Table 4.
Review of literature for pregnancy with paroxysmal nocturnal hemoglobinuria
| Case number | Reference | Number of cases | Maternal age at pregnancy | Anticoagulation therapy | Eculizumab therapy | ||
|---|---|---|---|---|---|---|---|
| Before pregnancy | During pregnancy | During pregnancy (duration of dose if stated) | Postpartum (mg) | ||||
| 1 | Alashkar, et al. | 9 | NS | NS | NS | 900 mg | 900 |
| 2 | Alashkar, et al. | 9 | NS | NS | 900–1800 mg | 900 | |
| 3 | Alashkar, et al. | 9 | NS | 1200–1800 mg | 1200 | ||
| 4 | Alashkar, et al. | 9 | NS | NS | NS | 900–1200 mg | 900 |
| 5 | Alashkar, et al. | 9 | NS | NS | NS | 900–1200 mg | 900 |
| 6 | Alashkar, et al. | 9 | NS | NS | NS | 900–1200 mg | 900 |
| 7 | Alashkar, et al. | 9 | NS | NS | NS | 900–1200 mg | 900 |
| 8 | Alashkar, et al. | 9 | NS | NS | NS | None | 900 |
| 9 | Alashkar, et al. | 9 | NS | NS | 900 mg | 900 | |
| 10 | Alashkar, et al. | 9 | NS | NS | 900 mg | 900 | |
| 11 | Alashkar, et al. | 9 | NS | NS | 900–1200 mg | 900 | |
| 12 | Alashkar, et al. | 9 | NS | NS | NS | None | None |
| 13 | Alashkar, et al. | 9 | NS | NS | 900 mg | 900 | |
| 14 | Alashkar, et al. | 9 | NS | NS | 900 mg | 900 | |
| 15 | Alashkar, et al. | 9 | NS | NS | NS | None | None |
| 16 | Alashkar, et al. | 9 | NS | NS | NS | 900 mg | 900 mg |
| 17 | Rodríguez-Ferreras, et al. | 1 | 39 | None | None | 600 mg for 4 weeks then 900 mg every 2 weeks | Yes |
| 18 | Bastos et al. | 1 | 38 | None | Prophylactic LMWH | 900–1200 mg (forced reduction due unavailability) | 1200 |
| 19 | Danilov et al. | 1 | 34 | Therapeutic heparin | Therapeutic heparin | From 30 weeks | Yes |
| 20 | Kelly et al. | 6 | 25 | Warfarin | Therapeutic heparin | Up to 5 weeks | No |
| 21 | Kelly et al. | 6 | 22 | Not known | Not known | Up to 14 weeks | No |
| 22 | Kelly et al. | 6 | 26 | Not known | Therapeutic heparin | Up to 4 weeks | No |
| 23 | Kelly et al. | 6 | 27 | No | Prophylactic heparin | Entire pregnancy (increased from 28 weeks) | Yes |
| 24 | Kelly et al. | 6 | 35 | No | Therapeutic heparin | From 27 weeks (weekly) | Yes |
| 25 | Kelly et al. | 6 | 28 | Warfarin | Therapeutic heparin | Entire pregnancy | Yes |
| 26 | Marasca et al. | 1 | 34 | No | Prophylactic heparin | Entire pregnancy | Yes |
| 27 | Ando et al. | 1 | 37 | No | No | Entire pregnancy | Yes |
| 28 | Sharma et al. | 1 | 32 | No | Prophylactic heparin | Entire pregnancy (increased from 30 weeks) | Yes |
| 29 | Patriquin et al. | 1 | 30 | No | Prophylactic heparin | Entire pregnancy (increased from 2nd trimester) | Yes |
| 30 | Miyasaka et al. | 3 | 34 | No | Prophylactic heparin | Entire pregnancy | Yes |
| 31 | Miyasaka et al. | 3 | 30 | No | Prophylactic heparin | From 27 weeks | Yes |
| 32 | Miyasaka et al. | 3 | 29 | No | Prophylactic heparin | From 18 weeks | Yes |
