Successful management of congenital protein C deficiency with recurrent pregnancy loss

Ogasawara, Mayumi; Sasa, H.; Kajiura, Shoji; Aoki, Koji; Yagami, Y.

doi:10.1016/0020-7292(95)02425-c

Cited by 8 publications

(7 citation statements)

References 4 publications

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“…Further, an understanding that a threshold level of maternal PC is critical to sustaining a successful pregnancy may lead to identification of a potential target for drug therapy in certain pregnancy disorders. Since recombinant aPC has been used for treatment of sepsis (21,42,43) and in the management of spontaneous abortion in PC +/-patients (44,45), studies with this low-PC model could add significantly to an understanding of the role of PC in certain pregnancy complications.…”

Section: Discussionmentioning

confidence: 99%

Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities

Lay¹,

Zhong²,

Rosen³

et al. 2005

J. Clin. Invest.

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Anticoagulant protein C (PC) is important not only for maintenance of normal hemostasis, but also for regulating the host immune response during inflammation. Because mice with a designed total genetic deficiency in PC (PC -/-mice) die soon after birth, attempts to dissect PC function in various coagulation/inflammationbased pathologies through use of mice with less than 50% of normal PC levels have not been successful to date. In the current investigation, we have used a novel transgenic strategy to generate different mouse models expressing 1-18% of normal PC levels. In contrast to PC -/-mice, mice with only partial PC deficiency survived beyond birth and also developed thrombosis and inflammation. The onset and severity of these phenotypes vary significantly and are strongly dependent on plasma PC levels. Our findings additionally provide the first evidence that maternal PC is vital for sustaining pregnancy beyond 7.5 days postcoitum, likely by regulating the balance of coagulation and inflammation during trophoblast invasion. These low PC-expressing transgenic mouse lines provide novel animal models that can be used to elucidate the importance of PC in maintenance of the organism and in disease.

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Section: Discussionmentioning

confidence: 99%

Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities

Lay¹,

Zhong²,

Rosen³

et al. 2005

J. Clin. Invest.

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“…The problem is that there is no consensus for therapy for these cases, although Ogasawara et al . concluded that anticoagulation therapy with heparin is a useful treatment when fetal loss is related to PC deficiency 74 …”

Section: Aspirin and Recurrent Pregnancy Loss In Women With Inheritedmentioning

confidence: 99%

Anticoagulant therapy and pregnancy

Makino¹,

Sugiura‐Ogasawara

2008

Reprod Medicine & Biology

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Low dose aspirin therapy is one of the anticoagulant treatments used during pregnancy. Anticoagulant agents may be useful for several disorders, such as recurrent miscarriage, preeclampsia, fetal growth restriction and infertility. However, it is unclear whether anticoagulant therapy can increase the live birth rate in all of these cases. Recent data suggest that a low-dose aspirin and heparin combination therapy is effective in the prevention of recurrent pregnancy loss in women with antiphospholipid syndrome. Thrombogenic diseases, for example, protein C deficiency, protein S deficiency, factor XII deficiency and hyperhomocysteinemia, may cause pregnancy loss. The etiology of recurrent miscarriage is often unclear and may be multifactorial, with much controversy regarding diagnosis and treatment. Although 70% of recurrent pregnancy losses are unexplained, anticoagulant therapy is effective in maintaining pregnancy without antiphospholipid antibody syndrome. We conclude that a low-dose aspirin and heparin combination therapy can be useful for unexplained cases of recurrent pregnancy loss without antiphospholipid antibody syndrome. (Reprod Med Biol 2008; 7: 1-10)

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“…This dearth of information and lack of published dosing protocols are frustrating. Due to inherent difficulties conducting prospective, randomized, controlled studies in pregnant patients, clinical experience with LMWHs in pregnancy is largely documented as abstracts, letters, [13][14][15][16][17][18][19][20][21][22][23] case reports, [24][25][26][27][28][29][30][31][32][33][34] case series (or experience reports), [35][36][37][38][39]45 and retrospective studies. [40][41][42][43] A few prospective studies 44,[46][47][48][49][50][51][52] were performed, most of which were nonrandomized and/or uncontrolled.…”

