Lymphocyte Disturbances in Primary Antiphospholipid Syndrome and Application to Venous Thromboembolism Follow-Up

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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CLINICAL OUTCOME AFTER ANTIPHOSPHOLIPID ANTIBODIES NEGATIVIZATION IN PRIMARY ANTIPHOSPHOLIPID SYNDROME. A 5 -YEAR FOLLOW-UP STUDY

10.26226/morressier.56e174dcd462b8028d88aeaa ◽

2016 ◽

Author(s):

Gabriela Medina

Keyword(s):

Clinical Outcome ◽

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Primary Antiphospholipid Syndrome ◽

Follow Up Study

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Flare of Antiphospholipid Syndrome in the Course of COVID-19

TH Open ◽

10.1055/s-0040-1716735 ◽

2020 ◽

Vol 04 (03) ◽

pp. e207-e210 ◽

Cited By ~ 3

Author(s):

Alexandre Thibault Jacques Maria ◽

Isabelle Diaz-Cau ◽

Jean-Marc Benejean ◽

Anaïs Nutz ◽

Aurélie Schiffmann ◽

...

Keyword(s):

Venous Thromboembolism ◽

Severe Acute Respiratory Syndrome ◽

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Adrenal Glands ◽

Primary Antiphospholipid Syndrome ◽

Increased Risk ◽

Risk For Thrombosis

AbstractWe report the case of a 48-year-old man followed since 2013 for primary antiphospholipid syndrome (APLS) revealed by venous thromboembolism in the presence of antiphospholipid antibodies (APL-Abs, anticardiolipin and anti-β-2-glycoprotein-1), who decompensated in the course of coronavirus disease (COVID-19). Despite efficient anticoagulation, he suffered bilateral adrenal glands hemorrhage and limb arterial ischemia. The tropism of severe acute respiratory syndrome coronavirus-2 for endothelium can lead to microangiopathy and increased risk for thrombosis. If APL-Abs positivity can be an epiphenomenon under inflammatory and prothrombotic conditions, COVID-19 was herein responsible for disseminated thrombosis and a threat of catastrophic APLS, despite efficient anticoagulation.

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Hydroxychloroquine Therapy and Netosis Regulators Expression in Patients with Primary Antiphospholipid Syndrome

Blood ◽

10.1182/blood-2018-99-116822 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 5049-5049

Author(s):

Bruna M Mazetto ◽

Bidossessi Wilfried Hounkpe ◽

Sabrina Saraiva ◽

Joyce Maria Annichino Bizzacchi ◽

Erich Vinicius De Paula ◽

...

Keyword(s):

