Serum markers thrombophilia in pregnant women with Systemic Lupus Erythematosus

Oliveira, Vanessa Marcon de; Figueiró-Filho, Ernesto Antonio; Ferreira, Cristiane Munaretto; Pereira, Erica Freire de Vasconcelos

doi:10.1590/1806-93042017000400012

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ORIGINAL ARTICLES • Rev. Bras. Saude Mater. Infant. 17 (4) • Oct-Dec 2017 • https://doi.org/10.1590/1806-93042017000400012 linkcopy

Serum markers thrombophilia in pregnant women with Systemic Lupus Erythematosus

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objectives: to determine the frequency of serum markers for hereditary and acquired thrombophilia and their association with pregnancy in women with Systemic Lupus Erythematosus (SLE).

Methods: a case-control study was conducted among 25 pregnant women with SLE (study group) and 32 pregnant women without known disease and with at least one previous pregnancy (control group). The presence of antiphospholipid antibodies and hereditary thrombophilia were examined in both groups. We used the y2 Test with Yates correction or Fisher's Exact Test to verify the associations and calculate the relative risk.

Results: thrombophilia was present in 72.0% of pregnant women with SLE and in 6.0% of patients in the control group. A significant association was found between the presence of SLE and serum markers for hereditary thrombophilia / antiphospholipid antibodies (p<0.05). The relative risks for antiphospholipid antibodies were 13.20 (ICR95%= 1.81 - 96.46) in pregnant women with SLE, 7.26 (CI95%= 1.77 - 29.86) for the presence of serum markers of hereditary thrombophilia and 7.92 (CI95%= 2.62 - 3.94) for the presence of hereditary thrombophilia and/or antiphospholipid antibodies.

Conclusions: the identification of markers for hereditary and/or acquired thrombophilia in pregnant women with lupus may be clinically useful to determine which patients have a higher risk of obstetric complications.

Key words
Systemic lupus erythematosus; Thrombophilia; Antiphospholipid syndrome; Pregnancy complications; hematologic

Clinical Criteria
1) Acute cutaneous lupus
a) including lupus malar rash (do not count if malar discoid)
i) bullous lupus
ii) toxic epidermal necrolysis variant of SLE
iii) maculopapular lupus rash
iv) photosensitive lupus rash
(1) in the absence of dermatomyositis
b) or subacute cutaneous lupus
i) nonindurated psoriaform and/or annular polycyclic lesions that resolve without scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias)
2) Chronic cutaneous lupus
a) including classical discoid rash
i) localized (above the neck)
ii) generalized (above and below the neck)
b) hypertrophic (verrucous) lupus
c) lupus panniculitis (profundus)
d) mucosal lupus
e) lupus erythematosus tumidus
f) chillblains lupus
g) discoid lupus/lichen planus overlap
3) Oral ulcers: palate
a) buccal
b) tongue
c) or nasal ulcers
d) in the absence of other causes, such as vasculitis, Behcets, infection (herpes), inflammatory bowel disease, reactive arthritis, and acidic foods
4) Nonscarring alopecia (diffuse thinning or hair fragility with visible broken hairs)
a) in the absence of other causes such as alopecia areata, drugs, iron deficiency and androgenic alopecia
5) Synovitis involving two or more joints, characterized by swelling or effusion OR tenderness in 2 or more joints and thirty minutes or more of morning stiffness.
6) Serositis
a) typical pleurisy for more than 1 day
i) or pleural effusions
ii) or pleural rub
b) typical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day
i) or pericardial effusion
ii) or pericardial rub
iii) or pericarditis by EKG
(1) in the absence of other causes, such as infection, uremia, and Dressler's pericarditis
7) Renal
a) Urine protein/creatinine (or 24 hr urine protein) representing 500 mg of protein/24 hr or
b) Red blood cell casts
8) Neurologic
a) seizures
b) psychosis
c) mononeuritis multiplex
i)in the absence of other known causes such as primary vasculitis
d) myelitis
e) peripheral or cranial neuropathy
i) in the absence of other known causes such as primary vasculitis, infection, and diabetes mellitus
f) acute confusional state
i) in the absence of other causes, including toxic-metabolic, uremia, drugs
9) Hemolytic anemia
10) Leukopenia (< 4,000/mm³ at least once)
i)in the absence of other known causes such as Felty's, drugs, and portal hypertension
b) Lymphopenia (< 1,000/mm³ at least once)
ii)in the absence of other known causes such as corticosteroids, drugs and infection
11)Thrombocytopenia (<100,000/mm³) at least once
a)in the absence of other known causes such as drugs, portal hypertension, and TTP
Immunological Criteria
1) ANA above laboratory reference range
2) Anti-dsDNA above laboratory reference range, except ELISA: twice above laboratory reference range
3) Anti-Sm
4) Antiphospholipid antibody: any of the following
a) lupus anticoagulant
b) false-positive RPR
c) medium or high titer anticardiolipin (IgA, IgG or IgM
d) anti- _2 glycoprotein I (IgA, IgG or IgM)
5) Low complement
a) low C3
b) low C4
c) low CH50
6) Direct Coombs test in the absence of hemolytic anemia

	Serum markers of antiphospholipid antibodies*						Serum markers of hereditary thrombophilia						Serum markers of hereditary thrombophilia and/or antiphospholipid antibodies
	Yes		No		Total		Yes		No		Total		Yes		No		Total
	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%	n	%
Study group 1	10	40.0	15	60.0	25	100.0	11	44.0	14	56.0	25	100.0	18	72.0	7	28.0	25	100.0
Control group 2	1	3.1	31	96.9	32	100.0	2	6.3	30	93.7	32	100.0	3	9.4	29	90.6	32	100.0
Total	11	19.3	46	80.7	57	100.0	13	22.8	44	77.2	57	100.0	21	36.8	36	63.2	57	100.0
RR (IC95%)	13.20 (1.81 - 96.46)						7.26 (1.77 - 29.86)						7.92 (2.62 - 23.94)
P	0.001						0.001						<0.001

Hereditary thrombophilia and / or antiphospholipid antibodies	Study Group 1	Control Group 2
	% (n/total group)	%(n/total group)
Isolated antiphospholipid antibodies	24.0% (6/25)	3.1%(1/32)
Antibody IgM anticardiolipin	4.0%(1/25)	3.1% (1/32)
Lupus anticoagulant	20.0% (5/25)	-(0/32)
Isolated hereditary thrombophilia	24.0% (6/25)	6.2% (2/32)
Protein C Deficiency	4.0% (1/25)	-(0/32)
Protein S Deficiency	4.0% (1/25)	3.1% (1/32)
Antithrombin Deficiency	12.0% (3/25)	3.1% (1/32)
Hyperhomocysteinemia	4.0% (1/25)	-(0/32)
Hereditary thrombophilia and / or antiphospholipid antibodies identified together	24.0% (6/25)	-(0/32)
Anticardiolipin antibody IgM + antithrombin deficiency	4.0% (1/25)	-(0/32)
Anticardiolipin antibody IgG + antibody anti- β₂GPI	4.0% (1/25)	-(0/32)
Lupus anticoagulant + antithrombin deficiency	8.0% (2/25)	-(0/32)
Deficiency of protein S + deficiency of antithrombin	8.0% (2/25)	-(0/32)

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[TFN1] Criteria are cumulative and need not be present concurrently. Adapted from Petri et al.³