SUMMARY:

Although very rare, thrombosis with thrombocytopenia syndrome (TTS) has been associated with AD26.COV2.S (J&J) vaccine in the US and similar events have been documented outside the US with use of the CHaDOx1 nCov-19 (AstraZeneca) vaccine. This syndrome has been referred to by alternate names in the literature, including vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or ‘vaccine-induced immune thrombotic thrombocytopenia (VITT)’. TTS is being used by the FDA and CDC. The American Society of Hematology has provided guidance on diagnosis and when to refer.

TTS Diagnostic Criteria

• All 4 criteria must be met
  • J&J or AstraZeneca vaccine within 4 to 30 days
  • Venous or arterial thrombosis (often cerebral or abdominal)
  • Thrombocytopenia (current TTS definition <150,000/μL)
  • Positive PF4 ‘HIT’ (heparin-induced thrombocytopenia) ELISA

Note: In early stage of TTS, thrombosis may be present prior to platelet count decrease

Clinical Findings

• Severe headache
• Visual changes
• Abdominal pain
• Nausea and vomiting
• Back pain
• Shortness of breath
• Leg pain or swelling
• Petechiae, easy bruising, or bleeding

Work-Up

Labs

1. CBC with platelet count and peripheral smear
   • Mean platelet count in published reports: 20,000/μL | There is a range from profound to mild
2. D-dimers: Most patients have significantly elevated levels
3. Fibrinogen: Some patients have low levels
4. PF4-heparin ELISA: almost all cases reported have positive assays | Most will have optical density >2.0 to 3.0

Note: Do not use non-ELISA rapid immunoassays for HIT | Non-ELISA tests are not sufficiently sensitive nor specific for TTS

Imaging for Thrombosis

• Imaging based on symptoms
• Focus on cerebral sinus venous thrombosis (CSVT) with use of CT or MRI venogram
• Patients may also have splanchnic thrombosis, pulmonary emboli, and/or DVT

Treatment

• IVIG 1 g/kg daily for two days
• Non-heparin anticoagulation
  • Parenteral direct thrombin inhibitors (argatroban or bivalrudin if aPTT is normal) or
  • Direct oral anticoagulants without lead-in heparin phase or
  • Fondaparinux or
  • Danaparoid

When to Treat

While waiting for PF4 ELISA

• Begin IV immune immunoglobin and nonheparin anticoagulation if there is clinical evidence of serious thrombosis AND ≥1 of the following
  • Positive imaging
  • Low platelets
• If PF4 ELISA returns negative and there is no thrombocytopenia, TTS is ruled out
  • Treat for venous thromboembolism using standard protocols

KEY POINTS:

• TTS is suspected
  • Obtain immediate CBC with platelet count and imaging for thrombosis based on symptoms
  • If thrombosis and/or thrombocytopenia is present, referral to hematologist with expertise in hemostasis is recommended
• Do not use non-ELISA rapid immunoassays for HIT
• Avoid heparin until TTS ruled out or other reasonable diagnosis has been established
• In addition

If thrombocytopenia but no thrombosis and negative PF4 ELISA, likely ITP

Microangiopathy with red cell fragmentation and hemolysis have not been features of reported cases, thus distinguishing this syndrome from TTP/HUS is straightforward

Avoid platelet transfusions unless other treatments have been initiated AND life-threatening bleeding or imminent surgery

Consider referral to tertiary care center if TTS is confirmed

Learn More – Primary Sources:

American Society of Hematology: Thrombosis with Thrombocytopenia Syndrome (also termed Vaccine-induced Thrombotic Thrombocytopenia)