thrombosis with thrombocytopenia syndrome (TTS / VITT / VIPIT)


  • thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially life threatening syndrome which is usually precipitated by response to AstraZeneca Covid-19 vaccine (it appears PF4 may bind to the vaccine and trigger platelet activation) or to heparin (when it is called type 2 HITS and due to antibodies against platelet factor 4-heparin complex)
  • has also been called vaccine induced prothrombotic immune thrombocytopenia (VIPIT) and vaccine-induced immune thrombotic syndrome (VITT)
  • early detection and treatment as in Australia has reduced mortality to 4% down from 20% that had been reported in Europe in early 2021.
  • it has been long known that IV adenovirus injection can cause thrombocytopenia via VWF and P-selectin interplays 1) and perhaps this is the mechanism of AZ vaccines


  • appears to occur in 1 in 100,000 in the 4-30 days after 1st dose vaccination with Covid-19 vaccination with Astra-Zeneca or J&J vaccines
  • peak time period for initial symptoms is between days 6 to 14 after vaccination


unlikely to have TTS

  • reduced platelet count without thrombosis with D dimer at or near normal and normal fibrinogen
  • thrombosis with normal platelet count and D dimer <2000 and normal fibrinogen

possible TTS

  • any patient presenting with acute thrombosis or new onset thrombocytopenia within 42 days of receiving COVID 19 vaccination

probable case of TTS

  • 4-42 days after vaccination with thrombosis features and D Dimers > 4000 mcg/L with or without low fibrinogen (or D Dimer > 2000 with strong clinical suspicion, especially if also low fibrinogen levels)
  • Mx as per “proven TTS” below

definite case of TTS

  • presenting 5-30 days after vaccination and characterised by thrombocytopenia, raised D Dimers and thrombosis, which is often rapidly progressive.
    • NB. 5% have normal platelet count on presentation but most of these develop thrombocytopenia over the next few days
    • NB. deep vein thromboses (DVT) and pulmonary emboli can present up to 42 days after vaccination and it is presumed the DVT develops subclinically between days 5-30.
  • PF4 antibodies positive by ELISA
  • Mx as per “proven TTS” below

Differential Dx

  • thrombocytopenia from other causes including immune thrombocytopenia post Covid-19 vaccine (which does not need to be treated as per TTS)
  • thrombosis from other causes
  • raised D-Dimer from other causes such as infection, post-surgery, cancers, etc

Clinical features

ED work up for a patient referred with abdominal pain, headache or thrombotic concern post Astra Zeneca Covid-19 vaccine

  • see above for possible features which raise thrombotic concern
  • did the headache or possible thrombotic condition commence before 4 days post vaccination or after 28 days
    • ⇒ NOT vaccine related thus manage patient on their clinical merits
  • symptoms of thrombotic concern developed 4 to 42 days post-vaccination:
    • send full blood examination (FBE / FBC)
      • if platelets > 150 x 109/L then very unlikely to be TTS HOWEVER 5% of patients have normal platelets initially
        • if no clinical features of emergency concern discharge home with advice to return if develop concerning symptoms for possible re-testing of FBE
        • if clinical features of concern:
          • send D-Dimer and clotting (coagulation profile with fibrinogen levels)
          • and/or repeat platelet count the next day
          • Mx on their merits but if above are normal then do not need to treat as for TTS
      • if platelets < 150 x 109/L then:
        • send D-Dimer and clotting (coagulation profile with fibrinogen levels)
          • if D-Dimer < 2000 mcg/L or < 5x upper limit of normal
            • very unlikely to be TTS, investigate for other causes as indicated
          • if D-Dimer > 2000 mcg/L or > 5x upper limit of normal +/- low fibrinogen
            • suspect TTS, contact haematologist for advice and consider imaging as indicated such as:
              • CT brain venogram if headache or neurologic features although MRI venography may be preferred in some centres
              • CTPA for chest pain/SOB
              • CT abdopelvis with contrast for abdominal pain

ED work up for patient with new thrombotic event 4-42 days post A-Z Covid-19 vaccine

  • send bloods for FBE, D-Dimer, coagulation profile
  • if normal platelet count
    • send blood for antibodies to Platelet Factor 4 (PF4)
    • repeat platelet count next day
    • Mx thrombotic event but consider avoiding giving heparin type anticoagulants or platelets until TTS fully excluded
  • if TTS proven then manage as per below

Management of proven TTS

  • manage as per thrombotic condition but note the warning below
  • if no thrombotic event evident but clinical picture suggests TTS then anticoagulate with non-heparins as below
  • do not give a second dose of the Astra Zeneca Covid-19 vaccine
  • before treating take extra 8 tubes of blood samples for ELISA testing if needed (4 tubes citrate and 4 tubes serum tubes)
  • DO NOT GIVE heparin or platelets and avoid aspirin - consult with haematologist to advise on treating with
    • NON-heparin therapeutic anticoagulation such as such as DOACs, fondaparinux, danaparoid or argatraban
    • URGENT IV Ig 1g/kg in two divisions over 2 days if needed
    • high doses steroids
      • especially if platelets < 50
      • benefits likely to outweigh harm especially in cerebral venous thrombosis
    • plasma exchange
      • early use may be indicated in those with extensive thrombosis (especially cerebral venous thrombosis) and platelets < 30 x 109/L2)
    • platelets and cryoprecipitate may be indicated if urgent neurosurgery is being considered3)
    • fibrinogen replacement
      • replace fibrinogen supplementation if needed, to ensure level does not drop below 1.5 g/L, using fibrinogen concentrate or cryoprecipitate
tts.txt · Last modified: 2021/12/26 10:20 by gary1

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