Acquired hemophilia A is an uncommon disease often presented with bleeding episodes causing a significant mortality risk. The main responsible for the threatening hemorrhagic disorder is the Factor VIII autoantibody’s development. Acquired inhibitors’ presence is frequently idiopathic, but it can be associated with malignancy, pregnancy, drugs and autoimmune diseases. In this report, we present the first case of acquired hemophilia A associated with primary biliary cholangitis. A 48-year-old man, presented with diffuse oral bleeding after a tooth extraction. Hemostasis testing revealed a markedly prolonged activated partial thromboplastin time. The search for an anti-factor VIII inhibitor returned positive. The etiological investigation concluded primary biliary cholangitis, and the patient was treated with bypassing agent, immunosuppressive therapy, and ursodeoxycholic acid.

Topic: 33. Bleeding disorders (congenital and acquired) Background: Von Willebrand disease (VWD) is defined as a defective or dysfunctional Von Willebrand Factor (VWF) that mediates platelet adhesion and aggregation at vascular damage sites. A minority of patients, particularly with type 3 VWD, develops alloantibodies to exogenous VWF whose arising complications are challenging. These antibodies make replacement VWF therapy ineffective and even dangerous by producing anaphylactic reactions. Aims: Our study aims to evaluate the clinico-biological, therapeutic and evolutionary characteristics of VWD patients with alloantibodies. Methods: Our study is retrospective, it concerned patients with VWD who developed alloantibodies. Data were recorded from VWD registry which includes patients with VWD in south of Tunisia during 23 years (from January 2000 to December 2022). Anti-VWF and anti-FVIII testing were performed in case of ineffective substitution or when an allergic reaction was occurred during substitution. The screening and the titration of inhibitors were performed by the modified Bethesda method using the coagulation analyzer Sysmex® CS-2100i in the anti-VWF testing and the STA-R® Stago automate in the anti-FVIII testing. Results: During the study period, we collected 89 cases of VWD, 44 cases had type 3. Six patients had alloimmunization: 1 had anti-VWF, 2 had non neutralisant antibodies and 3 had both anti-VWF and anti-FVIII. Thus, anti-VWF was found in 14% of patients with type 3 VWD. Median age at diagnosis of alloimmunization was 30 years [4 years - 47 years] with a female predominance (sex ratio M/F= 0.2). Circumstance of the discovery of alloimmunization were persistent hemorrhagic symptoms despite adequate substitution in 4 cases, a preoperative evaluation in 1 case and an anaphylactic reaction secondary to VWF concentrate administration in 1 case. Our patients were on replacement therapy with cryoprecipitate or VWF/FVIII plasma concentrates (Immunate®). The first patient had a hemarthrosis of the elbow resistant to substitution. Anti-VWF antibodies tested positive with a titre of 5.8 Bethesda units (BU). Recovery test of infused VWF/VLFIII plasma concentrates was carried out with a total absence of recovery for VWF. She was treated with by-passing agent combined with immunosuppressor, which allowed an inhibitor level decrease to 0 UB and a reintroduction of immunate without incident. The 2nd and 3rd patients had a non-neutralizing anti-VWF discovered during an episode of gingivorrhagia resistant to substitution for one of them and during a preoperative evaluation for the other. The anti-VWF and anti-FVIII antibodies’ screening were negative. However, an anti-VWF, considered non-neutralizing, was determined since there were a total absence of recovery for VWF. They were treated with by-passing agent (Novoseven®) combined with corticosteroid therapy with good resolution of the bleeding episode. The last 3 patients had both anti-VWF and anti-FVIII antibodies. They were revealed during an allergic reaction to the replacement therapy in 1 case and a severe bleeding syndrome resistant to substitution in 2 cases. They were treated with by-passing agent combined with immunosuppressor with good clinical resolution. Summary/Conclusion: Alloimunization in VWD is more frequently reported in our patients (14% versus 5-10% in published series). Several types of antibodies were documented. In our knowledge, the coexistence of anti-VWF and anti-FVIII is extremely rare and isn’t yet reported. In this challenging situations, by-passing agents such as Novoseven®, recombinant FVIII and immunosupressive therapy may be useful. Keywords: Bleeding disorder, von Willebrand factor (vWF), Antibody, von Willebrand’s disease

Childhood-onset systemic lupus erythematosus (cSLE) is a rare multisystem autoimmune disease characterized by inflammatory and autoimmune reaction in several organs. The diagnosis can be difficult due to the heterogeneity of clinical manifestations. Early diagnosis can lead to a proper diagnosis and treatment to control inflammation and to avoid life-threatening complications.

