Hematology in the post-COVID era: spotlight on vaccine-induced immune thrombotic thrombocytopenia and a conceptual framework (the 4P’s) for anti-PF4 diseases

Review

Author: Revilla, Ryan ; Arnold, Donald M. ; Hack, Michael ; Nazy, Ishac ; Gabarin, Nadia

INTRODUCTIONVaccine-induced immune thrombotic thrombocytopenia (VITT) is a life-threatening prothrombotic disorder first identified following the introduction of adenoviral vector vaccines for COVID-19. The condition is characterized by anti-PF4 antibodies and clinically presents with thrombocytopenia and thrombosis often in unusual anatomical sites.AREAS COVEREDIn this review, we discuss the clinical presentation, diagnostic testing, and treatment of VITT. We also review VITT-like syndromes that have been described in patients without previous vaccination. We propose a conceptual framework for the mechanism of anti-PF4 diseases that includes sufficiently high levels of PF4, the presence of a Polyanion that can form immune complexes with PF4, a Pro-inflammatory milieu, and an immunological Predisposition - the 4Ps.EXPERT OPINIONSignificant progress has been made in understanding the characteristics of the VITT antibody and in testing methods that can confirm that diagnosis. Future work should be directed at understanding long-term outcomes, mechanisms of thrombosis, and individual risk factors for this rare but dangerous immune-thrombotic disease.

01 Dec 2023·Journal of Thrombosis and Haemostasis

Fibrinogenolysis and fibrinolysis in vaccine-induced immune thrombocytopenia and thrombosis

Article

Author: Watson, Henry G ; Narwal, Anuj ; West, Eric ; Whyte, Claire S ; Page, Andrew R ; Mutch, Nicola J ; Bagot, Catherine N ; Martin, Jill ; Simpson, Megan

BACKGROUNDVaccine-induced immune thrombocytopenia and thrombosis (VITT) is a rare syndrome associated with adenoviral vector vaccines for COVID-19. The syndrome is characterized by thrombosis, anti-platelet factor 4 (PF4) antibodies, thrombocytopenia, high D-dimer, and hypofibrinogenemia.OBJECTIVESTo investigate abnormalities in fibrinolysis that contribute to the clinical features of VITT.METHODSPlasma samples from 18 suspected VITT cases were tested for anti-PF4 by ELISA and characterized as meeting criteria for VITT (11/18) or deemed unlikely (7/18; non-VITT). Antigen levels of PAI-1, factor XIII (FXIII), plasmin-α₂antiplasmin (PAP), and inflammatory markers were quantified. Plasmin generation was quantified by chromogenic substrate. Western blotting was performed with antibodies to fibrinogen, FXIII-A, and plasminogen.RESULTSVITT patients 10/11 had scores indicative of overt disseminated intravascular coagulation, while 0/7 non-VITT patients met the criteria. VITT patients had significantly higher levels of inflammatory markers, IL-1β, IL-6, IL-8, TNFα, and C-reactive protein. In VITT patients, both fibrinogen and FXIII levels were significantly lower, while PAP and tPA-mediated plasmin generation were higher compared to non-VITT patients. Evidence of fibrinogenolysis was observed in 9/11 VITT patients but not in non-VITT patients or healthy controls. Fibrinogen degradation products were apparent, with obvious cleavage of the fibrinogen α-chain. PAP complex was evident in those VITT patients with fibrinogenolysis, but not in non-VITT patients or healthy donors.CONCLUSIONVITT patients show evidence of overt disseminated intravascular coagulation and fibrinogenolysis, mediated by dysregulated plasmin generation, as evidenced by increased PAP and plasmin generation. These observations are consistent with the clinical presentation of both thrombosis and bleeding in VITT.

01 Aug 2023·Dermatologie (Heidelberg, Germany)

[Recurrent livedo-like skin lesions following a vector-based COVID-19 vaccine].

Article

Author: Arbab, Emad ; Kränke, Teresa ; Legat, Franz ; Kränke, Birger ; Cerpes, Urban

Starting in 2020, the global health system faced unprecedent challenges due to the coronavirus disease 2019 (COVID-19) pandemic and the consequences are still felt. All the more fascinating and of particular importance for health policy was the development of potent vaccines within about one year by several research groups after the first reports of COVID-19 infections. To date, three types of COVID-19 vaccines are available, i.e., messenger RNA-based vaccines, adenoviral vector vaccines, and inactivated whole-virus vaccines. We report a woman who developed reddish, partially urticarial skin lesions on her right arm and flank shortly after the first dose with the corona vaccination from AstraZeneca/Oxford (ChAdOx1). The lesions were transient, however reoccurred in loco and at other locations over several days. The clinical presentation was unusual and was correctly assigned due to the clinical course.

100 Deals associated with Adenoviral vector gene therapy(Institut Gustave Roussy EURL)

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