Etiology of hypercoagulable state in women with recurrent fetal loss without other causes of miscarriage from Southern Italy: new clinical target for antithrombotic therapy.
BACKGROUND
Recurrent fetal loss (RPL) is one of the most common cause of sterility. Several studies identified thrombophilia as the principal cause of recurrent pregnancy loss. However, reported studies often do not evaluate other causes of miscarriages in their inclusion and exclusion criteria. So the aim of our study was to investigate the role of inherited thrombophilia in patients with RPL and without other causes of RPL.


METHODS
Patients with 2 or more first trimester abortion or with 1 or more late pregnancy loss were considered for this study. In order to evaluate the causes of RPL we looked for chromosomal, endocrine, chronic inflammatory, and infectious alterations. 90 patients affected by unexplained RPL were enrolled and tested for hemostatic alterations. These women were tested for inherited and/or acquired thrombophilia by MTHFR C677T gene polymorphism, factor V Leiden gene polymorphism, PTHRA20210G gene polymorphism, protein S deficiency, protein C deficiency, antithrombin III deficiency, lupus anticoagulant, and anticardiolipin antibodies Ig G and Ig M.


RESULTS
Acquired and/or inherited thrombophilia are strongly associated with RPL when other common causes of miscarriage were excluded. 78% of tested women showed hemostatic abnormalities. Several women with combined thrombophilic defects were also identified by our data.


CONCLUSIONS
After a thorough evaluation of other causes of miscarriage women affected by RPL should be tested for thrombophilia. Our data demonstrated 78% of women with one or combined thrombophilic conditions. Differences with previous studies should be related to difference in the inclusion and exclusion criteria and ethnic background. Because these patients often also show a hypercoagulable state, it an antithrombotic treatment before and during pregnancy may improve their clinical outcome (ie, secondary prevention of miscarriage and primary thromboprophylaxis).
D'Uva
Maristella
M
Dipartimento Universitario di Scienze Ostetriche Ginecologiche e Medicina della Riproduzione, Area Funzionale di Medicina della Riproduzione ed Endoscopia Ginecologica, Università degli Studi di Napoli Federico II, via Pansini 5 Building 9, 80131, Naples, Italy.
Di Micco
Pierpaolo
P
Strina
Ida
I
Ranieri
Antonio
A
Alviggi
Carlo
C
Mollo
Antonio
A
Fabozzi
Francesca
F
Cacciapuoti
Lucia
L
di Frega
Maria Teresa Scotto
MT
Iannuzzo
Mariateresa
M
De Placido
Giuseppe
G
J Assoc Physicians India. 1999 May;47(5):496-8
10778558
N Engl J Med. 2000 Oct 5;343(14):1015-8
11018168
Hematol J. 2000;1(1):37-41
11920167
Hum Reprod. 2001 May;16(5):961-5
11331645
Aust N Z J Obstet Gynaecol. 1991 Nov;31(4):323-6
1799344
Fertil Steril. 2002 Feb;77(2):342-7
11821094
Fertil Steril. 1993 Nov;60(5):820-5
8224267
J Transl Med. 2004 Nov 09;2(1):38
15535889
Thromb Haemost. 2004 Apr;91(4):694-9
15045130
Br J Hosp Med. 1997 Nov 19-Dec 9;58(10):511-3
10193454
Hum Reprod. 2002 Jun;17(6):1633-7
12042290
Fertil Steril. 2005 Mar;83(3):684-90
15749498
Eur J Clin Chem Clin Biochem. 1992 Jun;30(6):377-9
1511073
Blood Coagul Fibrinolysis. 2000 Oct;11(7):657-62
11085286
Lancet. 1980 Feb 16;1(8164):339-40
6101792
Thromb Haemost. 1999 Jun;81(6):891-9
10404763
Am J Hematol. 2002 Dec;71(4):300-5
12447960
Br J Haematol. 2001 May;113(2):550-2
11380430
Int Angiol. 2003 Mar;22(1):55-7
12771857
Lupus. 1994 Aug;3(4):293-8
7804319
Am J Obstet Gynecol. 1999 Jul;181(1):126-30
10411807
Thromb Haemost. 1999 Jul;82(1):6-9
10456445
Clin Appl Thromb Hemost. 2001 Jan;7(1):25-8
11190900
Fertil Steril. 1993 Jan;59(1):98-101
8419231
Thromb Haemost. 1996 Mar;75(3):387-8
8701393
Thromb Haemost. 1998 Apr;79(4):706-8
9569177
J Transl Med. 2005 Dec 02;3:43
16324213
Am J Reprod Immunol. 2001 Aug;46(2):124-31
11506076
Am J Reprod Immunol. 2000 Jan;43(1):31-5
10698038
Obstet Gynecol. 1998 Aug;92(2):167-70
9699744
BJOG. 2001 Dec;108(12):1251-4
11843387
J Perinat Med. 1998;26(5):384-9
10027134
Am J Reprod Immunol. 2007 Feb;57(2):133-41
17217367
Thromb Res. 2003 Jan 25;109(2-3):73-81
12706634
N Engl J Med. 1991 Oct 10;325(15):1063-6
1909770
Int Angiol. 2000 Dec;19(4):314-8
11305729
Thromb Haemost. 1997 May;77(5):822-4
9184385
J Obstet Gynaecol Can. 2004 Aug;26(8):729-34
15307977
Br J Haematol. 2006 Jan;132(2):171-96
16398652
J Thromb Haemost. 2005 Feb;3(2):227-9
15670024