Romatoloji Pratiğinde Hipofibrinojenemi Nedenlerinin Değerlendirilmesi: Retrospektif, Tek Merkez Deneyimi
Abstract
Romatolojik hastalıkların takipleri sırasında ortaya çıkan hipofibrinojenemi şimdiye kadar araştırılmamıştır. Amacımız, romatoloji pratiğinde hipofibrinojenemi nedenlerini ortaya koymaktı. Romatoloji bölümünde takip edilen ve fibrinojen düzeyi düşük (<200 mg/dL) saptanan hastalar etyolojiye yönelik olarak retrospektif olarak tarandı. Hipofibrinojenemisi olan hastaların klinik bulguları, laboratuvar verileri, fibrinojen düşüklüğü için verilen tedaviler ve hasta sonlanımları ayrıntılı olarak değerlendirildi. Romatoloji bölümünde izlenen hastalarda 10 yıllık süre içinde hipofibrinojenemi sıklığını %1,78 (28/1573) olarak saptadık. Hipofibrinojenemi saptanan 28 hastanın 19’u (%67,9) kadın ve ortalama yaş ise 51,25±11,88 (28-75) yıl idi. Hipofibrinojenemi sırasında 8 hastada (%28,6) ateş, 7 hastada (%28,6) hepatomegali ve 4 hastada ise (%14,3) kanama bulguları vardı. Hipofibrinojenemi tespit edildiği sırada fibrinojen değerleri ortalaması 134,25±44,80 mg/dL (46,50-194,80) idi. Hipofibrinojenemi 8 (%28,6) hastada tosilizumab yan etkisi, 7 (%25) hastada dissemine intravasküler koagülasyon (DİK), 5 (%17,9) hastada kronik karaciğer hastalığı, 3 (%10,7) hastada plazmaferez, 2 (%7,1) hastada makrofaj aktivasyon sendromu (MAS) ve 1 (%3,6) hastada ise hemofagositik lenfohistiyositoza (HLH) bağlıydı. İki hastada etyoloji aydınlatılamadı. Dört (%14,3) hasta 5,25±4,64 (1-11) gün sonra ölmüştü. Ölen hastaların fibrinojen değerleri ortalaması 84,59±52,42 mg/dL idi ve tüm hastalarda DİK mevcuttu (p=0,029). Sonuç olarak, romatolojik hastalıkların takibinde hipofibrinojenemi ile karşılaşmak mümkündür. En sık neden interlökin (IL)-6 reseptör antagonisti olan ilaçlardır. Romatolojik hastalıklarda hipofibrinojeneminin gerçek sıklığını, nedenlerini, risk faktörlerini, ölüm için bağımsız risk faktörlerini belirlemek için çok merkezli, daha fazla hasta sayısını içeren prospektif çalışmalara gereksinim vardır.
Keywords
References
- 1. May JE, Wolberg AS, Lim MY. Disorders of Fibrinogen and Fibrinolysis. Hematology/Oncology Clinics of North America. 2021;35(6):1197-217.
- 2. Besser M, MacDonald S. Acquired hypofibrinogenemia: current perspectives. JBM. 2016;Volume 7:217-25.
- 3. Casini A, Undas A, Palla R, et al. Diagnosis and classification of congenital fibrinogen disorders: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16:1887.
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- 11. He T, Ling J, Yang J. Tocilizumab-induced hypofibrinogenemia in patients with systemic-onset juvenile idiopathic arthritis. Sci Rep. 2023 3;13(1):9050.
- 12. An Q, Ma R, Yuan D, Huang J, Luo J, Wang Y et al (2024) Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia. Clin Rheumatol 43:1491–1501.
- 13. Yıldırım R, Cansu DÜ, Dinler M, Korkmaz C. Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience. Rheumatol Int. 2024 ;44(12):2927-2934..
- 14. de Lucena LS, Noronha FJD, Oliveira H de P, Lima NM. Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial.
- 15. Ahmed S, Harrity C, Johnson S, Varadkar S, McMorrow S, Fanning R, Flynn CM, O' Riordan JM, Byrne BM. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage--an observational study. Transfus Med. 2012 ;22(5):344-9.
