What is TTP?


Thrombotic Thrombocytopenic Purpura (TTP) is known, in the majority of patients, as an autoimmune condition.

It is a rare blood disorder that affects between 1 and 4 people in every million.

TTP was first described in 1924 by Dr Eli Moschcowitz He had been treating a 16 year old female patient who was in a coma and had kidney failure. She died within 2 weeks. Moschcowitz described the characteristics of TTP based on his patient’s post mortem results.

Eli Moschcowitz Dr. Moschcowitz was the first to describe pulmonary hypertension and thrombotic thrombocytopenic purpura Information and photograph, courtesy of Mount Sinai Archives, New York.

Survival rates have improved greatly since 1924 With accurate diagnosis and prompt treatment, current survival rates are approximately 80%.

Below we describe what each word of the name Thrombotic Thrombocytopenic Purpura means:-

THROMBOTIC = Clotting of the blood;
THROMBOCYTOPENIC = Reduction in the number of platelets in the blood;
PURPURA = Bleeding in the skin causing purple spots / rash



Here you can see the red/purple spots that appear like a rash under the skin.
Source: the English Wikipedia: http://en.wikipedia.org/wiki/Image:Purpura.jpg


People with TTP have a fault in the enzyme that should break down the von Willebrand Factor, which, with platelets, normally prevents bleeding. This enzyme stops working properly and the platelets become sticky and forms blood clots in small vessels that can affect any organ. The enzyme is called ADAMTS 13.

To explain this in more detail - Usually, in a healthy individual the body produces a string of a substance known as von Willebrand factor (vWf) . The body also produces an enzyme known as ADAMTS13. This enzyme breaks down the vWf creating smaller pieces that the body can manage. The small sections of vWf and platelets work together to plug an area of bleeding.

In the 1980’s Moake noted that TTP patients have extra long vWf. We now know that an individual with TTP either has a reduction in the enzyme ADAMTS13 or it is not working correctly. This means that the von Willebrand factor is not broken down, and acts as a magnet for platelets to stick too.

All of this activity takes place within the blood vessels.

These pictures help to explain this. The picture on the left shows the string of von Willebrand factor with the ADAMTS13 breaking it up. In the second picture, the ADAMTS13 is not present and platelets become clumped around the large von Willebrand factor.


Moake JL (2002). "Thrombotic microangiopathies".
N. Engl. J. Med. 347 (8): 589–600
Copyright © [2002] Massachusetts Medical Society. All rights reserved.




These large clumps of platelets cause small blood clots in the body, typically in the blood vessels supplying the brain and kidneys. This is dangerous and could lead to strokes or failure of the major organs.

Whilst the platelets are clotting in this way they are not available for use at a site of injury - where you would expect them to be working.

Because they are misshapen they become an obstacle to the red cells that are trying to travel around the body. This causes the red cells to be broken up. You may hear this referred to as fragmentation.

Historically, when diagnosing TTP a doctor would look for 5 characteristics of the disease. These were:

• a low platelet count
• a low haemoglobin count (anaemia)
• fever
• neurological problems
• kidney problems

However, more recently doctors will look for low platelet and low haemoglobin count as not all patients will show all the other symptoms.

The following tests are done as a matter of routine when treating a TTP Patient;

Full Blood Count
(this will give a reading for both platelets and red cells or haemoglobin, amongst others)

Reticulocyte (immature red blood cells)

Clotting screen

Renal & Liver function

LDH (Lactate dehydrogenase – a marker of tissue breakdown)

Virus such as HIV or Hepatitis
(TTP may be a secondary condition in HIV and anti-HIV medication is needed as well as plasma therapy)

Blood Group (for future blood supplies)

Pregnancy test (pregnancy is a known trigger of TTP)

Some patients report having the following symptoms prior to diagnosis:

Headaches

Confusion

anxiety

stomach upset

fever

disturbed vision