Dr. Ralph Wendt is a German Physician specialized in Nephrology at St. Georg Clinic in Leipzig. He is an expert in patient care and clinical research in TTP and he worked at the Inselspital Bern from 2007 to 2010. Understanding TTP interviewed Dr. Wendt about signs and symptoms of TTP.

1. Is TTP easy to diagnose?

Because all the symptoms are not specific for TTP and can have many other causes or etiologies it takes usually an average of 5-7 days (range 1 to 35 days) from the start of the signs/symptoms to the diagnosis of TTP. But TTP is a life-threatening emergency and diagnosis and therapy must be started as early as possible.

2. What does TTP trigger exactly?

It’s unclear what triggers TTP, but several factors may play a role. These factors may include:

  • Some diseases and conditions, such as pregnancy, cancer, HIV, lupus, and infections
  • Some medical procedures, such as surgery and blood or marrow stem cell transplant
  • Some medicines, such as chemotherapy, hormone replacement therapy e.g. estrogens

But in the majority of cases, a trigger cannot be identified.

3. What are the main signs/symptoms we should know about TTP?

Although patients with TTP can present in many different ways, there are 5 signs/symptoms that are often observed. The frequency of the named signs and symptoms prior to diagnosing this rare disease can be best estimated looking into large registries. The numbers given below (in %) represent the frequency of signs/symptoms in two large Registries taken as examples, the Oklahoma TTP-HUS Registry1 and the Australian TTP/TMA registry2, but might not necessarily represent the frequency for different populations in different parts of the world.

  1. Gastrointestinal symptoms (abdominal pain, nausea and vomiting) – 39-69%
  2. Headache and/or confusion or stroke-like symptoms – 66-71%
  3. Fatigue – 63%
  4. Skin bleeding – purpura and petechiae – 39-54%
  5. Dyspnea (shortness of breath, especially on exertion) – 29%

4. Can you describe each of these 5 signs/symptoms?

Abdominal symptoms are reported frequently prior to diagnosing TTP, especially abdominal pain. Those symptoms most probably represent blood flow disturbances (ischemia) in the bowel or other organs in the abdomen. There are also cases of abdominal pain due to pancreatitis in TTP. On some occasions, an enlarged spleen dealing with an increased amount of destructed red blood cells can also cause abdominal pain. Diarrhea can occur but is usually more typical for other thrombotic microangiopathic diseases.

Many patients have minor neurologic symptoms like headache or dizziness that vary greatly in severity. Those symptoms can advance rapidly to more obvious or serious neurological manifestations such as paresthesias (abnormal sensation such as tingling, tickling, pricking…), dysarthrias (motor speech disorder), seizures, paresis (weakness or partial loss of voluntary movement) and coma. Those symptoms represent the consequences of disturbed blood flow in the brain (microthrombi in the vessels) causing ischemia with stroke-like symptoms.

Fatigue (weariness, weakness, exhaustion) mainly derives from low red blood cell count (anemia). Sometimes it is accompanied by higher heart rate (pulse) because the heart tries to compensate for the lower oxygen-transport capacity by increasing the turn-over of blood. Due to the destruction of red blood cells and the breakdown of released hemoglobin, a yellow compound called bilirubin is increasingly produced and can cause yellowish pigmentation of the skin and the eyes (jaundice).

Because of thrombocyte consumption in clot formation in the microcirculation, there are less thrombocytes available for the coagulation process and sealing of small cuts in the vessels. Therefore already small sometimes unrecognized trauma can cause bleeding under the skin (bruises). Typical signs of skin bleeding in TTP are “Petechiae” which are small pin-sized dots in red or purple in color. Purpura consists of multiple petechiae, sometimes a little bigger in size (3-10mm). They are non-bleachable, which means when the skin is pressed, the redness doesn’t go away.
Fortunately, severe bleeding is rare in TPP, most probably because the function of the remaining thrombocytes is preserved. Another often-reported bleeding sign in TTP is red urine (hematuria) or menorrhagia (menstrual periods with abnormally heavy or prolonged bleeding).

Dyspnea is mainly due to accompanying anemia, but can also indicate heart involvement. Anemia means reduction of the number of red blood cells and lower concentration of the red blood pigment called hemoglobin which transports oxygen through the body. Some might recognize additional signs of anemia like paleness of skin. Anemia is caused by the destruction of red blood cells when those cells flowing in the blood stream hit against clotted small vessels or fibers of ultralarge multimers of von Willebrand factor. Anemia caused by the destruction of red blood cells is called hemolytic anemia. In TTP you can usually see destructed erythrocytes under the microscope (so called schistocytes).

5. What should patients do in case of relapse?

Relapse happens frequently in TTP (40-60%) and relapsing patients are most of the time more aware of the symptoms and signs. In case of any new onset symptom or sign, even if not mentioned above, patients should not hesitate to see their doctor for clinical assessment and at least a blood sample (minimum: number of thrombocytes, hemoglobin, LDH and creatinine). It´s good to know that effective treatment is available and the armament of treatment options are likely to improve in the near future.

1 James N. George, Blood. 2010;116(20):4060-4069
2 Blombery P et al., Intern Med J. 2016 Jan;46(1):71-9.

The views, thoughts, and opinions expressed by Dr. Wendt in the text belong solely to him, and do not necessarily represent Ablynx nv. This content is shared for the purpose of general information and is in no way intended to replace professional medical care or attention by a healthcare professional.

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