Unusual Bleeding in a Patient after Bone Marrow Transplantation Caused by Acquired Deficiency of Coagulation Factors IX and XI

A 7.5-year-old boy reported here had received a bone marrow transplantation (BMT) for high-risk AML (FAB M5, CNS negative, complex aberrant karyotype), primary diagnosis in May 2018. Chemotherapy was performed according to the protocol of AML BFM 2012 in the high-risk group. His BMT from a 12/12 HLA-identical unrelated donor was given in September 2018. As posttransplant complications, he suffered from arterial hypertension, rhinovirus upper airway infection, hemorrhagic cystitis (BK virus) treated with cidofovir, and steroid refractory acute graft-versus-host disease (GVHD) of skin maximal Grade 3, intestinal maximal Grade 3, liver maximal Grade 0. The GVHD was treated with prednisone in October until December 2018, ruxolitinib in November 2018, a change from cyclosporine A to tacrolimus since November 2018, extracorporeal photophoresis (ECP) beginning in November 2018 (9 cycles), oral budesonide in November and December 2018, and adalimumab weekly starting end of November 2018. Adenovirus infection and EBV reactivation were treated with cidofovir and rituximab, respectively.

At the end of December 2018, he suffered from epistaxis with Hb-relevant bleeding after nose picking and from uncontrollable bleeding after a bone marrow aspiration in beginning of January 2019. Later, spontaneous hematomas on his lower legs appeared. A newly acquired prolongation of his aPTT from 26 to 70 seconds was seen which was, on further analysis, due to an acquired deficiency of factors IX (5.1%) and XI (<1%). The plasma mixing trial was highly pathological. Inhibitor testing showed a FIX inhibitor of 0.6 BU and a FXI inhibitor of 1.7 BU. For necessary invasive procedures, a preventive substitution of rFVIIa was used successfully to prevent bleeding. Over 8 months, factor activities recovered spontaneously to FIX 72% and FXI 45% with FIX inhibitor of <0.6 BU and FXI inhibitor of 0.7 BU. Clinical bleeding tendency disappeared.

Acquired hemophilia or inhibitor-mediated factor deficiency is very uncommon in childhood. Inhibitory antibodies—especially against factor VIII—were described on the basis of autoimmune (SLE, RA) or lymphoproliferative diseases, multiple sclerosis, GVHD after allogeneic BMT, asthma, inflammatory bowel disease, pemphigus, and after treatment with a variety of antibiotics. In adults, acquired factor deficiency has a biphasic age distribution with a small peak in young postpartum women and a major peak at 60 to 80 years of age.

Publication History

Article published online:
13 November 2020