PB2008: CUTANEOUS HEMORRHAGIC SYNDROME IN PATIENTS WITH AL-AMYLOIDOSIS

Abstract

Background: Hemorrhages on the skin and mucosa are seen in 30-40% of patients with systemic AL amyloidosis (AL-A). The pathogenesis and clinical significance of this syndrome are poorly understood. Aims: To analyze the relationship of cutaneous and mucous hemorrhagic syndrome in AL-A patients with the hemostatic system parameters and the leading clinical syndromes. Methods: A prospective study included 49 patients with newly diagnosed systemic AL-A. 18 (37%) patients were diagnosed with stage I, 16 (33%) with stage II, and 6 (12%) and 9 (18%) with stage III and stage IV, respectively (Mayo 2004/Europian). Activated partial thromboplastin time, thrombin time, fibrinogen concentration, XIIa-dependent fibrinolysis time, antithrombin III (ATIII), D-dimer, factors VIII (FVIII), X (FX) and Von Willebrand factor (VWF) activity were determined before therapy. Patients with cutaneous hemorrhagic syndrome were included in the Group №1, and those without cutaneous hemorrhages in the Group №2. Results: Cutaneous and mucosal hemorrhagic syndrome was observed in 23 (47%) patients. Hypercoagulable syndrome (increase of fibrinogen, D-dimer, FVIII, VWF, and decrease of ATIII) was registered in 18 (78%) patients, significantly more frequently than in Group №2 patients (11 patients - 42%; p=0,01). Eight (35%) patients with skin hemorrhages developed venous and arterial thrombosis before treatment, which were absent in the control group (p=0.002). Nephrotic syndrome was present in 19 (82%) group №1 patients, nephrotic syndrome was 2 times less frequent in group №2 (10 (38%) patients, p=0,001). Patients with hemorrhages had higher urinary protein loss (5.7 g/day vs 2.4 g/day; p=0.03) and lower serum albumin values (23 g/l vs 33 g/l; p=0.001). In patients from the first group, the development of hydropericardium, hydrothorax and anasarca was more often observed (p=0.02). We didn’t find significant correlation between cutaneous hemorrhagic syndrome and involvement of other organs, content of free light chains and cardiac markers. Summary/Conclusion: Cutaneous hemorrhagic syndrome is a clinical manifestation of hypercoagulable disorders in the hemostasis system in AL-A patients and associated with a high frequency of thrombosis development. Skin hemorrhages were more often associated with severe nephrotic syndrome, which may indicate a single pathogenetic mechanism in the form of small vessel lesions.