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802 Part VI: The Erythrocyte Chapter 51: Fragmentation Hemolytic Anemia 803

used peripartum. It can also be tried postpartum in the 5 percent of EPIDEMIOLOGY
patients who fail to improve within 72 to 96 hours of delivery. These Cancer-associated microangiopathic hemolytic anemia (MAHA) has
women are more likely to be younger than 20 years of age or nullipa- been described in a wide variety of malignancies (Table 51–1). MAHA
rous. Whether or not plasma exchange can effectively lower circulating is more likely to be associated with metastatic malignant disease than
7
levels of sVEGF and/or sEng is not known. Liver transplantation may with localized cancers or benign tumors. Approximately 80 percent
36
be necessary in occasional patients with HELLP complicated by large of the tumors are mucinous adenocarcinomas of either the stomach
hematomas or total hepatic necrosis. It is not yet known if replacement (55 percent), breast (13 percent), or lung (10 percent). The median age
with some (possibly modified) form of VEGF and/or TGF-β may have at diagnosis is 50 years, with a slight male predominance. 37
future therapeutic use in preeclampsia or HELLP. A single case report
describes the successful use of eculizumab to prolong by 17 days a preg-
nancy affected by severe HELLP, without associated maternal or fetal ETIOLOGY AND PATHOGENESIS
morbidity or mortality. 30 MAHA as a result of malignancy can be caused by either of two dis-
tinct mechanisms: (1) DIC with intravascular occlusions (often partial)
COURSE AND PROGNOSIS of small vessels by platelet-fibrin thrombi; or (2) intravascular tumor
1
Most patients stabilize within 24 to 48 hours following delivery; how- emboli. 35,38 In the first mechanism, intravascular activation of coagula-
ever, maternal death still occurs in 3 to 5 percent even with best sup- tion may occur from excessive exposure of tissue factor on phagocytes,
portive care. Mortality rates as high as 25 percent were reported prior activated endothelial cells, or tumor cells. Alternatively, a protease in
39
to 1980. Events leading to maternal death include cerebral hemorrhage, the mucin secreted by adenocarcinomas may directly activate factor X.
cardiopulmonary arrest, DIC, adult respiratory distress syndrome, Subsequent activation of coagulation factors, thrombin generation,
and hypoxic ischemic encephalopathy. Other complications include fibrin polymer deposition, and platelet aggregation result in the for-
5
infection, placenta abruptio, postpartum hemorrhage, intraabdomi- mation of intravascular platelet-fibrin thrombi, and the shearing of red
nal bleeding, and subcapsular liver hematomas with resultant rupture cells attempting to maneuver past the partial platelet-fibrin occlusions
(a fatal event in 50 percent of those in whom it occurs). The latter in the high-flow microvasculature. Also, circulating carcinoma mucins
6
patients complain of right-sided shoulder pain and are found to be in may interact with leukocyte L-selectin and platelet P-selectin, causing
40
shock with ascites or pleural effusions. The hematoma is usually present the rapid generation of platelet-rich microthrombi. In the second
2
in the anterior superior portion of the right lobe of the liver. If the liver mechanism, intravascular tumor emboli partially occlude small ves-
5
remains intact when discovered, abdominal palpation, seizures, and sels, mechanically or chemically disrupt the endothelium and promote
emesis should be avoided or prevented. Emergency surgery is required platelet adherence to exposed subendothelium, coagulation activa-
for hepatic artery embolization or ligation, hepatic lobectomy, or even tion and fibrin polymer formation, intimal hyperplasia, and vascular
35,37,38
liver transplantation in patients with total hepatic necrosis. 5,19 hypertrophy.
Renal complications of HELLP include acute renal failure, hypona-
tremia, and nephrogenic diabetes insipidus as a result of impaired
hepatic metabolism of vasopressinase and resultant “resistance to vaso- TABLE 51–1. Cancers Associated with Microangiopathic
pressin” (antidiuretic hormone). Pulmonary complications of HELLP
include of pleural effusions, pulmonary edema, and adult respiratory Hemolytic Anemia
distress syndrome. Neurologic sequelae of HELLP not mentioned above Gastric (55%) 37,40
include retinal detachment, postictal cortical blindness, and hypoglyce- Breast (13%) 129
mic coma. 31 35
Fetal morbidity and mortality are between 9 and 24 percent. Com- Lung (10%)
6
plications arise as a result of prematurity, placental abruption, and intra- Other Adenocarcinomas
uterine asphyxia. Intrauterine growth retardation is seen in 39 percent Unknown primary 38
of infants. One-third of all babies born to mothers with HELLP have 35
thrombocytopenia, but intraventricular hemorrhage is seen in only Prostate
4 percent of thrombocytopenic infants. 32 Colon 38
HELLP syndrome complicates 2 to 5 percent of all pregnancies, Gallbladder
5
and can recur in as many as 27 percent of those affected during sub-
sequent pregnancies. Other hypertensive disorders of pregnancy Pancreas
33
(preeclampsia or pregnancy-induced hypertension) are also relatively Ovary
common in future pregnancies (27 percent of second and subsequent Other Malignancies
pregnancies). Women who recover from preeclampsia/HELLP may
34
also be more likely to develop subsequent hypertension and cardiovas- Hemangiopericytoma 36
cular disorders, possibly because of some persistent abnormal balance Hepatoma
between proangiogenic and antiangiogenic factors. 17 Melanoma
Small cell cancer of the lung 130
DISSEMINATED MALIGNANCY Testicular cancer

DEFINITION AND HISTORY Squamous cell cancer of the oropharynx
The association between widespread malignancy and hemolytic ane- Thymoma
mia associated with pathologic changes in small blood vessels was first Erythroleukemia 131
noted by Brain and colleagues in 1962. 35

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