| 33 | Patel et al. | 1 | 24 | No | Prophylactic heparin | From 10 weeks | Yes |
| 34 | Vekemans et al. | 1 | 41 | No | Prophylactic LMWH | Entire pregnancy | Yes |
| 35 | Gessoni et al. | 1 | NS | No | Prophylactic LMWH | Entire pregnancy | Yes |
| 36 | Bjørge et al. | 1 | 35 | Warfarin | Therapeutic heparin | NS | NS |
| 37 | Lauritsch-Hernandez et al. | 1 | 27 | Oral anticoagulation, Vitamin K antagonist | Therapeutic heparin | Entire pregnancy | Yes |
| 38 | Singh et al. | 1 | 23 | No | No | No | No |
| 39 | Morita et al. | 2 | 30 | No | Prophylactic heparin | NS | NS |
| 40 | Morita et al. | 2 | 41 | NS | Therapeutic heparin | NS | NS |
| 41 | Bais et al. | 1 | 30 | No | No | No | No |
| 42 | Guibert et al. | 23 | 27 | No | No | NS | NS |
| 43 | Guibert et al. | 23 | 26 | No | No | NS | NS |
| 44 | Guibert et al. | 23 | 27 | No | LMWH | NS | NS |
| 45 | Guibert et al. | 23 | 27 | Therapeutic LMWH | LMWH | NS | NS |
| 46 | Guibert et al. | 23 | 21 | LMWH | LMWH | NS | NS |
| 47 | Guibert et al. | 23 | 38 | Danaparoid | Danaparoid | NS | NS |
| 48 | Guibert et al. | 23 | 21 | Danaparoid | Danaparoid | NS | NS |
| 49 | Guibert et al. | 23 | 32 | No | LMWH | NS | NS |
| 50 | Guibert et al. | 23 | 29 | Danaparoid | Danaparoid | NS | NS |
| 51 | Guibert et al. | 23 | 32 | Danaparoid | Danaparoid | NS | NS |
| 52 | Guibert et al. | 23 | 31 | LMWH | LMWH | NS | NS |
| 53 | Guibert et al. | 23 | 24 | LMWH | LMWH | NS | NS |
| 54 | Guibert et al. | 23 | 30 | No | No | NS | NS |
| 55 | Guibert et al. | 23 | 24 | Danaparoid | Danaparoid | NS | NS |
| 56 | Guibert et al. | 23 | 22 | LMWH | LMWH | NS | NS |
| 57 | Guibert et al. | 23 | 26 | LMWH | LMWH | NS | NS |
| 58 | Guibert et al. | 23 | 28 | No | No | NS | NS |
| 59 | Guibert et al. | 23 | 27 | Danaparoid | Danaparoid | NS | NS |
| 60 | Guibert et al. | 23 | 27 | NS | NS | NS | NS |
| 63 | Guibert et al. | 23 | 26 | LMWH | LMWH | NS | NS |
| 64 | Guibert et al. | 23 | 27 | No | No | NS | NS |
| 65 | Guibert et al. | 23 | 28 | No | No | NS | NS |
| 66 | Guibert et al. | 23 | NA | LMWH | LMWH | NS | NS |
| 67 | Sasano et al. | 1 (1.2) | 29 | No | Prophylactic heparin | No | No |
| 68 | Sasano et al. | 1 (2.2) | 33 | No | Therapeutic UFH | No | No |
| 69 | Our case 1 | 4 | 42 | No | Prophylactic LMWH | 1200 | 900 |
| 70 | Our case 2.1 | 4 | 29 | No | Prophylactic enoxaparin | No | No |
| 71 | Our case 2.2 | 4 | 29 | No | Prophylactic enoxaparin | No | No |
| 72 | Our case 2.3 | 4 | 29 | No | Prophylactic enoxaparin | No | No |
| 73 | Our case 3.1 | 4 | 38 | No | Fondaparinux (due to HIT) | 600 (started 31 weeks) | 600 |
| 74 | Our case 3.2 | 4 | 38 | No | No | 600 | 600 |
| 75 | Our case 3.3 | 4 | 38 | No | Not yet started (patient in 1st trimester) | 600 | 600 |
| 76 | Our case 4.1 | 4 | 37 | No | Enoxaparin | 900 | 900 |