A 65yearold woman with a history of diabetes and high blood pressure was admitted to the Respiratory Department for therapeutic care of a pleuropneumopathy following SARSCoV2 infection. Clinical examination revealed adenopathy and splenomegaly. Blood count showed anaemia (haemoglobin 68 g/L), thrombocytopenia (platelet count 56 × 109/L), leukocytosis (98 × 109/L) and monocytosis (22 × 109/L). A peripheral blood smear showed that 33% of cells were small to medium sized agranular blasts with finely dispersed chromatin and inconspicuous nucleoli (top right image, all images ×100 objective). Surprisingly, Auerrodlike inclusions were observed in the neutrophils (left and middle images). In some cases these resembled the bundles of Auer rods (seen in fagot cells). In contrast, the blast cells did not contain Auer rods (top right) and the inclusions did not stain positively with myeloperoxidase (bottom right). In addition, dysgranulopoiesis was observed in the most of neutrophils with hypogranulation and dense or clumped chromatin (left and middle images). Flow cytometry showed that the blast cells expressed Tcell lymphoïd markers: cytoplasmic CD3, CD7 and CD2. Nevertheless, CD1a, CD5, CD4 and CD8 were negative. The myeloid and hematopoïetic stemcell markers expressed were CD45, CD34, HLADR and CD117. Thus, diagnosis of an early T cell precursor lymphoblastic leukaemia was established. Auer rods in mature neutrophils are extremely rare, but are described in acute promyelocytic leukaemia, acute myeloid leukaemia t(8;21), mixed lineage leukaemia and acute myeloid leukaemia with maturation. To the best of our knowledge, this is the second case report of an early T cell precursor lymphoblastic leukaemia (ETPALL) associated with Auerrodlike inclusions in neutrophils, and is the first case following SARSCoV2 infection. We suggest that mechanism underlying Auer rod formation may be secondary to concomitant dysgranulopoiesis. Alternatively, it has been reported that abnormal immune response to viral infections may indirectly trigger the secondary mutational events that promote clinical leukaemia development. Finally, SARSCov2 that can interact significantly with the reninangiotensin system, which has been suggested to have a role in neoplastic haematopoiesis in genetically predisposed individual.

Acquired hemophilia A (AHA) is a potentially life-threatening hemorrhagic disorder with many etiologies. We report the first case in the literature describing the association of AHA with adult-onset Still's disease (AOSD).

Acquired hemophilia A (AHA) is a rare and severe bleeding disorder characterized by the development of autoantibodies against factor VIII. There is no previous study published in our country for AHA. The aim of this study that to describe the clinical symptoms, diagnostic criteria and treatment strategies in patients with AHA in the south of Tunisia. We retrospectively collected all patients diagnosed with AHA in the Department of Hematology of Hedi Chaker Hospital (Tunisia) from 2000 to 2017. The diagnosis was established in the presence of clinical hemorrhagic features associated with the isolated prolongation of the activated partial thromboplastin time (APTT), not corrected after two hours by incubating patient plasma with equal volumes of normal plasma, and with factor VIII less than 50%. We collected five patients with AHA in the South of Tunisia. There were 4 females and 1 male with the median age of 32 years old. The median FVIII C was 7% and the median value of FVIII inhibitor was 11 UB. The most common clinical symptoms were post-partum hematoma in 3 patients (60%), extensive cutaneous hematoma in one patient and hemorrhagic tooth extraction in one patient. All patients were treated in first-line therapy with bypassing agent FVIIa with successful response in 80% of cases. The first-line treatment of bleeding in AHA requires a bypassing agent and the optimal therapeutic strategy to eradicate the inhibitor include immunosuppression with corticosteroids alone or corticosteroids in combination with cyclophosphamide.

&NA; Factor XIII deficiency is a rare autosomal recessive disorder of hemostasis characterized by a plasmatic factor XIII level less than 1% in homozygote and bleeding as of the youth. The aim of the study is to describe the clinical features and the outcome of the patients and to determine molecular characteristics. A retrospective study, was conducted on seven patients with factor XIII deficiency in the department of hematology and pediatrics, Hedi Chaker Hospital, Sfax, Tunisia during the period of 14 years (2001–2014). The activity of factor XIII in plasma of the patients was less than 1%. Seven patients from five unrelated families were recorded (four men and three women). Median age at diagnosis was 3.5 years. All patients had consanguineous parents. Six patients presented umbilical bleeding and only three patients had intracranial bleeding. Other bleeding features were seen, including skin and mucosal bleeding, muscular hematoma, and splenic rupture. Recurrent abortions were observed in one patient. The standard screening tests were normal. Genetic analysis identified two mutations interesting the subunit A of factor XIII. All patients received transfusion of fresh frozen plasma monthly. One patient was died because of intracranial hemorrhage. Factor XIII deficiency is a rare bleeding disorder which frequently increases in areas with high consanguinity. In our study, we identified a founder mutation. The prognosis of the disorder is related to hemorrhagic complications especially to life-threatening intracranial bleeding. Prophylaxis consists of factor XIII concentrate or recombinant factor XIII. If these are unavailable, fresh frozen plasma may be used.