Antibody profile and clinical course in primary antiphospholipid syndrome with pregnancy morbidity

SummaryIn women diagnosed as having category I primary obstetric antiphospholipid syndrome, clinical characteristics and the risk of subsequent thromboembolic events and further unsuccessful pregnancy has not been clearly documented. Women with unexplained obstetric complications and no definite autoimmune systemic diseases were tested for lupus anticoagulant (LA), IgG/ IgM anticardiolipin (aCL) and IgG/IgM anti-human β2-Glycoprotein I (aβ2GPI) antibodies and diagnosed as having primary antiphospholipid syndrome (APS) in classification category I on the basis of more than one laboratory criteria present in any combination. Characteristics at the time of diagnosis and risk factors for subsequent clinical events during a mean follow-up of 6.3 years were evaluated. Fifty-three of 600 women studied were found to fulfil obstetric criteria and had more than one positive laboratory test at the time of diagnosis. All the women were a CL and aβ2GPI positive, and 16 were also LA positive. This latter group (triple positivity) had distinct features and had more frequently experienced previous thromboembolism (OR= 122.5, 95% CI 16–957, p<0.001).They also had an increased rate of late pregnancy loss (OR=16.2, 95%CI 0.9–292, p=0.01), and a higher IgG aβ2GPI titer at diagnosis (median, 25th and 75th percentile were 118, 37–962, vs. 23, 18–32, respectively, p<0.0001). During follow-up, the rate of thromboembolic events was significantly higher in the group of women with triple positivity and/ or previous thromboembolism (OR=57.5, 95% CI 2.7–1160, p=0.0004) which were the only independent predictors of TE in the multivariate model. Recurrent pregnancy loss took place in seven out of 47 women who had a new pregnancy. Triple positivity and/or previous thromboembolism were again the only independent markers (OR=34.4, 95% CI 3.5–335.1, p=0.003) of an unsuccessful new pregnancy. In conclusion, in primary APS with pregnancy morbidity in classification category I, quite different groups of patients may be identified on the basis of laboratory tests. Triple positivity and/or a history of thromboembolism predict new TE events and new unsuccessful pregnancies.

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Antiphospholipid-associated thrombocytopenia or autoimmune hemolytic anemia in patients with or without definite primary antiphospholipid syndrome according to the Sapporo revised classification criteria: a 6-year follow-up study

Blood ◽

10.1182/blood-2010-05-283507 ◽

2010 ◽

Vol 116 (16) ◽

pp. 3058-3063 ◽

Cited By ~ 34

Author(s):

Lucía Comellas-Kirkerup ◽

Gabriela Hernández-Molina ◽

Antonio R. Cabral

Keyword(s):

Hemolytic Anemia ◽

Antiphospholipid Syndrome ◽

Autoimmune Hemolytic Anemia ◽

Lupus Anticoagulant ◽

Thrombotic Event ◽

Classification Criteria ◽

Response To Treatment ◽

Primary Antiphospholipid Syndrome ◽

Pregnancy Morbidity

Abstract The updated Sapporo classification criteria for antiphospholipid syndrome (APS) only include thrombosis or pregnancy morbidity as clinical criteria. To test this notion, we studied 55 patients (80% women) with hematologic manifestations. All fulfilled the laboratory criteria for primary APS. Thirty-five patients (64%) had thrombocytopenia, 14 (25%) had autoimmune hemolytic anemia, and 6 (11%) had both. Twenty-five patients (22 women, 88%) also fulfilled one clinical criterion for APS after a median follow-up of 13.2 years (range, 1.45-37 years), whereas the remaining 30 patients (22 women, 73%) have not had any thrombotic event nor pregnancy morbidity after a median follow-up of 5.4 years (range, 0.12-24 years). No patient developed systemic lupus erythematosus during follow-up. The hematologic manifestation was asynchronous with the APS onset in 84% of patients. The response to treatment was similar regardless of the APS status. Patients with definite APS were more frequently positive for the lupus anticoagulant (63%) than lupus anticoagulant-positive patients without APS (30%; odds ratio, 3.5; 95% confidence interval, 1.07-11.4; P < .02). Anticardiolipin or anti–β2-glycoprotein-I antibodies were highly prevalent among the study groups. Our study suggests that, depending upon their antiphospholipid profile, patients with hemocytopenias appear to comprise a peculiar subset of patients with APS; some develop thrombotic and/or obstetric APS whereas others continue with hematologic APS.

