What are the signs of TTP

Thrombotic thrombocytopenic purpura (TTP), Moschcowitz disease



definition

It is a multisystem disease with thrombocytopenia, hemolytic anemia, neurological abnormalities, often with renal insufficiency and fever.

Epidemiology

The maximum age of the disease is around the age of 40, women are affected about twice as often as men. The incidence is around 3-10 in a million per year.

Etiology and pathogenesis

In patients with TTP, unusually large multimers of the von Willebrand factor are found, which induce platelet aggregation via the glycoprotein Iba component of the platelet glycoprotein complex Ib / IX / V. The cause of the formation of the large multimers is due to a reduced activity of the metalloprotease enzyme, which is known as ADAMTS13(e-disintegrin and metalloprotease with thrombospontin-I-like domains) referred to as. The cause of the acquired, more common form is the formation of inhibiting autoantibodies. A gene mutation in the ADAMTS13 gene on chromoson 9q34 is responsible for the familial form. The activity of this enzyme is less than 10% in the acute episode of the disease. In about 15% of all affected patients, the disease is stimulated by various causes. Since most multimers originate from the endothelium, damage to the endothelial cells leads to the multiplication of the multimers in the plasma.

Known possible triggers of a TTP or MAHA (microangiopathic hemolytic anemia)
Diseases and factors as the cause
  • Cavernous hemangioma (Kasabach-Merritt syndrome);
  • various infections (E. coli, Shigella dysenteriae, rickettsiae, fungi, viral infections including HIV, influenza and polio);
  • Sepsis (meningococci, pneumococci, staphylococci and other germs);
  • Carcinomas;
  • Snake bites;
  • malignant hypertension;
  • Late gestures;
  • Preeclampsia and eclampsia (HELLP syndrome);
  • Collagenoses;
  • acute glomerulonephritis;
  • Transplant rejection;
  • Pharmaceuticals: including ticlopidine, clopidogrel, mitomycin C, carboplatin, cisplatin, daunorubicin, cytosine arabinoside, ciclosporin A, bleomycin, interferon-gamma, ticlotidine, valaciclovir, quinine, tacrolimus;
  • Radiotherapy (whole body irradiation).

Symptoms

This is characteristic of the disease Triad out:

  • Thrombocytopenia,
  • microangiopathic hemolytic anemia and
  • CNS symptoms.

In addition, more than half of the patients show signs of renal insufficiency and occasionally petechial skin changes. Some of the patients (approx. 25%) complain of a fever.

Diagnosis

Diagnosing a TTP
Clinical examination:
  • Anemia,
  • Mild jaundice,
  • Petechiae,
  • Fever,
  • Neurological symptoms.
Laboratory diagnostics and findings
  • Differential blood count: often anemia, thrombocytopenia and increased fragmentocytes;
  • LDH: significantly increased;
  • Bilirubin: slightly to significantly increased;
  • Serum electrolytes (potassium, sodium) and urinary substances;
  • Coagulation parameters (prothrombin and thrombin time, fibrinogen, fibrinogen cleavage products): often largely normal;
  • Haptoglobin: decreased;
  • Detection of antibodies against metalloprotease in 80% of affected patients with the acquired form without cause;
  • Detection of a gene mutation in the familial form;
  • decreased activity of the metalloprotease ADAMTS13;
  • Detection of unusually large multimers of the von Willebrand factor.

therapy

Therapy of TTP
therapycomment
Plasma exchange /
Plasmapheresis /
Immune absorption
 
Forms of treatment with the greatest prospect of quick success.
Glucocorticoids Leads to success in patients with autoantibodies against the metalloprotease (ADAMTS13). High doses of prednisone are given.
Rituximab (anti-CD20) Effective in patients with autoantibodies against metalloprotease (ADAMTS13).
Splenectomy If therapy with glucocorticoids or rituximab is unsuccessful, splenectomy may be effective in treatment-refractory patients and proven autoantibodies.

forecast

Untreated thrombotic thrombocytopenic purpura used to lead to death in almost all cases. A TTP recognized and treated in good time has a good chance of permanent complete remission, but even today up to 10% of patients die. In up to 60% of cases, relapses are possible, which in turn can be treated.

Current reports from the 58th
ASH Annual Meeting 2016,
San Diego, California, USA [more]
2016 ASCO Annual Meeting - current reports. This service is funded by:
 
[More]





Editor: Prof. Dr. H. Link
Editorial Board: Prof. Dr. P. Albers, Prof. Dr. R. Andreesen, Priv.-Doz. Dr. A. Böhme, Prof. Dr. C. Bokemeyer, Prof. Dr. U. Creutzig, Prof. Dr. G. Ehninger, Prof. Dr. M. Freund, Prof. Dr. C. Garbe, Dr. N. Gökbuget, Prof. Dr. M. Hallek, Prof. Dr. J.T. Hartmann, Prof. Dr. R. Hehlmann, Prof. emerit. Dr. H. Heimpel, Prof. Dr. A. Hochhaus, Prof. Dr. K. Höffken, Dr. G. Huebner, Prof. Dr. Th. Junginger, Priv.-Doz. Dr. U. Kaiser, Priv.-Doz. Dr. R. Kath, Prof. Dr. C.-H. Koehne, Dr. R. Mahlberg, Prof. Dr. A. Matzdorff, Prof. Dr. R.-P. Müller, Prof. Dr. J. Preiss, Prof. Dr. H.-J. Schmoll, Prof. Dr. G. von Minckwitz