Purpura idiopathic thrombocytopenic D69.3

Idiopathic thrombocytopenic purpura was first described by Paul Gottlieb Werlhof (1699-1767). In 1735, he described "Purpura haemorrhagica" or "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 per 100,000 inhabitants per year.

Unexplained. 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 platelets. The sensitized platelets are destroyed by Fcy recognition, predominantly by macrophages, in the spleen. Platelet survival is reduced to a few hours. Laboratory chemistry can detect antiplatelet IgG on the surface of platelets.
Antibodies are detected by ELISA, immunofluorescence assay, or complement fixation assay.

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

Petechial or areal hemorrhages occur only with platelet counts < 30,000/ul.

Acute form: Hemorrhages on skin and mucosa, bleeding from the mouth or nasopharynx, melena, hematuria.

Chronic form: Usually insidious onset. Bleeding from the nose and/or gums. Menorrhagia, metrorrhagia, petechiae on the lower legs, petechial and areal skin hemorrhages.

Acute form: Severely decreased platelet count, short platelet survival.

Chronic form: Anemia, increase in megakaryocytes in the bone marrow, rarely reduction due to exhaustion. Shortened platelet survival. To exclude EDTA-induced pseudothrombocytopenia, control with citrated blood should be done.

Detection of free platelet-associated IgG antibodies (PA IgG) in >80% of patients.

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

In case of non-response to therapy, high doses of intravenous immunoglobulins (400-1000 mg/kg over 5 days). Mechanism of action: blockade of Fc receptors on macrophages.

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

If response is still insufficient, immunosuppression with e.g. vincristine, endoxan, azathioprine, ciclosporin (10-15 mg/kg/day). This is responded to by 20-40% of patients.

Another attempt at therapy of ITP is the administration of the CD20 antibody Rituximab with response rates of 20-25%.

Transfusion of platelets should be handled with as much restraint 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