Catastrophic antiphospholipid syndrome with Epstein-Barr virus-associated hemophagocytosis: A clinicopathological conference.

Catastrophic antiphospholipid syndrome (CAPS) is a severe variant of antiphospholipid syndrome associated with multiorgan thrombosis in a short term. We present the case of a 14-year-old immunocompetent girl who developed renal, intestinal, and pulmonary infarction; thrombocytopenia; and hemolytic anemia within 1 week. She was diagnosed with thrombotic microangiopathy. Hence, plasma exchange and corticosteroid therapy were initiated, which improved thrombocytopenia. However, the patient's platelet count decreased. Her general condition gradually worsened with eventual death. An autopsy revealed multiple infarctions in the kidneys bilaterally, jejunum, ileum, and pulmonary parenchyma. Microthrombi were not detected. Massive hemophagocytosis was observed in the splenic pulp, lymph nodes, and bone marrow. Several Epstein-Barr viruses (EBVs)-encoded small ribonucleic acid (RNA)-positive lymphocytes were also found in the bone marrow. The presence of antibodies to both viral capsid antigen-immunoglobulin G and EBV nuclear antigen indicated past infection. Antiphospholipid antibody was positive after her death. The patient was finally diagnosed with CAPS and EBV-associated hemophagocytosis, possibly due to EBV reactivation. Establishing a clinical diagnosis of CAPS was relatively difficult because two different causes of thrombocytopenia, CAPS and hemophagocytosis, led to a difficulty in understanding this case's pathogenesis.

Hemophilic pseudotumor of the maxillary sinus in an inhibitor-positive patient with hemophilia A receiving emicizumab: a case report.

A 14-year-old inhibitor-positive male patient with severe hemophilia A and severe psychomotor disability was admitted due to left buccal swelling and impaired downward movement of the left eye. He had been on noninvasive positive-pressure ventilation (NPPV) through a nasal mask for upper airway obstruction. The patient began to have repeated epistaxis 16 months after initiation of treatment with 6 mg/kg Q4W of emicizumab, and was thus administered a bypassing agent. Left buccal swelling and impaired downward movement of the left eye appeared during the subsequent month. Imaging examination revealed a mass in the left maxillary sinus and bone destruction. Endoscopic tumor resection and tracheostomy were performed using recombinant activated factor VII. NPPV was discontinued thereafter. Pathological examination revealed that the mass was a hemophilic pseudotumor (HP). After discharge the emicizumab-regimen dose was changed to 3 mg/kg, Q2W to increase serum emicizumab levels. No recurrent HP or bleeding requiring treatment was observed. Pressure applied to the damaged nasal mucosa by NPPV was suspected as the main cause of HP development. If a mass is observed in a patient with hemophilia, HP should be considered as a possible diagnosis even if the patient is receiving emicizumab.

[Acquired hemophilia A with reappearance of inhibitor 10 years after the completion of immunosuppressive therapy].

Acquired hemophilia A (AHA) is a disease that causes severe bleeding with the appearance of an inhibitor (INH) against blood coagulation factor VIII (FVIII). The prevalence of this condition is low; it occurs in only one in one to four million people per year; however, the number of diagnosed cases has increased in recent years owing to the greater awareness of the disease. It is noteworthy that this is a hemorrhagic disease that suddenly develops in the elderly. AHA treatment is divided into hemostatic treatment for bleeding and immunosuppressive therapy (IST) for removing FVIII-INH. As long as FVIII-INH remains, there is a risk of fatal bleeding; therefore, it is desirable to start IST soon after diagnosis. However, the use of immunosuppressive drugs for the elderly is often challenging due to concerns about adverse events, such as infectious diseases that have a considerable impact on prognosis. Ten years after the end of IST, we managed the case of a patient with AHA who had a relapse of FVIII-INH at the age of 84 years. In this case, relapse was detected early when there was no bleeding symptom, and remission was rapidly achieved with a small amount of IST without any adverse effects. There are few reports on AHA relapse; we believe that the present report will contribute meaningfully to the literature on this subject and would be useful when considering the long-term management of AHA.

