A rare case of influenza associated immune thrombotic thrombocytopenia purpura in a pediatric patient Free

Introduction

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare thrombotic microangiopathy (TMA) with “approximately 1 case per 1 million children” [1]. iTTP specifically is due to a deficiency of ADAMTS13 activity (<10%) caused by autoantibodies to ADAMTS13. In children, especially those under the age of 5, iTTP is sometimes misdiagnosed as other TMAs or autoimmune hematologic conditions, delaying appropriate treatment. Influenza has also been noted to be a trigger for TMA [2]. The traditional management of iTTP includes plasma exchange (PLEX) and immunosuppressive therapy, i.e. corticosteroids, and in some cases rituximab. Caplacizumab is a nanobody that inhibits the interaction between von Willebrand factor (vWF) and platelets and is now recognized as an first line treatment in adult iTTP [3]. It is not approved in pediatrics however real world data about its use in the pediatric population has demonstrated its safety [4]. Caplacizumab has been shown to accelerate platelet count recovery, reduce number of PLEX days, and hospital stay.

Methods

We describe the youngest person reported to have influenza associated iTTP and receiving treatment with caplacizumab.

Results

A 2 year and 2-month-old female who initially presented to the emergency department with 2 week history of leg pain, with increased bruising and pallor. Initial vitals taken showed tachycardia in the 150s, elevated blood pressure of 122/95, and tachypneic with a respiratory rate of 32 breaths per minute. Initial lab work was significant for a hemoglobin of 7.5, elevated reticulocyte count of 2.26, platelet count of 11,000, haptoglobin <10, LDH of 1,258, DAT negative and positive schistocytes on a peripheral blood smear. Nasopharyngeal viral PCR was positive for influenza A. She was diagnosed with microscopic angiopathic hemolytic anemia (MAHA) given the above results. With a diagnosis of MAHA and thrombocytopenia without signs concerning for hemolytic uremic syndrome such as bloody stools, kidney injury there was a suspicion of TTP. Given her age hTTP was assumed and plan to proceed with therapeutic plasma exchange (TPE). Prior to treatment with TPE she received two plasma infusions and one red blood cell infusion due to continued dropping numbers while awaiting central line placement. Her platelets had dropped to 4000 prior to receiving plasma infusion and there was no significant improvement in her lab parameters with plasma infusion. At this time her initial lab for ADAMSTS13 had resulted showing low activity. She received 5 days of PLEX where her platelets slowly improved from 15 to 28. On day 6 she lost central line access and due to very slow improvement on PLEX the decision there was suspicion for iTTP. Patient was started on rituximab and caplacizumab while still awaiting the results of her ADAMTS13 antibodies. After 2 doses of caplacizumab her platelets normalized. Prior to discharge labwork resulted demonstrating antibodies to ADAMTS13 confirming the diagnosis of immune mediated TTP. She was discharged home on day 7 of caplacizumab. She was treated with a total of 28 doses of caplacizumab. Our patient is now 6 months out from diagnosis without a relapse.

Conclusion

This case demonstrates the importance of early recognition and prompt management of immune thrombotic thrombocytopenic purpura (iTTP) in the pediatric population where it is often misdiagnosed. It is thought that our patient developed iTTP due to influenza A. The use of caplacizumab in conjunction with plasma exchange, corticosteroids, and rituximab led to rapid clinical improvement and normalization of ADAMTS13 activity. This case adds to the limited but growing body of evidence supporting the potential role of caplacizumab in pediatric iTTP, including in patients as young as 2 years old. Early diagnosis and timely initiation of targeted therapy are critical to improving outcomes and reducing the risk of morbidity and mortality in this vulnerable age group.