Severe, Refractory Immune Thrombocytopenia Occurring After SARS-CoV-2 Vaccine

Abstract

The rollout of the SARS-CoV-2 vaccine is underway, and millions have already been vaccinated. At least 25 reports of “immune thrombocytopenia” (ITP) or “thrombocytopenia” following the Moderna or Pfizer vaccine have been added to the Vaccine Adverse Event Reporting System (VAERS) in the US. ITP is a rare but known complication of several vaccinations. SARS-CoV-2 vaccine is new, with a novel mechanism of action, and understanding the epidemiology, clinical manifestations, treatment success and natural history of post-vaccination thrombocytopenia is evolving. We report a 74-year-old man who developed refractory thrombocytopenia within one day of receiving the Moderna SARS-CoV-2 vaccine. Several hours after vaccination, he developed significant epistaxis and cutaneous purpura. Severe thrombocytopenia was documented the following day, and he developed extremity weakness and encephalopathy with facial muscle weakness. Over a 14-day period, thrombocytopenia was treated first with high dose dexamethasone, intravenous immunoglobulin, platelet transfusions, rituximab, plasma exchange (for presumed acute inflammatory demyelinating polyneuropathy (AIDP)), and four daily doses of the thrombopoietin receptor agonist (TPO-RA) eltrombopag (Promacta™), without a platelet response. Three days later, he received the TPO-RA romiplostim (Nplate™). Five days later, his platelet count began to rise and by post-vaccination day 25, his platelet count was in the normal range. Thrombocytopenia was refractory to frontline and second-line treatment. The eventual rise in his platelet count suggests that one or both TPO-RAs may have impacted platelet recovery. Possibly, but less likely given the temporality, the drug-induced thrombocytopenia was subsiding. The aggressive use of immunosuppressive treatment may jeopardize the intended purpose of the SARS-CoV-2 vaccine, and earlier use of non-immunosuppressive second-line treatment for vaccine-related severe thrombocytopenia, such as with TPO-RAs, should be considered. While it is imperative to continue the global vaccination program, vigilance to the occurrence of post-vaccination severe thrombocytopenia is warranted.

Attention all anti-vaccinators: The cutaneous adverse events from the mRNA COVID-19 vaccines are not an excuse to avoid them!

“…The temporal associations in these studies may suggest immune-mediated platelet destruction following the Covid-19 vaccine, 36 , 37 , 38 as has previously been shown following rubella and influenza vaccines. 42 , 43 However, given the overall rarity, authors have also considered that underlying autoimmune conditions or idiopathic causes may play a role.…”

“…Authors have less frequently noted cases of more unusual cutaneous reactions to the Covid-19 vaccines, including erythromelalgia, 6 herpes zoster, 6 , 13 , 14 , 28 , 29 erythema multiforme, 6 , 30 , 31 reactions to dermatological fillers, 6 , 32 pernio/chilblains, 6 , 33 vasculitis, 6 , 34 pityriasis rosea, 6 , 35 and immune thrombocytopenia (ITP). 36 , 37 , 38 There are a small but growing number of these entities listed in the VAERS. 11 Post-authorization studies have been essential in describing these clinical findings; however, reports are limited in their ability to identify overall incidence rates, making it difficult to define a direct association to mRNA vaccinations.…”

“… 37 There is also a report of severe post-vaccination thrombocytopenia refractory to all standard therapies in a 72-year-old man with several comorbidities. 36 …”

Potential adverse events in Japanese women who received tozinameran (BNT162b2, Pfizer-BioNTech)

“…Recent experience with ChAdOx1 nCoV-19 [ 1 ] has demonstrated that pharmacovigilance is essential for the early detection of signs of severe adverse events. Reports of immune thrombocytopenia (ITP) following the administration of vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have raised concerns regarding their safety [ 1 – 5 ]. Cerebral venous sinus thrombosis (CVST) resulting from ITP is a neurovascular emergency typically affecting young adults and is more common in women than in men.…”

“…CVST often results in a potentially fatal intracranial hemorrhage (ICH; intracerebral and/or subarachnoid hemorrhage) [ 6 ]. Although no regulatory authority has recognized ICH as an adverse event associated with tozinameran (BNT162b2, Pfizer-BioNTech), fatal and non-fatal cases have been reported [ 4 , 5 ]. Autoimmune mechanisms common to Covid genetic vaccines [ 1 , 2 ] are proposed to induce ITP and internal bleeding.…”