| 77 | Our case 4.2 | 4 | 37 | No | Prophylactic enoxaparin | 900 | 900 |
| 78 | Our case 4.3 | 4 | 37 | No | No | 900 | 900 |
| Case number | Complications | Mode of delivery (indication) | Newborn status | ||||
| Intrapartum | Postpartum | ||||||
| 1 | Hemolysis, RBC trans | NS | Vaginal | Healthy | |||
| 2 | BH, RBC trans | NS | Vaginal | Healthy | |||
| 3 | BH, RBC trans | NS | Vaginal | Healthy | |||
| 4 | BH, BCS, RBC/PLT trans, cholecystitis | NS | CS | Healthy | |||
| 5 | BCS, cholecystitis RBC/PLT trans | NS | CS | Healthy | |||
| 6 | BH | NS | CS | Healthy | |||
| 7 | BH | NS | Vaginal | Healthy | |||
| 8 | Sp Ab, RBC trans | NS | Vaginal | Dead | |||
| 9 | Sp Ab | NS | Vaginal | Dead | |||
| 10 | Sp Ab | NS | Vaginal | Dead | |||
| 11 | BH | NS | CS | Healthy | |||
| 12 | Sp Ab, RBC trans | NS | Vaginal | Dead | |||
| 13 | Stillbirth | NS | Vaginal | Dead | |||
| 14 | Medical Ab | NS | - | Dead | |||
| 15 | Sp Ab | NS | Vaginal | Dead | |||
| 16 | RBC Trans, precplampsia | NS | CS | Stillbirth | |||
| 17 | Heavy vaginal bleeding, abdominal pain | None | Vaginal | Sp Ab (1st trimester) | |||
| 18 | AKF, hemolytic anemia, RBC trans | Hospitalized | Emergency CS | Healthy | |||
| 19 | Thrombocytopenia RBC/PLT trans | None | CS (twin-breech) | Healthy | |||
| 20 | None | None | NS | Healthy | |||
| 21 | None | FUO | NS | Healthy | |||
| 22 | None | None | NS | Healthy | |||
| 23 | BH, RBC trans | None | SVD | Healthy | |||
| 24 | None | PPH | CS (twin) | Healthy | |||
| 25 | Preeclampsia | None | CS (preeclampsia) | Healthy | |||
| 26 | None | None | SVD | Healthy | |||
| 27 | None | None | CS (breech) | Healthy | |||
| 28 | BH, RBC trans | None | CS (elective) | Healthy | |||
| 29 | BH, RBC trans | None | CS (placenta previa) | Healthy | |||
| 30 | BH, RBC trans | None | SVD | Healthy | |||
| 31 | Preeclampsia | None | CS (preeclampsia) | Healthy | |||
| 32 | None | PPH | SVD | Healthy | |||
| 33 | None | None | SVD | Healthy | |||
| 34 | RBC trans | RBC tans | SVD | Healthy | |||
| 35 | PE, BULT | PPE, PE, BULT, abdominal angina with TPI | CS (fetal distress) | Healthy | |||
| 36 | Chorioamnionitis secondry to IOL | PPH, LVT (liver failure, BCS, BMF) | CS (failed IOL) | Healthy | |||
| 37 | None | None | CS (transverse presentation) | Healthy | |||
| 38 | PROM | Sepsis, ARF, PRES | SVD | NS | |||
| 39 | None | None | Emergency CS (reduction fetal heartbeat) | NS | |||
| 40 | None | None | CS (breech) | NS | |||
| 41 | PLT trans | Hemolytic crisis, PMVT, IC | SVD | Healthy | |||
| 42 | None | None | NA | Healthy | |||
| 43 | HELLP, PLT trans | None | CS (failed IOL) | Healthy | |||
| 44 | None | None | SVD | Healthy | |||
| 45 | None | BCS | CS (failed IOL) | Healthy | |||
| 46 | None | None | CS (NS) | Healthy | |||
| 47 | Anemia, RBC trans | None | CS (failed IOL) | Healthy | |||
