Thrombosis with Thrombocytopenia Syndrome (TTS): Challenges in Prediction and Early Detection

Thrombosis with Thrombocytopenia Syndrome (TTS) is a rare but severe clotting disorder. While TTS is rare, certain COVID-19 vaccines, particularly those based on adenoviral vectors, have been associated with an increased risk of TTS events in some individuals. This syndrome involves blood clot formation (thrombosis) accompanied by low platelet levels (thrombocytopenia), often occurring within a few weeks of vaccination. While the occurrence of TTS post-vaccination is exceedingly rare, it sparked global concern and led to thorough investigations by health authorities.

The exact mechanism behind TTS is still under investigation, but it is believed to involve an immune-mediated response triggered by the vaccine, leading to the formation of antibodies that activate platelets, culminating in clot formation and platelet consumption.

Symptoms of TTS can vary depending on the location and severity of blood clots. Common signs may include:

• Severe headaches or migraines
• Abdominal pain or swelling
• Shortness of breath
• Vision changes
• Pain, swelling, or redness in limbs
• Easy bruising or bleeding

Risk Factors for TTS: Several risk factors have been identified that may predispose individuals to TTS. These include:

• Age and Gender: TTS predominantly affects younger individuals, particularly females under 50 years of age. The reasons behind this demographic predisposition are not yet fully understood but may involve hormonal factors and immune system variations.
• Prior History of Blood Clots: Individuals with a history of thrombosis or clotting disorders may be at increased risk of developing TTS post-vaccination.
• Underlying Health Conditions: Certain underlying health conditions, such as autoimmune disorders or inherited thrombophilias, may contribute to an increased susceptibility to TTS.
• Genetic Factors: Genetic predispositions may play a role in determining an individual's susceptibility to TTS. Variations in genes related to blood clotting and platelet function could influence the likelihood of developing TTS.

Diagnosing Thrombosis with Thrombocytopenia Syndrome (TTS) typically involves a comprehensive evaluation, including clinical evaluation, imaging studies (CT scan, USG, MRI),  specific blood tests {Like Platelet’s count, Coagulation profile, D-dimer, Platelet function assay, Anti-Platelet factor 4-heparin, Thromboelastography (TEG) and Thromboelastometry (ROTEM) and other blood chemistry tests},  and consultation with specialists such as hematologists or thrombosis experts.

There is currently no specific test that can reliably predict the development of TTS before the onset of symptoms. While research is ongoing to identify potential predictive markers for TTS, such as Platelet Factor 4 (PF4) antibodies and elevated D-dimer levels, these markers are primarily used for diagnosis rather than prediction. Additionally, TTS is a complex syndrome with variable clinical manifestations, and not all individuals with PF4 antibodies or other potential markers will go on to develop TTS.

Given the rarity of TTS and the relatively low incidence compared to the overall number of COVID-19 vaccine recipients, it is challenging to predict who will develop TTS before symptoms occur. 

Managing TTS involves a multi-faceted approach aimed at preventing further clot formation, restoring platelet levels, and addressing underlying triggers.

Dr Prashant Goyal