- 16. Squizzato A, Gallo A, Levi M, Iba T, Levy JH, Erez O, vd. Underlying disorders of disseminated intravascular coagulation: Communication from the ISTH SSC Subcommittees on Disseminated Intravascular Coagulation and Perioperative and Critical Care Thrombosis and Hemostasis. Journal of Thrombosis and Haemostasis. 2020;18(9):2400-7.
- 17. Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the current state of knowledge. Transfus Med Rev. 2009 ;23(3):177-88.
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- 19. Collins PW, Solomon C, Sutor K, et al. Theoretical modelling of fibrinogen supplementation with therapeutic plasma, cryoprecipitate, or fibrinogen concentrate. Br J Anaesth. 2014;113(4):585–595.
Evaluation of Causes of Hypofibrinogenemia in Rheumatology Practice: Retrospective, Single Center Experience
Abstract
Hypofibrinogenemia that occurs during the follow-up of rheumatological diseases has not been investigated so far. Our aim was to reveal the causes of hypofibrinogenemia in rheumatology practice. Patients who were followed up in the rheumatology department and were detected to have low fibrinogen levels (<200 mg/dL) were retrospectively screened for etiology. Clinical findings, laboratory data, treatments given for low fibrinogen levels, and patient outcomes of patients with hypofibrinogenemia were evaluated in detail. We found the frequency of hypofibrinogenemia to be 1,78% (28/1573) in patients followed up in the rheumatology department over a 10-year period. 19 (67,9%) of the 28 patients with hypofibrinogenemia were female and the mean age was 51,25±11,88 (28-75) years. During hypofibrinogenemia, 8 patients (28,6%) had fever, 7 patients (28,6%) had hepatomegaly, and 4 patients (14,3%) had bleeding findings. The mean fibrinogen values when hypofibrinogenemia was detected were 134,25±44,80 mg/dL (46,50-194,80). Hypofibrinogenemia was due to tocilizumab side effect in 8 (28,6%) patients, disseminated intravascular coagulation (DIC) in 7 (25%) patients, chronic liver disease in 5 (17,9%) patients, plasmapheresis in 3 (10,7%) patients, macrophage activation syndrome (MAS) in 2 (7,1%) patients, and hemophagocytic lymphohistiocytosis (HLH) in 1 (3,6%) patient. The etiology could not be elucidated in 2 patients. Four (14,3%) patients died after 5,25±4,64 (1-11) days. The mean fibrinogen value of the patients who died was 84,59±52,42 mg/dL and all patients had DIC (p=0,029). In conclusion, it is possible to encounter hypofibrinogenemia during follow-up of rheumatologic diseases. The most common cause is drugs that are interleukin (IL)-6 receptor antagonists. Multicenter, prospective studies with larger patient numbers are needed to determine the true frequency, causes, risk factors, and independent risk factors for death of hypofibrinogenemia in rheumatic diseases.
Keywords
References
- 1. May JE, Wolberg AS, Lim MY. Disorders of Fibrinogen and Fibrinolysis. Hematology/Oncology Clinics of North America. 2021;35(6):1197-217.
- 2. Besser M, MacDonald S. Acquired hypofibrinogenemia: current perspectives. JBM. 2016;Volume 7:217-25.
- 3. Casini A, Undas A, Palla R, et al. Diagnosis and classification of congenital fibrinogen disorders: communication from the SSC of the ISTH. J Thromb Haemost 2018; 16:1887.
- 4. Danés AF, Cuenca LG, Bueno SR, Mendarte Barrenechea L, Ronsano JBM. Efficacy and tolerability of human fibrinogen concentrate administration to patients with acquired fibrinogen deficiency and active or in high-risk severe bleeding. Vox Sang. 2008 ;94(3):221-226.
- 5. Amini A, Kariman H, Fattahi F, Rezaei MR. Prevalence of Hypofbrinogenemia Among Patients With Acute Gastrointestinal Bleeding: A Cross-Sectional Study Crescent Journal of Medical and Biological Sciences Year:2019 | Volume:6 | Issue:3 Page(s): 410-413.
