Decoding Thrombosis with Thrombocytopenia Syndrome (TTS): Covid Vaccine's Dreadful Adverse Effect-Dr Rahul Chawla

AstraZeneca recently acknowledged before a UK court that its Covid vaccine can lead to a rare blood clot side effect known as Thrombosis with Thrombocytopenia Syndrome. There have been hundreds of reported cases of this disease, implicating Covid vaccine as a possible etiology. Many are also speculating that Covid vaccines are responsible for the recent rise in heart attacks.

Let’s understand TTS and clear the air regarding Covid vaccine’s potential health risks.

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as Thrombosis with Thrombocytopenia Syndrome (TTS), is a rare but serious condition that has been associated with certain COVID-19 vaccines. It is characterised by venous or arterial thrombosis, particularly at unusual sites including cerebral sinus venous thrombosis (CSVT), mild to severe thrombocytopenia. VITT is an exceedingly rare condition (likely <1 in 100,000) (ref)

VITT/TTS is primarily associated with adenoviral vector-based COVID-19 vaccines (1). The condition is characterised by the development of blood clots (thrombosis) in unusual locations, such as cerebral venous sinuses (CVS) or splanchnic veins, accompanied by low platelet counts (thrombocytopenia).

CVST and thrombocytopenia together are called thrombosis-thrombocytopenia syndrome (TTS). TTS associated with COVID-19 vaccination has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT).

The exact mechanisms underlying VITT/TTS are not fully understood, but are believed to involve an immune-mediated response.

One of the mechanisms that have been implicated is related to the adenovirus-based vector of these vaccines (2).

The adenoviral vaccines appear to stimulate autoantibodies to platelet factor 4 (PF4), which activate platelets and causes thrombosis in the absence of heparin, similar to spontaneous or autoimmune heparin-induced thrombocytopenia (HIT).

Risk Factors

Several risk factors may contribute to the development of VITT/TTS, including:

1. Age and Gender: The condition has been reported more frequently in younger individuals, particularly women under 60 years of age.

2. Individuals with a history of blood clots or thrombotic disorders are at higher risk.

3. Certain medical conditions, such as autoimmune disorders or prothrombotic states, may increase susceptibility to VITT/TTS.

Symptoms

The symptoms of VITT/TTS can vary depending on the location and severity of blood clots. Common symptoms include:

1. Severe Headache: Especially if accompanied by visual changes or neurological deficits, which may indicate cerebral venous sinus thrombosis (CVST).

2. Abdominal Pain: Particularly if associated with nausea, vomiting, or signs of gastrointestinal bleeding, suggesting splanchnic vein thrombosis.

3. Leg Pain or Swelling: Deep vein thrombosis (DVT) in the lower extremities can cause pain, swelling, redness, or warmth.

4. Shortness of Breath: Pulmonary embolism (PE) resulting from clot migration to the lungs can lead to sudden onset of breathlessness, chest pain, and rapid heart rate.

5. Other Symptoms: These may include easy bruising, petechiae (small red or purple spots on the skin), and unexplained bleeding.

Diagnosis

Diagnosing VITT/TTS involves a combination of clinical assessment, laboratory tests, and imaging studies. Key steps in the diagnostic process include:

1.  Complete Blood Count (CBC): Detects low platelet counts (thrombocytopenia)

2. Coagulation Studies: Assess clotting factors, D-dimer levels (a marker of clot formation), and fibrinogen levels.

3. Antibody Testing: Detection of antibodies against PF4 using enzyme-linked immunosorbent assay (ELISA) or functional assays.

4. Imaging Studies: Depending on the suspected location of blood clots, imaging modalities such as, CT scans, MRI, or angiography may be used to visualize clots in veins or arteries.

Definitive Diagnosis of VITT/TTS (must meet all five criteria):

1. COVID vaccine administration 4 to 42 days prior to symptom onset

2. Any venous or arterial thrombosis (often cerebral or abdominal)

3. Thrombocytopenia (platelet count < 150 x 109/L)

4. Positive PF4 “HIT” (heparin-induced thrombocytopenia) ELISA

5. Markedly elevated D-dimer (> 4 times upper limit of normal)

Management

The management of VITT/TTS requires urgent hospital admission and a multidisciplinary approach and detailed workup. Treatment strategies may include:

• Anticoagulation: All individuals with VITT and thrombosis should receive full (therapeutic) dose anticoagulation. A non-heparin anticoagulant suggested rather than heparin, especially if HIT (including delayed or spontaneous HIT) remains in the differential.

• IVIG: intravenous immune globulin (IVIG) for all individuals with VITT (IVIG dose is 1 gm/kg daily for two days.

• Plasma exchange:Therapeutic plasma exchange can be used in refractory disease and individuals with especially concerning features (platelet count <30,000/microL with CVT; severe thrombocytopenia with multiple thromboses)

• Bleeding: Platelet transfusions are generally reserved for critical bleeding (bleeding into a critical anatomic site or hemodynamic or respiratory compromise). Administration of fibrinogen (concentrate, plasma, or cryoprecipitate) may be appropriate for individuals with critical bleeding and hypofibrinogenemia but should not be used for asymptomatic hypofibrinogenemia.

Conclusion

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as Thrombosis with Thrombocytopenia Syndrome (TTS), is a rare but serious condition associated with adenoviral vector-based COVID-19 vaccines. (1)

However, vaccines remain the primary means of preventing COVID-19. The risk of life-threatening thrombosis from COVID-19 greatly exceeds the risk of VITT. People who have recovered from VITT should not receive another adenoviral vectored vaccine, but an mRNA vaccine may be likely safe (1).

It is to be noted that this adverse effect of the vaccine is seen within few weeks of vaccine and long term cases have not been described. The likelihood of vaccine induced recent surge in the cases of heart attacks across the world remains low and there is no sufficient evidence to suggest vaccines as likely culprit of heart attacks.

References

1. https:// www.hematology.org/covid-19/vaccine-induced-immune-thrombotic-thrombocytopenia

2. Alam W. COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management. Sci Prog. 2021 Apr-Jun;104(2):368504211025927. doi: 10.1177/00368504211025927. PMID: 34120531; PMCID: PMC10358704.