Purpura idiopathic thrombocytopenic D69.3

The idiopathic thrombocytopenic purpura was first described by Paul Gottlieb Werlhof (1699-1767). In 1735 he described the "Purpura haemorrhagica" or also "Morbus maculosis Werlhofii".

Acute or chronic bleeding disorder with thrombocytopenia without a recognisable cause. The disease is characterized by a shortening of the survival time of the thrombocytes.

In children, idiopathic thrombocytopenic purpura (ITP) usually begins acutely, often associated with viral infections such as measles, rubella and mumps or after vaccinations. In about 80-90% of cases, remission occurs within up to six months, in which case therapy is not necessary. Rarely does ITP in children go into a chronic form (0.46/10,000 children/year).

In adults, ITP develops gradually and without previous infection. The clinical symptoms vary from slight mucous membrane bleeding to diffuse bleeding throughout the body. Women of childbearing age are most affected. The diagnosis is based on the exclusion of other hemorrhagic diatheses. Bone marrow cytology shows a reactive increase of megakaryocytes up to five times the norm.

The incidence is 6-7 new cases/ 100,000 inhabitants per year.

Unsolved. In the chronic form, autoantibodies, mostly of the IgG type, are detectable in 60-80% of cases. They bind to the GPIIb-GPIIIa receptors of the thrombocytes. The sensitized platelets are destroyed in the spleen by Fcy recognition, mainly by macrophages. The platelet survival time is reduced to a few hours. Antiplatelet IgG can be detected chemically on the surface of the platelets in the laboratory.
Antibodies are detected by ELISA or by immunofluorescence test or complement fixation test.

Illness > 6 months. Preferably adults! w:m=3:1

• Petechial or areal bleeding occurs only with platelet counts < 30,000/ul.
• Acute form: Haemorrhages of the skin and mucous membranes, bleeding from the mouth or nasopharynx, melena, haematuria.
• Chronic form: Usually insidious onset. Bleeding from the nose and/or gums. Menorrhagia, metrorrhagia, petechiae on the lower legs, petechial and areal skin haemorrhages.

• Acute form: Highly reduced platelet count, short platelet survival time.
• Chronic form: Anemia, increase of megakaryocytes in the bone marrow, rarely reduction due to exhaustion. Shortened platelet survival time. To exclude EDTA-induced pseudothrombocytopenia, a control with citrate blood should be performed.
• Detection of free platelet-associated IgG antibodies (PA IgG) in >80% of patients.

• Corticosteroids (1-1.5 mg/kg body weight), response 80%.

• If therapy does not respond, high doses of intravenous immunoglobulins (400-1000 mg/kg over 5 days). Principle of action: blockade of Fc receptors on macrophages.

• In case of further resistance to therapy and thrombocytopenia of < 50,000, splenectomy is indicated (previously vaccination with Pneumovac).

• If the response is still insufficient: immunosuppression with e.g. vincristine, endoxane, azathioprine, ciclosporin (10-15 mg/kg/day). 20-40% of patients respond to this.

• A further attempt to treat ITP is the administration of the CD20 antibody rituximab with response rates of 20-25%.

• The transfusion of platelets should be handled as cautiously as possible, as this can further stimulate antibody production.

1. Ancona KG et al (2002) Randomized trial of high-dose methylprednisolone versus intravenous immunoglobulin for the treatment of acute idiopathic thrombocytopenic purpura in children. J Pediatr Hematol Oncol 24: 540-544
2. Bolton-Maggs PH et al (2000) Idiopathic thrombocytopenic purpura. Arch Dis Child 83: 220-222
3. Jones HW, Tocantis LM (1933) The history of purpura hemorragica. Ann Med Hist 5: 349
4. Junca J (2000) The relationship between idiopathic thrombocytopenic purpura and pernicious anaemia. Br J Haematol 111: 513-516
5. Rosthoj S et al (2003) Duration and morbidity of newly diagnosed idiopathic thrombocytopenic purpura in children: A prospective nordic study of an unselected cohort. J Pediatr 143: 302-307
6. Schulz et al (2006) Generalized purpura as dermatological manifestation of thrombocytopenia. Dermatologist 57: 697-700
7. Werlhof PG (1735) Opera medica collegit et auxit. Wichmann (Ed.), Hannoverae impensis fratrum Helwingiorum, Hannover, p. 748
8. Williams JA (2003) Combination therapy for refractory idiopathic thrombocytopenic purpura in adolescents. J Pediatric Hematol Oncol 25: 232-235