Persistently high platelet factor 4 levels in an adolescent with recurrent late thrombotic complications after SARS-CoV-2 mRNA vaccination: A case report (preprint)

Background Thrombosis after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is a serious complication for patients with a thrombophilic predisposition. Factors that predict the risk of post-vaccination thrombosis should be explored. We report a case in which a patient with pediatric antiphospholipid syndrome (APS) developed deep vein thrombosis (DVT) six months after receiving a second dose of the BNT162b2 vaccine.Case presentation: A 17-year-old girl with no family history of thrombophilia developed DVT at six years of age. The thrombus was found in the right common iliac vein and the inferior vena cava, with concomitant left pulmonary infarction. After treatment with warfarin, the pulmonary infarction was resolved, but the thrombus became organized and persisted for the next 11 years. The patient was treated with anticoagulants for six years after DVT onset, with subsequent cessation of treatment for five years without thrombosis recurrence. She received the BNT162b2 vaccine at 17 years of age, one week before a routine outpatient visit. Elevation of platelet factor 4 level was detected 14 days after the first vaccination and remained for five months after that, but without thrombotic symptoms. A second dose of the BNT162b2 vaccine was administered; six months later, the DVT in the right common iliac vein recurred and was treated with a direct oral anticoagulant.Conclusions The BNT162b2 vaccine exacerbated her antiphospholipid antibody syndrome by activating the coagulation system, thereby exacerbating her thrombosis. Platelet factor 4 may be a useful indicator of the coagulation system. The persistence of high platelet factor 4 levels after vaccination suggests that the vaccine caused DVT by exacerbating the patient’s APS. After vaccination of patients with a predisposition to thrombosis, coagulation status and platelet activation markers should be monitored to prevent the development of DVT.

[Heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia: novel insights on anti-platelet factor 4 antibodies].

The levels of anti-platelet factor 4 (PF4) antibodies, also known as anti-PF4 or heparin complex antibodies, are used to diagnose heparin-induced thrombocytopenia (HIT). In HIT, anti-PF4 antibodies induced by heparin exposure cause thrombocytopenia and thrombosis. However, anti-PF4 antibodies were recently reported to be associated with the development of fatal vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination for coronavirus disease 2019. HIT and VITT are caused by anti-PF4 antibodies and have similar pathological conditions. However, the severity of these conditions differs and the detection sensitivity of their antibodies varies depending on the assays used. Herein, we review HIT and VITT associated with anti-PF4 antibodies.

A case of an adolescent with antiphospholipid syndrome and persistently high PF4 levels with recurrent late thrombotic complications after mRNA SARS-CoV-2 vaccine (preprint)

Background: Anti-phospholipid syndrome (APS) is an autoimmune disease causing arteriovenous thrombosis in the presence of antiphospholipid antibodies. Pediatric APS develops at less than 18 years of age. Various factors exacerbate pediatric APS. Herein, we report a case of a patient with pediatric APS who developed deep vein thrombosis (DVT) 6 months after second vaccination due to persistent platelet activation caused by exacerbation of APS after administration of the BNT162b2 vaccine. Case presentation: A 17-year-old female developed DVT at the age of 6 years. She had no family history of thrombophilia. The thrombus was found in the right common iliac vein to the inferior vena cava, with concomitant left pulmonary infarction. After treatment with warfarin, the pulmonary infarction resolved, but the thrombus from the right common iliac vein to the inferior vena cava became organized and remained until now. The patient was treated with anticoagulants for 6 years after the onset of DVT and then without treatment for 5 years without recurrence of thrombosis. The first dose of the BNT162b2 vaccine was administered 1 week before a routine outpatient visit. However, PF4 levels were elevated after vaccination and even after 5 months, but without thrombotic symptoms. A second dose of the BNT162b2 vaccine was administered; 6 months later, the patient developed recurrent deep vein thromboembolism in the right common iliac vein and was treated with direct oral anticoagulants. Conclusions: : The persistence of high PF4 levels after vaccination in a patient with DVT may indicate an association between the vaccine and DVT due to the exacerbation of APS by the BNT162b2 vaccine. After vaccination of patients with a predisposition to thrombosis, the state of coagulation, including platelet activation markers, should be monitored to prevent the development of DVT.