Chronic myelomonocytic leukaemia associated with acquired haemophilia A: case report and literature review

Abstract

Chronic myelomonocytic leukaemia (CMML) and acquired haemophilia A (AHA) are rare blood disorders. CMML is a clonal haematopoietic stem cell disorder, characterized by absolute monocytosis in the peripheral blood that persists for at least 3 months. According to the World Health Organization (WHO) classification, CMML is classified as a myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN). The incidence of CMML is lower than 10 cases per million people per year [1]. AHA is a bleeding disorder caused by autoantibodies against factor VIII (FVIII) with an estimated incidence of 1.48 cases per million people per year [2]. Although the underlying disorder cannot be identified in 50% of the patients [3], it is believed that AHA is associated with autoimmune disorders, malignancies, pregnancy, dermatological disorders and drug reactions. In this article, we describe a case of AHA in an old man with CMML; it is the fourth case of CMML associated with AHA to be reported in the literature, which makes the findings rare and valuable. Case ReportA 71-year-old Chinese male was admitted to the Department of Nephrology with a 3-day history of gross haematuria. In the course of the disease, he denied experiencing frequent, urgent micturition or urodynia. His medical history was unremarkable, except for hypertension that was controlled with plendil. He had neither a personal nor a family history of spontaneous bleeding. Physical examination detected multiple small ecchymoses on his left forearm. Moder-ate oedema was also found in both lower extremities. Laboratory examinations found white blood cell count (WBC, 79.48 9 10 9 L À1 ) and monocyte count (MO, 5.37 9 10 9 L À1 ) elevated, severe anaemia [haemoglobin (Hb), 53 g L À1 ] and thrombocytopenia [platelet count (PLT), 57 9 10 9 L À1 ]. Prolonged activated partial thromboplastin time (APTT) (118.6 s; normal range, 31-45 s) and deficiency in FVIII coagulant activity (FVIII:C) (6.70%; normal range, 50-150%) were also detected. Prothrombin time (PT), von Willebrand factor and other factors (II, V, VII, IX, X, XI and XII) were all normal. Factor VIII inhibitor was positive at a titre of 7.4 BU (normally it is negative). Urine examination found excessive amount of RBC. Rheumatoid factor and any autoantibodies such as anti-nuclear antibody, anti-dsDNA antibody, anti-Smith antibody, anti-cardiolipin antibody and lupus anticoagulant were negative. Bone marrow (BM) examination showed that the hypercellular marrow comprised 2% blasts with erythroid and megakaryocytic dysplasia. The karyotype was found to be normal (46,XY) by G-banding analysis, and the BCR/ ABL fusion gene was not detected by fluorescence in situ hybridization.The patient was diagnosed with CMML-1 with AHA based on the above findings, and transferred to our department for further treatment at the 7th hospital day. At that time, it revealed the presence of multiple large ecchymoses in the right thigh and lumbar back which caused by former BM aspiration. Treatment with hydroxycarbamide (HU) at a dose of 500 mg da...

Myelofibrosis and acquired hemophilia A: a case report

“…The association between AHA and hematologic malignancies, especially lymphoproliferative disorders, is in line with the broad range of autoimmune phenomena that frequently complicate these conditions [ 15 ]. Nevertheless, association between AHA and myeloid hematological malignancies has been reported [ 16 , 17 ]. In MF, clonal myeloproliferation is associated with reactive bone marrow fibrosis, osteosclerosis, angiogenesis, extramedullary hematopoiesis, and abnormal cytokine expression that may explicate the development of an autoimmune disorder [ 18 ].…”

Autoimmune Complications in Hematologic Neoplasms

“…Hypometylating agents used for CMML have been successfully used in about two thirds of AID manifestations [57]. Finally, few reports of acquired HA, TTP and APS exist, sometimes with fatal outcome [83][84][85].…”

Acquired Hemophilia A: A Case Report

“…The dose of the rFVIII used in their case was 6 to 10 IU/kg, with doses ranging from 500 to 750 IU, which was lower than the doses that we used in our patient. 15 For inhibitor eradication therapy, our patient received a combination of prednisone and rituximab, which is considered one of the first-line therapies. The other first-line options are corticosteroids alone and combined corticosteroids and cyclophosphamide.…”