Pseudothrombocytopenia in a patient with bipolar type 2 disorder on lurasidone: A case report.

Sir,

Ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia (PTCP) occurs due to in vitro agglutination of platelets in the blood collection tube in the absence of clinical signs of thrombocytopenia. Instances of PTCP with psychotropics such as olanzapine and valproate have been reported.[12] This is, to our knowledge, the first instance of PTCP associated with lurasidone.

A 28-year-old physician presented to our services with a diagnosis of bipolar affective disorder-Type 2, in a moderate depressive episode. She also met diagnostic criteria for emotionally unstable personality, polysubstance use (nicotine in dependence pattern with occasional use of alcohol, cannabis, and psychedelics).

At the time of presentation, she was on lithium 900 mg/d and lurasidone 80 mg/d for 4 months. She was abstinent from all substances except nicotine for 4 months. A platelet count done 4 months ago was within the normal reference range (2,20,000/uL). Menstrual cycles were normal, with the last menstrual period 20 days before presentation.

Her hemogram revealed persistently low platelet counts ranging from 20,000 to 30,000/uL. Total and differential white blood count, hemoglobin, and red blood counts were consistently within the normal limits. There was no history of febrile illness or recent weight loss. There were no signs of mucosal bleeding, petechiae, or purpuric patches. Tourniquet test was negative. Liver and renal functioning, hemoglobin, thyroid functions, Vitamin B12, venereal disease research laboratory, HIV, and hepatitis B surface antigen were unremarkable. History of autoimmune disorders was absent and there was no family history of hematological disorders.

On peripheral smear, adequate platelets (in clumps) were noted. A platelet count collected in a heparinized bulb revealed a count of 1,50,000/uL. Based on this, a diagnosis of PTCP was made by the consulting physician. As the condition is benign, conservative management was advised.

Lurasidone was ineffective in alleviating depression, so was tapered and stopped. Psychotherapy was initiated. Three months later, a repeat platelet count was within the normal reference range. A temporal correlation was noted with the onset and offset of PTCP with lurasidone [Table 1]. The Naranjo Adverse Drug Reaction Probability Scale[3] revealed a score of 6, suggestive of a probable adverse drug reaction to lurasidone.

Table 1

Variation in platelet counts with medication

Medication	October 2017 (baseline)	February 2018	April 2018	July 2018
Lithium	Not yet initiated	900 mg	900 mg	900 mg
Lurasidone	Not yet initiated	40-120 mg	120 mg - tapered and stopped	Off lurasidone for 3 months
Platelet count	220,000/uL at baseline (drug-free)	20-30,000/uL on repeated testing (EDTA). On testing with heparin bulb-150,000/uL	66,000/uL	150,000/uL

EDTA – Ethylenediaminetetraacetic acid

EDTA-associated PTCP is diagnosed when thrombocytopenia (<1,00,000) is seen when EDTA tubes are used for blood collection. Platelet aggregation and the absence of clinical manifestations of thrombocytopenia are also important indicators.[4] EDTA is routinely used as an anticoagulant in vitro, to prevent blood samples from clotting before reaching the laboratory. The use of EDTA as well as certain drugs helps in dissociation of the GPIIb/IIIa complex exposing GPIIb (crypto antigen), which allows binding to antibodies directed against these receptors or other naturally occurring antibodies.[1] The use of an alternate anticoagulants such as citrate and heparin may help in confirming the diagnosis.[1]

Although many medical conditions are known to be associated with this condition, this case was significant for the absence of associated medical pathology. The Naranjo score also suggested that lurasidone may have contributed to PTCP. In such circumstances, it may be prudent to get a peripheral smear, and a platelet count using non-EDTA anticoagulants, which may preclude the need for more invasive tests (for example bone marrow aspiration).

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Conflicts of interest

There are no conflicts of interest.