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Circulating Procoagulant Microparticles in Women with Unexplained Pregnancy Loss: a New Insight

Thrombosis and Haemostasis ◽

10.1055/s-0037-1612657 ◽

2001 ◽

Vol 85 (01) ◽

pp. 18-21 ◽

Cited By ~ 85

Author(s):

I. Laude ◽

C. Rongières-Bertrand ◽

C. Boyer-Neumann ◽

M. Wolf ◽

V. Mairovitz ◽

...

Keyword(s):

Pregnancy Loss ◽

Cell Activation ◽

Fetal Death ◽

Late Pregnancy ◽

Clinical Settings ◽

Thrombotic Risk ◽

High Prevalence ◽

Circulating Microparticles ◽

History Of

SummaryOne of the frequently proposed mechanisms for pregnancy losses refers to uteroplacental thrombosis. However the contribution of classical thrombotic risk factors remains questionable and, if real, does not account for a large number of pregnancy losses. The aim of this study was to investigate the presence of circulating procoagulant microparticles, a new marker of cell activation already associated with various prothrombotic clinical settings. Microparticles were assessed by an original prothrombinase assay on platelet depleted plasma obtained from 74 women with a history of pregnancy loss without apparent cause and 50 controls. Patients were studied at least 2 months after the last obstetrical event and were classified into 2 groups: 49 women with at least 3 consecutive spontaneous abortions at or before the 10th postmenstrual week and 25 with at least one fetal death beyond the 10th postmenstrual week. Among the 74 patients, 41 had increased levels of circulating microparticles, 29 belonging to the group of early pregnancy loss (59%) and 12 to the group of late pregnancy loss (48%). The high prevalence of increased levels of procoagulant microparticles in both groups makes this new marker very promising for the understanding, follow up and therapeutical handling of pregnancy loss.

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The significance of autoantibodies against β2-glycoprotein I

Blood ◽

10.1182/blood-2012-03-378646 ◽

2012 ◽

Vol 120 (2) ◽

pp. 266-274 ◽

Cited By ~ 85

Author(s):

Philip G. de Groot ◽

Rolf T. Urbanus

Keyword(s):

Autoimmune Disease ◽

Infectious Diseases ◽

Antiphospholipid Syndrome ◽

Plasma Protein ◽

Antiphospholipid Antibodies ◽

Fetal Loss ◽

Thrombotic Risk ◽

Pregnancy Morbidity ◽

Glycoprotein I ◽

History Of

AbstractThe antiphospholipid syndrome (APS) is defined by the persistent presence of antiphospholipid antibodies in patients with a history of thrombosis and/or pregnancy morbidity, including fetal loss. APS is an autoimmune disease with a confusing name because the pathologic auto-antibodies are shown to be directed against the plasma protein β2-glycoprotein I and not against phospholipids. In fact, auto-antibodies that recognize phospholipids themselves are not associated with thrombosis but with infectious diseases. One of the intriguing questions is why autoantibodies against β2-glycoprotein I are so commonly found in both patients and the healthy. Several potential mechanisms have been suggested to explain the increased thrombotic risk in patients with these autoantibodies. In this overview, we will summarize our knowledge on the etiology of the autoantibodies, and we will discuss the evidence that identify autoantibodies against β2-glycoprotein I as the culprit of APS.

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INCREASED LEVELS OF β2 GLYCOPROTEIN-I ANTIGEN AND β2 GLYCOPROTEIN-I BINDING ANTIBODIES ARE ASSOCIATED WITH A HISTORY OF THROMBOEMBOLIC COMPLICATIONS IN PATIENTS WITH SLE AND PRIMARY ANTIPHOSPHOLIPID SYNDROME

Rheumatology ◽

10.1093/rheumatology/34.11.1031 ◽

1995 ◽

Vol 34 (11) ◽

pp. 1031-1036 ◽

Cited By ~ 58

Author(s):

T. McNALLY ◽

I. J. MACKIE ◽

S. J. MACHIN ◽

D. A. ISENBERG

Keyword(s):

Antiphospholipid Syndrome ◽

Primary Antiphospholipid Syndrome ◽

Thromboembolic Complications ◽

Glycoprotein I ◽

History Of

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Relationship between antiphosphatidylserine/prothrombin and conventional antiphospholipid antibodies in primary antiphospholipid syndrome

