Serum Soluble Fas in the Syndrome of Hemolysis, Elevated Liver Enzymes, and Low Platelets Hassan Harirah, MD, Sahar E. Donia, MVD, and Chaur-Dong Hsu, MD, MPH OBJECTIVE: To assess whether serum levels of soluble Fas and soluble Fas ligand are altered in the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). METHODS: Serum samples from 22 pregnant women diag- nosed with HELLP syndrome were compared with sera from 37 healthy women with noncomplicated singleton pregnancies. Serum levels of soluble Fas and soluble Fas ligands were determined by enzyme immunoassay. Stu- dent t,  2 , Pearson’s correlation coefficient, and multiple regression tests were used for statistical analyses. RESULTS: Both soluble Fas and soluble Fas ligand were detected in the sera of normal pregnancies as well as in those with HELLP syndrome. The mean serum level of soluble Fas was significantly higher in women with HELLP syndrome than in healthy gravidas (10.75  0.93 versus 5.81  0.37 U/mL, P < .001). However, there was no significant difference in mean serum soluble Fas ligand levels of the two groups (0.60  0.06 compared with 0.50  0.22 ng/mL, P  .23). In women with HELLP syndrome, there were no significant correlations between serum levels of soluble Fas or soluble Fas ligand with liver transami- nases (aspartate and alanine aminotransferase) and plate- let count. CONCLUSION: Serum levels of soluble Fas, but not soluble Fas ligand, are significantly higher in women with HELLP syndrome than healthy gravidas. The source of elevated serum levels of soluble Fas in HELLP syndrome remains to be determined. (Obstet Gynecol 2001;98:295– 8. © 2001 by the American College of Obstetricians and Gynecolo- gists.) The syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP) is a variant of severe preeclamp- sia, which carries statistically significant perinatal risks to both mother and fetus. 1 Elevation of liver transaminases in HELLP syndrome reflects marked derangement in hepatic functions and integrity. HELLP syndrome also shares many clinical and laboratory characteristics with systemic inflammatory response syndrome and dissem- inated intravascular coagulation. 2 The pathogenesis of hepatic damage in cases of severe preeclampsia and HELLP syndrome, in particular, is not fully understood. Autopsy of fatal cases of HELLP syndrome showed periportal hemorrhagic necrosis in the periphery of the liver lobules. However, such lesions are seldom identi- fied by liver biopsy in nonfatal cases. 3 Apoptosis or programmed cell death is a requisite physiologic process for normal development and repro- ductive function in a number of mammalian tissues. It is a process through which individual cells carry out a suicide program in otherwise healthy organs or tissues. The Fas-Fas ligand system is one of the best-studied death systems that can mediate apoptosis. Fas, a member of the tumor necrosis factor receptor superfamily, is a 36 to 45 kDa type I surface protein containing a single transmembrane region and induces apoptosis by Fas-Fas ligand binding. 4 Fas ligand is a 40 kDa type II transmem- brane protein of the tumor necrosis factor receptor fam- ily. 5 Soluble Fas (sFas) is produced as the form lacking 21 amino acid residues of the transmembrane domain by alternative splicing of Fas mRNA. 6 It protects the cells from Fas-mediated apoptosis by binding to Fas ligand and consequently preventing it from stimulating Fas receptors on cell membranes. 7 Soluble Fas ligand, a 26 kDa, is generated by metalloproteases proteolytic cleav- age on the membrane-bound form of Fas ligand protein. It is functionally active against cells that are highly sensitive to Fas-mediated apoptosis; however, it has less apoptosis-inducing activity than membrane-bound Fas ligand. 8 Apoptosis has recently been reported to occur in nor- mal hepatocytes and in liver damage associated with hepatitis B and C. This was shown by increased expres- sion of Fas and Fas ligand in liver tissue. 9 Apoptosis has also been found to be involved in different inflammatory and immune disorders. Our objective was to assess whether serum levels of sFas and sFas ligand are altered in HELLP syndrome. We compared the levels of sFas and sFas ligand in the sera of patients with HELLP syndrome and healthy gravidas. From the Division of Maternal-Fetal Medicine, The University of Texas Medical Branch, Galveston, Texas; and The University of Nebraska Medical Center, Omaha, Nebraska. 295 VOL. 98, NO. 2, AUGUST 2001 0029-7844/01/$20.00 © 2001 by The American College of Obstetricians and Gynecologists. Published by Elsevier Science Inc. PII S0029-7844(01)01415-6