Low-molecular-weight heparin and aspirin use in relation to pregnancy outcome in women with systemic lupus erythematosus and antiphospholipid syndrome: A cohort study

Figures & data

Table 1. Baseline characteristics per included pregnancy.

	No LMWH or aspirin (n = 66)	Aspirin only (n = 30)	LMWH only(n = 12)	LMWH + aspirin (n = 76)
Number of women	47	19	8	50
General
Age (years)	31.8 ± 4.1	32.5 ± 5.1	30.5 ± 3.8	32.1 ± 4.4
Non-Caucasian	7/62	3/29	6/12	11/71
	(11.3)	(10.3)	(50)	(15.3)
BMI (kg/m^2)	23.0 ± 3.6	224.0 ± 3.9	24.2 ± 3.4	24.6 ± 5.3
Smoking	7/65	2/29	1/11	6/71
	(10.8)	(6.9)	(9.1)	(8.5)
Obstetric history
Nulliparous	33/66	13/30	6/12	28/76
	(50.0)	(43.3)	(50.0)	(36.4)
Spontaneous miscarriages (at least one)	10/66	8/30	2/12	40/76
	(15.2)	(26.7)	(16.7)	(52.6)
HD	5/27	7/17	2/5	17/50
	(18.5)	(41.2)	(40.0)	(34.0)
IUFD	3/32	5/17	0/6	17/47
	(9.4)	(29.4)	(0)	(36.2)
Placental abruption	0/35	1/17	0/6	5/50
	(0)	(5.9)	(0)	(10.0)
Preterm birth	9/33	6/19	4/6	18/50
	(27.3)	(31.6)	(66.7)	(36.0)
SGA	6/33	6/16	2/6	8/42
	(18.2)	(37.5)	(33.3)	(19.0)
General history
Lupus nephritis	20/66	16/30	5/9	14/55
	(30.3)	(53.3)	(55.6)	(25.5)
Minor flare before pregnancy	2/64	1/30	1/8	1/33
	(3.1)	(3.3)	(12.5)	(3.0)
Arterial thrombosis	1/66	3/30	0/12	12/76
	(1.5)	(10.0)	(0)	(15.8)
Venous thrombosis	1/66	0/30	4/11	29/76
	(1.5)	(0)	(36.4)	(38.2)
Hypertension	7/66	4/30	2/11	10/75
	(10.6)	(13.3)	(18.2)	(13.3)
Diabetes	4/66	0/30	0/12	2/75
	(6.1)	(0)	(0)	(2.7)
Time between onset SLE/APS and pregnancy (years)	7.9 ± 4.6	8.7 ± 5.5	5.3 ± 2.4	5.9 ± 5.3

LMWH: low-molecular-weight heparin, BMI: body mass index, HD: hypertensive disorders of pregnancy, IUFD: intra-uterine fetal death, SGA: small-for-gestational age (<p10), CDLE: chronic discoid lupus erythematosus. Data depicted as mean ± SD or numbers (%).

Table 2. Treatment with aspirin and/or LMWH during and after pregnancy per patient group.

	SLE without aPL	SLE with aPL	SLE with APS	Primary APS
	(n = 109)	(n = 14)	(n = 13)	(n = 48)
During pregnancy
Aspirin only	28	2	0	0
	(25.7)	(14.3)	(0)	(0)
LMWH only	6*	1	2	3
	(5.5)	(7.1)	(15.4)	(6.1)
Prophylactic dose	3	1	1	—
Therapeutic dose	2	—	1	3
Aspirin and LMWH	15*	5	11	45^#
	(13.8)	(35.7)	(84.6)	(93.8)
Prophylactic dose	13	5	6	25
Therapeutic dose	1	—	5	18
No treatment with aspirin or LMWH	60	6	0	0
	(55.0)	(42.9)	(0)	(0)
Postpartum
LMWH use	29/100	10/14	9/11	46/46
	(29.0)	(71.4)	(81.8)	(100)

* of 1 patient the dose of LMWH was unknown, ^# of 2 patients the dose of LMWH was unknown.

SLE: systemic lupus erythematosus, aPL: antiphospholipid antibodies, APS: antiphospholipid syndrome, LMWH: low-molecular-weight heparin.

Data depicted as numbers (%).

Table 3. History of women including prophylactic and therapeutic dose of low-molecular-weight heparin per patient group (15,16).

	SLE without aPL		SLE with aPL		SLE with APS		Primary APS
	Prophylactic dose	Therapeutic dose	Prophylactic dose	Therapeutic dose	Prophylactic dose	Therapeutic dose	Prophylactic dose	Therapeutic dose
Previous arterial thrombosis	–	n = 1	–	–	–	n = 1	–	n = 3
Previous venous thrombosis	n = 1	–	–	–	n = 2	n = 2	n = 4	n = 15
Both previous arterial and venous thrombosis	–	–	–	–	n = 1	–	–	–
History of nephritis	n = 2	n = 1	n = 4	–	n = 2	n = 2	–	–
Both previous venous thrombosis and history of nephritis	n = 7	–	–	–	–	n = 1	–	–
Primary APS solely	NA	NA	NA	NA	NA	NA	n = 21	n = 3
Unknown	n = 6	n = 1	n = 2	–	n = 2	–	–	–

SLE: systemic lupus erythematosus, aPL: antiphospholipid antibodies, APS: antiphospholipid syndrome, NA: not applicable.

