Page 827 - Williams Hematology ( PDFDrive )

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

capable of binding to and inactivating the proangiogenic growth factors, of endothelial damage; however, no unusually large VWF multimers are
23
TGF-β and TGF-β . The presence of elevated serum levels of both present in plasma and ADAMTS13 (a disintegrin and metallopro-
1
3
sFLT-1 (sVEGFR-1) and sEng may be associated with the progression teinase with thrombospondin domains-13) levels are within a broad
of preeclampsia to HELLP. 17,18 normal range (ADAMTS13 normally declines moderately during preg-
nancy). 24,25 This is in contrast to the severe deficiency of ADAMTS13
CLINICAL FEATURES in familial and autoantibody-mediated types of thrombotic thrombo-
26
Ninety percent of patients with HELLP syndrome present with malaise cytopenic purpura (TTP). Unlike TTP, the thrombi found in organs
involved in the HELLP syndrome contain increased amounts of fibrin
and right upper quadrant or epigastric pain. Between 45 and 86 percent and low levels of VWF. 23
have nausea or vomiting, 55 to 67 percent have edema, 31 to 50 percent In patients with severe liver involvement, hepatic ultrasonogra-
have headache, and a smaller percentage complain of visual changes. phy shows large, irregular, well-demarcated (or “geographical”) areas of
Fever is not typically seen. Although hypertension is found in 85 per- increased echogenicity. Liver biopsy shows periportal or focal necro-
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cent of affected patients, 15 percent of those with HELLP syndrome do sis, platelet-fibrin deposits in the sinusoids, and vascular microthrombi.
not develop either hypertension or proteinuria. 6 As the disease progresses, large areas of necrosis can coalesce and dis-
sect into the liver capsule. This produces a subcapsular hematoma and
LABORATORY FEATURES the risk of hepatic rupture. 5
There is no consensus regarding the laboratory criteria necessary to
diagnose HELLP syndrome, so clinical judgment in conjunction with DIFFERENTIAL DIAGNOSIS
judicious interpretation of a variety of laboratory tests constitute the Other complications of pregnancy that can be confused with HELLP
diagnostic standard. In 54 to 86 percent of patients, the blood film has include TTP and the hemolytic uremic syndrome, sepsis, dissemi-
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schistocytes, helmet cells, and burr cells consistent with microangio- nated intravascular coagulation (DIC), connective tissue disease, anti-
pathic hemolytic anemia. Reticulocytosis can be present. Low hapto- phospholipid antibody syndrome, and acute fatty liver of pregnancy.
globin levels are both sensitive (83 percent) and specific (96 percent) This latter entity is also seen in the last trimester or postpartum and
for confirming the presence of hemolysis, and return to normal within presents with thrombocytopenia and right upper quadrant pain, but
24 to 30 hours postpartum. 6 the levels of AST and ALT only rise to 1 to 5 times normal and the PT
Lactate dehydrogenase (LDH) levels are usually above normal. and partial thromboplastin time (PTT) are both prolonged. Oil-red-O
The ratio of LDH-5 (an isoenzyme found specifically in the liver) to staining of liver biopsies demonstrates fat in the cytoplasm of centri-
total LDH is elevated in proportion to the severity of HELLP. The high lobular hepatocytes, and routine stains show inflammation and patchy
LDH seen in HELLP is most likely the result, principally, of liver dam- hepatocellular necrosis as a result of the HELLP syndrome. Because it
age rather than hemolysis. Serum levels of aspartic acid transaminase causes right upper quadrant pain and nausea, HELLP has also been
(AST) and alanine transaminase (ALT) can be more than 100 times misdiagnosed as viral hepatitis, biliary colic, esophageal reflux, chole-
normal, whereas alkaline phosphatase values are typically only about cystitis, and gastric cancer. Conversely, other conditions misdiagnosed
twice normal and total bilirubin ranges between 1.2 and 5.0 mg/dL. as HELLP syndrome include cardiomyopathy, dissecting aortic aneu-
Liver enzymes usually return to normal within 3 to 5 days postpartum. 6 rysm, acute cocaine intoxication, essential hypertension and renal dis-
The degree of thrombocytopenia has been used in a classifica- ease, and alcoholic liver disease. 19
tion system to predict maternal morbidity and mortality, the rapidity
of postpartum recovery, the risk of disease recurrence, and perinatal
outcome. This Mississippi triple-class system places those patients with THERAPY
platelet counts less than 50 × 10 /L in class 1 (approximately 13 per- Supportive care of HELLP includes intravenous administration of mag-
9
cent incidence of bleeding); those with platelet counts between 50 and nesium sulfate to control hypertension and prevent eclamptic seizures,
9
100 × 10 /L in class 2 (approximately 8 percent incidence of bleeding); management of fluids and electrolytes, judicious transfusion of blood
and those with a platelet count greater than 100 × 10 /L in class 3 (no products, stimulation of fetal lung maturation with beclomethasone,
9
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increased bleeding risk). Patients with class 1 HELLP syndrome suffer and delivery of the fetus as soon as possible. Indications for delivery
the highest incidence of perinatal morbidity and mortality, and have include a severe disease presentation, maternal DIC, fetal distress, and
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the most protracted recovery periods postpartum. There is a direct a gestational age greater than 32 weeks with evidence of lung maturity.
6
correlation between the extent of thrombocytopenia and measurements Cesarean section under general anesthesia is used in 60 to 97 percent
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of liver function, but the same cannot be said for the severity of asso- of cases, but vaginal delivery after induction can be attempted if the
ciated hepatic histopathologic changes. If a marrow aspiration and fetus is older than 32 weeks of age and the mother’s cervical anatomy is
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biopsy are performed, abundant megakaryocytes are found consistent favorable. Postpartum curettage is helpful in lowering the mean arterial
with a consumptive thrombocytopenia causing reduction of the normal pressure and increasing the urine output and platelet count. Transfu-
19
platelet life span of approximately 10 days to 3 to 5 days. The platelet sion therapy with packed red cells, platelets, or fresh-frozen plasma is
count nadir occurs 23 to 29 hours postpartum, with subsequent nor- indicated in cases complicated by severe anemia or bleeding because of
malization within 6 to 11 days. 7 coagulopathy.
The prothrombin time (PT) and activated partial thromboplastin Although previously thought to be beneficial based upon the
time (aPTT) are usually within normal limits, although one report cited results of observational studies and small randomized trials, the use
a prolonged aPTT in 50 percent of patients. Although low fibrinogen of dexamethasone has fallen out of favor after large randomized trials
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levels are inconsistently found, other measures of increased coagulation found that it didn’t reduce the duration of hospitalization, amount of
and secondary fibrinolysis may be present. These include decreased pro- blood products transfused, maternal complications, or time to normal-
tein C and antithrombin III (AT III) levels, and increased D-dimer and ization of laboratory abnormalities. 29
thrombin-AT III values. von Willebrand factor (VWF) antigen levels Plasma exchange cannot arrest or reverse HELLP syndrome when
increase in proportion to the severity of the disease, reflecting the extent used antepartum, but may minimize hemorrhage and morbidity when

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