Long-term safety and efficacy of emicizumab for up to 5.8 years and patients' perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A.

INTRODUCTION: Safety and efficacy results of the phase 1 study and phase 1/2 extension study of the bispecific antibody emicizumab in patients with severe haemophilia A with or without factor VIII inhibitors for up to 2.8 years were reported previously. AIM: To evaluate further longer-term data including patients' perceptions at study completion. METHODS: Emicizumab was administered subcutaneously once weekly at maintenance doses of 0.3, 1 or 3 mg/kg with potential up-titration. All patients were later switched to the approved maintenance dose of 1.5 mg/kg. RESULTS: Eighteen patients received emicizumab for up to 5.8 years. Most adverse events were mild and unrelated to emicizumab. Annualized bleeding rates (ABRs) for bleeds treated with coagulation factors decreased from pre-emicizumab rates or remained zero in all patients. The median ABRs were low at 1.25, 0.83 and 0.22 during the 0.3, 1 and 3 mg/kg dosing periods, respectively. Of 8 patients who decreased their doses from 3 to 1.5 mg/kg, ABRs decreased in 4, remained at zero in 2, and increased in 2. Total time spent with symptoms associated with treated bleeds decreased in all patients except 2. All patients answered 'improved' for bleeding severity and time until bleeding stops, except 1 answering 'slightly improved'. Most patients answered 'improved' or 'slightly improved'' for daily life and feelings; in particular, all patients except 1 answered 'improved' or 'slightly improved' for anxiety. CONCLUSIONS: Long-term emicizumab prophylaxis for up to 5.8 years was safe and efficacious, and may improve patients' daily lives and feelings, regardless of inhibitor status.

Chronic mandibular osteomyelitis caused by Granulicatella adiacens in an immunocompetent child.

We report a pediatric case aged 10 years with Granulicatella adiacens-associated chronic mandibular osteomyelitis. The causative pathogen was uncertain because polymicrobial species were detected from the bacterial culture in bone marrow fluid. In contrast, G. adiacens was predominantly identified in the clone library analysis of the bacterial 16S rRNA gene sequence. Vancomycin to which G. adiacens was reported to be susceptible was not administrated sufficiently to this patient because of its adverse event, whereas linezolid and ciprofloxacin was alternatively effective for the treatment of chronic mandibular osteomyelitis.

[A Pediatric Case of Acquired Hemophilia A: The Usefulness of the Activated Partial Thromboplastin Time (APTT) Cross-Mixing Test for Early Diagnosis].

Acquired hemophilia A (AHA), a bleeding disorder caused by autoantibodies against FVIII, has the potential for life-threatening bleeding. The annual onset rate is said to be one in 4 million people, but diagnosis examples increase in adults because a disorder concept penetrated. AHA is quite rare in children, with an incidence rate of 0.045 per 1 million, but early detection is crucial because serious bleeding can happen, as in adults. We report a pediatric case who received an early diagnosis of AHA by an activated partial thromboplastin time (APTT) cross-mixing test. The 12-year-old girl had neither a past history nor a family history of bleeding episodes. She presented with intramuscular bleeding and epistaxis without trauma or medication. At diagnosis, her blood test showed prolonged APTT. Other hemostatic tests, such as the platelet count, prothrombin time and fibrinogen concentration, were within the normal range. We administered an APTT cross-mixing test that detected an inhibitor pattern and inhibitory antibodies against factors VIII. As a result, we administered prednisolone and the inhibitor disappeared after 1.5 months. In conclusion, AHA is a bleeding disorder which should be considered even in children due to the potential for life-threatening bleeding. Furthermore, the APTT cross-mixing test is useful for screening coagulation factor deficiencies and inhibitors.