Anticoagulation as a confounding factor in the diagnosis of acquired hemophilia

Cabra Rodríguez, Rocío; Ruíz Márquez, María José

doi:10.1016/j.medcle.2021.03.026

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Hospital de Riotinto, Minas de Riotinto, Huelva, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Anticoagulación como factor de confusión en el diagnóstico de una hemofilia adquirida" ] ] "textoCompleto" => "Acquired haemophilia (AH) is an autoimmune coagulopathy that predisposes to haemorrhagic events, caused by the production of specific circulating autoantibodies that inhibit some of the clotting factors. Frequently these autoantibodies are directed against coagulation factor viii (FVIII) (AH A [AHA]) or coagulation factor IX (acquired haemophilia B).<a class="elsevierStyleCrossRef" href="#bib0005">1</a>The incidence of AH is estimated to be 1–3 cases per million inhabitants per year, with a mean age of around 65 years upon presentation. Although it has been related to certain clinical conditions (pregnancy or the post-partum period, autoimmune diseases, infections, drugs, cancer), AH is considered idiopathic in 50% of cases.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>We present the case of an 82-year-old man with permanent atrial fibrillation anticoagulated with Sintrom® (Rovi Pharma Industrial Services, SA; local representative: Norgine de España SLU). The anticoagulation treatment was temporarily halted due to a hematoma in the lower limb, which was related to an overdose of oral anticoagulants (OAC). The patient was admitted due to extensive spontaneous hematoma in the right pectoral region which extended to the lateral cervical region and presented with pain.When the patient was examined, he said the region felt sore when touched although there were no signs of superinfection. The first analytical study from the Emergency Department showed haemoglobin 12.1 g/dl (12−16′), leukocytes 10 × 103/μl (5.00–14.50), segmented 79.1% (25.00–65.00), lymphocytes 13.7% (20.00–53.00), platelets 285 × 103/μl (130–450), folic acid 2.24 ng/ml (6.5–38.4). Prothrombin time (PT) ratio and PT (INR) were normal. The activated partial thromboplastin time (APTT) was elevated, with a ratio of 2.02, which corrected with normal, non-incubated plasma and which was prolonged in the incubated mix with the absence of lupus anticoagulant.A cervical ultrasound showed compatibility with a hematoma in the right supraclavicular region, with approximate dimensions of 11 × 4 cm. Other tests were conducted including a haematological study of haemostasis-fibrinolysis, which showed: APTT (ratio): 2.83 ratio (0.70–1.20), APTT (1 patient + 1 normal; ratio): 1.51 ratio (0.70–1.20), FVIII (coagulative): 4.7% (60.0–160.0), factor xii (coagulative): 53.1% (60.0–150.0), with normal levels of the rest of the coagulation factors and quantification of the specific FVIII inhibitor: 7.5 Bethesda units.Finally, the patient was diagnosed with acquired haemophilia A and folic acid deficiency, since the FVIII inhibitor study was positive. The treatment indicated was oral prednisone for 4 weeks in a descending regimen. Initially, a 2 dose of FVII (eptacog α activated) and tranexamic acid had to be administered; the latter as a one off, due to the thrombotic risk in this patient. The response was favourable with the hematoma evolving without evidence of neurovascular compression or superinfection and giving a negative result to the specific FVIII inhibitor study. Therefore, oral anticoagulation was able to be reintroduced early since the patient was at high cardiovascular risk. Finally, the folic acid deficit was corrected with oral supplementation. The follow-up of the patient by the Haematology department has revealed no signs of relapse to date.AHA can present with severe bleeding disorder in approximately 20–30% of cases.<a class="elsevierStyleCrossRef" href="#bib0015">3</a> It is found in people without a history of bleeding disorders and is a rare cause of bleeding diathesis. 10% of patients do not present bleeding and, therefore, a prolonged APTT should never be ignored prior to performing any invasive procedure.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>AHA should be suspected when there is an elongated APTT that cannot be corrected with normal plasma and normal PT. In addition, a reduction should be detected in functional FVIII < 50%, with levels of the rest of the coagulation factors in the normal range, presence of the anti-FVIII inhibitor ≥ 0.6 Bethesda units/ml, preferably by the Nijmegen Bethesda method (recommended by the International Society on Thrombosis and Haemostasis), absence of LA and other coagulopathies.