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Severe thrombocytopenia is associated with high mortality in systemic lupus erythematosus—analysis from Indian SLE Inception cohort for Research (INSPIRE)

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Abstract

Thrombocytopenia in patients with systemic lupus erythematosus (SLE) is associated with higher morbidity and mortality. We report frequency, associations and short-term outcome of moderate-severe thrombocytopenia in a prospective inception cohort from India (INSPIRE). We evaluated consecutive SLE patients classified per SLICC2012 for the occurrence of thrombocytopenia and its associations. The outcomes assessed included bleeding manifestations, kinetics of thrombocytopenia recovery, mortality and recurrence of thrombocytopenia. Among a total of 2210 patients in the cohort, 230 (10.4%) had incident thrombocytopenia, of whom moderate (platelet count [PC] 20–50 × 109/L) and severe thrombocytopenia (PC < 20 × 109/L) were noted in 61 (26.5%) and 22 (9.5%), respectively. Bleeding manifestations were generally limited to the skin. Compared to controls, cases had a higher proportion of autoimmune haemolytic anaemia (p < 0.001), leukopenia (p < 0.001), lymphopenia (p < 0.001), low complement (p < 0.05), lupus anticoagulant (p < 0.001), higher median SLEDAI 2 K (p < 0.001) and lower proportion of anti-RNP antibody (p < 0.05). There was no significant difference in these variables between moderate and severe thrombocytopenia. There was a sharp rise in PC by 1 week that was sustained in the majority through the period of observation. There was three times higher mortality in the severe thrombocytopenia group as compared to moderate thrombocytopenia and controls. The thrombocytopenia relapse and lupus flare rates were similar across categories. We report a low occurrence of major bleeds and higher mortality in those with severe thrombocytopenia as compared to moderate thrombocytopenia and controls.

Key Points

• Severe thrombocytopenia occurs in 1% of patients with SLE; however, major bleeds are uncommon.

• Thrombocytopenia has a strong association with other lineage cytopenias and lupus anticoagulants.

• Response to initial glucocorticoids therapy is quick and is well sustained with additional immunosuppressants.

• Severe thrombocytopenia increases mortality threefold in SLE.

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Fig. 1

Data availability

Data will be shared on a reasonable request to the corresponding author.

Abbreviations

SELENA-SLEDAI:

Safety of Estrogens in Systemic Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index

SLEDAI 2K:

Systemic Lupus Erythematosus Disease Activity Index 2000

SLICC 2012:

Systemic Lupus International Collaborating Clinics (SLICC) group 2012

EULAR/ACR:

European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR)

AIHA:

Autoimmune haemolytic anaemia

LA:

Lupus anticoagulant

C4, C3:

Complement

ACL:

Anticardiolipin antibody

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Funding

This work was supported by the Department of Biotechnology, Government of India (BT/PR23111/MED/30/1852/2017).

Author information

Authors and Affiliations

  1. Department of Clinical Immunology and Rheumatology, St. John’s Medical College Hospital, Bengaluru, India

    Vineeta Shobha & Vasudha Bhat

  2. Department of Clinical Immunology & Rheumatology, Nizam Institute of Medical Sciences, Hyderabad, India

    Liza Rajasekhar

  3. Department of Clinical Immunology & Rheumatology, Christian Medical College, Vellore, India

    Ashish J. Mathew

  4. Department of Clinical Immunology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India

    Chengappa Kavadichanda

  5. Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India

    Manish Rathi

  6. Department of Rheumatology, All India Institute of Medical Sciences, New Delhi, India

    Ranjan Gupta

  7. Division of Epidemiology and Biostatistics, St. John’s Research Institute, Bengaluru, India

    Sumithra Selvam

  8. Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India

    Amita Aggarwal

Authors
  1. Vineeta Shobha
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  2. Liza Rajasekhar
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  8. Sumithra Selvam
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  9. Amita Aggarwal
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Consortia

on behalf of INSPIRE investigators

Contributions

1) Conception and design of the study—Vineeta Shobha, Liza Rajasekhar

2) Analysis and interpretation of data—Vineeta Shobha, Vasudha Bhat, Sumithra Selvam

3) Data acquisition—all authors

4) Drafted the work and revised it critically for important intellectual content—all authors

5) Approved the version to be published—all authors

6) Agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved—all authors

Corresponding author

Correspondence to Amita Aggarwal.

Ethics declarations

Ethics approval

Ethics approval was obtained from the respective ethics committees of the participating centres. The coordinating centres’ approval number is as follows: Institutional Ethics Committee, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IEC Ref No. 2017–14-EMP-95 dated 19.05.2018.

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Shobha, V., Rajasekhar, L., Bhat, V. et al. Severe thrombocytopenia is associated with high mortality in systemic lupus erythematosus—analysis from Indian SLE Inception cohort for Research (INSPIRE). Clin Rheumatol 42, 2279–2285 (2023). https://doi.org/10.1007/s10067-023-06641-5

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  • DOI: https://doi.org/10.1007/s10067-023-06641-5

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