Page 13 - 2021_06-Haematologica-web

Editorials
the knowledge of VITT, which, however, still remains poorly defined because many questions await to be answered. First and foremost, how common is this com- plication after vaccination with ChAdOx1 nCoV-2? At present, a total of only 49 cases have been described and the disease therefore appears exceptionally rare consider- ing that millions of people have received this drug. However, VITT was only identified in April 2021 and, therefore, its diagnosis was impossible prior to this date and, hence, this complication may currently be greatly underreported.
As of 4 April 2021, a total of 169 cases of CVST and 53 cases of splanchnic vein thrombosis were reported to EudraVigilance in around 34 million people vaccinated in the EEA and UK (Europenan Medicine Agency).6 How many of these patients had VITT? Furthermore, the diag- nosis of cerebral venous sinus and splanchnic vein throm- bosis is not always easy, and we cannot exclude that their occurrence has so far been underestimated. We fear that the number of cases of VITT reported after the ChAdOx1 nCoV-19 vaccine will augment in the coming months, as specific testing for anti PF4-polyanion complexes will be increasingly applied to clinically suspected cases.
Another important question is whether VITT is caused only by the ChAdOx1 nCoV-19 vaccine or may be trig- gered by other adenoviral vaccines. The answer to this question was given by a paper7 published at the end of April 2021 that described 12 patients who developed a disease with the clinical and laboratory characteristics of VITT 5 to 26 days after vaccination with Ad26.COV2.S COVID-19 (Johnson & Johnson/Janssen). This drug, too, uses a human adenoviral vector, which, however, differs in many respects from that used by the ChAdOx1 nCoV- 19 vaccine. It is, therefore, possible that the risk of VITT is a common feature of drugs that use adenoviral vectors. It is important at this point to emphasize that adenoviral vectors are presently employed not only for vaccines against SARS-CoV-2 and EBOLA,8 but they are under investigation for vaccines against other infectious dis- eases,8 for cancer immunotherapy9 and for gene therapy of inherited disorders.10 Should it be shown that the risk of VITT is intrinsic to different adenovirus-based treat- ments, the risk-benefit ratio would be completely differ- ent if this approach is used to treat cancer or to prevent an infectious disease that has a mortality of about 1-2% (and in some age groups very close to 0%).
A final question is how to treat patients with VITT. Clinicians who have reported their experience in this field have generally suggested avoiding the use of heparin and platelet transfusions, given to correct the
profound thrombocytopenia and associated cerebral hemorrhage. Instead, they believe that non-heparin anti- coagulants and high-dose intravenous immunoglobulin could have some efficacy. These recommendations are mainly based on previous experience with heparin- induced thrombocytopenia and heparin-induced autoim- mune thrombocytopenia, and are currently only anec- dotal experiences suggesting their use in VITT. A better understanding of the pathogenic mechanisms of VITT and prospective clinical studies are required to identify the best treatment for VITT, which is a rare or even very rare disease. Only large international collaborations will be able to ensure the provision of credible results in a short time. Furthermore, it has not been established if these treatments are also appropriate for any atypical thrombosis after vaccination, particularly in the absence of the specific laboratory features of VITT. A long way of laboratory and clinical research lies ahead.
Disclosures
No clonflicts of interest to disclose.
References
1.Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov- 19 Vaccination. N Engl J Med. 2021;384(22):2092-2101.
2. Schultz NH, Sørvoll IH, Michelsen AE, et al. Thrombosis and throm- bocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(22):2124-2130.
3. Scully M, Singh D, Lown R, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021;384(23):2202-2211.
4. Althaus K, Möller P, Uzun G, et al. Antibody-mediated procoagulant platelets in SARS-CoV-2-vaccination associated immune thrombotic thrombocytopenia. Haematologica. 2021;106(8):2170-2179.
5. Pomara C, Sessa F, Ciaccio M, et al. Post-mortem findings in vaccine- induced Thrombotic Thombocytopenia. Haematologica. 2021;106 (8)2291-2293.
6.European Medicines Agency. AstraZeneca’s COVID-19 vaccine: EMA finds possible link to very rare cases of unusual blood clots with low blood platelets. https://www.ema.europa.eu/en/news/ astrazenecas-covid-19-vaccine-ema-finds-possible-link-very-rare- cases-unusual-blood-clots-low-blood. Accessed 11 May 2021
7. See I, Su JR, Lale A, et al. US Case Reports of Cerebral Venous Sinus Thrombosis With thrombocytopenia after Ad26.COV2.S vaccina- tion, March 2 to April 21, 2021. JAMA. 2021 Jun 22;325(24):2448- 2456
8. Tomori O, Kolawole MO. Ebola virus disease: current vaccine solu- tions. Curr Opin Immunol. 2021;71:27-33.
9.Tessarollo NG, Domingues ACM, Antunes F, et al. Nonreplicating adenoviral vectors: improving tropism and delivery of cancer gene therapy. Cancers (Basel). 2021;13(8):1863.
10.van Haasteren J, Li J, Scheideler OJ, Murthy N, Schaffer DV. The delivery challenge: fulfilling the promise of therapeutic genome edit- ing. Nat Biotechnol. 2020;38(7):845-855.
haematologica | 2021; 106(8)
2041