Section: Studies Of Low-molecular-weight Heparin Therapy In Pregnancymentioning

confidence: 99%

“…Forty citations were identified; abstracts were 1015 [35][36][37][38][39]45 ; 11 case reports [24][25][26][27][28][29][30][31][32][33][34] ; and 11 letters to the editor. [13][14][15][16][17][18][19][20][21][22][23] According to the U.S. Preventive Services Task Force rating scale, 53 only 2 studies qualified as level I, 50, 52 3 were level II-1, 47-49 3 were level II-2, 39, 46, 51 4 were level II-3, 35, 38, 43, 45 9 were level III, 16,19,22,36,37,[40][41][42]44 and the remaining 19 were classified as other (i.e.…”

Section: Study Designsmentioning

confidence: 99%

“…23 The other clinical indication for treatment was recurrent miscarriage (51 pregnancies, 7%) in association with antiphospholipid antibody syndrome, impaired fibrinolytic capacity, or familial thrombophilia. 29,32,44,46,49 Three patients had antiphospholipid antibody syndrome based on history of thrombosis and/or recurrent miscarriage. 41 To assess placental transfer, 64 women (9%) were given LMWH just before delivery at term or before second-or thirdtrimester termination of pregnancy.…”

Section: Patient Profiles and Indicationsmentioning

confidence: 99%

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Low‐Molecular‐Weight Heparins in Pregnancy

Ensom

Stephenson

1999

Pharmacotherapy

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We conducted a systematic review, with MEDLINE and Cochrane Library data base searches and bibliographic reviews, of English-language reports describing therapy with low-molecular-weight heparin (LMWH) in pregnancy. Altogether 40 citations, excluding abstracts, were identified. When the quality of evidence was categorized according to the method outlined by the U.S. Preventive Services Task Force, 2 articles were level I, 3 were level II-1, 3 were level II-2, 4 were level II-3, 9 were level III, and the remaining 19 were classified as other (i.e., below level III). Of the 728 pregnant women and 1 postpartum woman described in the 40 citations, 340 (47%) received dalteparin, 192 (26%) enoxaparin, 108 (15%) certoparin, 54 (7%) nadroparin, 30 (4%) other LMWH, and 6 (< 1%) unspecified. The indication for LMWH in most patients (606 pregnancies, 83%) was for thromboprophylaxis. Daily doses ranged from 2500-22,000 U for dalteparin, 20 mg (2000 U)-80 mg (8000 U) for enoxaparin, 3000 U for certoparin, and 2050-15,000 U for nadroparin. Regimens included fixed dosages, increasing dosages as pregnancy progressed, dosages based on body weight, and dosages titrated according to anti-Xa levels. Duration of therapy ranged from a single dose to 476 days. Maternal anti-Xa levels were reported for 255 pregnancies. Target anti-Xa levels ranged from 0.1-0.6 U/ml and measured values from 0.0-0.7 U/ml. Major maternal findings were 18 local and generalized skin reactions, 27 bleeding complications, 9 thromboembolic events, 8 deep vein thromboses, 1 bilateral renal vein thrombosis, 4 pulmonary emboli, 1 hepatic infarction, 4 cases of thrombophlebitis, 12 cases of preeclampsia, 1 placental abruption, and 2 osteoporotic vertebral fractures. A major fetal finding was lack of anti-Xa activity in fetal or cord blood. Published experience suggests that LMWHs are generally safe and effective when administered for thromboprophylaxis during pregnancy. Until prospective, randomized, controlled trials comparing them with unfractionated heparin are performed, their benefits in pregnancy will remain inconclusive.

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Successful management of congenital protein C deficiency with recurrent pregnancy loss

Cited by 8 publications

References 4 publications

Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities

Mice with a severe deficiency in protein C display prothrombotic and proinflammatory phenotypes and compromised maternal reproductive capabilities

Anticoagulant therapy and pregnancy

Low‐Molecular‐Weight Heparins in Pregnancy

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