Acquired Hemophilia A: Bleeding Pattern and Hemostatic Therapeutic Strategies

Abstract

Acquired Hemophilia A (AHA) is a rare autoimmune disorder characterized by the onset of a sudden and unexpected bleeding episode in a patient with no personal or family history of bleeding diathesis, and with a typical laboratory feature, i.e., a prolonged activated partial thromboplastin time that is not otherwise explained. This bleeding disorder is caused by autoantibodies directed against the coagulation factor VIII (FVIII). AHA is idiopathic in 50% of cases and is secondary to well-defined diseases in the remaining 50%. AHA affects elderly patients although it has also been observed in the post-partum period. Bleeding manifestations are heterogeneous, ranging from mild to life-threatening bleeds involving limbs and organs. Severe bleeding with a significant decrease in hemoglobin levels must be promptly and adequately treated in order to avoid a worsening of the hemorrhages and their complications. According to international recommendations, the bypass agents (i.e., activated prothrombin complex concentrate and activated recombinant factor VII) and the replacement therapy with recombinant porcine FVIII are considered as the first-line therapy for bleeding control, due to their proven clinical efficacy. Plasma-derived or recombinant FVIII concentrates could be used as second-line treatments. Emicizumab may represent a valid and interesting therapeutic option for prophylaxis of bleeding recurrences.

Navigating challenges in diagnosing acquired hemophilia A: A case report from Syria

“…The severity of AHA‐related bleeding can vary widely from mild to life‐threatening, often presenting as extensive subcutaneous bruises, muscle hematomas, and mucosal bleeds, along with prolonged postoperative bleeding. 5 AHA that is linked to pregnancy is most commonly seen during the postpartum phase, typically from 1 to 4 months after delivery. 3 In patients with new abnormal bleeding, particularly the elderly, peripartum, or postpartum women, an isolated prolonged aPTT with normal PT warrants consideration of AHA.…”

“…The remaining cases are associated with autoimmune disorders (such as SLE, rheumatoid arthritis (RA), and thyroid disorders), hematologic or solid cancers, infections, dermatological diseases, drugs, and pregnancy. 5 Autoimmune diseases often lead to the development of autoantibodies against FVIII, particularly in conditions like RA and SLE. These conditions are typically associated with high titer inhibitors and a poor response to steroid treatment.…”

Genetics and Epigenetics in Acquired Hemophilia A: From Bench to Bedside

“…Hemostatic agents that can be used include recombinant FVIIa (rFVIIa), activated prothrombin complex concentrates (aPCCs), and recombinant porcine FVIII (rpFVIII) [ 23 , 85 ]. Data from retrospective and prospective studies support that the clinical efficacy of the three agents in the management of AHA is similar [ 86 , 87 ].…”

“…The rest of these cases have been attributed to autoimmune disorders (such as systemic lupus erythematosus and rheumatoid arthritis), hematological malignancies (such as b-lymphoproliferative disorders), solid tumors, infections, drugs, and pregnancy [ 18 , 20 , 21 , 22 ]. Moreover, AHA is characterized by the sudden onset of bleeding, spontaneously or after an invasive procedure, in a patient without a personal or family history of bleeding [ 23 ]. The laboratory confirmation of AHA is established by low FVIII levels and the detection of an anti-FVIII antibody, quantified in Bethesda units (BUs) [ 24 ].…”