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VITT Is a HITT

December 11, 2022

Lately, VITT has been a hit in the hematology world. VITT, formally known as “vaccine-induced thrombosis and thrombocytopenia,” is a rare acute procoagulant syndrome associated with COVID-19 adenoviral vector-based vaccines (AstraZeneca and Johnson & Johnson vaccines, in particular). Though its incidence remains exceedingly low, VITT has garnered significant enthusiasm in the past year. With universal vaccinations resulting in hundreds of cases worldwide, the need for educational clarity surrounding VITT is paramount. Rest assured, this year’s ASH annual meeting has you covered.

Now, you may be thinking to yourself, “all this talk about VITT sounds remarkably familiar.” If so, you are not alone! We’ve encountered this before, albeit in a slightly different form: heparin-induced thrombocytopenia and thrombosis (HITT). In fact, VITT, like HITT, is a type of platelet factor 4 (PF4)-mediated thrombosis  that shares clinical and pathophysiologic characteristics of HITT. In other words, VITT truly is a HIT(T)!

In the Scientific Spotlight Session, Drs. Vivien Chen and Jonathan Coutinho will delve into the complex vascular biology and unique clinical findings of this novel, and increasingly mysterious disorder. Dr Chen illustrates the detailed, highly pathogenic mechanism of platelet and pan-cellular activation by anti-PF4 antibodies in response to vaccination. Activated platelets, neutrophils, monocytes, and endothelial cells trigger the coagulation cascade that results in pronounced thrombosis and coagulation factor consumption, often in highly unusual locations such as the splanchnic veins and/or cerebral venous sinuses. Dr. Coutinho further describes the unique molecular and anatomical features of the cerebral venous sinuses that may contribute to their predilection for thrombosis in VITT. These valuable and distinct insights into the cerebral vasculature have potentially significant ramifications for treatment targets in the future.

The next Scientific Spotlight Session turns the clock back — way back, to a time before vaccinations; that is, the in utero origin of childhood leukemia and myeloproliferative neoplasms. Make no mistake: some of the crowning achievements of 21st century hematology are the extraordinary breakthroughs in the treatment of pediatric blood cancers like acute lymphoblastic leukemia (ALL), which now boasts a five-year survival rate of more than 90 percent. Despite these remarkable advancements, ALL diagnosed in infancy remains a devastating illness with poor survival. However, research focusing on the complex properties of fetal cells that contribute to malignant transformation is rapidly growing, and the results speak for themselves.

Dr. Anindita Roy will review the molecular and genetic factors, that give rise to ALL in infants. Dr. Roy will highlight the role of MLL fusion proteins, the most common being the MLL-AF4 fusion protein, in promoting the development of an aggressive and treatment-resistant form of infant-ALL. In infants, a single mutation in utero appears to be enough to induce this dismal manifestation of ALL; however, in older children, a second mutation is typically acquired postnatally before ALL develops. What underlies this stark difference between infant-ALL and childhood-ALL? Why is infant-ALL, with its aggressive, treatment-resistant clinical presentation, the product of merely one MLL rearrangement?

The answer, Dr, Roy posits, is hidden in the fetal progenitors — the primary hematopoietic cells in utero — in which the MLL translocations first arise. If we can understand how the MLL-AF4 fusion protein induces fetal-specific gene expression in these progenitor cells, perhaps we can unlock the door to curing infant-ALL once and for all.

Dr Jyoti Nangalia, rounds out this back-to-the-future Scientific Spotlight Session with an exploration into the fetal origins of myeloproliferative neoplasms. Dr Nangalia uses whole genome sequencing and demonstrates that adult myeloproliferative neoplasms are often born out of early mutations in childhood and gestation. We all know about the role of the JAK2 mutation in polycythemia vera, primary myelofibrosis and essential thrombocythemia, but did you know that driver mutations in JAK2 can arise at as early as 33 weeks gestation? This novel insight into the development of adult myeloproliferative neoplasms may soon influence how we detect and treat these disorders.

VITT is a hit, and gestation is a fascination. With cutting-edge research on the cusp of great new discoveries, be on the lookout at this year’s meeting for some fascinating spotlights on the latest news in hematology.


Dr. Jonathan Hermel and Dr. David Hermel indicated no relevant conflicts of interest.

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