Case 1
A 34-year-old pregnant woman at 30+ 3 weeks gestation required hospitalization due to decreased fetal movement for one day. The patient received no regular prenatal care, amniocentesis, or Down’s syndrome screening. The history provided was as follows: gravidity two and parity zero, and a history of stillbirth with unknown cause at 27+ weeks gestation by induced vaginal delivery. The patient was diagnosed with gestational diabetes mellitus after admission. Routine blood and liver biochemical, kidney and thyroid function tests yielded normal results. The fetus was assessed 2–3 times daily using cardiotocography (CTG) and regularly monitored by Doppler ultrasound (Table 1). Ultrasound at 30+ 4 weeks gestation showed a normal fetal size (umbilical artery systolic/diastolic phase: 2.1, amniotic fluid index: 14.98 cm). Two umbilical arteries seemed to be visualized, and the inner diameter of the smaller artery was approximately 0.15 cm. Nevertheless, only one umbilical artery blood flow signal was detected, where the umbilical cord entered the fetus near the fetal bladder. The fetus was suspected to have a single umbilical artery (Fig. 1). Doppler ultrasound demonstrated a pulsating umbilical vein (Fig. 2). An emergency cesarean section was performed at 31+ 1 weeks gestation because of fetal distress, which was noted on abnormal CTG and Doppler ultrasound findings. The female newborn weighed 1815 g with an Apgar score of 3-8-8. Umbilical cord examination showed thrombosis in both umbilical arteries. The umbilical cord, 20 cm in length, showed 12 reverse laps and no entanglement (Fig. 3). Blood coagulation and rheumatoid immune activity examinations showed nRNP/Sm antibody (+) and SS antibody (+++). A subcutaneous injection of nadroparin calcium (0.4 mL, 4000IU) was administered every 12 hours. Blood coagulation parameters, including ACL-IgG IgM IgA, Sm, Ro-52, SS-B, Sc1-70, PM-Sc1, Jo-1, CENP B, PCNA, dsDNA, NUKLEOSOMEN, nehistone, RIB P PRO, AMA-M2 (-), nRNP/Sm (+), and SS-A (+++) were assessed daily over the next 5 days (Table 2). The patient was diagnosed with antiphospholipid-antibody syndrome. The infant blood coagulation parameters were tested on postpartum days 1 and 3 (Table 3).
Table 1
Doppler ultrasound and CTG results in Case 1 fetus from 30+ 2 to 31+ 1 weeks of gestation
Parameter | 30+ 2 w | 30+ 3 w | 30+ 4 w | 30+ 6 w | 31+ 1 w |
Umbilical artery PI | 0.59 (˂ 5th ) | 0.49 (˂ 5th ) | 0.74 (˂ 5th ) | 0.77 (5-50th ) | 2.73 (˃95th ) |
Umbilical artery RI | 0.44 (˂ 5th ) | 0.39 (˂ 5th ) | 0.52 | 0.54 (5-50th ) | 0.83 |
Umbilical artery S/D | 1.8 (˂ 5th ) | 1.63 (˂ 5th ) | 2.1 | 2.19 (5-50th ) | 5.91 |
Middle cerebral artery PI | 1.57 (5-95th ) | 1.25 (5-95th ) | 1.81 (50-95th ) | 1.87 (50-95th ) | 0.53 (˂ 5th ) |
Middle cerebral artery RI | 0.77 (5-95th ) | 0.71 (5-95th ) | 0.81 (50-95th ) | 0.82 (50-95th ) | 0.39 |
Middle cerebral artery S/D | 4.41 (5-95th ) | 3.41 (5-95th ) | 5.37 (50-95th ) | 5.69 (50-95th ) | 1.65 |
Cerebro-placental ratio RI | 1.75 | 1.82 | 1.56 | 1.52 | 0.47 |
A-wave | Positive | Positive | Positive | Positive | Umbilical veins was pulsating |
AFI (cm) | 14.98 | 19 | 16.43 | 14.84 | 14.93 |
CTG | I | I | I | I | II |
Abbreviations: AFI = Amniotic fluid index, CTG = cardiotocography( fetal heart rate monitoring), PI = peak systolic velocity, RI = Resistance index, S/D = Systolic/diastolic phase. |
Table 2
Maternal blood coagulation parameters in Case 1 before and after administration of anticoagulation therapy
Parameter | 30+ 2 w | 30+ 3 w | 30+ 4 w | 30+ 6 w | 31+ 1 w |
APTT (s) | 25.2↓ | 30.3 | 28.9 | 36.2 | 38.3 |
PT (s) | 10.5 | 11.7 | 10.80 | 12.7 | 12.9 |
INR | 0.88 | 0.85 | 0.91 | 0.94 | 0.96 |
FIB (g/L) | 5.23↑ | 5.28↑ | 5.42↑ | 6.26↑ | 5.29↑ |
TT (s) | 12.1 | 16.6 | 11.70 | 17.4 | 19.2 |
D-dimer (ug/ml) | N/A | 8.06↑ | N/A | 2.08↑ | 2.00↑ |
FDP (ug/ml) | N/A | 27.01↑ | N/A | 6.64↑ | 8.12↑ |
* Day of the cesarean section. |
Abbreviations: APTT = activated partial thromboplastin time, D-D = D-dimer, FIB = Fibrinogen, INR = international normalized ratio, N/A = not assessed, PT = determination of plasma prothrombin time, TT = prothrombin time. FDP:fibrin degradation products. Arrows indicate elevation above the normal range. |
Table 3
Infant blood coagulation parameters in Case 1.
