Selected studies examining the impact of anticoagulation on pregnancy outcomes in women with inherited thrombophilia
| Author, year, sample size . | Inclusion criteria . | Inherited thrombophilia Sample Size . | Intervention . | Live birth outcome* . | Overall findings for impact of anticoagulation on live birth . | |
|---|---|---|---|---|---|---|
| All inherited thrombophilias N (%) . | Sample size of FVL or PGM homozygosity (N) . | |||||
| Randomized controlled trials | ||||||
| Quenby, 2023 N = 326 | Women with FVL, PGM, AT, PC or PS, and RPL | 326 (100%) | N = 5 FVL HOM N = 5 in Group 1 N = 0 in Group 2 N = 2 PGM HOM N = 0 in Group 1, N = 2 in Group 2 | Group 1: LMWH Group 2: no treatment | 72% Group 1 71% Group 2 | No difference on live birth outcomes |
| Karadag, 2020 N = 174 | Women with FVL and RPL | 174 (100%) | 62 = FVL HOM N = 23 in Group 1, N = 21 in Group 2, N = 18 in Group 3 | Group 1: Aspirin Group 2: LMWH + ASA Group 3: LMWH | 86.9% Group 1 86.4% Group 2 83.3% Group 3 | No difference on live birth outcomes |
| Schleussner, 2015 N = 449 | Women with a history of at least 2 consecutive early miscarriages or 1 late miscarriage Patients were then screened for FVL, PGM, AT, PS, PC | 63 (14%) | FVL HOM and PGM HOM patients were excluded | Group 1: LMWH Group 2: No treatment | 86% Group 1 86.7% Group 2 | No difference on live birth outcomes |
| Rodger, 2014 N = 289 | Women with FVL, PGM, AT, PS, PC or APS and previous pregnancy complications or venous thromboembolism risk factors 62/164 in intervention group and 67/143 in control group had history of pregnancy loss | 283 (97%) | N = 4 FVL HOM Did not specify which group | Group 1: LMWH Group 2: No treatment | Pregnancy Loss Group 1: 8.2% Group 2: 7% | No difference on pregnancy loss outcomes |
| Martinelli, 2012 N = 135 | Women with FVL, PGM, AT, PS, PC and history of pregnancy complications (25/67 in intervention and 24/68 in control group had a history of intrauterine fetal death) | 131 (97%) | Did not specify | Group 1: LMWH Group 2: No treatment | Intrauterine fetal death Group 1: 3.2% Group 2: 1.5% | No difference in intrauterine fetal death |
| Visser, 2011 N = 207 | Women with RPL, with or without FVL, PGM, PS, PC | 26 (12.5%) | Specifically excluded high risk thrombophilia of FVL HOM or PGM HOM | Group 1: LMWH + placebo Group 2: LMWH + ASA Group 3: ASA | Group 1: 71% Group 2: 65% Group 3: 61% Outcomes in IT: Group 1: 13/17 Group 2: 9/15 Group 3: 12/19 | No difference on pregnancy loss outcomes |
| Clark, 2010 N = 294 | Women with at least 2 consecutive early pregnancy losses, once enrolled each was screened for IT | 10 (3%) | None | Group 1: LMWH + ASA Group 2: No treatment | Pregnancy loss Group 1: 22% Group 2: 20% | No difference on pregnancy loss outcomes |
| Kaandorp, 2010 N = 364 | Women with FVL, PGM, AT, PS, PC and a history of unexplained recurrent miscarriages | 47 (12%) | Did not specify | Group 1: LMWH + ASA Group 2:ASA Group 3: Placebo | Group 1: 69.1% Group 2: 61.6% Group 3: 67% | No difference in live birth rate |
| Laskin, 2009 N = 88 | Women with FVL, PGM, PS, PC, MTHFR mutation, positive antinuclear antibody, or positive antiphospholipid antibody and a history of recurrent pregnancy loss | 19 (21.5%) | None | Group 1: LMWH + ASA Group 2: ASA | Group 1: 77.8% Group 2: 79.1% | No difference on pregnancy loss outcomes |
| Gris, 2004 N = 160 | Women with FVL, PGM, PS, and 1 unexplained pregnancy loss | 160 (100%) | None | Group 1: LMWH Group 2: ASA | Group 1: 86% Group 2: 29% | The only RCT that showed a benefit to LMWH |
| Observational Studies | ||||||
