ConditionBlood & immune system
Thrombotic Thrombocytopenic Purpura (TTP)
Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening blood disorder in which tiny blood clots form in small blood vessels throughout the body. The clots use up platelets, causing bruising and bleeding, and break red blood cells apart, causing anemia. They also block blood flow to the brain, heart and kidneys. Most cases are caused by antibodies against an enzyme called ADAMTS13. Without treatment, most people die; with urgent plasma exchange and modern drugs, about 90 percent survive.
Also called: TTP, Moschcowitz syndrome, immune TTP (iTTP), acquired TTP, congenital TTP (Upshaw-Schulman syndrome)
At a glance
- What it is
- Widespread small-vessel clotting with low platelets and red cell breakdown.
- Main cause
- Autoantibodies against ADAMTS13 (immune TTP); rarely inherited ADAMTS13 deficiency.
- Symptoms
- Bruising, tiny red spots, fatigue, confusion, headache, stroke-like symptoms, dark urine, abdominal pain.
- Diagnosis
- Low platelets, fragmented red cells on smear, very low ADAMTS13 activity.
- Treatment
- Emergency plasma exchange, steroids, rituximab and caplacizumab.
When to get help
Call 911 or go to the ER
- Sudden confusion, speech difficulty, weakness, numbness, severe headache or seizure, especially with bruising or tiny red spots: call 911 or your local emergency number
- Chest pain or shortness of breath with low platelets
- Heavy bleeding that will not stop
See a doctor within a day or two
- New widespread bruising or pinpoint red-purple spots (petechiae), with fatigue or paleness
- Dark or blood-tinged urine, or yellowing of the skin or eyes, with bruising
- Anyone with a history of TTP who develops bruising, tiny red spots or neurological symptoms (possible relapse)
Book a routine appointment
- Regular ADAMTS13 monitoring after recovery from immune TTP
- Pregnancy planning with a history of TTP
What happens in TTP
ADAMTS13 is an enzyme that trims von Willebrand factor, a sticky protein that helps platelets clump at injury sites. When ADAMTS13 is missing or blocked, very large von Willebrand factor strands accumulate in the bloodstream and grab platelets, forming tiny clots in small vessels everywhere.
The results:
- thrombocytopenia: platelets are used up, causing bruising and bleeding
- microangiopathic hemolytic anemia: red cells are sliced as they squeeze past clots, causing anemia and fragments called schistocytes
- organ ischemia: reduced blood flow damages the brain, heart, kidneys and gut
Types
- immune (acquired) TTP: about 95 percent of cases; the immune system makes antibodies against ADAMTS13. Often in adults aged 30 to 50, more often women and Black individuals. Triggers include pregnancy, infections, autoimmune disease (such as lupus) and some medicines, but often none is found.
- congenital TTP: inherited ADAMTS13 deficiency; may appear in childhood or first in pregnancy.
Symptoms
- bruising and petechiae (tiny red-purple spots)
- fatigue, weakness and paleness from anemia
- neurological symptoms: headache, confusion, personality change, speech difficulty, weakness, seizures, coma; these can come and go
- abdominal pain, nausea and vomiting
- chest pain and heart rhythm problems
- dark or reddish urine
- jaundice
- fever in some people
The classic "pentad" (low platelets, hemolytic anemia, neurological symptoms, kidney problems and fever) is present in only a minority; doctors do not wait for all five.
TTP vs ITP vs HUS
| TTP | ITP | HUS | |
|---|---|---|---|
| Platelets | Low | Low | Low |
| Red cell breakdown (schistocytes) | Yes | No | Yes |
| Neurological symptoms | Common | Rare | Less common |
| Kidney failure | Usually mild | No | Severe |
| ADAMTS13 | Very low (under 10 percent) | Normal | Usually normal |
| Typical trigger | Autoantibody | Autoantibody against platelets | Shiga toxin E. coli in children; complement disorders |
Disseminated intravascular coagulation (DIC) also causes low platelets but has abnormal clotting tests, unlike TTP.
Diagnosis
TTP is a medical emergency, and treatment often starts before all results are back.
- complete blood count: low platelets and hemoglobin
- blood smear: schistocytes (fragmented red cells)
- hemolysis markers: high LDH and bilirubin, low haptoglobin, high reticulocytes
- clotting tests: usually normal
- ADAMTS13 activity: under 10 percent confirms TTP; inhibitor tests show antibodies
- kidney function, troponin, pregnancy test
- PLASMIC score: helps estimate the likelihood of TTP while waiting for ADAMTS13 results
Treatment
Immune TTP
- therapeutic plasma exchange: daily removal of the patient's plasma (containing antibodies and large von Willebrand factor) and replacement with donor plasma (containing ADAMTS13), continued until platelets recover
- corticosteroids to suppress the immune response
- rituximab to reduce antibody production and lower relapse risk
- caplacizumab: blocks von Willebrand factor from binding platelets, speeding platelet recovery and reducing clots and deaths
- platelet transfusions are generally avoided unless there is life-threatening bleeding, because they can fuel clotting
Congenital TTP
- plasma infusions or recombinant ADAMTS13 replacement on a regular schedule, and during pregnancy
Relapse and long-term health
About 30 to 50 percent of people with immune TTP relapse, sometimes years later. Monitoring ADAMTS13 activity allows preventive rituximab if levels fall. Survivors have higher risks of depression, cognitive problems, high blood pressure and stroke, so long-term follow-up with a hematologist is important.
Frequently asked questions
What is TTP?
Thrombotic thrombocytopenic purpura is a rare blood disorder in which tiny clots form in small blood vessels throughout the body, using up platelets and breaking red blood cells. It can damage the brain, heart and kidneys and is a medical emergency.
What are the symptoms of TTP?
Symptoms include bruising, tiny red-purple spots on the skin, fatigue, paleness, confusion, headache, speech or vision problems, abdominal pain, dark urine and sometimes fever. Neurological symptoms can come and go.
What causes TTP?
Most TTP is caused by the immune system making antibodies against ADAMTS13, an enzyme that controls clotting proteins. Rarely, people are born with an inherited ADAMTS13 deficiency. Triggers can include pregnancy, infections and some medicines.
How is TTP treated?
TTP is treated urgently with plasma exchange, steroids, rituximab and caplacizumab. These remove antibodies, replace the missing enzyme and stop clot formation. With prompt treatment, about 90 percent of people survive.
What is the difference between TTP and ITP?
Both cause low platelets. ITP is caused by antibodies against platelets and does not cause clots or red cell breakdown. TTP causes widespread small clots, red cell destruction and organ damage, and needs emergency plasma exchange.
Sources
This guide was written from current patient and clinical guidance, including:
- International Society on Thrombosis and Haemostasis (ISTH): Guidelines for the Diagnosis and Treatment of TTP
- American Society of Hematology: TTP
- National Heart, Lung, and Blood Institute: Thrombotic Thrombocytopenic Purpura
- Answering TTP Foundation: About TTP
- MedlinePlus: Thrombotic thrombocytopenic purpura