| 48 | None | None | SVD | Healthy | |||
| 49 | None | NET infections | NA | Healthy | |||
| 50 | None | Febrile neutropenia | SVD | Healthy | |||
| 51 | None | Cerebral infarction | SVD | Healthy | |||
| 52 | None | None | CS (failed IOL) | Healthy | |||
| 53 | None | Hepatic and splenic VTE | SVD | Healthy | |||
| 54 | None | None | SVD | Healthy | |||
| 55 | Hemorrhagic delivery | None | SVD | Healthy | |||
| 56 | None | None | CS (failed IOL) | Healthy | |||
| 57 | None | None | CS (failed IOL) | Healthy | |||
| 58 | None | Thrombocytopenia, PLT trans, PPH, mesenteric VTE | SVD | Healthy | |||
| 59 | None | Uterine hematoma, RBC trans | SVD | Healthy | |||
| 60 | NS | NS | NS | Therapeutic abortion | |||
| 63 | None | None | CS (NS) | Healthy | |||
| 64 | None | None | SVD | Fetal death | |||
| 65 | None | None | CS (failed IOL) | AFD | |||
| 66 | None | Cerebral VTE | NA | Healthy | |||
| 67 | RBC trans, mild preeclampsia | None | SVD | Healthy | |||
| 68 | RBC trans | None | SVD | Healthy | |||
| 69 | RBC, PLT trans | PSMVT, thrombocytopenia, PLT Trans | CS (IOL) | NICU, dysmorphic features | |||
| 70 | None | None | SVD | Healthy | |||
| 71 | None | None | Emergency CS (fetal distress) | Healthy | |||
| 72 | Lower abdominal pain, PV bleeding | None | Emergency evacuation/curettage | Missed Ab | |||
| 73 | PV bleeding, thrombocytopenia, hemolysis, RBC/PLT trans (before introducing eculizumab) | None | SVD | Healthy | |||
| 74 | Unknown | Unknown | SVD | Missed Ab | |||
| 75 | None | Pregnant | Pregnant | - | |||
| 76 | IUFD, PLT trans | None | SVD | IUFD | |||
| 77 | PV bleeding | None | SVD | Sp Ab | |||
| 78 | None | None | SVD | Sp Ab | |||
Trans – Transfusion; NS – Not stated; PLT – Platelets; RBC – Red blood cells; BH – Breakthrough hemolysis; BCS – Budd-chiari syndrome; SP – Spontaneous; AB – Abortion; PVT – Portal vein thrombosis; CS – Caesarean section; FUO – Fever of unknown origin; SVD – Spontaneous vaginal delivery; PPH – Postpartum hemorrhage; PPE – Pleural peritoneal effusion; PE – Pulmonary embolism; BULT – Bilateral upper limb thrombophlebitis; TPI – Transient paralytic ileus; LVT – Liver vein thrombosis; IOL – Induction of labor; BMF – Bone marrow failure; ARF – Acute renal failure; PRES – Posterior reversible encephalopathy syndrome; PMVT – Portal mesenteric vein thrombosis; IC – Ischemic colitis; NA – Not available; NET – Nose-ear-throat; VTE – Venous thromboembolism; PSMVT – Portal and superior mesenteric vein thrombosis; ICU – Intensive care unit; HIT – Heparin indiced thrombocytopenia; IUFD – Intrauterine fetal death; IUFD – Intrauterine fetal deaths; PV – Per vaginal; LMWH – Low-molecular-weight heparin; UFH – Unfractionated heparin; PROM – Preterm rupture of membranes; AKF – Acute kidney failure; HELLP – Hemolysis elevated liver enzymes and low platelets