[en] OBJECTIVES: The aim of this investigation is the study of the aVWS (acquired von Willebrand syndrome) related with different pathologies, to propose a diagnostic algorithm based in the haemorrhagic phenotype and in the defects of VWF (von Willebrand factor), and the evaluation of therapeutic strategies, used to control of bleeding and to treat the underlying disease. METHODS: A single-centre, ambispective study was conducted, with restropective analysis of the clinical and haemorrhagic history of patients with suspition of aVWS, and prospective analysis of the events since the enrolment until the resolution of aVWS or until 2 years. The laboratory tests used for aVWS diagnostic were: PFA (platelet function analyser); RIPA (ristocetin induced platelet agglutination); FVIII:C (factor VIII procoagulant activity); VWF:Ag (VWF antigen quantification); VWF:RCo (FVW ristocetin cofactor activity); VWF:CB (FVW collagen binding); Multimeric analysis of VWF. The aVWS diagnostic was based in at least two of the following criteria: 1. Abnormal PFA and RIPA values; VWF <30 UI/dL and/or ratios VWF functional/FVW:Ag <0.7; 3. Alterations in multimeric analysis. A comparative study was made between patients with confirmed diagnostic of aVWS and Control group. In patients with cardiovascular diseases (CVD), with need of cardiac surgery (CS) we: used a self-made hemorragic risk score to establish prophylactic treatment during surgery; evaluated the treatment efficacy; made a comparative study pre and post-surgery, between aVWS and Control group. In other subtypes, we made a descriptive study of the clinical and analytical characteristics, and the answer to different treatments. RESULTS: Clinical and analytical differences were observed between aVWS and Control cases. We found a significative association between BAT (ISTH-SSC bleeding assessment tool) ≥3, and aVWS diagnostic (OR=12.7 with IC 95% 3.9-40.9). Patients with aVWS presented: High PFA (p 0.001); diminished RIPA (p 0.006); functional VWF/VWF:Ag diminished (p 0.003 and 0.000); and 94% had loss of multimers in multimeric analysis, that was the most sensitive (94%) and specific (100%) test, but it were necessary at least two abnormal tests to consider aVWS diagnostic. We observed great heterogeneity of clinical and laboratory results according to the underlying diseases. In CVD: VWF values were high, and cut point of functional VWF/VWF:Ag <0.8 was more adequate that the one used on hereditary VWD (<0.7), and multimeric analysis was the most sensitive (97%) and specific (100%) test. The periprosthesis mitral leakages (PML) and mitral and aortic insufficiencies (MAOI) showed more alterations of VWF, and also higher BAT (≥3), more RESUMEN 18 bleeding episodes, hospitalizations and blood products administrations, due to higher shear stress. The correction of the cardiac defects with CS implied the immediate correction of FVW defects and, until at least 3 months after surgery. The prophylactic treatment during CS showed 81% effectivity in patients with high risk of hemorrhage. In low risk patients with aVWF and Control group, bleeding in CS can be multifactorial. In monoclonal gammopathies (MG): had higher BAT (5.2), and the most severe haemorrhagic phenotype. VWF values were <30 IU/dL, multimeric analysis showed absence of multimers similar to type 3 VWD, or loss of multimers similar to type 2 VWD. Genetic analysis allowed to discard hereditary VWD. The response to different hemostatic treatments was poor, except for IVIg (intravenous immuneglobulins), even having transitory response, are the indicated treatment. In myeloproliferative syndromes: mean BAT was 1, and was the disease with less bleeding. VWF values were normal, and functional VWF/VWF:Ag <0.7; Multimeric analysis showed loss of high weight multilmers. High platelet values (>3000 x109 mg/dL) coincide with more FVW defects and more bleeding. Treatment with cytorreductive therapy, implies normalization of VWF defects. In cáncer and autoinmune disease (AD): The haemorrhagic phenotype was more severe in AD (BAT was 10), and in cancer was variable. VWF values were <30UI/dL, and multimeric analysis showed presence of multimers, or loss of multimers. Genetic analysis allowed to discard hereditary VWD. With the treatment of the underlying diseases we observed normalization of VWF. CONCLUSIONS: The diagnostic algorithm must include BAT, and at least two abnormal laboratory tests to confirm AVWS. The multimeric analysis is the most sensitive and specific test, followed by ratios of functional VWF/VWF:Ag. Clinical and laboratory heterogeneity and different therapeutic strategies were observed according to each underlying disease. Treatment of underlying disease, if possible, leads to treatment of AVWS, except for MG.

