"a Needle in a Haystack". Let´s Talk about Acquired Hemophilia in Pediatrics

Introduction

Acquired hemophilia (AH) is a rare disorder due to the production of autoantibodies against factor VIII or IX procoagulant function. The development of these autoantibodies results in hemorrhagic symptoms in patients without previous coagulopathy. The typical clinical manifestations of the acquired hemophilia are: extensive cutaneous purpura and internal hemorrhages while hemarthrosis are not common. Acquired hemophilia is less frequent than the inherited form of the disease, with an estimated incidence of 2 to 4 cases/million inhabitants/year, value that increases with age, but is extremely infrequent in children (0.045 cases/million/year). It affects all ethnic groups and has a biphasic distribution with a peak incidence in subjects between 20 and 30 years and another peak between 60 and 80 years.

Objective

To report a case of AH in a 2-year-old child.

• Clinical data: Hematoma in the left iliac flank, forearm and legs.

• Personal history: Otherwise healthy 2-year-old boy with a twin brother and both parents without a history of bleeding disorders. Prior to the onset of bruising, the patient suffered an important trauma on one foot without bleeding complications.

A short time after this episode he presented a hematoma in the gluteus that was interpreted as result of a slight trauma due to a fall. Subsequently, he presented multiple spontaneous hematomas that motivate the consultation.

• Laboratory upon admission: Hemoglobin: 12.8g/dL; PT: 11" (Control: 11"); APTT:>180" (Control: 30"). Plt: 543000/mm3

• Clinical evolution: With the suspicion of bleeding reactivation, he was referred to the Rosario Hemophilia Foundation to be evaluated. Reactivation of bleeding was ruled out and imaging had shown subcutaneous bleeding without muscle involvement. The presence of an inhibitor to Factor VIII was detected. The patient was commenced on Prednisolone 1mg/kg/day to eradicate the acquired antibody.

• Laboratory Results: Hb: 12.6 g/dL, Plt: 575000/mm3, PT: 12" (11") (Innovin), APTT: 76" (30") (Actin FSL) which does not normalize after addition of normal plasma and potentiate when was incubated 2 hours at 37°C, TT: 14"(14") (Trombin), FVIII <1%, FIX 45%, FXI 80% (Siemens), the dilution curves of FVIII and FIX rule out the presence of an inhibitor of interference. Lupus Anticoagulant was negative. The inhibitor titer was quantified by the Nijmegen-Bethesda Assay and was 32 UNB/mL.

Conclusions

AH is a rare autoimmune disease first described in 1940 and is extremely infrequent in children younger than 16 years. Although it is usually associated with other autoimmune disorders, in our patient, we have not found other autoimmunity markers. We should suspect this pathology in all patients who begin with cutaneo-mucosal bruising without a previous history of bleeding, with prolonged APTT that does not correct with the addition of normal plasma and whose prolongation potentiates after incubating the mixture for 2 hours at 37˚C. These results are usually associated with PT and normal platelets count. The FVIII inhibitor can be quantified by the Bethesda-Nijmegen method. Although the title of the Inhibitor does not correlate well with the clinical severity of the patient, its value is useful in monitoring the immunosuppressive therapeutic response. Finally, although AH is unusual in pediatrics, it must be taken into account among the differential diagnoses.