Acquired hemophilia A that required surgical hemostasis of hematomas occupying oral cavity: a case report

Background Acquired hemophilia A is a rare coagulopathy caused by inhibitors of blood coagulation factor VIII. Patients with acquired hemophilia A have a higher mortality risk (5–10%) than those with congenital hemophilia. Moreover, there is no established evidence of management recommended for patients with acquired hemophilia A. Previous studies have reported the presence of hematomas in the oral cavities of patients with acquired hemophilia A, which were treated conservatively. Here, we describe the case of a patient with acquired hemophilia A, where emergency surgical hemostasis was required for large intraoral hematomas. Case presentation A 65-year-old Japanese man was referred to our hospital with a chief complaint of bleeding from large intraoral hematomas. On examination, he could not close his mouth because of the hematomas, which were bleeding spontaneously. Computed tomography angiography revealed no evidence of arteriovenous malformation, and blood test results showed that the activated partial thromboplastin time was elevated beyond the normal limit. To avoid a life-threatening hemorrhage from hematomas, emergency surgical hemostasis was performed with nasotracheal intubation using fiberoptic bronchoscopy. Hemostasis was successfully performed, as the hematomas were carefully removed. Moreover, the clinical course was successfully completed using intravenously administered activated prothrombin complex concentrate for hemostasis after operation. Conclusions Acquired hemophilia A can cause a life-threatening hemorrhage without predictive factors. Intraoral hematoma may cause airway obstruction. There is no consensus regarding the management of hemorrhage in patients with acquired hemophilia A. As shown here, exophytic hematomas in the oral cavity can be safely removed and nasotracheal intubation with fiberoptic bronchoscopy may be useful in patients with coagulopathy disease.

Investigation of the Optimal Dose aPCC in Reversing the Effect of Factor Xa Inhibitors—An In Vitro Study

Factor (F) Xa inhibitors are safe and effective alternatives to warfarin. There are concerns about the lack of a reversal strategy in case of serious bleeds or need for emergency surgery in situations when the antidote andexanet alfa is not available. Factor concentrates are widely used, but there are few clinical studies regarding the reversal effect of activated prothrombin complex concentrate (aPCC). Because of the feared thrombogenicity, administration of the lowest effective dose would be desirable. To determine the lowest concentration of aPCC sufficient to reverse the effect of rivaroxaban and apixaban. Blood from 18 healthy volunteers were supplemented with apixaban or rivaroxaban. aPCC was added to obtain 10 different concentrations ranging from 0.08-1.60 U/mL. Thromboelastometry and thrombin generation assay were used to assess the reversal effect. aPCC concentrations of 0.08 and 0.16 U/mL restored thromboelastometry clotting time to baseline in apixaban ( P = 1.0) and rivaroxaban ( P = 1.0)-containing samples, respectively. The concentrations 0.08 U/mL ( P = 0.5) and 0.24 U/mL ( P = 0.2) were sufficient to restore thrombin generation. Concentrations of 0.56 U/mL and higher, caused significantly higher ETP than baseline in apixaban-containing samples ( P < 0.05). aPCC concentrations lower than previously reported were effective in reversing the effect of FXa inhibitors in vitro.

Long-term outcomes with emicizumab prophylaxis for hemophilia A with/without FVIII inhibitors from the HAVEN 1-4 studies

Prophylaxis with emicizumab-a subcutaneously administered, bispecific, humanized, monoclonal antibody-promotes effective hemostasis in persons with hemophilia A (PwHA). The primary efficacy, safety and pharmacokinetics of emicizumab were reported previously, but long-term data were limited. Here, data from 401 pediatric and adult PwHA with/without factor VIII inhibitors who were enrolled in the Phase III HAVEN 1, HAVEN 2, HAVEN 3, and HAVEN 4 studies have been pooled to establish a long-term efficacy, safety and pharmacokinetic profile. Across a median (interquartile range) efficacy period of 120.4 (89.0-164.4) weeks (data cut-off May 15, 2020), the model-based treated annualized bleed rate (ABR) was 1.4 (95% confidence interval, 1.1-1.7). ABRs declined and then maintained at &lt;1 in an analysis of 24-week treatment intervals; at Weeks 121-144 (n=170) the mean treated ABR was 0.7 (0-5.0). During Weeks 121-144, 82.4% of participants had zero treated bleeds, 97.6% had ≤3 treated bleeds, and 94.1% reported zero treated target joint bleeds. Bleeding into target joints decreased substantially. Emicizumab was well tolerated, and no participants discontinued due to adverse events beyond the five previously described. This data-cut includes the previously reported 3 thrombotic microangiopathies (1 in the PwHA with fatal rectal hemorrhage), and 2 thromboembolic events, all associated with activated prothrombin complex concentrate use; and additionally, a myocardial infarction and a venous device occlusion. With 970.3 patient-years of exposure, emicizumab prophylaxis maintained low bleed rates in PwHA of all ages with/without FVIII inhibitors and remains well tolerated, with no new safety concerns identified. Clinical trials registered as NCT02622321, NCT02795767, NCT02847637, NCT03020160.

Critical Bleeding in Acquired Hemophilia A: Bypassing Agents or Recombinant Porcine Factor VIII?

Acquired hemophilia A (AHA) is caused by autoantibodies neutralizing coagulation factor VIII (FVIII). In the presence of inhibitors against FVIII, acute bleeds can be managed with bypassing agents, including recombinant factor VIIa (eptacog alfa activated, NovoSeven) and activated prothrombin complex concentrate (FEIBA), as well as recombinant porcine FVIII (susoctocog alfa, Obizur). Studies comparing these agents directly are not available, and indirect evidence suggests an overall similar efficacy. Selecting an agent in clinical practice therefore depends on (1) availability of agent, (2) safety profile, (3) monitoring requirements, (4) cost, and (5) personal experience. This review examines available data and collects additional considerations to support decision making for bleeding emergencies in AHA.