| Dugalic, 2019 Prospective N = 358 | Women with (FVL, PGM, AT, PC, PS; also included PA1, and MTHFR) with previous pregnancy outcomes including miscarriage and intrauterine fetal demise | 195 (54%) | Did not specify | Group 1: LMWH Group 2: Control | Group 1: 100% Group 2: 91.5% | Live birth rate was higher when LMWH was implemented |
| Calvijo, 2019 Retrospective N = 88 | Women with IT (FVL, PGM, AT, PC, PS) Early pregnancy loss <10 weeks (26/88) Late pregnancy loss >10 weeks (11/88) | 88 (100%) | None | Group 1: before IT diagnosis, and no LMWH Group 2: following IT, treated with LMWH | OR for miscarriage (M) or fetal loss (FL) following LMWH use: M: 0.41 (0.20-0.82) P = 0.012 FL: 0.08 (00.5-1.39) P = 0.085 | Miscarriage rate was lower when LMWH was implemented |
| Aracic, 2016 Prospective N = 50 | Women with IT and history of adverse pregnancy outcomes (conventional IT: FVL, PGM, AT, PC, PS) and others included (MTHFR, PAI-1 polymorphism, ACE polymorphism) 80/128 prior pregnancies resulted in first or second term pregnancy loss | 50 (100%) | None | Group 1: LMWH Group 2 = no treatment | Group 1: 96% Group 2: 37.5% | Live birth rate was higher when LMWH was implemented |
| Aynioglu, 2016 Retrospective N = 153 | Women with history of prior pregnancy loss and IT (FVL, PGM, AT, PS, PC and included MTHFR) | 153 (100%) | N = 1 FVL HOM Group 1 N = 1 PGM HOM Group 2 | Group 1: LMWH + ASA Group 2: untreated | Proportion of the 85 live births in the cohort attributed to each group: Group 1: 80% Group 2: 20% | Live birth rate was higher in intervention group |
| Sokol, 2016 Retrospective N = 70 | Women with IT (FVL, PGM, AT, PS, PC, and MTHFR) with mean number of prior pregnancy loss >1 | 70 (100%) | N = 1 FVL HOM N = 1 PGM HOM | Group 1: LMWH Group 2: control | Miscarriage rate Group 1: 1.7% Group 2: 30% | Miscarriage rate was lower when LMWH was implemented |
| Tormene, 2012 Bidirectional N = 416 | Women with FVL or PGM Mean number of prior pregnancy loss Group 1: 1.15 Group 2: 1.58 Group 3: 1.52 Group 4: 0.53 | 416 (100%) | Group 1: N = 1 PGM HOM N = 8 FVL HOM N = 14 compound heterozygotes Group 2: none Group 3: none Group 4: N = 2 PGM HOM, N = 14 FVL HOM, N = 23 compound heterozygotes | Group 1: LMWH Group 2: LMWH + ASA Group 3: ASA Group 4: none | LMWH protective effect on miscarriages (OR 0.52; 95% CI, 0.29-0.94) | Miscarriage rate was lower when LMWH was implemented |
| Kupferminc, 2011 Retrospective N = 116 | Women with IT (FVL, PGM, PS, PC) and history of adverse pregnancy outcomes 17/87 in Group 1 had pregnancy loss 6/29 in Group 2 had pregnancy loss | 116 (100%) | Did not specify | Group 1: LMWH Group 2: no treatment | Pregnancy loss >20 weeks Group 1: 0 Group 2: 7% | LMWH did not change pregnancy loss >20 weeks |
| Grandone, 2008 Retrospective N = 32 | Women with pregnancy loss and AT, PS or PS | 32 (100%) | Did not specify | Group 1: LMWH in 8 pregnancies Group 2: no treatment in 95 pregnancies | Group 1: 88.9% Group 2: 28.4% | Live birth rate was higher with LMWH |
| Carp, 2003 Prospective N = 85 | Women with IT (FVL, PGM, AT, PS, PC, and MTHFR) and pregnancy loss | 85 (100%) | Did not specify | Group 1: LMWH Group 2: no treatment | Group 1: 70.2% Group 2: 43.8% | Live birth rate was higher with LMWH |
| Brenner, 2000 Prospective N = 50 | Women with IT (FVL, PGM, PS, PC, MTHFR), also included APS and recurrent pregnancy loss | 50 (100%) | Did not specify | Group 1: LMWH Group 2: no treatment | Group 1:75% Group 2: 20% | Live birth rate was higher with LMWH |
