Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report

Blerina Dhamo; Resmije Tozharaku; Valbona Gashi; Olta Ramaj; Elvana Rista; Blerim Arapi

doi:doi:10.11648/j.ajim.20251306.11

Research Article |

| Peer-Reviewed

Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report

Blerina Dhamo^*

, Resmije Tozharaku, Valbona Gashi, Olta Ramaj, Elvana Rista, Blerim Arapi

Published in American Journal of Internal Medicine (Volume 13, Issue 6)

Received: 26 November 2025 Accepted: 12 December 2025 Published: 31 December 2025

Views: Downloads:

Download PDF

Share This Article

Twitter
Linked In
Facebook

Abstract

Aromatase inhibitors (AIs) are the standard adjuvant therapy for hormone-receptor–positive breast cancer in postmenopausal women and are considered less thrombogenic than tamoxifen. However, rare autoimmune complications, including lupus-like syndromes, inflammatory arthritis, and hepatitis, have been described. Antiphospholipid syndrome (APS), an autoimmune prothrombotic disorder is exceedingly rare in patients taking aromatase inhibitors. We present the case of a 68-year-old woman with breast cancer treated with surgery, chemotherapy, and letrozole for 3 years who subsequently developed deep venous thrombosis, ischemic stroke, severe thrombocytopenia, severe gastrointestinal bleeding, and triple-positive antiphospholipid antibody profile consistent with primary APS. Laboratory and imaging work-up excluded secondary causes of thrombosis such as systemic lupus erythematosus, bone marrow disease, metastatic cancer and heparin-induced thrombocytopenia. Her course was further complicated by refractory gastrointestinal bleeding which continued even after discontinuation of low-molecular-weight heparin (LMWH). Bleeding resolved only after argon plasma coagulation (APC). Because of ongoing thrombosis risk, anticoagulation was transitioned from LMWH to warfarin, and hydroxychloroquine was initiated, resulting in platelet stabilization (23 → 145 × 10⁹/L). She had no further bleeding, and no recurrent thrombotic events. This case presents the clinical course, diagnostic work-up, and management of primary APS emerging during prolonged aromatase inhibitor therapy and summarizes relevant considerations for evaluation of thrombosis and thrombocytopenia in patients treated with endocrine therapy for breast cancer.

Published in	American Journal of Internal Medicine (Volume 13, Issue 6)
DOI	10.11648/j.ajim.20251306.11
Page(s)	89-94
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2025. Published by Science Publishing Group

Keywords

Antiphospholipid Syndrome, Aromatase Inhibitor, Letrozole, Thrombocytopenia, Argon Plasma Coagulation, Warfarin, Hydroxychloroquine, Breast Cancer

References

[1]	Miyakis S, et al. J Thromb Haemost. 2006; 4: 295–306. https://doi.org/10.1111/j.1538-7836.2006.01753.x Wiley Online Lib.
[2]	Tektonidou MG, et al. Ann Rheum Dis. 2019; 78: 1296–1304. https://doi.org/10.1136/annrheumdis-2019-215213
[3]	Ordi-Ros J, et al. Ann Intern Med. 2019; 171: 685–694. https://doi.org/10.7326/M19-0291PubMed
[4]	Lazzaroni M G, et al. Front Immunol. 2019; 10: 1996. https://doi.org/10.3389/fimmu.2019.01996
[5]	Straub R H. Endocr Rev. 2007; 28: 521–574 https://doi.org/10.1210/er.2007-0005
[6]	Matthews A, et al. BMJ. 2018; 363: k3845. https://doi.org/10.1136/bmj.k3845
[7]	Trancart M, et al. Br J Dermatol. 2008; 158: 628–629. https://doi.org/10.1111/j.1365-2133.2007.08526.x
[8]	Bao T, et al. Breast Cancer Res Treat. 2010; 121: 789–791. https://doi.org/10.1007/s10549-009-0701-x
[9]	Wahl DG, et al. Br J Haematol. 2020; 189: 212–223. https://doi.org/10.1111/bjh.16411
[10]	Pierangeli SS, et al. Immune pathways in APS. Autoimmun Rev. 2011. https://doi.org/10.1016/j.autrev.2011.01.014

Cite This Article

Plain Text BibTeX RIS

APA Style

Dhamo, B., Tozharaku, R., Gashi, V., Ramaj, O., Rista, E., et al. (2025). Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report. American Journal of Internal Medicine, 13(6), 89-94. https://doi.org/10.11648/j.ajim.20251306.11

Copy | Download

ACS Style

Dhamo, B.; Tozharaku, R.; Gashi, V.; Ramaj, O.; Rista, E., et al. Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report. Am. J. Intern. Med. 2025, 13(6), 89-94. doi: 10.11648/j.ajim.20251306.11

Copy | Download

AMA Style

Dhamo B, Tozharaku R, Gashi V, Ramaj O, Rista E, et al. Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report. Am J Intern Med. 2025;13(6):89-94. doi: 10.11648/j.ajim.20251306.11

