The Moschcowitz Syndrome, or Thrombotic Thrombocytopenic Purpura, is a rare disease classically characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, microvascular thrombosis, and neuro-psychiatric disorders, often associated with fever and renal involvement. It was first described by Moschcowitz in 1925.
It is a rare disease with an estimated incidence of 2 to 4 cases per million, with a higher frequency in females, and the most affected age group being between 20 and 50 years.
ETIOLOGY AND PATHOGENESIS
The etiology af the the Moschcowitz Syndrome not known precisely, but since the onset of the pathology has been observed in conjunction with viral or autoimmune diseases, it is believed that a non-specific triggering factor should be recognized in individuals with a particular genetic predisposition.
Several studies have identified specific genetic alterations that lead to the deficiency of a protein called ADAMTS 13. This latter is a metalloprotease that intervenes in the breakdown of von Willebrand factor into smaller and less efficient subunits, whose deficiency causes increased platelet aggregation in case of endothelial damage (the layer of cells lining blood vessels). The result, in case of endothelial damage, is therefore the exacerbation of platelet aggregation capacity with the formation of microthrombi diffused in the microcirculation, typical of this disease.
Acquired forms have been described, caused by the formation of autoantibodies against the ADAMTS 13 protein, and congenital forms in which the deficiency of the protein function is caused by one or more alterations of the encoding gene located in chromosome 9q34.
SYMPTOMATOLOGY AND CLINICAL FORMS
The clinical picture of the Moschcowitz Syndrome quite complex, and the presentation, beyond common characteristics, can vary. Thrombocytopenia, often severe with values even well below 50,000 u/mL, is caused by the persistent consumption of platelets due to the continuous formation of microthrombi in the microcirculation of all organs, causing cutaneous hemorrhages (purpura) but can also cause more severe hemorrhagic conditions, including cerebral.
The formation of microvascular thrombi spares practically no organ, therefore the following can be present:
- a neurological clinical picture whose severity varies (from simple paresthesia to that of a stroke);
- acute abdominal pain (microinfarctions and/or parenchymal ischemia);
- chest and joint pains;
- renal involvement (oliguria, hematuria, azotemia, etc.).
But practically every organ or body district can be affected by ischemic and/or hemorrhagic lesions, including the heart. Anemia is constant and caused by the reduced survival of traumatized red blood cells during their passage through partially thrombosed small vessels, therefore it is a “hemolytic” anemia due to the rupture of red blood cells and “microangiopathic” because of a pathology of small blood vessels.
Typical in this regard is the presence in peripheral blood of an increase in red blood cell fragments whose production is excessively fast compared to the spleen’s removal capacity from the circulation. Frequent subicterus, if not true jaundice, are related to hemoglobin degradation products not removed from the circulation quickly enough. Fever and hepatosplenomegaly are also common.
DIAGNOSIS OF MOSCHCOWITZ SYNDROME
The diagnosis is based on the clinical picture associated with thrombocytopenia, anemia with greater than 10% schistocytes in peripheral blood (schistocytes being fragments of red blood cells), and a negative Coombs test. Various techniques have also been proposed for the detection of antibodies against the ADAMTS 13 protein or for the measurement of its activity, but they are not readily available and their use is not yet sufficiently standardized.
TREATMENT AND PROGNOSIS
Untreated, the Moschcowitz Syndrome leads to death in 75% of cases within 2-3 months, while with treatment it is cured in almost 90% of cases, but relapses are possible. Since there is a fundamental autoantibody component, the use of high-dose corticosteroids has become standard with good results, but other immunosuppressants such as rituximab have also been used effectively.
The treatment of choice, however, is plasmapheresis, a technique that involves the removal of the patient’s blood plasma through a procedure called apheresis and its replacement with donor plasma. The rationale for the therapy, which in the past was performed with excellent results but without understanding the therapeutic mechanism, is the replacement of defective ADAMTS 13 protein with the “healthy” protein from the donor’s plasma and the removal of anti-ADAMTS 13 autoantibodies. Aspirin and dipyridamole (as antiplatelet agents) are also used, but to a lesser extent.
Another therapeutic procedure used, in some cases with significant reported efficacy, is splenectomy, perhaps because a source of autoantibody production is eliminated.
Supportive therapy is essential, including blood transfusions if necessary, support for diuresis up to hemodialysis, and cardiac therapy if necessary.
Other resources on Moschcowitz Syndrome:
This link leads to a PubMed research page on the syndrome: http://www.ncbi.nlm.nih.gov/PubMed?term=moschcowitz%20syndrome
Dr. Salvatore Nicolosi
General Practitioner with National Health Service agreement in Italy