Experience of danaparoid to treat vaccine-induced immune thrombocytopenia and thrombosis, VITT

Abstract

Background Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and may cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management. Danaparoid has good efficacy and safety in treatment of heparin-induced thrombocytopenia. We report here our experience of the administration and monitoring danaparoid in VITT. Methods We diagnosed a series of six hospitalized cases of VITT, based on the international diagnostic guidance. All VITT-related data were from the local electronic medical and laboratory record system and were analyzed with IBM SPSS Statistics. Results Predominately women in their late 40’s developed VITT on average 24 days (range 9–59) after the first ChAdOx1 dose. Clinical presentation included single or multiple venous and/or arterial thrombosis, moderate thrombocytopenia and high D-dimer levels. After detecting PF4 antibodies subcutaneous danaparoid was our first-line antithrombotic treatment with an average duration of three weeks. The median plasma anti-FXa activity was in the lower part of the therapeutic range and during the first week of danaparoid administration clinical symptoms, platelet counts, and fibrin turnover resolved or significantly improved. The average duration of hospital admission was 10 days [2–18]. One patient died but the other five patients recovered completely. Conclusions The clinical outcomes of our small cohort align with the earlier published reports, and support danaparoid as a rational option for the initial anticoagulation of VITT patients.

Vaccine-induced immune thrombotic thrombocytopenia: what do we know hitherto?

“…Accordingly, non-heparin anticoagulation such as thrombin inhibitors (e.g., argatroban) and factor Xa inhibitors (e.g., fondaparinux) have been recommended and have been used to mitigate thrombotic events in VITT (25,34,[154][155][156]161). The indirect thrombin inhibitor, danaparoid, has also been used with positive outcomes (162). Interestingly, danaparoid and heparin, but not fondaparinux or argatroban, interfere with anti-PF4 binding to PF4 in vitro (163).…”

Heparin, Heparan Sulphate and Sepsis: Potential New Options for Treatment

“…It has been shown in sepsis experimental models that danaparoid can inhibit systemic inflammation and prevent multiple organ failure [ 47 , 48 ], and it was proven to be superior to heparin when used in combination with antithrombin [ 49 ]. Danaparoid has also been used successfully in reported cases of vaccine induced immune thrombocytopenia and it is possible that the reduction in the proinflammatory C-reactive protein may have contributed to its success [ 50 ]. Pentosan polysulphate is a semi-synthetic sulphated xylan, once used as an antithrombotic and antilipemic agent and now licensed for treatment of interstitial cystitis in human and osteoarthritis in animals.…”

Treatment of vaccine-induced immune thrombotic thrombocytopenia (VITT)

“…Taking this into account, non-aPTT-adjusted therapies, including fondaparinux, danaparoid, and direct oral anticoagulants (DOACs; either Xa or IIa-inhibiting), may be preferred in the treatment of VITT and HIT on theoretical grounds. A small case-series (n=6) describing use of danaparoid (often administered by subcutaneous injection) from Finland reported generally favorable outcomes, with recovery in 5 of 6 patients; the single fatal outcome was the first patient in Finland diagnosed with VITT, who presented with myocardia infarction and CVT with cerebral hemorrhages, and in whom high-dose IVIG therapy was not administered up-front [36] .…”