Thrombotic thrombocytopenic purpura (TTP) is a blood disorder characterized by low platelets (i.e., thrombocytopenia), small areas of bleeding under the skin (i.e., purpura), low red blood cell count, and hemolytic anemia. TTP causes blood clots (thrombi) to form in small blood vessels throughout the body. These clots can cause serious medical problems if they block vessels and decrease or stop blood flow to organs such as the brain, kidneys, and heart. Complications may include neurological problems (such as personality changes, headaches, confusion, and slurred speech), fever, abnormal kidney function, abdominal pain, and heart problems. Hemolytic anemia can lead to paleness, jaundice, fatigue, shortness of breath, and a rapid heart rate. An episode of TTP usually occurs suddenly and lasts for days or weeks, but it may continue for months. Relapses (or flareups) can occur in up to 60% of people who have the acquired TTP. One of the triggers for TTP is stress.
Other Names: Purpura, thrombotic thrombocytopenic; TTP; Moschowitz syndrome
Pathophysiology and Epidemiology
There are two types of TTP: acquired TTP, in which the person develops antibodies against ADAMTS13, and inherited TTP, in which the person the ADAMTS13 gene does not produce sufficient levels of a functioning enzyme. Acquired TTP usually begins in adulthood but can affect children.
In both forms, the decreased activity of this enzyme leads to an accumulation of ULvWF multimers which bind to platelets and induce aggregation. The net result is severe thrombocytopenia, tissue ischemia, and organ dysfunction which can be life-threatening.
Signs and Symptoms
Common signs of TTP include:
- Purpura
- Petechiae
- Paleness or jaundice
- Fatigue
- Fever
- A fast heart rate or shortness of breath.
- Nausea or vomiting
- Headache, speech changes, confusion, coma, stroke, or seizure
- A low amount of urine, or protein or blood in the urine
Acquired TTP usually presents as severe low red blood cell count due to destruction of red blood cells and thrombocytopenia in a previously healthy individual. Due to earlier diagnosis and improved treatments, fewer people with acquired TTP become critically ill. TTP affects the central nervous system and/or gastrointestinal system in over 1/3 of cases. Kidneys and other organs such as the heart may also be damaged by TTP, but the lungs are rarely affected.
Management and Current Treatment
The following is a list of management guidelines and good practices when caring for TTP patients:
- ISTH guidelines for treatment of thrombotic thrombocytopenic purpura
- Good practice statements (GPS) for the clinical care of patients with thrombotic thrombocytopenic purpura
Treatment includes plasma exchange and, in some cases, may also include corticosteroid therapy or rituximab. The newly approved orphan drug, caplacizumab, is also recommended. Caplacizumab blocks platelet-von Willebrand factor interactions and thereby prevents the formation of microvascular thrombosis in small vessels.
Clinical Trial Information
For a full list of clinical trials relating to TTP, go here.
Resources
Congenital thrombotic thrombocytopenic purpura – NIH
Additional Content
TTP and Pregnancy
For more information about TTP and other rare blood disorders, visit checkrare.com/diseases/hematologic-disorders/