Table 4. Maternal and perinatal outcomes per treatment group.

	No LMWH or aspirin (n = 66/67)^	Aspirin only (n = 30/31)^	OR	LMWH only(n = 12)	OR	LMWH + aspirin (n = 76/77)^	OR	p-value
Patient group
SLE without aPL	n = 60	n = 28		n = 6		n = 15
SLE with aPL	n = 6	n = 2		n = 1		n = 5
SLE with APS	n = 0	n = 0		n = 2		n = 11
Primary APS	n = 0	n = 0		n = 3		n = 45
Maternal complications
HD	6/64	7	3.32	6	6.42	14	2.45	0.12
	(9.4)	(23.3)	(0.90–12.29)	(50.0)	(1.26–32.79)	(18.4)	(0.78–7.71)
Placental abruption	0	0		0		2		0.70
	(0)	(0)		(0)		(2.7)
Preterm birth	11	13	5.05	9	24.54	28	3.52	<0.001
	(16.7) *^□ⱷ	(43.3)*	(1.81–14.14)	(75.0)^□°	(4.36–138.2)	(36.8)°^ⱷ	(1.46–8.49)
Perinatal complication
IUFD	1	2	4.55	2	13.20	4	3.57	0.10
	(1.5)	(6.5)	(0.40–52.21)	(16.7)	(1.09–159.4)	(5.2)	(0.39–32.73)
SGA	12/66	2/29	0.48	4/11	2.30	13/72	1.46	0.39
	(18.2)	(6.9)	(0.10–2.39)	(36.4)	(0.49–10.82)	(18.1)	(0.56–3.85)
Admission NICU or medium care	25/63	21/28	4.31	7/10	2.82	36/69	1.44	0.035
	(39.7)*	(75.0)*	(1.55–12.00)	(70.0)	(0.62–12.76)	(52.2)	(0.68–3.06)

^ There were three twin pregnancies; number is different for neonatal outcomes, * significant difference between treatment with aspirin only and no anticoagulant treatment, □ significant difference between treatment with LMWH only and no anticoagulant treatment, ⱷ significant difference between treatment with LMWH and aspirin and no anticoagulant treatment, ° significant difference between treatment with LMWH only and treatment with LMWH and aspirin, α significant difference between treatment with aspirin only and treatment with LMWH and aspirin.

LMWH: low-molecular-weight heparin, OR: odds ratio, HD: hypertensive disorders of pregnancy, SGA: small-for-gestational age infant (weight <p10), NICU: neonatal intensive care unit.

The analysis of SGA showed a quasi-separation of the data, caused by chronic hypertension; none of the women with chronic hypertension had a SGA child. Sub-analysis without correction for chronic hypertension did not show any difference in outcome; the p-value remains the same. Shown OR depict the analysis without correction for chronic hypertension.

Data depicted as mean ± SD or numbers (%) and Odds ratios (95% confidence interval).

Table 5. Maternal and perinatal outcomes in women with SLE without aPL.

	No LMWH or aspirin (n = 60)		Aspirin only (n = 28-29)^		LMWH only (n = 6)		LMWH + aspirin (n = 15-16)^		p-value
Maternal complications
HD	4/58	(6.9)^□	7	(25.0)	4	(66.7)^□	4	(26.7)	0.001
Placental abruption	0	(0)	0	(0)	0	(0)	1	(6.7)	0.19
Pre-term birth	10	(16.7)*^ⱷ□	13	(46.4)*	6	(100)^□	9	(60.0)^ⱷ	<0.001
Perinatal outcomes
IUFD	1	(1.7)	2	(6.9)	2	(33.3)	1	(6.3)	0.022
SGA	10	(16.9)	2	(7.4)	3	(60.0)	2	(13.3)	0.052
Admission NICU or medium care	23/56	(41.0)*^ⱷ	20/26	(76.9)*	4/4	(100)	11/13	(84.6) ^ⱷ	<0.001

^ There were two twin pregnancies; number is different for neonatal outcomes, * significant difference between treatment with aspirin only and no anticoagulant treatment, □ significant difference between treatment with LMWH only and no anticoagulant treatment, ⱷ significant difference between treatment with LMWH and aspirin and no anticoagulant treatment, ° significant difference between treatment with LMWH only and treatment with LMWH and aspirin, α significant difference between treatment with aspirin only and treatment with LMWH and aspirin.

LMWH; low-molecular-weight heparin, HD; hypertensive disorders of pregnancy, SGA; small-for-gestational age infant (weight <p10). NICU: neonatal intensive care unit.

Data depicted as mean ± SD or numbers (%).