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>In the case of our patient, elongation of the APTT that corrected immediately with normal plasma but did not in the incubated mixture raised the suspicion of the presence of a slow-reacting or time-dependent inhibitor (most of the FVIII inhibitors and 8% of LAs).<a class="elsevierStyleCrossRef" href="#bib0020">4</a>Preanalytical aspects that make it difficult to correctly identify AHA have been described, which include OACs, causing reduced levels of most coagulation factors and an inhibitory test pattern as a consequence of said treatment.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> This would explain the difficulty of a correct diagnosis when faced with the first episode of hematoma in our patient.The prevention and control of bleeding is recommended in AHA, starting treatment with activated recombinant FVII, activated prothrombin complex or recombinant porcine FVIII, and the eradication of autoantibodies, using corticosteroid therapy, cyclophosphamide and rituximab, or combinations of the same. In addition, an individualised evaluation of the immunosuppressive therapy is necessary to minimise the adverse effects in frail patients.<a class="elsevierStyleCrossRef" href="#bib0025">5</a>The pharmacological approach in these patients constitutes an important medical challenge, many of whom are anticoagulated due to a high thrombotic risk, and we have to balance the risk of thrombosis and bleeding in frail patients with high comorbidity." "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Cabra Rodríguez R, Ruíz Márquez MJ. Anticoagulación como factor de confusión en el diagnóstico de una hemofilia adquirida. Med Clin (Barc). 2022;158:44–45." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Hemofilia adquirida: epidemiología, clínica, diagnóstico y tratamiento" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M.E. Mingot-Castellano" 1 => "R. Núñez" 2 => "F.J. Rodríguez-Martorell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medcli.2016.11.030" "Revista" => array:5 [ "tituloSerie" => "Med Clín (Barc)" "fecha" => "2017" "volumen" => "148" "paginaInicial" => "314" "paginaFinal" => "322" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "International recommendations on the diagnosis and treatment of acquired hemophilia A" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Tiede" 1 => "P. Collins" 2 => "P. Knoebl" 3 => "J. Teitel" 4 => "C. kessler" 5 => "M. Shima" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3324/haematol.2019.230771" "Revista" => array:6 [ "tituloSerie" => "Haematologica" "fecha" => "2020" "volumen" => "105" "paginaInicial" => "1791" "paginaFinal" => "1801" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/32381574" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Treatment guidelines for acquired hemophilia A" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Windyga" 1 => "B. Baran" 2 => "E. Odnoczko" 3 => "A. Buczma" 4 => "K. Drews" 5 => "P. Laudanski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5603/GP.2019.0063" "Revista" => array:6 [ "tituloSerie" => "Ginekol Pol" "fecha" => "2019" "volumen" => "90" "paginaInicial" => "353" "paginaFinal" => "364" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31276188" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Importancia de la orientación diagnóstica en hemofilia A adquirida" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C.P. Casas Patarroyo" 1 => "C.D.P. Agudelo López" 2 => "K. Galvez" 3 => "J. Lagos Ibarra" 4 => "S. Martínez Rojas" 5 => "L. Ibatá Bernal" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.4067/S0034-98872019000300334" "Revista" => array:6 [ "tituloSerie" => "Rev Méd Chile" "fecha" => "2019" "volumen" => "147" "paginaInicial" => "334" "paginaFinal" => "341" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/31344171" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tratamiento de la hemofilia adquirida en el paciente anciano. Estudio de 10 casos" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J.A. Rodríguez-García" 1 => "V. Martínez-Robles" 2 => "B. Pérez-Gutiérrez" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.medcli.2018.02.020" "Revista" => array:5 [ "tituloSerie" => "Med Clín (Barc)" "fecha" => "2019" "volumen" => "152" "paginaInicial" => "34" "paginaFinal" => "36" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015800000001/v2_202201200752/S2387020621006859/v2_202201200752/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015800000001/v2_202201200752/S2387020621006859/v2_202201200752/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621006859?idApp=UINPBA00004N"]

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Vol. 158. Issue 1.