Use of D-dimer measurement to guide anticoagulant treatment in recurrent pregnancy loss associated with antiphospholipid syndrome
Corresponding Author
Shi Hua Bao
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Correspondence
Shi Hua Bao, Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
Email: [email protected]
Search for more papers by this authorShi Le Sheng
Department of Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
Search for more papers by this authorHong Liao
Department of Cervical Diseases, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorQian Zhou
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorSophia Twum Frempong
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorWei Yan Tu
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorCorresponding Author
Shi Hua Bao
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Correspondence
Shi Hua Bao, Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China.
Email: [email protected]
Search for more papers by this authorShi Le Sheng
Department of Nuclear Medicine, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, China
Search for more papers by this authorHong Liao
Department of Cervical Diseases, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorQian Zhou
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorSophia Twum Frempong
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorWei Yan Tu
Department of Reproductive Immunology, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai, China
Search for more papers by this authorAbstract
Problem
To examine whether the level of plasma D-dimer can guide anticoagulant treatment in recurrent pregnancy loss (RPL) associated with antiphospholipid syndrome (APS).
Methods
A total of 1096 RPL women with APS between 2012 and 2015 in a single-center hospital were randomly divided into two groups (group A, 75 mg of low-dose aspirin [LDA] daily; group B, 75 mg of LDA plus 4100 U of low molecular weight heparin [LMWH] subcutaneously daily); 1015 of the total successfully completed the trial. Plasma D-dimer level and live birth rates were estimated.
Results
For APS women with an elevated D-dimer level at baseline, higher live birth rates were reached in LDA plus LMWH group compared to LDA alone group (92.71% vs 61.68%, P < .0001); however, no significant differences were found between the two groups of women with a normal D-dimer level (87.08% vs 83.76%, P = .48). Women with a normal D-dimer level at all blood draw points had the highest live birth rates (92.88%), as compared with those with persistently abnormal D-dimer at all blood draw points or increased D-dimer level after treatment (P < .001).
Conclusion
The combination therapy with LDA and LMWH is not essential for all APS women, but has proven to be beneficial for women with an elevated D-dimer level.
Supporting Information
| Filename | Description |
|---|---|
| aji12770-sup-0001-TableS1.docxWord document, 25.4 KB |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Rai R, Regan L. Recurrent miscarriage. Lancet. 2006; 368: 601-611.
- 2Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010; 376: 1498-1509.
- 3Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006; 4: 295-306.
- 4Rand JH, Wu XX, Andree HA, et al. Pregnancy loss in the antiphospholipid-antibody syndrome – a possible thrombogenic mechanism. N Engl J Med. 1997; 337: 154-160.
- 5Roubey RA, Hoffman M. From antiphospholipid syndrome to antibody-mediated thrombosis. Lancet. 1997; 350: 1491-1493.
- 6Viall CA, Chamley LW. Histopathology in the placentae of women with antiphospholipid antibodies: a systematic review of the literature. Autoimmun Rev. 2015; 14: 446-471.
- 7Alalaf S. Bemiparin versus low dose aspirin for management of recurrent early pregnancy losses due to antiphospholipd antibody syndrome. Arch Gynecol Obstet. 2012; 285: 641-647.
- 8de Jesus GR, Rodrigues G, de Jesus NR, Levy RA. Pregnancy morbidity in antiphospholipid syndrome: what is the impact of treatment? Curr Rheumatol Rep. 2014; 16: 403.
- 9Farquharson RG, Quenby S, Greaves M. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2002; 100: 408-413.
- 10Hoppe B, Burmester GR, Dorner T. Heparin or aspirin or both in the treatment of recurrent abortions in women with antiphospholipid antibody (syndrome). Curr Opin Rheumatol. 2011; 23: 299-304.
- 11Kutteh WH. Antiphospholipid antibody-associated recurrent pregnancy loss: treatment with heparin and low-dose aspirin is superior to low-dose aspirin alone. Am J Obstet Gynecol. 1996; 174: 1584-1589.
- 12Laskin CA, Spitzer KA, Clark CA, et al. Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled HepASA Trial. J Rheumatol. 2009; 36: 279-287.
- 13Rai R, Cohen H, Dave M, Regan L. Randomised controlled trial of aspirin and aspirin plus heparin in pregnant women with recurrent miscarriage associated with phospholipid antibodies (or antiphospholipid antibodies). BMJ. 1997; 314: 253-257.
- 14Mak A, Cheung MW, Cheak AA, Ho RC. Combination of heparin and aspirin is superior to aspirin alone in enhancing live births in patients with recurrent pregnancy loss and positive anti-phospholipid antibodies: a meta-analysis of randomized controlled trials and meta-regression. Rheumatology (Oxford). 2010; 49: 281-288.
- 15von Dadelszen P, Kent N. Antiphospholipid syndrome in pregnancy: a randomized, controlled trial of treatment. Obstet Gynecol. 2003; 101: 618.
