Acquired hemophilia in the patient suffering from rheumatoid arthritis

Abstract

Acquired hemophilia is a severe bleeding diathesis caused by autoantibodies against a coagulation factor VIII (FVIII inhibitor). Massive bleeding diathesis, often life threatening are observed in almost 90% of patients. In 50-60% of cases, inhibitor emerges spontaneously. However, there are some conditions like pregnancy, puerperium, autoimmune disorders or cancers that seem to induce acquired hemophilia. We report a case of a 49-year-old woman suffering from rheumatoid arthritis (RA) for several years, who was diagnosed with acquired hemophilia in September 2011. The patient had been treated by steroids and leflunomide during the last few months. At the time of diagnosis, diffuse bruising of the forearms and the trunk was observed. The patient was treated with recombinant activated factor VII, and the first-line immunosuppressive therapy was introduced (cyclophosphamide and prednisone). We observed the elimination of symptoms and the disappearance of diathesis. Significant reduction of the titer of inhibitor was achieved, but only partial remission was obtained. It lasted until the beginning of December 2011, when the titer of the inhibitor increased again and massive bleeding to the left lower limb occurred. It was necessary to administer recombinant factor VIIa together with the second-line immunosuppressive therapy based on the Budapest protocol. The rapid reduction of the diathesis and improvement of the patient's general condition was achieved as previously. However, still there was no complete remission. After 2 weeks of treatment, the titer of inhibitor diminished, and factor VIII activity increased slightly. Because of RA, the patient was treated with methylprednisolone in maintenance doses during the next few weeks. Unfortunately, after over a month, the increase of inhibitor titer and the decrease of FVIII level were observed again. Some bruises appeared. It was necessary to increase doses of corticosteroids to therapeutic levels and add cyclophosphamide in low doses to prevent the appearance of more hemorrhagic diathesis. Partial remission was achieved a second time at the end of April 2012. The patient was given methylprednisolone with chloroquine as a maintenance treatment and the control of RA. The titer of the inhibitor increased again in June 2012, but there were no signs of diathesis. In August 2012, some bruises were detected, and we decided to add cyclophosphamide again instead of escalating the doses of methylprednisolone to prevent the occurrence of side-effects of corticosteroids. Cyclophosphamide was given with intervals only depending on activated partial thromboplastin time. No further diathesis was observed in spite of the lack of remission. We were forced to withdrawn cyclophosphamide completely in October 2012 because of signs of hematuria. Fortunately, right nephrolithiasis and urinary tract infection were the cause of that condition. These symptoms vanished after standard supportive treatment. Maintenance doses of corticosteroids and chloroquine were continued as the main treatment....

Acquired Hemophilia in a Patient With Rheumatoid Arthritis: Case Report and Literature Review

“…second choice therapy [20,35,39,45,48,50]; in all those reports, treatment ended with eradication of the inhibitory antibodies and disease control. Alternative immunosuppressive drugs were cyclosporine [29,30] and azathioprine [19,36,44], while intravenous immunoglobulin were used in association with cyclophosphamide or azathioprine in two patients and as monotherapy in just one, showing however no efficacy [23,40,44].…”

“…In our literature review, 11 patients required antihemorrhagic treatment, which consisted in: factor VIII concentrates, recombinant factor VIIa, FIX plasma concentrate, factor eight inhibitor bypassing activity (FEIBA), or activated prothrombin complex concentrates (aPCC) [20,21,23,25,29,30,35,37,38,40,50].…”

“…Cyclophosphamide was the main immunosuppressant reported, since its administration was observed in 15 patients [20,[22][23][24][25]28,[35][36][37][38]40,48,49,51] as firstline treatment or after failure of other immunosuppressive drugs, showing to be effective in 11 of them. Rituximab was another choice, mainly as weekly infusion, as in our case.…”

“…We found 35 cases ( Figure 1): 15 in systemic lupus erythematosus (SLE) [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32], 12 in rheumatoid arthritis [28,[33][34][35][36][37][38][39][40][41][42][43], 4 in Sjögren's syndrome (SS) [44][45][46][47], 2 in polymyalgia rheumatica (PMR) [48,49], 1 in systemic sclerosis (SSc) [50], and 1 in psoriatic arthritis (PA) [51].…”

“…The main clinical presentation was ecchymosis/cutaneous hematomas, (19 of 23, 82%) [19][20][21][22]24,25,28,29,[35][36][37][38]40,44,45,48,50,51] followed by muscular hematomas (10 of 23, 43%) [22,23,28,3 6,37,39,40,44,49,51], the latters mainly in the RA group (Table II). As expected, hemarthroses were quite rare in the literature, described in just two cases, one in RA and RA, since it is indicated in the treatment of RA [52].…”