Thrombotic Thrombocytopenic Purpura - Causes, Symptoms, Diagnosis and Treatment

What Is Thrombotic Thrombocytopenic Purpura (TTP)

Thrombotic thrombocytopenic purpura is a rare, fatal blood disorder; it involves small clot formation in the blood vessels present all over the body, which may get clogged, and the flow of the blood to the different tissues and the organs such as the heart, brain, kidneys is disturbed.

This clot formation is done by the platelet cells in the bloodstream, which reduces the platelet count. Because of the reduction of platelet count, whenever there is an injury, the platelets cannot adhere and form a clot at the site of the damage, causing blood loss. Thrombotic thrombocytopenic purpura can be referred to as thrombotic means blood clots, thrombocytopenic means reduced platelet count; and purpura means dark purple color bruises caused by the bleeding beneath the skin. Thrombotic thrombocytopenic purpura induces excessive destruction of the red blood cells causing hemolytic anemia.

What Are the Types of Thrombotic Thrombocytopenic Purpura (TTP)?

Thrombotic thrombocytopenic purpura (TTP) is of two types -

1. Inherited Thrombotic Thrombocytopenic Purpura (TTP) -

Thrombotic thrombocytopenic purpura is an inherited autosomal recessive disorder. It can be genetically transmitted by the mutational changes in the ADAMTS13 gene. The ADAMTS13 gene works for the blood clotting process; because of the gene mutation, there is an overactive blood clot formation.

2. Immune-Mediated Thrombotic Thrombocytopenic Purpura (TTP) -

Thrombotic thrombocytopenic purpura (TTP) is an autoimmune disorder, and it is caused by the production of antibodies in the body that blocks the activity of the enzyme ADAMTS13 resulting in excessive clot formation. It is more common than the inherited thrombotic thrombocytopenic purpura.

What Is the Pathophysiology of Thrombotic Thrombocytopenic Purpura (TTP)?

Thrombotic thrombocytopenic purpura is a severe blood disorder resulting in clot formation throughout the body. In a typical case, whenever there is an injury in the blood vessel, the cellular lining of endothelium releases a factor called– The Von Willebrand factor. The Von Willebrand factor allows the flowing platelet to adhere at the site of the injury and starts the plug formation resulting in a blood clot. Later the enzyme ADAMTS13 regulates the Von Willebrand factor and breaks down the factor when it is no longer needed. However, in Thrombotic thrombocytopenic purpura, there is a severe deficiency of the enzyme ADAMTS13, so the factor does not get regulated. Without sufficient availability of the enzyme ADAMTS13 in the blood, large pieces of Von Willebrand factor can move around the blood vessels and increase adhesion to the platelets, clotting, and destruction of the red blood cells.

What Are the Causes of Thrombotic Thrombocytopenic Purpura (TTP)?

• The thrombotic thrombocytopenic purpura has an idiopathic cause; if it is inherited, the mutation changes of the ADAMTS13 gene can be a related cause of the disorder.

• Some underlying disorders can also cause thrombotic thrombocytopenic purpura.

• Antibodies blocking the ADAMTS13 enzyme activity lead to the deficiency of platelets and can be a cause of thrombotic thrombocytopenic purpura.

• Some additional therapy can cause thrombotic thrombocytopenic purpura, like chemotherapy, hormonal therapy, and immunosuppressant drugs.

What Are the Clinical Manifestations of Thrombotic Thrombocytopenic Purpura (TTP)?

Thrombotic thrombocytopenic purpura (TTP) has the following clinical manifestations -

1. All ages can get affected, especially the age group of 20 to 50 years; it can affect children also.

2. The probability of women getting affected is more than that of males.

3. The incidence of the disorder can be seen in 4 out of 100,000 people each year.

4. It can be seen in patients with HIV (Human Immunodeficiency Virus) and collagen vascular diseases.

5. It can also be seen during the time of pregnancy.

6. Low platelet count with abnormal red blood cells is present.

7. Neurological problems like headache, confusion, ataxia, and seizures.

What Are the Signs and Symptoms of Thrombotic Thrombocytopenic Purpura (TTP)?

Thrombotic thrombocytopenic purpura (TTP) has the following signs and symptoms -

1. Bleeding beneath the skin causes purpuric spots.

2. Fatigue.

3. Hemolytic anemia.

4. High-grade fever.

5. Weakness.

6. Breathing difficulties.

7. Tachycardia (increased heart rate).

8. Headache.

9. Confusion.

10. Petechiae (pinpoint bleeding beneath the skin).

11. Abdominal discomfort causes vomiting and diarrhea.

12. Speech abnormalities.

13. Partial paralysis.

14. Seizures.

15. Heavy bleeding.

16. Coma.

17. Stroke.

18. Acute renal failure.

19. Pale skin.

What Are the Investigations for the Thrombotic Thrombocytopenic Purpura (TTP)?

The following tests can investigate the Thrombotic Thrombocytopenic Purpura -

1. Complete Blood Count - The complete blood count test presents the total count of the platelets, red blood cells, and white blood cells.

2. Blood Smear - The blood sample observed under the microscope shows reputed red blood cells.

3. Bilirubin Test - If the content of bilirubin is high in the blood, it could say the possibility of thrombotic thrombocytopenic purpura.

4. Creatinine Test - If the creatinine level is high in the blood, it indicates thrombotic thrombocytopenic purpura.

5. Urine Test and Renal Function Test - The presence of protein and blood cells may be seen in the urine test.

6. Lactate Dehydrogenase Test - Lactate dehydrogenase enzyme level is high in the blood if there is cell destruction.

7. ADAMTS13 Assay - ADAMTS13 Assay is done to check the activity of the enzyme ADAMTS13. If the action is low, it indicates thrombotic thrombocytopenic purpura positive.

How to Diagnose the Thrombotic Thrombocytopenic Purpura (TTP)?

The diagnosis can be made by evaluating the patient's signs and symptoms, recording medical history, by conducting physical examinations. The diagnosis can be confirmed by performing a blood investigation showing the deficiency or antibodies against ADAMTS13 enzymes.

What Are the Treatments for Thrombotic Thrombocytopenic Purpura (TTP)?

Thrombotic thrombocytopenic purpura can be treated either as inherited or acquired.

1. Medication -

Corticosteroids or glucocorticosteroids are administered to reduce the production of antibodies against the ADAMTS13 enzyme. Other medications like Rituximab, Vincristine, Cyclophosphamide, and Cyclosporine A are used to treat.

2. Plasma Exchange Therapy -

Plasma exchange therapy can be done to treat thrombotic thrombocytopenic purpura. This procedure requires trained and experienced healthcare workers to perform the process. Plasma exchange is a process in which the old plasma is replaced by the new plasma through the I.V. (Intravenous) route. It is performed by taking the blood and replacing the deficient plasma with healthy plasma, and after centrifugation, it is injected back into the body.

3. Surgical Procedure -

The surgical procedure is performed in severe cases; it involves splenectomy. The spleen is the site of antibody production, so the spleen's removal stops the antibody production and treats the disorder.

Conclusion

The thrombotic thrombocytopenic purpura is a life-threatening disease causing tiny blood clots all over the body that can lead to significant problems like heart attacks, strokes, brain damage, and many more. Early diagnosis will lead to a reasonable prognosis of the disease. In many cases, treatment is possible for both inherited and acquired diseases; after the treatment, it may cause a flare-up.