| Author, year, sample size . | Inclusion criteria . | Inherited thrombophilia Sample Size . | Intervention . | Live birth outcome* . | Overall findings for impact of anticoagulation on live birth . | |
|---|---|---|---|---|---|---|
| All inherited thrombophilias N (%) . | Sample size of FVL or PGM homozygosity (N) . | |||||
| Randomized controlled trials | ||||||
| Quenby, 2023 N = 326 | Women with FVL, PGM, AT, PC or PS, and RPL | 326 (100%) | N = 5 FVL HOM N = 5 in Group 1 N = 0 in Group 2 N = 2 PGM HOM N = 0 in Group 1, N = 2 in Group 2 | Group 1: LMWH Group 2: no treatment | 72% Group 1 71% Group 2 | No difference on live birth outcomes |
| Karadag, 2020 N = 174 | Women with FVL and RPL | 174 (100%) | 62 = FVL HOM N = 23 in Group 1, N = 21 in Group 2, N = 18 in Group 3 | Group 1: Aspirin Group 2: LMWH + ASA Group 3: LMWH | 86.9% Group 1 86.4% Group 2 83.3% Group 3 | No difference on live birth outcomes |
| Schleussner, 2015 N = 449 | Women with a history of at least 2 consecutive early miscarriages or 1 late miscarriage Patients were then screened for FVL, PGM, AT, PS, PC | 63 (14%) | FVL HOM and PGM HOM patients were excluded | Group 1: LMWH Group 2: No treatment | 86% Group 1 86.7% Group 2 | No difference on live birth outcomes |
| Rodger, 2014 N = 289 | Women with FVL, PGM, AT, PS, PC or APS and previous pregnancy complications or venous thromboembolism risk factors 62/164 in intervention group and 67/143 in control group had history of pregnancy loss | 283 (97%) | N = 4 FVL HOM Did not specify which group | Group 1: LMWH Group 2: No treatment | Pregnancy Loss Group 1: 8.2% Group 2: 7% | No difference on pregnancy loss outcomes |
| Martinelli, 2012 N = 135 | Women with FVL, PGM, AT, PS, PC and history of pregnancy complications (25/67 in intervention and 24/68 in control group had a history of intrauterine fetal death) | 131 (97%) | Did not specify | Group 1: LMWH Group 2: No treatment | Intrauterine fetal death Group 1: 3.2% Group 2: 1.5% | No difference in intrauterine fetal death |
| Visser, 2011 N = 207 | Women with RPL, with or without FVL, PGM, PS, PC | 26 (12.5%) | Specifically excluded high risk thrombophilia of FVL HOM or PGM HOM | Group 1: LMWH + placebo Group 2: LMWH + ASA Group 3: ASA | Group 1: 71% Group 2: 65% Group 3: 61% Outcomes in IT: Group 1: 13/17 Group 2: 9/15 Group 3: 12/19 | No difference on pregnancy loss outcomes |
| Clark, 2010 N = 294 | Women with at least 2 consecutive early pregnancy losses, once enrolled each was screened for IT | 10 (3%) | None | Group 1: LMWH + ASA Group 2: No treatment | Pregnancy loss Group 1: 22% Group 2: 20% | No difference on pregnancy loss outcomes |
| Kaandorp, 2010 N = 364 | Women with FVL, PGM, AT, PS, PC and a history of unexplained recurrent miscarriages | 47 (12%) | Did not specify | Group 1: LMWH + ASA Group 2:ASA Group 3: Placebo | Group 1: 69.1% Group 2: 61.6% Group 3: 67% | No difference in live birth rate |
| Laskin, 2009 N = 88 | Women with FVL, PGM, PS, PC, MTHFR mutation, positive antinuclear antibody, or positive antiphospholipid antibody and a history of recurrent pregnancy loss | 19 (21.5%) | None | Group 1: LMWH + ASA Group 2: ASA | Group 1: 77.8% Group 2: 79.1% | No difference on pregnancy loss outcomes |
| Gris, 2004 N = 160 | Women with FVL, PGM, PS, and 1 unexplained pregnancy loss | 160 (100%) | None | Group 1: LMWH Group 2: ASA | Group 1: 86% Group 2: 29% | The only RCT that showed a benefit to LMWH |
| Observational Studies | ||||||
| Dugalic, 2019 Prospective N = 358 | Women with (FVL, PGM, AT, PC, PS; also included PA1, and MTHFR) with previous pregnancy outcomes including miscarriage and intrauterine fetal demise | 195 (54%) | Did not specify | Group 1: LMWH Group 2: Control | Group 1: 100% Group 2: 91.5% | Live birth rate was higher when LMWH was implemented |