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2014-1129 ◽

2015 ◽

Vol 53 (8) ◽

Cited By ~ 19

Author(s):

Ariela Hoxha ◽

Amelia Ruffatti ◽

Elena Mattia ◽

Lauro Meneghel ◽

Marta Tonello ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Primary Antiphospholipid Syndrome ◽

Clinical Criteria ◽

Pregnancy Morbidity ◽

Glycoprotein I ◽

Coagulation Tests ◽

Healthy Control ◽

Independent Risk Factors ◽

Ig G

AbstractAntiphosphatidylserine/prothrombin complex (aPS/PT) antibodies are emerging as an important marker for antiphospholipid syndrome (APS). We aimed to compare their performance with that of conventional antiphospholipid antibodies (aPL) such as lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2-glycoprotein I (anti-β2GPI) in APS and to assess their frequency in APS-negative (APS-ne) patients.We considered 160 APS patients and 128 APS-ne patients with clinical criteria for APS but tested negative for conventional aPL. Immunoglobulin (Ig)G/IgM aPS/PT, IgG/IgM aCL, and IgG/IgM anti-β2GPI were detected using ELISA assay and LA with a series of coagulation tests.IgG aPS/PT were significantly associated with IgG aCL, IgG anti-β2GPI, and LA (p<0.0001 for all). IgM aPS/PT were significantly associated only with LA (p<0.0001) instead. There was a significant correlation between IgG aPS/PT and both IgG aCL and IgG anti-β2GPI levels (ρ=0.42 and ρ=0.40, respectively). Both IgG aPS/PT and IgM aPS/PT positivity significantly correlated with LA (ρ=0.44 and ρ=0.5, respectively). IgG and IgM aPS/PT were significantly more frequent in triple than in double and in single positivity (p<0.0001). According to multivariate analysis, IgG and/or IgM aPS/PT were independent risk factors for LA. APS/PT antibodies were found in 9.4% of the APS-ne patients vs. 2% of healthy control (p=0.043); those antibodies were significantly more frequent in the thrombosis with respect to the pregnancy morbidity subset (p=0.01).Our data attribute a clinical relevance to both IgG and IgM aPS/PT antibodies. In particular, the significant prevalence of aPS/PT in APS-ne patients suggests including them as additional laboratory criterion for APS.

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Obstetrical Considerations and Management of Antiphospholipid Syndrome

The Open Urology & Nephrology Journal ◽

10.2174/1874303x01508020022 ◽

2015 ◽

Vol 8 (1) ◽

pp. 22-26

Author(s):

Karen J Gibbins ◽

Robert M Silver

Keyword(s):

Antiphospholipid Syndrome ◽

Pregnancy Loss ◽

Laboratory Finding ◽

Clinical Criteria ◽

Glycoprotein I ◽

Thrombosis Risk ◽

History Of ◽

Obstetric Morbidity ◽

Therapeutic Doses ◽

Recurrent Early Pregnancy Loss

Antiphospholipid syndrome is a pro-thrombotic, pro-inflammatory condition defined by at least one clinical criterion and one laboratory finding. Clinical criteria are met by history of thrombosis or obstetric morbidity, including recurrent early pregnancy loss, fetal death, or delivery prior to 34 weeks gestation due to pre-eclampsia or placental insufficiency. Laboratory criteria are evidence of lupus anticoagulant or high titers of anticardiolipin or anti-β2-glycoprotein-I IgG or IgM. Treatment during pregnancy is primarily based on anticoagulant therapy, either at prophylactic or therapeutic doses depending on thrombosis history. This treatment certainly reduces thrombosis risk and may also improve obstetric outcome.

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Laboratory Diagnostics of Antiphospholipid Syndrome

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0037-1601331 ◽

2017 ◽

Vol 44 (05) ◽

pp. 439-444 ◽

Cited By ~ 5

Author(s):

Elisa Bison ◽

Gentian Denas ◽

Seena Jose ◽

Giacomo Zoppellaro ◽

Alessandra Banzato ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Pregnancy Loss ◽

