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Exploration of Coagulation Disorders, von Willebrand Factor and ADAMTS13 in a Cohort of 45 Patients with Hemophagocytic Lymphohistiocytosis

1Université de Paris, AP-HP Nord, Hôpital Lariboisière, Service d'Hématologie Biologique, Paris, France, 2Université de Paris, EA 3518 Institut de Recherche Saint-Louis, Paris, France, 3Université de Paris, AP-HP Nord, Hôpital Saint-Louis, Service de Réanimation Médicale, Paris, France, 4KU Leuven Campus Kulak Kortrijk, Laboratory for Thrombosis Research, Kortrijk, Belgium, 5Université de Paris, AP-HP Nord, Hôpital Saint-Louis, Service d'Immunopathologie Clinique, Paris, France, 6Université de Paris, AP-HP Nord, Hôpital Saint-Louis, Service d'Hématologie Biologique, Paris, France

Abstract Number: PB1861

Meeting: ISTH 2020 Congress

Theme: Thrombotic Microangiopathies » ADAMTS13 and TTP

Background: Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition associated with multiorgan dysfunction. HLH is related to an inappropriate stimulation and proliferation of cytotoxic lymphocytes and macrophages inducing the secretion of cytokines leading to an uncontrolled hyperinflammatory response. Coagulation and fibrinolysis disorders are common in HLH patients.
Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) syndrome defined by a severe deficiency in ADAMTS13, the specific von Willebrand factor (VWF)-cleaving protease. Several cases of TMA syndrome associated to HLH have been reported.

Aims: To describe and correlate fibrinolysis disorders and VWF-ADAMTS13 system in patients with HLH.

Methods: Critically ill patients with a diagnosis of HLH were prospectively included in a monocentric study. An exhaustive analysis of clinical records was assessed. At diagnosis, fibrinolysis disorders were evaluated by the measurement of fibrinogen, D-dimers, fibrin monomers, plasminogen, t-PA and PAI-1. VWF-ADAMTS13 system was also investigated by the measurement of VWF antigen levels, VWF multimers analysis, ADAMTS13 activity, anti-ADAMTS13 IgG titer, ADAMTS13 antigen levels and ADAMTS13 conformation.

Results: Forty-five patients with HLH were included in the study: median age of 53 years, sex ratio of 1.6F/1M, clinical context of lymphoma in 32 patients. In most patients, hypofibrinogenemia, decreased plasminogen levels, increased D-dimers, fibrin monomers, t-PA and PAI-1 levels were consistent with hyperfibrinolysis. All patients exhibited increased VWF antigen levels and high molecular weight multimers. Surprisingly, a non-immune-mediated severe functional deficiency of ADAMTS13 (activity < 15%, negative anti-ADAMTS13 IgG) associated with a closed ADAMTS13 conformation (conformation index < 0.5) was reported in 16 patients who also exhibited thrombocytopenia, anemia, increased LDH levels. No correlation was found between hyperfibrinolysis and VWF-ADAMTS13 abnormalities.

Conclusions: We reported hyperfibrinolysis in most patients with HLH at diagnosis and a potential TTP-like syndrome in 1/3 of them. The study of degradation products of ADAMTS13 may be warranted to understand the loss of ADAMTS13 activity.


[ADAMTS13 activity and conformation in 45 patients with hemophagocytic lymphohistiocytosis, at diagnosis.]

To cite this abstract in AMA style:

Launois A, Valade S, Roose E, Mariotte E, Darmon M, Galicier L, Zafrani L, Lemiale V, Azoulay E, Mathis S, Kalidi I, Stepanian A, Vanhoorelbeke K, Veyradier A, Joly B. Exploration of Coagulation Disorders, von Willebrand Factor and ADAMTS13 in a Cohort of 45 Patients with Hemophagocytic Lymphohistiocytosis [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/exploration-of-coagulation-disorders-von-willebrand-factor-and-adamts13-in-a-cohort-of-45-patients-with-hemophagocytic-lymphohistiocytosis/. Accessed September 29, 2023.

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