Mild to moderate reduction of a von Willebrand factor cleaving protease (ADAMTS-13) in pregnant women with HELLP microangiopathic syndrome.
OBJECTIVE
Among the array of microangiopathies that may occur during pregnancy, HELLP syndrome and thrombotic thrombocytopenic purpura (TTP) produce similar laboratory findings (hemolytic anemia and thrombocytopenia), although neurological symptoms prevail in TTP and abnormal liver function in HELLP syndrome. It is clinically important to distinguish the two entities given that their managements differ (prompt induction of delivery in HELLP syndrome, plasma exchange in TTP). The purpose of this study was to evaluate whether or not ADAMTS-13, the metalloprotease that disposes ultralarge, highly thrombogenic multimers of von Willebrand factor (VWF) and is severely deficient or undetectable in many patients with TTP, is deficient in HELLP syndrome.


METHODS
We measured ADAMTS-13 and VWF (antigen, ristocetin cofactor activity, collagen binding, multimeric structure) in 17 pregnant women during HELLP syndrome and after 6 months during clinical remission. Controls were 25 healthy pregnant women and 50 healthy non-pregnant women.


RESULTS
All the women with HELLP syndrome had lower plasma levels of ADAMTS-13 activity (median and range: 31%, 12-43) than did the healthy pregnant (71%, 48-105) and non-pregnant women (101%, 45-152); the reduced levels returned to normal on remission (115%, 90-170). Reduced levels were not due to the presence of inactivating autoantibodies and in no case was the protease undetectable in plasma. Ultralarge VWF multimers were not present in plasma, the levels of VWF were higher than in normal pregnancy.


CONCLUSIONS
Because none of the pregnant women diagnosed with HELLP syndrome had undetectable ADAMTS-13 levels in pregnancy-associated thrombotic microangiopathies, the finding of severe ADAMTS-13 deficiency would argue against a diagnosis of HELLP syndrome and for a diagnosis of TTP.
Lattuada
Antonella
A
Immunohematology and Blood Transfusion Service, L. Sacco Hospital, Milan, Italy.
Rossi
Edoardo
E
Calzarossa
Cinzia
C
Candolfi
Rosaria
R
Mannucci
Pier Mannuccio
PM
D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D005260:Female; D017359:HELLP Syndrome / Q000097:blood* / Q000150:complications*; D006801:Humans; D008666:Metalloendopeptidases / Q000097:blood / Q000172:deficiency* / Q000276:immunology; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000097:blood* / Q000201:enzymology*; D011697:Purpura, Thrombotic Thrombocytopenic / Q000097:blood / Q000150:complications; D014841:von Willebrand Factor / Q000378:metabolism
D001323:Autoantibodies; D014841:von Willebrand Factor; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human