Copy | Download

@article{10.11648/j.ajim.20251306.11,
  author = {Blerina Dhamo and Resmije Tozharaku and Valbona Gashi and Olta Ramaj and Elvana Rista and Blerim Arapi},
  title = {Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report},
  journal = {American Journal of Internal Medicine},
  volume = {13},
  number = {6},
  pages = {89-94},
  doi = {10.11648/j.ajim.20251306.11},
  url = {https://doi.org/10.11648/j.ajim.20251306.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20251306.11},
  abstract = {Aromatase inhibitors (AIs) are the standard adjuvant therapy for hormone-receptor–positive breast cancer in postmenopausal women and are considered less thrombogenic than tamoxifen. However, rare autoimmune complications, including lupus-like syndromes, inflammatory arthritis, and hepatitis, have been described. Antiphospholipid syndrome (APS), an autoimmune prothrombotic disorder is exceedingly rare in patients taking aromatase inhibitors. We present the case of a 68-year-old woman with breast cancer treated with surgery, chemotherapy, and letrozole for 3 years who subsequently developed deep venous thrombosis, ischemic stroke, severe thrombocytopenia, severe gastrointestinal bleeding, and triple-positive antiphospholipid antibody profile consistent with primary APS. Laboratory and imaging work-up excluded secondary causes of thrombosis such as systemic lupus erythematosus, bone marrow disease, metastatic cancer and heparin-induced thrombocytopenia. Her course was further complicated by refractory gastrointestinal bleeding which continued even after discontinuation of low-molecular-weight heparin (LMWH). Bleeding resolved only after argon plasma coagulation (APC). Because of ongoing thrombosis risk, anticoagulation was transitioned from LMWH to warfarin, and hydroxychloroquine was initiated, resulting in platelet stabilization (23 → 145 × 109/L). She had no further bleeding, and no recurrent thrombotic events. This case presents the clinical course, diagnostic work-up, and management of primary APS emerging during prolonged aromatase inhibitor therapy and summarizes relevant considerations for evaluation of thrombosis and thrombocytopenia in patients treated with endocrine therapy for breast cancer.},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report
AU  - Blerina Dhamo
AU  - Resmije Tozharaku
AU  - Valbona Gashi
AU  - Olta Ramaj
AU  - Elvana Rista
AU  - Blerim Arapi
Y1  - 2025/12/31
PY  - 2025
N1  - https://doi.org/10.11648/j.ajim.20251306.11
DO  - 10.11648/j.ajim.20251306.11
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 89
EP  - 94
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20251306.11
AB  - Aromatase inhibitors (AIs) are the standard adjuvant therapy for hormone-receptor–positive breast cancer in postmenopausal women and are considered less thrombogenic than tamoxifen. However, rare autoimmune complications, including lupus-like syndromes, inflammatory arthritis, and hepatitis, have been described. Antiphospholipid syndrome (APS), an autoimmune prothrombotic disorder is exceedingly rare in patients taking aromatase inhibitors. We present the case of a 68-year-old woman with breast cancer treated with surgery, chemotherapy, and letrozole for 3 years who subsequently developed deep venous thrombosis, ischemic stroke, severe thrombocytopenia, severe gastrointestinal bleeding, and triple-positive antiphospholipid antibody profile consistent with primary APS. Laboratory and imaging work-up excluded secondary causes of thrombosis such as systemic lupus erythematosus, bone marrow disease, metastatic cancer and heparin-induced thrombocytopenia. Her course was further complicated by refractory gastrointestinal bleeding which continued even after discontinuation of low-molecular-weight heparin (LMWH). Bleeding resolved only after argon plasma coagulation (APC). Because of ongoing thrombosis risk, anticoagulation was transitioned from LMWH to warfarin, and hydroxychloroquine was initiated, resulting in platelet stabilization (23 → 145 × 109/L). She had no further bleeding, and no recurrent thrombotic events. This case presents the clinical course, diagnostic work-up, and management of primary APS emerging during prolonged aromatase inhibitor therapy and summarizes relevant considerations for evaluation of thrombosis and thrombocytopenia in patients treated with endocrine therapy for breast cancer.
VL  - 13
IS  - 6
ER  -

Copy | Download

Author Information

Blerina Dhamo

Internal Medicine Service, Hygeia Hospital, Tirana, Albania

Contact Email

http://orcid.org/0009-0003-2195-2211
Resmije Tozharaku

Internal Medicine Service, Hygeia Hospital, Tirana, Albania
Valbona Gashi

Internal Medicine Service, Hygeia Hospital, Tirana, Albania
Olta Ramaj

Internal Medicine Service, Hygeia Hospital, Tirana, Albania
Elvana Rista

Internal Medicine Service, Hygeia Hospital, Tirana, Albania
Blerim Arapi

Internal Medicine Service, Hygeia Hospital, Tirana, Albania

Download PDF

Submit an Article

Sections

Plain Text BibTeX RIS

APA Style

Dhamo, B., Tozharaku, R., Gashi, V., Ramaj, O., Rista, E., et al. (2025). Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report. American Journal of Internal Medicine, 13(6), 89-94. https://doi.org/10.11648/j.ajim.20251306.11