| Calvijo, 2019 Retrospective N = 88 | Women with IT (FVL, PGM, AT, PC, PS) Early pregnancy loss <10 weeks (26/88) Late pregnancy loss >10 weeks (11/88) | 88 (100%) | None | Group 1: before IT diagnosis, and no LMWH Group 2: following IT, treated with LMWH | OR for miscarriage (M) or fetal loss (FL) following LMWH use: M: 0.41 (0.20-0.82) P = 0.012 FL: 0.08 (00.5-1.39) P = 0.085 | Miscarriage rate was lower when LMWH was implemented |
| Aracic, 2016 Prospective N = 50 | Women with IT and history of adverse pregnancy outcomes (conventional IT: FVL, PGM, AT, PC, PS) and others included (MTHFR, PAI-1 polymorphism, ACE polymorphism) 80/128 prior pregnancies resulted in first or second term pregnancy loss | 50 (100%) | None | Group 1: LMWH Group 2 = no treatment | Group 1: 96% Group 2: 37.5% | Live birth rate was higher when LMWH was implemented |
| Aynioglu, 2016 Retrospective N = 153 | Women with history of prior pregnancy loss and IT (FVL, PGM, AT, PS, PC and included MTHFR) | 153 (100%) | N = 1 FVL HOM Group 1 N = 1 PGM HOM Group 2 | Group 1: LMWH + ASA Group 2: untreated | Proportion of the 85 live births in the cohort attributed to each group: Group 1: 80% Group 2: 20% | Live birth rate was higher in intervention group |
| Sokol, 2016 Retrospective N = 70 | Women with IT (FVL, PGM, AT, PS, PC, and MTHFR) with mean number of prior pregnancy loss >1 | 70 (100%) | N = 1 FVL HOM N = 1 PGM HOM | Group 1: LMWH Group 2: control | Miscarriage rate Group 1: 1.7% Group 2: 30% | Miscarriage rate was lower when LMWH was implemented |
| Tormene, 2012 Bidirectional N = 416 | Women with FVL or PGM Mean number of prior pregnancy loss Group 1: 1.15 Group 2: 1.58 Group 3: 1.52 Group 4: 0.53 | 416 (100%) | Group 1: N = 1 PGM HOM N = 8 FVL HOM N = 14 compound heterozygotes Group 2: none Group 3: none Group 4: N = 2 PGM HOM, N = 14 FVL HOM, N = 23 compound heterozygotes | Group 1: LMWH Group 2: LMWH + ASA Group 3: ASA Group 4: none | LMWH protective effect on miscarriages (OR 0.52; 95% CI, 0.29-0.94) | Miscarriage rate was lower when LMWH was implemented |
| Kupferminc, 2011 Retrospective N = 116 | Women with IT (FVL, PGM, PS, PC) and history of adverse pregnancy outcomes 17/87 in Group 1 had pregnancy loss 6/29 in Group 2 had pregnancy loss | 116 (100%) | Did not specify | Group 1: LMWH Group 2: no treatment | Pregnancy loss >20 weeks Group 1: 0 Group 2: 7% | LMWH did not change pregnancy loss >20 weeks |
| Grandone, 2008 Retrospective N = 32 | Women with pregnancy loss and AT, PS or PS | 32 (100%) | Did not specify | Group 1: LMWH in 8 pregnancies Group 2: no treatment in 95 pregnancies | Group 1: 88.9% Group 2: 28.4% | Live birth rate was higher with LMWH |
| Carp, 2003 Prospective N = 85 | Women with IT (FVL, PGM, AT, PS, PC, and MTHFR) and pregnancy loss | 85 (100%) | Did not specify | Group 1: LMWH Group 2: no treatment | Group 1: 70.2% Group 2: 43.8% | Live birth rate was higher with LMWH |
| Brenner, 2000 Prospective N = 50 | Women with IT (FVL, PGM, PS, PC, MTHFR), also included APS and recurrent pregnancy loss | 50 (100%) | Did not specify | Group 1: LMWH Group 2: no treatment | Group 1:75% Group 2: 20% | Live birth rate was higher with LMWH |
(or similar) for entire population (not just IT group).
ACE, angiotensin converting enzyme polymorphism; APS, antiphospholipid antibody syndrome; ASA, aspirin; AT, antithrombin deficiency; HOM, homozygosity; PC, protein C deficiency; PS, protein S deficiency.