Clozapine remains the gold standard of treatment for schizophrenic patients with treatment-resistant symptoms. Sometimes patients develop unusual hematological reactions with increased mostly red blood cells, which rises differential diagnostic issues: is it a side effect of clozapine treatment or is it a primary medical condition?

To elucidate the etiology of the hematological disturbances in order both to control psychotic symptoms as well as to maintain an optimal somatic profile of the patient.

41 years female with a long history of schizophrenia became refractory of treatment, so clozapine was instituted as treatment of first choice. by monitoring paraclinical parameters we found progressive increased of the blood cells, mainly red blood cells, which has un unpredictable risk for somatic complications. We approached this case by interdisciplinary management-psychiatric and hematological to find the etiology of this peculiar comorbid condition.

The evaluations performed led us to the conclusion that there are two different nosologic entities, treatment of the psychiatric condition revealing polycythemia vera. This conclusion required reducing clozapine dose and adding another atypical antipsychotic. All subsequent evaluations demonstrated the efficiency in managing the psychiatric disorder and even an improvement in hematological condition.

Treatment-resistant schizophrenia remains a challenge for psychiatrists, clozapine treatment requiring for an active monitoring because it can be a trigger for an unusual somatic disease-polycythemia vera.