RESUMO
INTRODUCTION: Qualitative and quantitative antithrombin deficiency predisposes to thrombosis, although patients with heparin-binding dysfunction have a lower incidence than other sub-types. Assays discriminating between qualitative sub-types are not widely available. PATIENTS/METHODS: Extended heparin incubation in antithrombin activity assays can overestimate levels in patients with HBDs. Plasmas from genetically proven HBD patients were assayed for antithrombin activity by factor Xa-inhibition and thrombin-inhibition at varying incubation times. Optimal pairings were assessed for generating a quantifiable discrepancy in HBDs by deriving a ratio between results from short and prolonged heparin-incubation assays respectively, the Heparin-antithrombin binding (HAB) ratio. Fourteen patients with hereditary antithrombin deficiency, including five with HBDs, were analysed. RESULTS: The FXa-inhibition assay with 30s and 300s incubations clearly identified a heterozygous p.Pro73Leu and homozygous p.Leu131Phe, giving HAB ratios of 0.24 and 0.67 respectively (reference range 0.90 - 1.01). However, three plasmas containing mutations with markedly reduced or absent heparin affinity (p.Lys146Glu, p.Gln150Pro, p.Arg79Cys) gave normal results. Nine antithrombin deficient plasmas were tested with the thrombin-inhibition assay and all generated reduced HAB ratios whilst two normal donors did not. The three available HBD plasmas generated lower values than non-HBD plasmas. The mildly reduced HAB ratios in non-HBD deficiencies may have been due to heparin cofactor II reacting with bovine thrombin during extended incubation. CONCLUSIONS: HAB ratio from FXa-inhibition assays distinguishes some but not all HBD from non-HBD antithrombins, and thrombin-inhibition assays may be diagnostically applicable with sub-type specific cut-offs.
Assuntos
Deficiência de Antitrombina III/diagnóstico , Deficiência de Antitrombina III/imunologia , Antitrombinas/química , Heparina/química , Adolescente , Adulto , Animais , Bovinos , Fator Xa/química , Feminino , Hemostasia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Reprodutibilidade dos Testes , Trombina/química , Adulto JovemAssuntos
Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Deficiência de Antitrombina III/complicações , Deficiência de Antitrombina III/tratamento farmacológico , Complicações Hematológicas na Gravidez/tratamento farmacológico , Aborto Habitual/etiologia , Aborto Habitual/prevenção & controle , Adulto , Anticorpos Antifosfolipídeos/análise , Síndrome Antifosfolipídica/imunologia , Síndrome Antifosfolipídica/fisiopatologia , Antitrombina III/uso terapêutico , Deficiência de Antitrombina III/imunologia , Deficiência de Antitrombina III/fisiopatologia , Saúde da Família , Feminino , Humanos , Gravidez , Complicações Hematológicas na Gravidez/imunologia , Complicações Hematológicas na Gravidez/fisiopatologia , Resultado da Gravidez , Trombose Venosa/etiologia , Trombose Venosa/prevenção & controleRESUMO
Acquired angioedema (AAE) due to the functional deficiency of the C1 inhibitor (C1-INH) is a rare disease characterized by recurrent bouts of edema that involve subcutaneous tissues, the larynx or the gastrointestinal tract. In the present paper, we report the case of a male patient with symptoms of AAE and recurrent deep venous and arterial thrombosis. As a trigger of AAE in the present patient, we revealed primary antiphospholipid syndrome accompanied by antithrombin III deficiency, along with malignancy in the history, and angiotensin-converting enzyme inhibitor therapy. Although anti-C1-INH titers (type I AAE) were normal initially, we observed a sharp increase in anti-C1-INH titers (suggestive of type II AAE) during follow-up. It seems that thrombosis might worsen angioedematous attacks in functional C1-INH deficiency. Thrombophilia should be considered a provoking factor of AAE and should be carefully sought for in these patients, as the key to successful management of AAE is the effective treatment of the underlying disease.