Gene Expression ◽

Treatment Period ◽

Antiphospholipid Syndrome ◽

Primary Antiphospholipid Syndrome ◽

Gene Expressions ◽

The Mean ◽

The Difference ◽

Mean Differences ◽

Relative Gene

Abstract Introduction: Primary antiphospholipid syndrome (PAPS) is an autoimmune pro-thrombotic condition that affects different vascular beds, with no detectable underlying diseases. Immunothrombosis is at the basis of thrombosis development in PAPS and neutrophil activation and generation of neutrophil extracellular traps (termed NETosis) have been described as part of the immunological process. NETosis involves the orchestrated participation of several proteins such as peptidyl arginine deaminase (PADI4), neutrophil elastase (ELANE) and myeloperoxidase (MPO). PADI4 mediates histone citrullination, so that inhibition of PADI4 could be considered a potential therapeutic strategy to prevent NETosis. Hydroxychloroquine (HCQ) is an anti-malarial drug prescribed for patients with autoimmune diseases as complementary treatment for prevention of immune activation and thrombosis. Whether HCQ treatment affects the NETosis process is not known. Objective: The aim of this study was to evaluate whether HCQ use is associated with the expression of NETosis regulators proteins PADI4, ELANE, and MPO in patients with PAPS. Methods: This is a cross-over study in which patients with PAPS were selected to receive HCQ at 400mg per day for 6 months and then discontinue the drug. The study had two periods of follow-up: 6 months of HCQ treatment and 6 months of no HCQ treatment. A wash-out period of 6 months between the two study periods was allowed. The mean gene expression and 95% confidence intervals (95% CI) of PADI4, ELANE, and MPO were calculated at baseline and at the end of the study periods. The within periods change in gene expression from baseline to the end of the treatment and the difference in gene expression between periods at the end of the follow-up were determined. Results: The study comprised 20 patients. Mean age was 45 years, 70% were women. In HCQ treatment period, mean relative gene expressions of PADI4, ELANE, and MPO were respectively: 1.0 (SD=0.6), 0.5 (SD=0.7) and 0.6 (SD=0.7) at baseline and 0.8 (SD=0.3), 0.9 (SD=1.5) and 0.6 (SD=0.9) at the end of the period. The mean changes in PADI4, ELANE, and MPO relative gene expressions during HCQ treatment period were: -0.1 (95%CI:-0.4;0.1), 0.4 (95%CI: -0.5;1.4), 0 (95%CI: -0.6;0.5), respectively. In the period when HCQ was not used, mean relative gene expressions of PADI4, ELANE, and MPO were respectively: 1.2 (SD=0.6), 0.6 (SD=1.4) and 0.8 (SD=1.3) at baseline and 0.8 (SD=0.4), 0.4 (SD=0.9) and 0.6 (SD=0.6) at the end of the period. The mean changes in PADI4, ELANE, and MPO relative gene expressions during period of no treatment were: -0.4 (95%CI:-0.6;-0.2), -0.2 (95%CI:-0.5;0.1) and -0.2 (95%CI -0.5;0), respectively. In comparison with no treatment period, treatment with HCQ had no effect on the relative gene expressions of PADI4, ELANE, and MPO. The mean differences in PADI4 ELANE, and MPO relative gene expression between HCQ treatment and no treatment at the end of the periods were 0.1 (95%CI:-0.1; 0.3), 0.5 (95%CI:-0.2; 1.3) and 0.1 (95%CI:-0.3; 0.5), respectively. Conclusion: The results suggest that HCQ treatment has no effect on NETosis process, as measured by the gene expression of NETosis regulators proteins, in patients with PAPS. Disclosures De Paula: Hematology and Transfusion Medicine Center, University of Campinas: Employment.

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Primary antiphospholipid syndrome progressing to systemic lupus erythematosus: a case report

Italian Journal of Medicine ◽

10.4081/itjm.2010.116 ◽

2013 ◽

pp. 116-121

Author(s):

Rocco Manganelli ◽

Salvatore Iannaccone ◽

Walter De Simone

Keyword(s):

Systemic Lupus Erythematosus ◽

Case Report ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Primary Antiphospholipid Syndrome ◽

Systemic Lupus ◽

Anionic Phospholipids ◽

Serological Studies ◽

Homogeneous Pattern

Introduction: Primary antiphospholipid syndrome (APS) is a thrombophilic disease that should be suspected in the presence of thrombotic events associated with hematologic abnormalities such as thrombocytopenia and prolongation of the activated partial thromboplastin time. The diagnosis must be confirmed by the demonstration of autoantibodies directed against anionic phospholipids and/or phospholipid-binding proteins. The disease can cause arterial thrombosis in any vascular district, including those of the kidney and central nervous system. Case report: In 2006 a 29-year-old male presented with kidney and brain involvement that was attributed to primary APS. The clinical diagnosis was confirmed by the results of a renal biopsy, which excluded the presence of systemic lupus erythematosus (SLE). The patient remained stable through 32 months of follow-up and then developed a malar rash with deteriorating renal function, decreasing platelet count, and reduced complement levels. Serological studies revealed positivity for ANA (homogeneous pattern), dsDNA, ACA, and beta-2-glycoprotein-1 antibodies. The diagnosis was revised to APS secondary to SLE. Conclusions: A diagnosis of primary APS should not be considered permanent: progression to SLE can occur, in some cases years after the original diagnosis. This case highlights the importance of ongoing follow-up of patients diagnosed with primary APS to detect changes that herald the emergence of SLE.

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

Thrombosis and Haemostasis ◽

10.1160/th06-05-0287 ◽

2006 ◽

Vol 96 (09) ◽

pp. 337-341 ◽

Cited By ~ 117

Author(s):

Amelia Ruffatti ◽

Marta Tonello ◽

Teresa Del Ross ◽

Anna Cavazzana ◽

Chiara Grava ◽

...

