Thrombosis and thrombocytopenia in antiphospholipid syndrome: their association with mean platelet volume and hematological ratios
Introduction
Antiphospholipid syndrome (APS) is an autoimmune entity characterized by recurrent arterial and venous thrombosis, and obstetric manifestations such as fetal loss and morbidity during pregnancy. However, it also encompasses other clinical features such as thrombocytopenia [1]. The pathophysiology of APS is complex and involves several pathways such as the activation of endothelial cells, monocytes and platelets, which induce the expression of adhesion molecules and proinflammatory cytokines. Inhibition of natural anticoagulants, activation of the complement system, and an impaired fibrinolytic system are also part of the pathophysiology [2].
Specifically, platelet activation by antiphospholipid antibodies (aPL) induces thrombogenic agents (i.e. thromboxane A2) and increase expression of glycoprotein IIb-IIIa [3]. Platelet size, measured as mean platelet volume (MPV), has emerged as a reliable marker of thrombopoiesis and platelet function. An increase MPV has been proposed as a biomarker and predictor of cardiovascular risk [[4], [5], [6], [7], [8]]. Also, higher values have been found in patients with deep venous thrombosis (DVT) and pulmonary thromboembolism [9]. An increase of platelet size may be a prognostic factor for early mortality in patients with venous thrombosis [6]. Recent findings suggest that neutrophils also have an important role in atherothrombotic events. In this sense, the platelet-to-lymphocyte ratio (PLR) and the neutrophil-to-lymphocyte ratio (NLR) are indicators of systemic inflammation and risk of thrombosis [10]. MPV, PLR, MPV-to-lymphocyte ratio, and NLR ratio are also significantly higher in acute DVT and ischemic stroke [11,12].
Although an increase in the mean MPV, together with the NLR, PLR and the MPV-to-lymphocyte ratio have been associated with inflammation and cardiovascular risk in several studies [4,6], little is known about their clinical role in APS. Up to date, only two studies have tested the MPV, finding higher values in APS patients than healthy controls; and none of them assessed the aforementioned ratios, although neutrophils have been increasingly recognized as relevant targets of aPL [13].
Thus our aim was to explore the MPV, NLR, PLR and MPV-to-lymphocyte ratio among APS patients, and to test them according to their clinical (thrombosis, obstetric or hematological) and serological status, shift through the time and other comorbidities.
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Methods
We conducted this study at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, a tertiary referral center. Using the method of our parent study [14], all the patients fulfilled the revised APS classification Sydney criteria [15] and/or had hematological features (thrombocytopenia and/or autoimmune hemolytic anemia) but also fulfilled the serologic Sydney criteria. Patients were excluded if they had less than 2 years of follow-up after the first thrombotic, obstetric or
Results
This study included 96 patients of whom 70 were women (72.9%). The mean age at inclusion was 47.9 ± 14.6 years. Overall, patients had a median follow-up of 132 months (range: 24–360).
Seventy-four patients (77%) had thrombotic, 36 (37.5%) obstetric and 66 (68.8%) hematological events (non-exclusive groups). Among the group with thrombosis, 31 did not have any hematological feature during the follow-up. Regarding, the hematological features, we observed thrombocytopenia in 61 patients (63.5%) and
Discussion
Our study tested the behavior of the MPV, NLR, PLR and MPV-to-lymphocyte ratio in patients with primary APS. We observed that a lower baseline MPV and a higher PLR characterized the thrombotic group; however, in an acute event, both variables increased. The thrombocytopenic group had a higher baseline MPV and a lower PLR, whereas during an acute event the PLR decreased more deeply. These findings were not related with the aPL antibody status or titers nor with the presence of comorbidities.
Conclusion
Baseline MPV and PLR might help to identify APS patients that will develop thrombotic or hematological features during follow up. These variables change during the acute events and might be the reflection of physiopathogenic and/or compensatory mechanisms in APS.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was the thesis of the specialty of Internal Medicine of Dr. Amaya Llorente-Chávez. Programa de Especialidad en Medicina Interna, Universidad Nacional Autónoma de México.
References (23)
- et al.
Beyond current concepts in anti-phospholipid syndrome: the 16th International Congress on Anti-phospholipid Antibodies (ICAPA) in Manchester
Autoimmun. Rev.
(2020) - et al.
Clinical utility of mean platelet volume and immature platelet fraction in acute coronary syndrome
Biom. J.
(2019) - et al.
Relationship between mean platelet volume and pulmonary embolism in patients with deep vein thrombosis
Heart Lung Circ.
(2015) - et al.
Prevalence and associations of antiphosphatidylserine/prothrombinantibodies with clinical phenotypes in patients with primaryantiphospholipid syndrome aPS/PT antibodies in primary antiphospholipid syndrome
Thromb. Res.
(2019) - et al.
International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS)
J. Thromb. Haemost.
(2006) - et al.
Update of the guidelines for lupus anticoagulant detection. Subcommittee on lupus anticoagulant/antiphospholipid antibody of the scientific and standardisation Committee of the International Society on Thrombosis and Haemostasis
J. Thromb. Haemost.
(2009) - et al.
Comprehensive platelet phenotyping supports the role of platelets in the pathogenesis of acute venous thromboembolism - results from clinical observation studies
EBioMedicine.
(2020) - et al.
Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1000 patients
Arthritis Rheum.
(2002) - et al.
Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms
Semin. Thromb. Hemost.
(2008) - et al.
Mean platelet volume: a link between thrombosis and inflammation
Curr. Pharm. Des.
(2011)
Mean platelet volume as a prognostic factor for venous thromboembolic disease
Rev. Med. Chil.
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