Parameter | First day of birth | Third day of birth |
APTT (s) | 62 | 50.3 |
PT (s) | 22 | 16.4 |
INR, | 1.86 | 1.38 |
FIB (g/L) | 1.09↓ | 1.98↓ |
TT (s) | 21.20 | 11.20 |
Abbreviations: APTT = activated partial thromboplastin time, FIB = Fibrinogen, INR = international normalized ratio, PT = determination of plasma prothrombin time, TT = prothrombin time. Arrows indicate values below the normal range. |
Case 2
A 33-year-old woman with twin pregnancy at 34+ 4 weeks gestation required hospitalization after detecting a single umbilical artery in fetus A and abnormal maternal coagulation. Upon admission, the following were noted: 1. Dichorionic twin pregnancy; 2. Chronic hepatitis B surface antigen virus carrier; 3. In vitro fertilization embryo transfer pregnancy. The patient underwent regular obstetric examinations throughout the pregnancy, and no obvious abnormalities were found in maternal thyroid function and glucose tolerance tests, fetal neck transparent layer thickness, non-invasive DNA testing, systematic ultrasound, and cardiac ultrasound (Table 4). The initial systematic ultrasound of the fetus at 24+ 3 weeks gestation showed no abnormalities, but routine fetal ultrasound at 27+ 1 weeks gestation showed only one umbilical artery between fetus A and the placenta. The patient’s blood test results showed anti-nRNP/Sm antibody (+) in the rheumatoid immune activity test at 27+ 3 weeks gestation, and was prescribed 0.4 mL daily enoxaparin sodium subcutaneous injection and 75 mg oral aspirin. At 32+ 3 weeks gestation, anti-nRNP/Sm antibodies (++) were rechecked, and protein S and antithrombin III levels were decreased (Table 5). At 34+ 4 weeks gestation, the fetal routine ultrasound suggested a single umbilical artery, with the umbilical cord wrapped around the fetus’s neck, and a "U"-shaped induration noted on the fetal neck. It was recommended that a caesarean section should be performed at 34+ 6 weeks gestation. Fetus A was found to be a boy with a weight of 2510g and an Apgar score of 10-10-10. Both fetus A and B umbilical cord blood test results showed anti-nRNP/Sm antibody (++). Pathological examination of the umbilical cord and placenta showed the presence of old thrombosis in one of the umbilical arteries of fetus A, multiple pseudoknots of the distal umbilical cord, and surrounding interstitial edema. Placentae A and B were found to have small amounts of inflammatory cell infiltration of the fetal focal areas, uneven maturity of the placental villi, and villous edema in some areas, of which placenta B also showed violar space thrombosis, with the focal area seen in individual vascular villus.
Table 4
Doppler ultrasound and CTG results in Case 2 fetus from 27+ 1 to 34+ 6 weeks of gestation
Parameter | 27+ 1 w | 29+ 1 w | 31+ 1 w | 33+ 1 w | 34+ 4 w | 34+ 5 w | 34+ 6 w |
Umbilical artery PI | 0.79(5-50th ) | 0.65(˂5th ) | 0.69(˂ 5th ) | 0.7 (˂ 5th ) | 0.77(5-50th ) | 0.78(5-50th ) | 0.79(5-50th ) |
Umbilical artery RI | 0.53 | 0.5 | 0.52 | 0.49 | 0.54 | 0.54 | 0.53 |
Umbilical artery S/D | 2.13 | 2 | 2.08 | 1.97 | 2.19 | 2.18 | 2.12 |
Middle cerebral artery PI | 1.84(5-50th ) | 1.68(5-50th ) | 1.86(50-95th ) | 1.93(50-95th ) | 1.62(5-50th ) | 1.65(5-50th ) | 1.63(5-50th ) |
Middle cerebral artery RI | 0.84 | 0.8 | 0.83 | 0.85 | 0.78 | 0.8 | 0.8 |
Middle cerebral artery S/D | 6.1 | 4.89 | 6 | 6.64 | 4.58 | 4.9 | 4.95 |
Cerebro-Umbilical ratio PI | 2.33 | 2.58 | 2.69 | 2.75 | 2.1 | 2.11 | 2.06 |
AFV, cm | 5.8 | 3.9 | 6.8 | 4.9 | 5.1 | 4.7 | 4.1 |
Abbreviations: AFV = Amniotic fluid vertical depth,PI = peak systolic velocity, RI = Resistance index, S/D = Systolic/diastolic phase. |
Table 5
Maternal blood coagulation parameters in Case 2 after anticoagulation therapy
Parameter | 27+ 3 w | 32+ 3 w |
APTT (s) | 30.3 | 24 |
PT (s) | 11.4 | 11 |
INR | 0.99 | 0.95 |
FIB (g/L) | 4.4↑ | 4.97↑ |
TT (s) | 18.3 | 16 |
D-dimer (ug/ml) | 2.34↑ | 2.21↑ |
FDP (ug/ml) | 4.75 | 4.78 |
PC (%) | 90.7 | N/A |
PS (%) | 29.4↓ | N/A |
ATIII | 66.2↓ | N/A |
Abbreviations: APTT = activated partial thromboplastin time, FIB = Fibrinogen, INR = international normalized ratio, PT = determination of plasma prothrombin time, TT = prothrombin time,FDP:fibrin degradation products,PC:Protein CPS:Protein S,ATIII:Antithrombin III. Arrows indicate values below the normal range. |