key: cord-0749424-rv6at0u6
authors: Candelli, Marcello; Rossi, Elena; Valletta, Federico; De Stefano, Valerio; Franceschi, Francesco
title: Immune thrombocytopenic purpura after SARS‐CoV‐2 vaccine
date: 2021-05-02
journal: Br J Haematol
DOI: 10.1111/bjh.17508
sha: 2a722c8ef9a8ee4bd5d433188a113c01a0a270bb
doc_id: 749424
cord_uid: rv6at0u6

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During the visit to the ED, a complete blood test showed 2 9 10 9 /l platelets (confirmed on citrate blood tube), while white blood cells (WBCs), red blood cells (RBCs) and heamoglobin (Hb) levels were within normal limits, as well as the international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, serum glucose, nitrogen urea, creatinine, sodium, potassium, calcium, total proteins, albumin, glutamate pyruvate transaminase (GPT), lactate dehydrogenase (LDH), total bilirubin, and amylase. A nasopharyngeal swab for SARS-CoV-2 resulted negative. The clinical and laboratory findings being compatible with ITP, treatment with dexamethasone (40 mg/day) was started and the patient was admitted to our Haematology ward. A second complete blood test showed 7 9 10 9 /l platelets, lymphocyte typing tested resulted normal. Protein electrophoresis was negative for any qualitative alteration of gamma-globulins; anti-thrombin, anti-coagulant protein C, free protein S, normalized activated protein C sensitivity ratio, homocysteine, folic acid, vitamin B-12 and C-reactive protein were within the normal limits. High values of blood factor VIII activity (226Á3%) and D-dimer (2270 iu/l) were found. Autoimmune screening tested positive for lupus anti-coagulant (LA) with a dilute Russell viper venom time ratio (DRVVTr) of 1Á78, but negative for anti-cardiolipin antibodies, anti-b2-glycoprotein, anti-thyroglobulin, anti-thyroid peroxidase, anti-neutrophil cytoplasmic anti-bodies (ANCA), rheumatoid factor, and anti-nuclear anti-bodies. Serological tests for hepatitis B virus, hepatitis C virus, cytomegalovirus, Epstein-Barr virus and human immuniodeficiency virus RNA were negative. Urine chemical analysis found traces of RBCs and a chest X-ray resulted normal. Abdominal ultrasound showed normal spleen dimension and morphology, and no alterations to the kidney, urinary tract, biliary tract, liver, or pancreas. During his hospital stay, the patient maintained a good clinical condition, and cutaneous purpura progressively improved. The control blood test after four days of dexamethasone 40 mg/day showed 27 9 10 9 /l platelets and the patient was discharged on 12 March, 2021, with instructions for a short-term outpatient follow-up. After 10 days of follow-up, platelet count was 31 9 10 9 /l, and another cycle of four days of dexamethasone was planned (Fig 2) .

The current SARS-CoV-2 pandemic is cornering the global healthcare system and all countries are committed to a rush to vaccinate most of the population in the shortest possible time. So far, in western countries, four vaccines against Sars-Cov-2 have been approved in Europe. Two of them, adenovirus that has been modified to contain the genetic information for producing the same SARS-CoV-2 spike proteins. Safety studies provided by each pharmaceutical company show how the incidence of severe adverse effects is low and similar between vaccines and placebo groups. Among these, there is no mention of ITP. [2] [3] [4] [5] ITP is an immune-mediated disorder characterized by a low platelet blood count that causes mucocutaneous petechial brush, andrarelyfatal gastrointestinal or cerebral bleedings. Several triggers can induce ITP. Among these, vaccines are thought to act by a viral molecular mimicry. 1 In particular, ITP has been associated with measles-mumps-rubella (MMR) and varicella/zoster vaccines. 1 However, a few cases of ITP following Pfizer-BioNTech and Moderna have been reported recently. 1 Moreover, it has been shown that human adenoviral vectors can induce thrombocytopenia in mice through complex mechanisms involving endothelium, platelets, and macrophages mediated by both Von Willebrand factor and P-selectin. 6 According to the current literature, this is the first case of ITP following the AZD1222 administration. The positivity to LA in our patients is not surprising since it is found in around 15-20% of patients with ITP. The presence of LA, however, may indicate a pre-existing auto-immune coagulation disorder revealed by the administration of the vaccine. The presence of LA, anyway, has to be confirmed after 12 weeks. Our patient presented with a clear condition of thrombocytopenic purpura. Because he had been recently vaccinated against SARS-CoV-2 with AZD1222 vaccine, and after having carefully excluded several alternative etiologies, the diagnosis of AZD1222-induced ITP was suspected. However, we cannot completely rule out the other described mechanisms or the possibility of a random temporal association between the onset of ITP and vaccination. The rarity of these events does not affect, in our opinion, the benefits provided globally by vaccination.

Dr. Marcello Candelli and dr. Federico Valletta wrote the first draft of the paper. Dr. Elena Rossi and Prof. Valerio De Stefano revised the manuscript critically for important intellectual content. Prof. Francesco Franceschi supervised and wrote the final draft of the paper. All authors approved the submitted version of the paper.

The authors report no conflicts of interest for the submitted manuscript.

The conduct of this research did not need external financial support.

Written consent for publication and the use of personal data and pictures was obtained from the patient involved. 

Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination

C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine

Oxford COVID Vaccine Trial Group. Safety and efficacy of the ChA-dOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK

COVE Study Group. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine

Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine

Adenovirus-induced thrombocytopenia: the role of von Willebrand factor and Pselectin in mediating accelerated platelet clearance