Purpura, thrombotic thrombocytopenic

Thrombotic Thrombocytopenic Purpura

Thrombotic Thrombocytopenic Purpura (TTP) is a rare blood disorder characterized by the formation of small blood clots (thrombi) throughout the small blood vessels of the body. This can lead to a low platelet count (thrombocytopenia), hemolytic anemia, and organ damage due to restricted blood flow.

Pathophysiology

TTP is primarily caused by a deficiency of the enzyme ADAMTS13, which is responsible for cleaving von Willebrand factor (vWF) multimers. In the absence of adequate ADAMTS13 activity, unusually large vWF multimers accumulate, promoting excessive platelet aggregation and microthrombi formation. This results in the characteristic symptoms of TTP.

Clinical Presentation

Patients with TTP often present with a pentad of symptoms:

1. Microangiopathic hemolytic anemia - due to the destruction of red blood cells as they pass through the microthrombi. 2. Thrombocytopenia - low platelet count due to consumption in the formation of thrombi. 3. Neurological symptoms - such as confusion, headaches, or seizures, resulting from microthrombi in the brain. 4. Renal dysfunction - due to microthrombi affecting the kidneys. 5. Fever - although not always present, it can occur due to systemic inflammation.

Diagnosis

The diagnosis of TTP is based on clinical presentation and laboratory findings. Key laboratory tests include:

- Complete blood count (CBC) showing anemia and thrombocytopenia. - Peripheral blood smear revealing schistocytes (fragmented red blood cells). - Lactate dehydrogenase (LDH) levels, which are typically elevated due to hemolysis. - ADAMTS13 activity assay to confirm reduced enzyme activity.

Treatment

The mainstay of treatment for TTP is plasma exchange (plasmapheresis), which removes the large vWF multimers and replenishes ADAMTS13. Additional treatments may include:

- Corticosteroids to reduce inflammation and immune response. - Rituximab for refractory cases or those with an autoimmune component. - Caplacizumab, a monoclonal antibody that inhibits vWF, may be used in acute episodes.

Prognosis

With prompt treatment, the prognosis for TTP has improved significantly. However, relapses can occur, and long-term follow-up is necessary.

Also see

- Hemolytic-uremic syndrome - Disseminated intravascular coagulation - Immune thrombocytopenic purpura - Von Willebrand disease