- 6. Wada H, Kawasugi K, Honda G, Kawano N, Uchiyama T, Madoiwa S, Takezako N, Suzuki K, Seki Y, Ikezoe T, Iba T, Okamoto K. Sepsis-Associated DIC with Decreased Levels of Antithrombin and Fibrinogen is the Target for Combination Therapy with Thrombomodulin Alfa and Antithrombin. TH Open. 2023 22;7(1):e65-e75.
- 7. Weinkove R, Rangarajan S. Fibrinogen concentrate for acquired hypofibrinogenaemic states. Transfus Med. 2008 Jun;18(3):151-7.
- 8. Wang J, Rong W, Yan H. Eighty-six cases of clinical characteristics and outcomes of systemic lupus erythematosus-associated macrophage activation syndrome: A meta-analysis study. Immun Inflamm Dis. 2024;12(8):e1364.
- 9. Sule Yasar Bilge N, Korkmaz C. Hypofibrinogenemia in a patient with systemic lupus erythematosus: always a bad sign? Or not. Lupus. 2011;20(6):660-2.
- 10. Üsküdar Cansu D, Demirtaş E, Andiç N, Üsküdar Teke H, Korkmaz C. Is it required to routinely check fibrinogen level in patients with rheumatic diseases on tocilizumab? Case-based review. Rheumatol Int. 2019;39(4):743-750.
- 11. He T, Ling J, Yang J. Tocilizumab-induced hypofibrinogenemia in patients with systemic-onset juvenile idiopathic arthritis. Sci Rep. 2023 3;13(1):9050.
- 12. An Q, Ma R, Yuan D, Huang J, Luo J, Wang Y et al (2024) Clinical observation of hypofibrinogenemia induced by the treatment of tocilizumab in rheumatic diseases and exploration of risk factor for hypofibrinogenemia. Clin Rheumatol 43:1491–1501.
- 13. Yıldırım R, Cansu DÜ, Dinler M, Korkmaz C. Evaluation of tocilizumab-induced hypofibrinogenemia in rheumatology practice: a retrospective, real-life, single-center experience. Rheumatol Int. 2024 ;44(12):2927-2934..
- 14. de Lucena LS, Noronha FJD, Oliveira H de P, Lima NM. Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial.
- 15. Ahmed S, Harrity C, Johnson S, Varadkar S, McMorrow S, Fanning R, Flynn CM, O' Riordan JM, Byrne BM. The efficacy of fibrinogen concentrate compared with cryoprecipitate in major obstetric haemorrhage--an observational study. Transfus Med. 2012 ;22(5):344-9.
- 16. Squizzato A, Gallo A, Levi M, Iba T, Levy JH, Erez O, vd. Underlying disorders of disseminated intravascular coagulation: Communication from the ISTH SSC Subcommittees on Disseminated Intravascular Coagulation and Perioperative and Critical Care Thrombosis and Hemostasis. Journal of Thrombosis and Haemostasis. 2020;18(9):2400-7.
- 17. Callum JL, Karkouti K, Lin Y. Cryoprecipitate: the current state of knowledge. Transfus Med Rev. 2009 ;23(3):177-88.
- 18. Casini A. How I treat quantitative fibrinogen disorders. Blood. 2024 Dec 19:blood.2024025712.
- 19. Collins PW, Solomon C, Sutor K, et al. Theoretical modelling of fibrinogen supplementation with therapeutic plasma, cryoprecipitate, or fibrinogen concentrate. Br J Anaesth. 2014;113(4):585–595.
Details
| Primary Language | Turkish |
|---|---|
| Subjects | Internal Diseases, Rheumatology and Arthritis |
| Journal Section | ORİJİNAL MAKALE |
| Authors | |
| Publication Date | June 18, 2025 |
| Submission Date | January 6, 2025 |
| Acceptance Date | May 7, 2025 |
| Published in Issue | Year 2025 Volume: 47 Issue: 4 |