A case of thrombocytopenia and multiple thromboses after vaccination with ChAdOx1 nCoV-19 against SARS-CoV-2

Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged. We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine. Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases. Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs). Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumption coagulopathy are highly unusual. A maximum 4T heparin-induced thrombocytopenia (HIT) score and a positive immunoassay for anti-platelet factor 4/heparin antibodies identified autoimmune HIT as a potential pathogenic mechanism. Although causality has not been established, our case emphasizes the importance of clinical awareness. Further studies of this potentially new clinical entity have suggested that it should be regarded as a vaccine-induced immune thrombotic thrombocytopenia.

A large right atrial thrombus penetrating through a patent foramen ovale in a patient with Prothrombin G2120 Mutation

The Prothrombin mutation G2021 alone is considered a minor risk factor for thromboembolism, but thromboembolic events are more likely in the presence of additional risk factors. We report on a 44-year-old female with an atrial thrombus causing pulmonary embolism and transiting through a patent foramen ovale. The thrombus was extracted by open heart operation. The patient had a family history for thromboembolic events. Further diagnostic after surgery found the patient positive for the Prothrombin mutation G2021, but not for the Factor V Leiden mutation. After surgery, a permanent oral anticoagulation has been started.

Facing Deep Venous Thrombosis (DVT) in University Tertiary Hospital: Role of Conventional Thrombophilia Testing in Idiopathic DVT Treatment

INTRODUCTION: Deep venous thrombosis (DVT) is a frequent cause or morbidity and mortality, and multiple genetic and environmental factors are involved in its etiopathogenesis. According to it, besides investigating about personal and familiar DVT history, thrombophilia testing is often asked by physicians in order to diagnose patients, even if current validated markers can't predict the risk of recurrence of the disease. METHODS: We developed an observational and prospective study between January 2017 and December 2017, in order to register the patients with DVT that were treated in our DVT unit. As secondary objectives, we wanted to know how many had an idiopathic DVT, if we tested all of them for thrombophilia, which of them stopped treatment and the results after one year of follow up. RESULTS: We included 172 patients with DVT, 56.9% were men, and the average age was 66.4 years old with an increased incidence above the 50 years old. In our study group we found 43.6% (75) of patients without major risk factors for DVT, classified as idiopathic DVT and we will refer to them in this abstract from now on. Just 36.7% of them had a positive personal history of DVT and 36.7% had familiar history. Almost all were localized in the lower limbs (98.7%) and 17.3% presented in association with pulmonary embolism (PE) at diagnosis. All of them started treatment with LMWH, and after the first clinical visit, 26.7% continued with it, while 51.2% changed to VKA and 22.1% to DOACs. Only 45 (60%) of idiopathic DTVs were tested for thrombophilia (patients younger than 60 years old, with extensive DVT, or personal or familiar history of DVT): 31 had a negative study, 11 had a positive study for hereditary thrombophilia (4 S protein deficiency, 3 C protein deficiency, 2 V Leiden factor mutation + prothrombin mutation, 1 V Leiden factor mutation, 1 prothrombin mutation), and 3 were diagnosed of antiphospholipid syndrome. All these patients with positive study or antiphospholipid syndrome received indefinite anticoagulation. From all the patients with idiopathic DVT, 77.3% received indefinite anticoagulation, 17.3% were treated for 3-6 months, 4% for >6-12 months and 1,3% for 15 months. Only one patient who stopped treatment after 3 months had a recurrent DVT and had to restart it. CONCLUSIONS: DVT is the most frequent indication for thrombophilia testing and regarding its multifactorial etiology, it must be performed specially in incidental cases. In our incidental DVT study group (with PE associated or not), we found a 31.1% of positive studies, consistent with what is expected in general DVT population, but in contrast with it is described in the literature, we found more cases of S and C deficiency than V Leiden factor and prothrombin mutations. We also had only one patient with recurrence DVT after few months of stopping anticoagulation, no thrombophilia was found. This low rate of recurrence that differs from the latest data published, might be explained by the short time of follow up that we have, so it would be interesting to increase it, as well as the number of patients in the cohort studied. There is a need for investigating new clinical and genetic scores in order to improve the poor predictive role in recurrent disease with the current thrombophilia markers. Disclosures Bosch: F. Hoffmann-La Roche Ltd/Genentech, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Honoraria, Research Funding; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban

SummaryWe sought to investigate whether the G20210A prothrombin mutation modifies plasma fibrin clot properties in patients after venous thromboembolism (VTE) and how rivaroxaban treatment affects these alterations. We studied 34 prothrombin mutation heterozygous carriers and sex- and age-matched 34 non-carriers, all at least three months since the first VTE episode, before and during treatment with rivaroxaban. Clot permeability (Ks) and clot lysis time (CLT) with or without elimination of thrombin activatable fibrinolysis inhibitor (TAFI) were assessed at baseline, 2–6 hours (h) after and 20–25 h after intake of rivaroxaban (20 mg/day). At baseline, the prothrombin mutation group formed denser clots (Ks −12 %, p=0.0006) and had impaired fibrinolysis (CLT +14 %, p=0.004, and CLT-TAFI +13 %, p=0.03) compared with the no mutation group and were similar to those observed in 15 healthy unrelated prothrombin mutation carriers. The G20210A prothrombin mutation was the independent predictor for Ks and CLT before rivaroxaban intake. At 2–6 h after rivaroxaban intake, clot properties improved in both G20210A carriers and non-carriers (Ks +38 %, and +37 %, CLT −25 % and −25 %, CLT-TAFI −20 % and −24 %, respectively, all p<0.001), but those parameters were worse in the prothrombin mutation group (Ks −12.8 %, CLT +17 %, CLT-TAFI +13 %, all p<0.001). Rivaroxaban concentration correlated with fibrin clot properties. After 20–25 h since rivaroxaban intake most clot properties returned to baseline. Rivaroxaban-related differences in clot structure were confirmed by scanning electron microscopy images. In conclusion, rivaroxaban treatment, though improves fibrin clot properties, cannot abolish more prothrombotic fibrin clot phenotype observed in prothrombin mutation carriers following VTE.