated. tors is reduced; (2) their fibrinolytic potential is decreased because of a
HELLP syndrome tends to recur in subsequent gestations. 298 low plasminogen level; and (3) their capacity to synthesize coagulation
factors and inhibitors is limited. 311,312 Criteria for diagnosis of DIC in
Sepsis During Pregnancy newborns are different from those for diagnosis in adults. Important
313
Gram-negative bacteria, group A streptococci, and Clostridium perfrin- to consider are the physiologic hemostatic findings common at this age,
gens are among the more common causes of sepsis during pregnancy. which include low levels of the vitamin K–dependent factors, reduced
These infections are frequently associated with fulminant DIC. The AT and protein C levels, and prolonged thrombin time. The laboratory
pathogens gain entry into the circulation during abortion, via amni- evidence of DIC in the newborn is based on the progressive decline of
onitis that may follow invasive procedures or rupture of membranes, by hemostatic parameters, thrombocytopenia, and reduced levels of fibrin-
endometritis developing during labor, and by way of the urinary tract. ogen, factor V, and factor VIII. 311,314,315
Approximately 40 percent of bacteremic patients experience shock, DIC occurs in sick neonates and particularly in those who are
299
which is associated with significant mortality. In addition, a high rate premature. More than one underlying cause usually can be identified
of bleeding and organ dysfunction affects the kidneys, lungs, and cen- in newborns with DIC. The most frequent underlying conditions are
tral nervous system. sepsis, hyaline membrane disease (respiratory distress syndrome),
Treatment of all cases of sepsis-related DIC should include antibi- asphyxia, necrotizing enterocolitis, intravascular hemolysis, abruptio
otics, support of vital functions, and surgical intervention to remove any placentae, and eclampsia. 312,316
local nidus of infection. Abortion or hysterectomy may be considered. Bleeding from multiple sites is the most common manifestation
of DIC in newborns, with intracranial hemorrhage being the most
Dead Fetus Syndrome life-threatening condition. No clinical manifestations of DIC are appar-
Several weeks after intrauterine fetal death, approximately one-third of ent in approximately 20 percent of neonates, so a high index of suspi-
314
patients may exhibit laboratory signs of DIC, occasionally accompanied cion in patients at risk is essential.
by bleeding. 278,300 Apparently, TF from the retained dead fetus or placenta
slowly enters the maternal circulation and initiates DIC, which some-
times is accompanied by significant fibrinolysis. This complication THERAPY
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currently is rarely observed because labor is induced promptly after the
diagnosis of fetal death is made. However, if labor induction is unavoid- Controlled studies of patients with DIC are difficult to perform in view
ably delayed, serial blood coagulation tests should be performed. of the variabilities in DIC triggers, clinical presentations, and grades
The entity of fetal death and DIC can occur following the demise of severity. Figure 129–4 shows general guidelines for management of
of one of multiple gestations. If it occurs at term, therapy is started as patients with DIC, but decisions regarding treatment must be individu-
discussed. If it occurs prior to fetal maturity, prolonged administration alized after careful consideration of all clinically important aspects.
of heparin can be useful. Interestingly, when selective termination of
the life of an anomalous fetus is performed in women with multiple TREATMENT OF UNDERLYING DISORDERS AND
pregnancies, hemostatic abnormalities develop in only approximately VITAL SUPPORT
3 percent of cases. 301
The survival of patients with DIC depends on vigorous treatment of the
Acute Fatty Liver underlying disorder to alleviate or remove the inciting injurious cause.
Acute fatty liver of pregnancy is a rare disorder that occurs during the For sepsis-induced DIC, treatment includes aggressive use of intrave-
third trimester of pregnancy. It can lead to hepatic failure, encepha- nous organism-directed antibiotics and source control (e.g., by surgery
302
lopathy, and death of the mother and fetus. 303–306 In 15 to 20 percent of or drainage). Other examples of vigorous treatment of underlying con-
cases, acute fatty liver of pregnancy is associated with fetal homozygos- ditions are cancer surgery or chemotherapy, uterus evacuation or even
ity or compound heterozygosity for long-chain acyl-coenzyme A dehy- hysterectomy in patients with abruptio placentae, resection of aortic
drogenase (LCAD) deficiency. Infants born with LCAD deficiency aneurysm, and debridement of crushed tissues.
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