Guideline sources The following summarized guidelines for the evaluation and management of vaccine-induced thrombotic thrombocytopenia are prepared by our editorial team based on guidelines from the American Society of Hematology (ASH 2021). 1 Guidelines 1. Screening and diagnosis Diagnostic criteria: Diagnose vaccine-induced thrombotic thrombocytopenia if all four criteria are met: COVID-19 vaccine (Johnson & Johnson/AstraZeneca only to date) 4 to 30 days previously venous or arterial thrombosis (often cerebral or abdominal) thrombocytopenia positive PF4 ELISA (heparin-induced thrombocytopenia assay). E Show 2 more Clinical presentation: be aware that a patient presenting with thrombosis and a normal platelet count after vaccination might be in an early stage of thrombosis with thrombocytopenia syndrome. Obtain continued assessment for development of thrombocytopenia/thrombosis with thrombocytopenia syndrome. E Differential diagnosis: https://web.pathway.md/diseases/recBemIEeKheXBJc9 1/4 6/29/23, 3:23 AM Vaccine-induced thrombotic thrombocytopenia Pathway Consider making a diagnosis of immune thrombocytopenia, rather than vaccine-induced thrombotic thrombocytopenia, in patients with all of the following: thrombocytopenia no thrombosis negative PF4 ELISA. E Consider making a diagnosis of a non-vaccine linked VTE in the presence of mild thrombocytopenia or a single low normal value. Consider avoiding the use of heparins in patients presenting with VTE in the post-vaccine window while awaiting PF4 ELISA and following the platelet count. E 2. Diagnostic investigations Indications for workup: Obtain urgent medical evaluation for thrombosis with thrombocytopenia syndrome if any of the following develop 4 to 30 days after vaccination: severe headache visual changes abdominal pain nausea and vomiting back pain shortness of breath leg pain or swelling petechiae, easy bruising, or bleeding. E Laboratory investigations: Obtain the following in the initial evaluation of patients with suspected vaccine-induced thrombotic thrombocytopenia: CBC with platelet count and peripheral smear (mean platelet count reported 20 10 / L; with a range from profound to mild, current thrombosis with thrombocytopenia syndrome definition < 150 10 / L) imaging for thrombosis based on signs/symptoms, focused on detection of cerebral sinus venous thrombosis with CT or MRI venogram, splanchnic thrombosis, pulmonary emboli, and/or DVT PF4 ELISA (almost 100 percent sensitivity, with optical density > 2-3 in the majority) fibrinogen and D-dimers (the majority of patients reported to have markedly elevated D- dimers values, and some patients reported to have low fibrinogen values). E Show 3 more PF4 ELISA: consider obtaining a PF4 ELISA to assist with diagnosis of thrombosis with thrombocytopenia syndrome, if thrombocytopenia is worsened from baseline, in patients followed by hematologists/oncologists who present after vaccination with potential other reasons for thrombocytopenia and thrombosis. E 3. Medical management https://web.pathway.md/diseases/recBemIEeKheXBJc9 2/4 6/29/23, 3:23 AM Vaccine-induced thrombotic thrombocytopenia Pathway Urgent specialist consultation: obtain urgent consultation from hematologist with expertise in hemostasis in patients with suspected vaccine-induced thrombotic thrombocytopenia. E Avoidance of heparin: avoid using heparin until thrombosis with thrombocytopenia syndrome has been ruled out or until an alternative other plausible diagnosis has been made. D Show 2 more Anticoagulation and IVIg: Initiate therapy with IVIG plus non-heparin anticoagulation while awaiting PF4 ELISA results in the presence of signs/symptoms of serious thrombosis and at least one of the following: positive imaging thrombocytopenia. E Show 4 more Aspirin: avoid using aspirin as either treatment or prophylaxis for patients with thrombosis with thrombocytopenia syndrome. D Corticosteroids: insufficient evidence to support the use of corticosteroids for patients with thrombosis with thrombocytopenia syndrome. I 4. Therapeutic procedures Platelet transfusion: avoid administering platelet transfusions unless other treatments have been initiated and life-threatening bleeding or imminent surgery. D Plasma exchange: do not perform plasma exchange unless the patient shows continued thrombosis despite IVIG plus non-heparin anticoagulation. D 5. Patient education Vaccine-related risks: Recognize that incidence of vaccine-induced thrombotic thrombocytopenia is extremely low. E Recognize that the risk of death and serious outcome of COVID-19 infection, including thrombosis, far outweigh risk of thrombosis with thrombocytopenia syndrome possibly associated with highly efficacious vaccines. E 6. Follow-up and surveillance Indications for referral: Refer for urgent consultation from hematologist with expertise in hemostasis if thrombocytopenia or thrombosis are present. E Consider referring to a tertiary care center if thrombosis with thrombocytopenia syndrome is confirmed. E References https://web.pathway.md/diseases/recBemIEeKheXBJc9 3/4 6/29/23, 3:23 AM Vaccine-induced thrombotic thrombocytopenia Pathway 1. James B. Bussel, Jean M. Connors, Douglas B. Cines et al. Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia). ASH. 2021 Apr 29;v1.4. 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