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Chapter 139 Disseminated Intravascular Coagulation 2069

Disseminated Intravascular Coagulation in which forms a complex with factor VII(a) to activate factors IX and
X, and a cancer procoagulant (CP), a cysteine protease with factor
Obstetric Complications X–activating properties. In breast cancer, TF is expressed by vascular
endothelial cells as well as by the tumor cells. TF also appears to be
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Placental abruption is a leading cause of perinatal death. Older involved in tumor metastasis and angiogenesis. CP is an endopepti-
multiparous women or patients with one of the hypertensive disorders dase that can not only be found in extracts of neoplastic cells but also
of pregnancy are thought to be at highest risk. The severe hemostatic in the plasma of patients with solid tumors. The exact role of CP in
failure accompanying abruptio placentae is the result of acute DIC the pathogenesis of cancer-related DIC is unclear. Interactions of
emanating from the introduction of large amounts of TF into the P- and L-selectins with mucin from mucinous adenocarcinoma can
circulation from the damaged placenta and uterus. Amniotic fluid induce the formation of platelet microthrombi, which probably
has been shown to activate coagulation in vitro, and the degree of constitute a third mechanism of cancer-related thrombosis. Depend-
placental separation correlates with the extent of DIC, suggesting that ing on the rate and quantity of exposure or influx of shed vesicles
leakage of thromboplastin-like material from the placental system is from tumors containing TF, a covert or overt DIC develops.
responsible for the DIC. Abruptio placentae occurs in 0.2% to 0.4% There are numerous reports of DIC and excessive fibrinolysis
of pregnancies, but only 10% of these cases are associated with DIC. complicating the course of acute leukemia. In 161 consecutive
Different grades of severity are found among those who develop DIC, patients presenting with acute myeloid leukemia, DIC was diagnosed
with only the more severe forms resulting in shock and fetal death. in 52 (32%). In acute lymphoblastic leukemia, DIC was diagnosed
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Amniotic fluid embolism is a rare but serious complication of in 15% to 20%. Some reports suggest that the incidence of DIC
pregnancy and delivery. A maternal mortality rate of 86% was in acute leukemia patients may increase even more during remission
reported in a 1979 review of 272 cases, but in a more recent induction with chemotherapy. In patients with APL, DIC is present
population-based study, the maternal mortality was 26%. Patients in more than 90% of patients at the time of diagnosis or after initia-
predisposed to amniotic fluid embolism are multiparous women tion of remission induction. The pathogenesis of hemostatic distur-
whose pregnancies are postmature with large fetuses and women bance in APL is related to properties of the malignant cells and their
undergoing a tumultuous labor after pharmacologic or surgical interaction with host endothelial cells. APL cells express TF and CP,
induction. Amniotic fluid is introduced into the maternal circulation which can initiate coagulation, and they release IL-1β and TNF-α,
through tears in the chorioamniotic membranes, rupture of the which downregulate endothelial thrombomodulin, thereby compro-
uterus, and injury of uterine veins. TF in amniotic fluid is the likely mising the protein C anticoagulant pathway. APL cells also express
trigger for DIC. Mechanical obstruction of pulmonary blood vessels increased amounts of annexin II, which binds plasminogen and tPA
by fetal debris, meconium, and other particulate matter in the and promotes plasmin generation. The net result of these processes
amniotic fluid enhances local fibrin–platelet thrombus formation and is DIC and hyperfibrinolysis, which can lead to bleeding that can be
fibrinolysis. The extensive occlusion of the pulmonary arteries and fatal. All-trans-retinoic acid, which is used for induction and main-
an acute anaphylactoid response reminiscent of severe systemic tenance therapy of APL, inhibits the deleterious effect of APL cells
inflammatory response syndrome provoke sudden dyspnea, cyanosis, in vitro and in vivo and has reduced the frequency of early hemor-
acute cor pulmonale, left ventricular dysfunction, shock, and convul- rhagic death.
sions. These symptoms are followed within minutes to several hours
by severe bleeding in 37% of patients. Hemorrhage is particularly
severe from the atonic uterus, puncture sites, gastrointestinal tract, Disseminated Intravascular Coagulation With
and other organs. Vascular Disorders
Some studies provide evidence of activation of coagulation, in its
most extreme form DIC, in preeclampsia and eclampsia. In a large Rarely, vascular anomalies can trigger DIC. With some large aortic
series of patients, a good correlation was noted between the clinical aneurysms, localized consumption of platelets and fibrinogen can
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severity and abnormalities in platelet counts and fibrin(ogen) degra- produce coagulation abnormalities and bleeding. In a series of
dation products. Also consistent with DIC were results of assays of patients with aortic aneurysms, 40% had elevated levels of fibrin(ogen)
sensitive parameters of thrombin generation and activation of fibri- degradation products, but only 4% had laboratory evidence of DIC
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nolysis, such as TAT complexes, D-dimer, and fibrinopeptide Bβ1–42. or bleeding. Factors that predispose such patients to the develop-
Despite these observations, administration of heparin to patients with ment of DIC include large aneurysms, dissection, and expansion.
preeclampsia and eclampsia has not resulted in convincing benefits. Coagulation in these cases likely is triggered by the abundant TF in
The HELLP syndrome, which is comprised of hemolysis, elevated atherosclerotic plaques.
liver enzymes, low platelet count, and severe epigastric pain, is Kasabach and Merritt were the first to describe bleeding in associa-
another complication of pregnancy-induced hypertension. Liver tion with giant cavernous hemangiomas, benign tumors found in
biopsy findings of fibrin deposition in hepatic blood vessels and labo- newborns or children that can evolve into convoluted masses of
ratory tests consistent with DIC are found in a significant proportion abnormal vascular channels that sequester and consume platelets and
of patients suggesting that DIC plays a role in the pathogenesis of fibrinogen. Localized pain may occur, likely from thrombosis of these
the syndrome. However, according to current insights, thrombotic vascular channels and there may be bleeding after trauma or surgery
microangiopathy rather than DIC causes the coagulation abnormali- because of the consumptive process. Increased fibrinogen consump-
ties in patients with hypertensive disorders of pregnancy. tion reflects hyperfibrinolysis, which may be driven by tPA released
from the abnormal endothelium lining the tumor walls. Patients with
this syndrome exhibit accelerated platelet turnover, and accumulation
Disseminated Intravascular Coagulation in Malignancy of labeled platelets and fibrinogen in the hemangiomas.
Hemangiomas may regress spontaneously; some respond to radia-
Patients with solid tumors are vulnerable to risk factors and additional tion or laser therapy.
triggers for DIC that can aggravate thromboembolism and bleed-
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ing. Risk factors include advanced age, stage of the disease, and use
of chemotherapy or antiestrogen therapy. Triggers include septicemia, Disseminated Intravascular Coagulation With
immobilization, and hepatic metastases, which can compromise the Liver Disease
capacity of the liver to control DIC. Microangiopathic hemolytic
anemia frequently is induced by DIC in patients with malignancies The levels of most coagulation factors, endogenous anticoagulants,
and is particularly severe in patients with widespread intravascular and major components of the fibrinolytic system are reduced in
metastases of mucin-secreting adenocarcinomas. Solid tumor cells patients with severe liver disease reflecting reduced synthesis. In addi-
can express different procoagulant molecules including tissue factor, tion, the capacity of the liver to clear factors IXa, Xa, XIa, and tPA