TABLE 4.
Major Societal Recommendations Regarding Management and Treatment of Patients With Vaccine-Induced Immune Thrombotic Thrombocytopenia
| Society | Recommendations | Additional Considerations |
|---|---|---|
| Centers for Disease Control and Prevention guidelines | Do not treat patients with heparin unless HIT testing is negative | Not mentioned |
| Administer nonheparin anticoagulants if HIT testing is positive or unable to be performed | ||
| High-dose IVIG should be strongly considered | ||
| Report adverse events to Vaccine Adverse Event Reporting System, including serious and life-threatening adverse events and deaths in patients following receipt of COVID-19 vaccines as required under the Emergency Use Authorizations for COVID-19 vaccines | ||
| Aspirin should be continued if part of the patient’s routine medication regimen, but it is not recommended to start aspirin before or after vaccination given that inhibition of thromboxane does not block platelet activation in HIT, there is an associated risk of bleeding, and the incidence of VITT is rare | ||
| International Society for Thrombosis and Haemostasis’s interim guidance | Do not wait for results if diagnosis of VITT seems likely | Consider steroids (e.g., prednisone 1 to 2 mg/kg) if platelet count is less than 50 × 109/L |
| Give IVIG immediately (0.5–1 g/kg daily for 2 d) | ||
| Avoid platelet transfusions (unless patient requires urgent surgery), heparin, low-molecular-weight heparin, and vitamin K antagonists | Consider early plasma exchange or fibrinogen substitution to > 1.0 g/L if platelet count remains less than 30 × 109/L despite IVIG and steroid treatment or fibrinogen level is less than 1 g/L | |
| Give a nonheparin anticoagulant such as fondaparinux, argatroban, or a DOAC (e.g., apixaban, rivaroxaban) if platelet count is over 50 × 109/L and there is no serious bleeding | ||
| Consult an expert in thrombosis, such as hematology or vascular medicine | ||
| No mention regarding aspirin use | ||
| American Society of Hematology | Urgent consultation from hematologist with expertise in hemostasis | Consider referral to tertiary care center if TTS is confirmed |
| Avoid use of heparin until TTS has been ruled out or until an alternative other plausible diagnosis has been made | ||
| Initiate therapy with IVIG | ||
| Administer nonheparin anticoagulation pending PF4 ELISA results if signs or symptoms of serious thrombosis and positive imaging or low platelets are present | ||
| Avoid platelet transfusions unless other treatments have been initiated and life-threatening bleeding or imminent surgery | ||
| If PF4 ELISA returns negative and there is no thrombocytopenia, TTS is ruled out; treat as standard venous thromboembolism | ||
| Aspirin should be avoided as treatment or prophylaxis for TTS as it is not effective in preventing HIT antibodies from activating platelets and could increase risk of bleeding | ||
| American College of Cardiology | Treatment by a hematologist or other thrombosis expert is appropriate | Not mentioned |
| Recommends against the use of medications such as aspirin to prevent VITT given the lack of evidence and the rare incidence of VITT | ||
| Expert Haematology Panel from the British Society for Haematology | Treat first while awaiting confirmatory diagnosis | Steroids may also be helpful, and although this is unknown, the benefit is likely to outweigh risks of harm |
| Give IVIG urgently as this is the treatment most likely to influence the disease process. Give 1 g/kg (divided into 2 d if needed), irrespective of the degree of thrombocytopenia, and review clinical course. Repeated IVIG may be required | Plasma exchange may be considered if very severe or resistant disease. This may be required daily for up to 5 d if recovery is slow | |
| Anticoagulate with nonheparin-based therapies such as DOACs, fondaparinux, danaparoid, or argatroban depending on the clinical picture. Bleeding and thrombotic risk needs to be carefully balanced and low-dose fondaparinux or critical illness dose argatroban may be appropriate while platelet count is < 30 × 109/L | Transfer patients with cerebral venous thrombosis to a center with a neurosurgical unit and consider early recourse to neuroradiology and/or neurosurgery if deterioration/progressive bleed | |
| If urgent neurosurgery is required, transfuse platelets to > 100 × 109/L and cryoprecipitate to maintain fibrinogen > 1.5 g/L | It is unclear whether platelet transfusions will exacerbate the condition, the risk/benefit in supporting | |
| Replace fibrinogen if needed, to ensure level does not drop below 1.5 g/L, using fibrinogen concentrate or cryoprecipitate | Patients with platelets < 50 × 109/L on anticoagulation who have a secondary cerebral bleed and not requiring procedures is unknown, and therefore, clear advice cannot be given at present | |
| No mention regarding aspirin use | ||
| It is unknown whether heparin exacerbates the condition but until further evidence is available, as the syndrome mimics HIT, heparin is best avoided, including heparin flushes | ||
| For patients who are refractory to repeat doses of IVIG and plasma exchange | ||
| Rituximab can be considered, although there is no evidence of its efficacy in VITT at present | ||
| American Heart Association and American Stroke Association | It is strongly suggested that care be provided collaboratively by vascular neurology and hematology, vascular medicine, or other consultant with expertise in managing HIT with cerebral or systemic thrombosis | Consider administration of steroids |
| IVIG 1 g/kg body weight daily for 2 d | ||
| No heparin products in any dose should be given | ||
| Anticoagulation should follow recent guidelines on HIT with thrombosis that recommend alternative anticoagulants to heparin including argatroban, bivalirudin, danaparoid, fondaparinux, or a DOAC at therapeutic anticoagulant dose intensity. Dosing strategy may require alteration if there is severe thrombocytopenia (i.e., < 20,000 per mm3) or low fibrinogen | ||
| Anticoagulation should be used in cerebral venous sinus thrombosis even in the presence of secondary intracranial hemorrhage, as it is necessary to prevent progressive thrombosis to control this bleeding. In severely ill patients, parenteral agents with short half-life are preferred | ||
| Platelet transfusion should be avoided | ||
| Report thrombosis cases after SARS-CoV-2 vaccines (as well as any suspected adverse events) to the Department of Health and Human Services Vaccine Adverse Event Reporting System | ||
| No mention regarding aspirin use |
COVID-19 = coronavirus disease 2019, DOAC = direct oral anticoagulant, ELISA = enzyme-linked immunosorbent assay, HIT = heparin-induced thrombocytopenia, IVIG = IV immunoglobulin, PF4 = platelet factor 4, TTS = thrombocytopenia syndrome, VITT = vaccine-induced immune thrombotic thrombocytopenia.