clozapine has been known to cause haematological side effects like agranulocytosis , neutropenia , leucocytosis , eosinophilia and thrombocytopenia .
although some data is available with regard to leucopenia , data for thrombocytopenia is limited . in this report
we present the case of a patient who developed thrombocytopenia with clozapine and review the existing literature .
a woman aged 22 , suffering from paranoid schizophrenia ( as diagnosed by dsm - iv ) for the past three years , presented with an acute episode .
she had received adequate trials of olanzapine , risperidone and quetiapine along with electroconvulsive therapy .
taking this into account she was started on clozapine . prior to starting of clozapine her hemogram including
platelet count did not reveal any abnormality . for the management of acute symptoms in view of the suicidal risk , she was treated with electroconvulsive therapy , lorazepam up to 4 mg / day and
was started on clozapine and the dose was gradually increased to 187.5 mg / day over the period of four weeks because of side effects of hypersalivation and constipation .
while clozapine was increased , leucocyte count and platelet counts were monitored regularly on weekly basis and serial monitoring did not reveal any abnormality . with this she achieved symptomatic remission following which lorazepam was stopped . while on clozapine 187.5 mg / day , low platelet count ( 101,000 and 98,000/l on two occasions ) was noted for the first time after 17 weeks of continuation of clozapine at the above said dose without reduction in the leucocyte count or haemoglobin levels . following this monitoring
was increased and platelet count kept on fluctuating between 1,20,000/l to 1,35,000/l . over the period , platelet count started dropping . by another 24 weeks of clozapine therapy ,
the platelet count dropped to 60,000/l without any reduction in the leucocyte count and the haemoglobin levels .
the drop occurred despite reduction in the dose of clozapine upto 125 mg / day .
clozapine was stopped completely as a result . throughout this period she never had any fever , skin rash , purpura , excessive menstrual bleeding or bleeding from any other source , arthritis , arthralgia , muscle pain and muscle weakness .
her investigations in the form of serum electrolytes , liver function test , renal function test , prothrombin time , bleeding time , clotting time and ultrasound abdomen and pelvis did not reveal any abnormality .
she was also evaluated by physician and the opinion was that the low platelet count may be related to clozapine . within a week of
stopping clozapine platelet counts started improving and by six weeks her platelet count was 1,80,000/l . in the meanwhile , with stoppage of clozapine , she had relapse of symptoms and required inpatient care , was treated with electroconvulsive therapy , lorazepam and chlorpromazine , with which she achieved remission . during this period her platelet count remained within the normal range .
thrombocytopenia is defined as platelet count of less than 100  10/l . only two studies and a small case series
have reported incidence of thrombocytopenia associated with clozapine and only few case reports have focused on this association.[410 ] the findings are summarized in table 1 .
literature reporting clozapine associated thrombocytopenia although in most of the literature thrombocytopenia associated with clozapine has been reported to be transitory to at best last for 13 weeks , in a case report thrombocytopenia persisted for 40 months after stopping clozapine .
there are also few case reports of clozapine associated thrombocytosis . in one of this case
reports thrombocytosis was seen in a patient treated with granulocyte colony stimulating factor for clozapine associated agranulocytosis . as with thrombocytopenia , an immunological mechanism
thrombocytopenia was noted for the first time after 17 weeks of stable dose of clozapine , which kept on worsening with continuation of clozapine , even on the lower dose and subsided only after stoppage of clozapine and normalization of platelet count required six weeks .
however , in contrast to some of the reports , in the index case , platelet count kept on falling consistently with continuation of clozapine and improved only after stoppage of clozapine , suggesting that in certain cases the side effects may be transitory and can lead to fatal outcome . from the above literature
it can be concluded that there is a wide variation in the incidence of thrombocytopenia with clozapine , which possibly is influenced by the sample size studied .
there is lack of consensus with regard to resolution , with some reports suggesting that resolution requires stoppage of clozapine , as was seen in the index case too ; whereas others suggest that thrombocytopenia resolves on its own .
most of the available literature is silent about the possible mechanism , except for one report which demonstrated underlying immunological mechanism in a case of persistent thrombocytopenia even after stopping clozapine .
considering the fact that the thrombocytopenia may be transitory as suggested in some of the case reports , an informed decision about rechallenge must be made after weighing the risk and benefits . from the above it
hence , besides monitoring the leucocyte count , platelet count of patients receiving clozapine should also be monitored .
 although agranulocytosis as a side effect of clozapine is well known , there is scarcity of data with regard to thrombocytopenia associated with clozapine . in this report 
 we describe a case of clozapine induced thrombocytopenia and review the existing literature . a 22 year old female patient developed thrombocytopenia while on clozapine 187.5 mg / day for 17 weeks . 
 thrombocytopenia persisted for 24 weeks even after reduction in the dose of clozapine and ultimately clozapine had to be stopped , which led to resolution of thrombocytopenia . 
 clozapine - induced thrombocytopenia is a less well - known , but potentially serious , adverse effect that should be screened for in practice . 
 the case highlights the fact that besides monitoring the leucocyte count , platelet count of patients receiving clozapine should also be monitored . 
INTRODUCTION
CASE REPORT
DISCUSSION