Copy | Download

ACS Style

Dhamo, B.; Tozharaku, R.; Gashi, V.; Ramaj, O.; Rista, E., et al. Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report. Am. J. Intern. Med. 2025, 13(6), 89-94. doi: 10.11648/j.ajim.20251306.11

Copy | Download

AMA Style

Dhamo B, Tozharaku R, Gashi V, Ramaj O, Rista E, et al. Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report. Am J Intern Med. 2025;13(6):89-94. doi: 10.11648/j.ajim.20251306.11

Copy | Download

@article{10.11648/j.ajim.20251306.11,
  author = {Blerina Dhamo and Resmije Tozharaku and Valbona Gashi and Olta Ramaj and Elvana Rista and Blerim Arapi},
  title = {Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report},
  journal = {American Journal of Internal Medicine},
  volume = {13},
  number = {6},
  pages = {89-94},
  doi = {10.11648/j.ajim.20251306.11},
  url = {https://doi.org/10.11648/j.ajim.20251306.11},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20251306.11},
  abstract = {Aromatase inhibitors (AIs) are the standard adjuvant therapy for hormone-receptor–positive breast cancer in postmenopausal women and are considered less thrombogenic than tamoxifen. However, rare autoimmune complications, including lupus-like syndromes, inflammatory arthritis, and hepatitis, have been described. Antiphospholipid syndrome (APS), an autoimmune prothrombotic disorder is exceedingly rare in patients taking aromatase inhibitors. We present the case of a 68-year-old woman with breast cancer treated with surgery, chemotherapy, and letrozole for 3 years who subsequently developed deep venous thrombosis, ischemic stroke, severe thrombocytopenia, severe gastrointestinal bleeding, and triple-positive antiphospholipid antibody profile consistent with primary APS. Laboratory and imaging work-up excluded secondary causes of thrombosis such as systemic lupus erythematosus, bone marrow disease, metastatic cancer and heparin-induced thrombocytopenia. Her course was further complicated by refractory gastrointestinal bleeding which continued even after discontinuation of low-molecular-weight heparin (LMWH). Bleeding resolved only after argon plasma coagulation (APC). Because of ongoing thrombosis risk, anticoagulation was transitioned from LMWH to warfarin, and hydroxychloroquine was initiated, resulting in platelet stabilization (23 → 145 × 109/L). She had no further bleeding, and no recurrent thrombotic events. This case presents the clinical course, diagnostic work-up, and management of primary APS emerging during prolonged aromatase inhibitor therapy and summarizes relevant considerations for evaluation of thrombosis and thrombocytopenia in patients treated with endocrine therapy for breast cancer.},
 year = {2025}
}

Copy | Download

TY  - JOUR
T1  - Primary Antiphospholipid Syndrome Emerging During Long-term Aromatase Inhibitor Therapy: A Clinical Case Report
AU  - Blerina Dhamo
AU  - Resmije Tozharaku
AU  - Valbona Gashi
AU  - Olta Ramaj
AU  - Elvana Rista
AU  - Blerim Arapi
Y1  - 2025/12/31
PY  - 2025
N1  - https://doi.org/10.11648/j.ajim.20251306.11
DO  - 10.11648/j.ajim.20251306.11
T2  - American Journal of Internal Medicine
JF  - American Journal of Internal Medicine
JO  - American Journal of Internal Medicine
SP  - 89
EP  - 94
PB  - Science Publishing Group
SN  - 2330-4324
UR  - https://doi.org/10.11648/j.ajim.20251306.11
AB  - Aromatase inhibitors (AIs) are the standard adjuvant therapy for hormone-receptor–positive breast cancer in postmenopausal women and are considered less thrombogenic than tamoxifen. However, rare autoimmune complications, including lupus-like syndromes, inflammatory arthritis, and hepatitis, have been described. Antiphospholipid syndrome (APS), an autoimmune prothrombotic disorder is exceedingly rare in patients taking aromatase inhibitors. We present the case of a 68-year-old woman with breast cancer treated with surgery, chemotherapy, and letrozole for 3 years who subsequently developed deep venous thrombosis, ischemic stroke, severe thrombocytopenia, severe gastrointestinal bleeding, and triple-positive antiphospholipid antibody profile consistent with primary APS. Laboratory and imaging work-up excluded secondary causes of thrombosis such as systemic lupus erythematosus, bone marrow disease, metastatic cancer and heparin-induced thrombocytopenia. Her course was further complicated by refractory gastrointestinal bleeding which continued even after discontinuation of low-molecular-weight heparin (LMWH). Bleeding resolved only after argon plasma coagulation (APC). Because of ongoing thrombosis risk, anticoagulation was transitioned from LMWH to warfarin, and hydroxychloroquine was initiated, resulting in platelet stabilization (23 → 145 × 109/L). She had no further bleeding, and no recurrent thrombotic events. This case presents the clinical course, diagnostic work-up, and management of primary APS emerging during prolonged aromatase inhibitor therapy and summarizes relevant considerations for evaluation of thrombosis and thrombocytopenia in patients treated with endocrine therapy for breast cancer.
VL  - 13
IS  - 6
ER  -

Copy | Download