Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?
Abstract
:1. Introduction
1.1. Diagnosis of APS
1.2. Diagnosis of Primary ITP
1.3. The Coexistence of APS and ITP
- IgG and IgM antibodies against b2GP1 and IgM antibodies to FVII/VIIa are more common in APS, as well as IgM against phospholipids (aCL, aPC, aPS, aPE);
- IgG antibodies against phospholipids are more common in ITP and generally recognize fewer antigens (<3) than the antibodies detected in APS (>3).
2. APS and Thrombocytopenia
Clinical Significance of APL-Positivity in ITP
- A study by Diz-Kücükkaya et al. found that 45.1% of a cohort of ITP patients who were persistently positive for aPL developed later APS [29];
- A study by Machin et al. showed that the statistically most relevant risk factor for thrombosis in patients with thrombocytopenia is the co-diagnosis of APS, over an average 5-years follow-up [30];
- A study by Hisada et al. found that the combination of aPL and thrombocytopenia doubled the risk of future thrombosis over an average 10-years follow-up [27]
- A study by Funauchi et al. demonstrated that women with ITP and aPL-positivity had increased thrombosis and obstetric complications risks when compared to the aPL-negative group [31];
- An interesting cross-sectional study reported that the platelet counts of patients with a diagnosis of high-risk APS (triple positive: LAC, anti-beta2-GPI, and aCL) decreased earlier before the appearance of a full clinical picture of CAPS [32]. Therefore, the screening for aPL may identify a subgroup of ITP patients at higher risk of thrombosis.
- The already mentioned International Consensus Panel stated that thrombocytopenia occurring in patients with persistent aPL-positivity is associated with increased thrombotic risk and therefore should be considered different from simple ITP [3];
- Data from the Italian Registry of Antiphospholipid Antibodies reported that 40% of the APS patients with moderate thrombocytopenia and 9% of the APS patients with severe thrombocytopenia developed thrombosis [24];
- A review by Frison et al. on the records of 233 outpatients with primary or secondary thrombocytopenia (platelet count < 100 × 109/L) concluded that triple-positive patients had a significantly lower median platelet count compared to other patients with aPL-positivity [33].
3. Clinical Significance of Thrombocytopenia and aPL-Positivity in Patients with Systemic Lupus Erythematosus
3.1. Therapeutic Management of SLE-Associated Thrombocytopenia
3.2. Prevention of aPL-Associated Complications in SLM
4. An Overview of the Treatment of Antiphospholipid Antibodies Syndrome: The Latest Guidelines
5. Management of aPL-Associated Thrombocytopenia
5.1. Definition of Clinical Response
5.2. The Role of anti-CD20 MoAb in Treating aPL-Associated Thrombocytopenia
5.3. Thrombopoietin Receptor Agonists in the II Line Treatment of Connettive Tissue Disease-Associated Thrombocytopenia
5.4. Hydroxychloroquine as a Possible Second Line Agent in APS-Associated Thrombocytopenia
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical and Laboratory Criteria | |
---|---|
Vascular thrombosis |
|
Pregnancy morbidity |
|
Laboratory criteria |
|
Pathogenesis Hypothesis | Pathway |
---|---|
Secondary Immune Thrombocytopenia |
|
Decreased platelet production |
|
Increased platelet pooling |
|
Increased platelet consumption |
|
Patient Group | Clinical History | I Line Therapy |
---|---|---|
non-triple-positive aPL carrier | No thrombotic events | No prophylaxis required |
triple-positive aPL carrier | No thrombotic events | Primary prophylaxis with LDA may be considered |
thrombotic APS | VTE | Secondary prophylaxis with LT-VKA (target INR 2.5, range 2–3) |
thrombotic APS | Arterial thrombosis | Secondary prophylaxis with LT-VKA (target INR 3.5, range 3–4) or LDA |
obstetric APS | VTE/arterial thrombosis | LDA + LMWH |
CAPS | Without secondary CTD * | Anticoagulation + glucocorticoids + HD-IVIG + PEX |
CAPS | Secondary CTD | Anticoagulation + glucocorticoids + HD-IVIG + PEX + cyclophosphamide |
Thrombotic APS/CAPS | Refractory disease; Microangiopathic hemolytic anemia | Anticoagulation + glucocorticoids + HD-IVIG + PEX + rituximab |
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Tomasello, R.; Giordano, G.; Romano, F.; Vaccarino, F.; Siragusa, S.; Lucchesi, A.; Napolitano, M. Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary? Biomedicines 2021, 9, 1170. https://doi.org/10.3390/biomedicines9091170
Tomasello R, Giordano G, Romano F, Vaccarino F, Siragusa S, Lucchesi A, Napolitano M. Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary? Biomedicines. 2021; 9(9):1170. https://doi.org/10.3390/biomedicines9091170
Chicago/Turabian StyleTomasello, Riccardo, Giulio Giordano, Francesco Romano, Federica Vaccarino, Sergio Siragusa, Alessandro Lucchesi, and Mariasanta Napolitano. 2021. "Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?" Biomedicines 9, no. 9: 1170. https://doi.org/10.3390/biomedicines9091170