[gl] OBXETIVOS: O obxetivo principal deste traballo de investigación é estudar o SVWa (Síndrome de von Willebrand adquirido) asociado a diversas patoloxías, para propor un algoritmo de diagnóstico, basado no fenotipo hemorráxico e nas alteracions do FVW (Factor de von Willebrand), e evaluar as estratexias terapéuticas utilizadas para o control da hemostasia e para o tratamento da patoloxía de base. MÉTODOS: Levouse a cabo un estudo unicéntrico, ambispectivo, no que analizouse retrospectivamente a historia clínica e hemorráxica dos pacientes incluidos con sospeita de SVWa, e fíxose un seguimento prospectivo dos eventos ocurridos dende a inclusión ata a resolución do SVWa ou ata 2 anos. As probas de laboratorio utilizadas para o diagnóstico de SVWa foron: PFA (Análise da función plaquetar); RIPA (aglutinación plaquetar por indución de ristocetina); FVIII:C (Factor VIII coagulativo); FVW:Ag (Cantificación do antíxeno do FVW); FVW:RCo (Actividade do FVW como cofactor da ristocetina); FVW:CB (Unión ao coláxeno do FVW); Análise multimérico (AM) do FVW. O diagnóstico de SVWa efectuóuse en base polo menos dous criterios biolóxicos dos seguintes: 1. PFA e RIPA alterados; 2. FVW <30 UI/dL e/o cocientes FVW funcional/FVW:Ag <0.7; 3. análisis multimérico alterado. Fíxose un estudo comparativo entre pacientes con diagnóstico confirmado de SVWa e Grupo Control. Nos pacientes con ECV (enfermidades cardiovasculares), con necesidade de CC (ciruxía cardíaca): estableceuse un baremo de risco hemorráxico para establecer tratamento profiláctico durante a ciruxía; avaliouse a efectividad do tratamento profiláctico; e fíxose un estudo comparativo pré e post ciruxía, entre grupo con SVWa e Grupo Control. Nas demais enfermidades subxacentes, fíxose un estudo descriptivo das características clínicas e analíticas e da resposta a tratamentos. RESULTADOS: Encontráronse diferenzas significativas tanto clínicas como analíticas entre os casos con SVWa e grupo Control. Encontrouse unha asociación significativa entre, presentar BAT (ISTH-SSC bleeding assessment tool) ≥3, e o diagnóstico de SVWa (OR=12.7 con IC 95% 3.9-40.9). Pacientes con SVWA presentaron: PFA superior (p 0.001); RIPA inferior (p 0.006); FVW funcional/FVW:Ag disminuido (p 0.003 y 0.000); y 94% tiñan análise multimérico alterado. O análise multimérico foi a proba mais sensible (94%) e mais específica (100%), pero son necesarias polo menos duas probas alteradas para diagnosticar SVWa. Observouse unha grande heteroxeneidad de resultados, tanto clínicos como de laboratorio según a enfermidade subxacente relacionada co SVWa. Nas ECV: Os valores de FVW foron elevados, el punto de corte FVW funcional/FVW:Ag <0.8 foi mais adecuado que o utilizado na EVW hereditaria (<0.7), e o analise multimérico mostrou pérdida de multímeros de alto peso molecuar (MAPM). Foi a proba mais sensible (97%) e específica (100%). As FPM (fugas periprotésicas mitrales) e IMAO (insuficiencias mitro-aórticas) mostraron mais alteracións de FVW, coincidindo BAT ≥3 e mais episodios de DH, hospitalizacions e administración de hemoderivados, debido a maior forza de cizalladura do fluxo. A corrección das valvulopatías coa CC implicó a corrección inmediata do FVW e a desaparición do SVWa, que mantívose aos 3 meses da CC. O tratamento profiláctico durante a CC tivo efectividad de 81% nos pacientes con elevado risco hemorráxico. Nos casos de SVWa con baixo risco hemorráxico o por ser grupo Control, a ocurrencia de DH foi multifactorial. Nas GM (gammapatias monoclonais): foi a enfermidade con maior BAT (5.2) e fenotipo hemorráxico mais grave. Os valores de FVW foron <30 UI/dL, e o análisis miltimérico presentou ausencia de multímeros similar a EVW tipo 1 grave/tipo 3 ou pérdida de MAPM similar a EVW tipo 2A. O análise xenético do FVW permite descartar EVW hereditaria. A resposta foi pobre en todos os tratamentos hemostáticos, excepto no caso de las IgIV, que ainda que a resposta é transitoria, son o tratamento mais indicado. Nos SMP (síndromes mieloproliferativos): tiveron o BAT medio de 1, e menos episodios hemorráxicos. Os valores de FVW foron normales, e os cocientes FVW funcional/FVW:Ag <0.7; o análise multimérico mostrou pérdida MAPM. Pacientes con plaquetas mais altas (>3000 x109 mg/dL) tiveron mais alteracións do FVW e mais episodios de DH. O tratamento citorreductor, implicou a desaparición do SVWa. Nos pacientes con Cáncer e enfermidade autoinmune (EA): o fenotipo hemorráxico foi mais grave na EA (BAT de 10), e no cáncer foi variable. Os valores de FVW foron <30UI/dL en ambas enfermidades, e o análise multimérico mostrou presenza de multímeros ou pérdida de MAPM. O análise xenético do FVW permitiu descartar EVW hereditaria. A desaparición da enfermidade subxacente implicou a normalización das características do FVW. CONCLUSIONES: O algoritmo diagnóstico de SVWa debe incluir el BAT, e polo menos dous pruebas de diagnóstico de laboratorio de FVW alteradas. O análise multimérico e a proba mais sensible e específica, seguido dos cocientes FVW funcional/FVW:Ag. Existe gran heteroxeneidad dos resultados clínicos e de laboratorio según a enfermidade de base, así como das estratexias terapéuticas a utilizar. O tratamento da enfermidade de base, se é posible, implica o tratamento de SVW, salvo en las GM.