A previously healthy 12-year-old boy developed petechiae and a small haematoma approximately one week after the onset of a respiratory infection. Initial investigations showed severe thrombocytopenia, markedly elevated D-dimer concentrations and hypofibrinogenaemia. Further analyses demonstrated strongly positive anti–platelet factor 4 (PF4)–heparin IgG antibodies and PF4-dependent platelet-activating antibodies, supporting the diagnosis of virus-induced immune thrombocytopenia and thrombosis.
During hospitalisation, the patient developed left iliofemoral deep-vein thrombosis and bilateral peripheral pulmonary emboli. Adenovirus was isolated from a nasopharyngeal sample, and sequencing identified human adenovirus type B3 (HAdV-B3). The anti-PF4 antibodies showed the characteristic VITT clonotype, including the somatic K31E hypermutation in the IGLV3-21*02 light chain, establishing a mechanistic link with vaccine-induced immune thrombocytopenia and thrombosis (VITT). The patient also carried a heterozygous factor V Leiden mutation.
Initial prednisolone administration was discontinued and treatment with intravenous immunoglobulin and rivaroxaban was initiated. Platelet counts rapidly improved, but as thrombosis progressed into the lower-limb veins, a second cycle of intravenous immunoglobulin was necessary. At follow-up after 389 days, the patient was asymptomatic, although residual thrombosis of the iliac veins persisted with partial recanalisation.
This case provides direct evidence that natural adenovirus infection can trigger a VITT-like anti-PF4 immune response through a mechanism involving somatic hypermutation and molecular mimicry between the adenoviral core protein VII (pVII) and PF4. It highlights the importance of considering virus-induced immune thrombocytopenia and thrombosis in patients with thrombocytopenia, high D-dimer concentrations and thrombosis following adenovirus infection. Furthermore, the case underscores the value of isolating and sequencing the causative adenovirus, both to define VITT-relevant pVII motifs and to guide the future design of safer adenoviral vector platforms.
Original article:
Irsara C, Benainouna H, Wang JJ, et al. Human Adenovirus B3–Induced Immune Thrombocytopenia and Thrombosis. New England Journal of Medicine. 2026;395:1136–1138. doi:10.1056/NEJMc2605960.