- 16Negrini S, Pappalardo F, Murdaca G, Indiveri F, Puppo F. The antiphospholipid syndrome: from pathophysiology to treatment. Clin Exp Med. 2017; 17: 257-267.
- 17Devreese K, Peerlinck K, Hoylaerts MF. Thrombotic risk assessment in the antiphospholipid syndrome requires more than the quantification of lupus anticoagulants. Blood. 2010; 115: 870-878.
- 18Devreese KM. Antiphospholipid antibodies: evaluation of the thrombotic risk. Thromb Res. 2012; 130(Suppl 1): S37-S40.
- 19Eichinger S, Hron G, Kollars M, Kyrle PA. Prediction of recurrent venous thromboembolism by endogenous thrombin potential and D-dimer. Clin Chem. 2008; 54: 2042-2048.
- 20Perrier A, Bounameaux H. Cost-effective diagnosis of deep vein thrombosis and pulmonary embolism. Thromb Haemost. 2001; 86: 475-487.
- 21Galioto NJ, Danley DL, Van Maanen RJ. Recurrent venous thromboembolism. Am Fam Physician. 2011; 83: 293-300.
- 22Lakos G, Favaloro EJ, Harris EN, et al. International consensus guidelines on anticardiolipin and anti-beta2-glycoprotein I testing: report from the 13th International Congress on Antiphospholipid Antibodies. Arthritis Rheum. 2012; 64: 1-10.
- 23Pengo V, Tripodi A, Reber G, et al. Update of the guidelines for lupus anticoagulant detection. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the International Society on Thrombosis and Haemostasis. J Thromb Haemost. 2009; 7: 1737-1740.
- 24Khalafallah AA, Morse M, Al-Barzan AM, et al. D-Dimer levels at different stages of pregnancy in Australian women: a single centre study using two different immunoturbidimetric assays. Thromb Res. 2012; 130: e171-e177.
- 25Bombeli T, Raddatz-Mueller P, Fehr J. Coagulation activation markers do not correlate with the clinical risk of thrombosis in pregnant women. Am J Obstet Gynecol. 2001; 184: 382-389.
- 26Reger B, Peterfalvi A, Litter I, et al. Challenges in the evaluation of D-dimer and fibrinogen levels in pregnant women. Thromb Res. 2013; 131: e183-e187.
- 27Kawaguchi S, Yamada T, Takeda M, et al. Changes in d-dimer levels in pregnant women according to gestational week. Pregnancy Hypertens. 2013; 3: 172-177.
- 28Empson M, Lassere M, Craig J, Scott J. Prevention of recurrent miscarriage for women with antiphospholipid antibody or lupus anticoagulant. Cochrane Database Syst Rev. 2005: Cd002859.
- 29Galarza-Maldonado C, Kourilovitch MR, Perez-Fernandez OM, et al. Obstetric antiphospholipid syndrome. Autoimm Rev. 2012; 11: 288-295.
- 30Fishman P, Falach-Vaknin E, Sredni B, et al. Aspirin-interleukin-3 interrelationships in patients with anti-phospholipid syndrome. Am J Reprod Immunol. 1996; 35: 80-84.
- 31Alvarez AM, Mulla MJ, Chamley LW, Cadavid AP, Abrahams VM. Aspirin-triggered lipoxin prevents antiphospholipid antibody effects on human trophoblast migration and endothelial cell interactions. Arthritis Rheumatol (Hoboken, NJ). 2015; 67: 488-497.
- 32Gris JC, Bouvier S, Molinari N, et al. Comparative incidence of a first thrombotic event in purely obstetric antiphospholipid syndrome with pregnancy loss: the NOH-APS observational study. Blood. 2012; 119: 2624-2632.
- 33Arkel YS, Paidas MJ, Ku DH. The use of coagulation activation markers (soluble fibrin polymer, TpP, prothrombin fragment 1.2, thrombin-antithrombin, and D-dimer) in the assessment of hypercoagulability in patients with inherited and acquired prothrombotic disorders. Blood Coagul Fibrinolysis. 2002; 13: 199-205.
- 34Palareti G, Cosmi B, Legnani C, et al. D-dimer to guide the duration of anticoagulation in patients with venous thromboembolism: a management study. Blood. 2014; 124: 196-203.
- 35Di Nisio M, Klerk CP, Meijers JC, Buller HR. The prognostic value of the D-dimer test in cancer patients treated with and without low-molecular-weight heparin. J Thromb Haemost. 2005; 3: 1531-1533.
- 36Stricker H, Marchetti O, Haeberli A, Mombelli G. Hemostatic activation under anticoagulant treatment: a comparison of unfractionated heparin vs. nadroparin in the treatment of proximal deep vein thrombosis. Thromb Haemost. 1999; 82: 1227-1231.
- 37Adam SS, Key NS, Greenberg CS. D-dimer antigen: current concepts and future prospects. Blood. 2009; 113: 2878-2887.