Keyword(s):

Antiphospholipid Syndrome ◽

Pregnancy Loss ◽

Late Pregnancy ◽

Primary Antiphospholipid Syndrome ◽

Thromboembolic Events ◽

Pregnancy Morbidity ◽

Glycoprotein I ◽

History Of ◽

Classification Category

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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Therapeutic response to glucocorticoids, anticoagulation and plasma exchange in a patient with primary antiphospholipid syndrome presenting with purpura fulminans

Lupus ◽

10.1177/0961203318804884 ◽

2018 ◽

Vol 27 (13) ◽

pp. 2170-2173

Author(s):

M Plüß ◽

M Zeisberg ◽

G A Müller ◽

R Vasko ◽

P Korsten

Keyword(s):

Plasma Exchange ◽

Antiphospholipid Syndrome ◽

Therapeutic Response ◽

Therapeutic Option ◽

Purpura Fulminans ◽

High Dose ◽

Primary Antiphospholipid Syndrome ◽

Internal Organs ◽

Catastrophic Antiphospholipid Syndrome

We report the case of a 25-year-old female patient who presented with purpura fulminans as a manifestation of primary antiphospholipid syndrome. Purpura fulminans is considered a rare cutaneous manifestation of antiphospholipid syndrome. Most frequently, it occurs in the context of catastrophic antiphospholipid syndrome and is associated with significant morbidity and mortality, either due to loss of affected extremities or thromboembolic damage to internal organs. After insufficient efficacy of parenteral anticoagulation and oral glucocorticosteroid treatment, we escalated treatment to high-dose intravenous glucocorticosteroid and five consecutive sessions of plasma exchange with good and sustained clinical response. At follow-up six months after admission, skin manifestations had healed with scarring, and no additional thrombotic events had occurred. Plasma exchange may hold promise as a therapeutic option in refractory or severe cases of antiphospholipid syndrome-related purpura fulminans with extensive cutaneous necrosis, although evidence is limited.

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Antiphospholipid syndrome damage index (DIAPS): distinct long-term kinetic in primary antiphospholipid syndrome and antiphospholipid syndrome related to systemic lupus erythematosus

Lupus ◽

10.1177/0961203320901598 ◽

2020 ◽

Vol 29 (3) ◽

pp. 256-262 ◽

Cited By ~ 1

Author(s):

A Kuhl Torricelli ◽

M Remião Ugolini-Lopes ◽

E Bonfá ◽

D Andrade

Keyword(s):

Systemic Lupus Erythematosus ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Damage Index ◽

Diagnosis Delay ◽

Primary Antiphospholipid Syndrome ◽

Systemic Lupus ◽

Tertiary Center

Background Antiphospholipid syndrome (APS) is an acquired thrombophilia that affects young productive individuals, with permanent damage and negative impact on quality of life. Recently, a damage index specific for APS (DIAPS) was developed. There are, however, no data regarding the comparison of its performance and long-term damage in primary antiphospholipid syndrome (PAPS) and APS related to systemic lupus erythematosus (SLE; APS + SLE). The primary purpose of this study was therefore to compare the long-term damage in patients with these conditions. Methods This is a retrospective analysis of a single tertiary center cohort followed for approximately 10 years using a standardized prospective electronic chart database. Fifty consecutive PAPS patients age matched with 50 APS+SLE patients were consecutively selected for the study, and DIAPS was calculated once a year during follow-up. Long-term damage and damage kinetics in both groups were compared. Results PAPS and APS + SLE had comparable age (47.10 ± 12.4 vs. 44.04 ± 10.80 years; p = 0.19) and time of follow-up (9.40 ± 3.60 vs. 10.94 ± 4.50 years; p = 0.06). At diagnosis, PAPS had higher DIAPS than APS + SLE (1.72 ± 1.17 vs. 0.82 ± 0.96; p < 0.001). At the end of the 10-year follow-up, both groups presented comparable mean damage scores (2.04 ± 1.50 vs. 2.24 ± 1.61; p = 0.52). The damage increment throughout the observation period for PAPS was solely 35%, whereas for APS + SLE it was gradual, persistent and reached 139% at the end of follow-up, with a total damage increment for PAPS lower than APS + SLE (0.43 ± 0.30 vs. 1.22 ± 1.24; p < 0.001). Of note, the frequency of individuals who acquired damage was lower in PAPS than in APS + SLE (32% vs. 71%; p < 0.001). PAPS also had a longer delay in diagnosis than APS + SLE (4.00 ± 4.20 vs. 2.54 ± 3.05 years; p = 0.04). This delay was positively correlated with a higher damage score at diagnosis ( r = 0.36, p < 0.001) in all groups. Conclusion We identified a distinct pattern of damage in PAPS and APS related to SLE. Damage in PAPS is an early event, while APS+SLE is associated with higher long-term damage, with a striking increment of damage along the follow-up. A diagnosis delay is correlated with higher damage scores. Damage surveillance therefore requires different approaches for these two conditions.

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