Laboratory Diagnostics ◽

Thromboembolic Events ◽

Clinical Events ◽

Glycoprotein I ◽

Triple Test ◽

Laboratory Profile

AbstractDiagnosis of antiphospholipid syndrome (APS) lies in the recognition of antiphospholipid antibodies (aPL). As standardization of tests for the detection of aPL is far from being optimal and reference material is not available, inappropriate diagnoses of APS are not unusual. In the last few years, the concept of triple test positivity has emerged as a useful tool to identify patients with APS. Clinical studies on patients and carriers of triple positivity clearly show that these individuals are at high risk of thromboembolic events and pregnancy loss. Moreover, triple positivity arises from a single (probably pathogenic) antibody directed to domain 1 of β2-glycoprotein I, a protein whose function is still unknown. Studies on homogenous group of patients with single or double positivity are scant, and uncertainties arise on their association with clinical events. Promising but undetermined results come also from the determination of antibodies directed to phosphatidylserine/prothrombin complex. Interpretation of laboratory profile in APS is challenging, and the collaboration between clinical pathologists and clinicians is highly desirable.

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Diagnosis of dengue fever in a patient with early pregnancy loss

BMJ Case Reports ◽

10.1136/bcr-2021-243968 ◽

2021 ◽

Vol 14 (8) ◽

pp. e243968

Author(s):

Naomi N Adjei ◽

Anna Y Lynn ◽

Ernest Topran ◽

Oluwatosin O Adeyemo

Keyword(s):

Neonatal Death ◽

Vaginal Bleeding ◽

Pregnancy Loss ◽

Clinical Evidence ◽

Adverse Outcomes ◽

Intravenous Fluids ◽

Early Pregnancy Loss ◽

Orbital Pain ◽

History Of

Dengue is a mosquito-borne virus that causes an influenza-like illness ranging in severity from asymptomatic to fatal. Dengue in pregnancy has been associated with adverse outcomes including miscarriage, preterm birth and fetal and neonatal death. We present the case of a multiparous woman who presented at 9 weeks’ gestation with vaginal bleeding and abdominal cramping after a 1 month stay in Mexico. She was initially diagnosed with miscarriage with plan for outpatient follow-up. She was readmitted 3 days later with fever, retro-orbital pain, arthralgia, rash, pancytopenia and transaminitis and managed with intravenous fluids and acetaminophen. Of note, dengue serology was initially negative but retesting 2 days later was positive. It is imperative that clinicians have heightened suspicion for dengue in pregnant women with history of travel to or residence in a dengue-endemic area and consistent clinical evidence.

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Pregnancy, pregnancy loss and the risk of diabetes in Chinese women: findings from the China Kadoorie Biobank

European Journal of Epidemiology ◽

10.1007/s10654-019-00582-7 ◽

2019 ◽

Vol 35 (3) ◽

pp. 295-303

Author(s):

Sanne A. E. Peters ◽

◽

Ling Yang ◽

Yu Guo ◽

Yiping Chen ◽

...

Keyword(s):

Pregnancy Loss ◽

Cox Regression ◽

Chinese Women ◽

Later Life ◽

Induced Abortion ◽

Hazard Ratios ◽

Increased Risk ◽

History Of ◽

Incident Cases

AbstractPregnancy and pregnancy loss may be associated with increased risk of diabetes in later life. However, the evidence is inconsistent and sparse, especially among East Asians where reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy and pregnancy loss (miscarriage, induced abortion, and still birth) with the risk of incident diabetes in later life among Chinese women. In 2004–2008, the nationwide China Kadoorie Biobank recruited 302 669 women aged 30–79 years from 10 (5 urban, 5 rural) diverse localities. During 9.2 years of follow-up, 7780 incident cases of diabetes were recorded among 273,383 women without prior diabetes and cardiovascular disease at baseline. Cox regression yielded multiple-adjusted hazard ratios (HRs) for the risk of diabetes associated with pregnancy and pregnancy loss. Overall, 99% of women had been pregnant, of whom 10%, 53%, and 6% reported having a history of miscarriage, induced abortion, and stillbirth, respectively. Among ever pregnant women, each additional pregnancy was associated with an adjusted HR of 1.04 (95% CI 1.03; 1.06) for diabetes. Compared with those without pregnancy loss, women with a history of pregnancy loss had an adjusted HR of 1.07 (1.02; 1.13) and the HRs increased with increasing number of pregnancy losses, irrespective of the number of livebirths; the adjusted HR was 1.03 (1.00; 1.05) for each additional pregnancy loss. The strength of the relationships differed marginally by type of pregnancy loss. Among Chinese women, a higher number of pregnancies and pregnancy losses were associated with a greater risk of diabetes.

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