Psychosomatics 43:421-423, October 2002
© 2002 The Academy of Psychosomatic Medicine
Olanzapine-Induced EDTA-Dependent Pseudothrombocytopenia
Chun-Hsien Tu, M.D., and
Stone Yang, M.D.
Received March 26, 2002; accepted April 16, 2002. From the Department of Psychiatry, Veterans Hospital of Lungchan, Taiwan. Address reprint requests to Dr. Tu, No. 1, Anping Lane 1, Jausheng Rd., Lungtan Tsuen, Neipu Shiang, Pingtung, 912, Taiwan, R.O.C.; aromatu{at}yahoo.com.tw (e-mail).
Thrombocytopenia is an uncommon but potentially dangerous side effect of antipsychotic drugs; pseudothrombocytopenia is an even rarer phenomenon that must be differentiated from thrombocytopenia in evaluating patients with a low platelet count.1 Olanzapine is an atypical antipsychotic used in the acute and maintenance treatment of schizophrenia and other psychotic disorders. Many reports have described its hematological side effects, including leukopenia, granulocytopenia, neutropenia, pancytopenia, thrombocytopenia, and anemia,2–7 but we could find no reports of pseudothrombocytopenia. This article reports a case of olanzapine-induced pseudothrombocytopenia that was confirmed by rechallenge with the same drug.
Case Report
Mr. W was a 74-year-old single man without a prior or family history of thrombocytopenia, bleeding disorder, alcohol abuse, autoimmune disease, recent radiation therapy, or blood transfusion. He had a history of gastric ulcer and gallstone, but he had not received regular medication or surgical intervention. About 4 years ago he began to have bizarre behaviors and queer thoughts, including talking to himself, hearing voices from the gods, falsely believing that he had three wives, setting fires, and committing destructive acts secondary to the delusion that his neighbors stole his land. He was first admitted to a local mental ward, where a diagnosis of late-onset schizophrenia was made. Three months later, his second hospitalization took place on our ward, where testing with the Mini-Mental State Examination revealed the possibility of early dementia. He was treated with chlorpromazine or fluanxol throughout the subsequent 3 years. In February 2001, because of his insensitivity to these drugs, a dose of 5 mg of olanzapine at night was initiated. During the period from June 1998 to September 2000, the platelet counts from blood treated with ethylenediaminetetraacetic acid (EDTA) ranged from 11.9 to 27.9 x 104/µl (transfer time was about 4 hours; blood was stored at room temperature).
The dose of olanzapine was increased to 5 mg b.i.d. on day 44 of olanzapine therapy (Table 1). On day 49, severe drowsiness was noted (Glasgow coma scale rating of 3, indicating no eye opening, no verbal response, and no motor response). Data from laboratory tests showed a platelet count of 2.3 x 104/µl in EDTA-anticoagulated blood (transfer time was approximately 0.5 hour); other biochemical data were within normal limits. The patient was given an injection of flumazenil, and his consciousness became partly clear. Physical examination revealed no petechiae or purpura. Olanzapine was suspected as the cause of the low platelet count, so it was immediately discontinued.
View this table:
[in this window]
[in a new window]
|
TABLE 1. Platelet Counts (104/µl) in Blood Samples Anticoagulated With Ethylenediaminetetraacetic Acid in a Patient With Schizophrenia Treated With Olanzapine and Other Antipsychotic Medications, by Blood Sample Storage Temperature and Transfer Time
|
Platelet clumping had been noted by the laboratory technician and the automatic blood analyzer (Sysmex 2000, Sysmex, Kobe, Japan) at initial testing, yet we still managed Mr. W under the impression that olanzapine-induced immune thrombocytopenia had occurred. Later, on day 79 after initiation of olanzapine, progressive decrease in the platelet count aroused our interest, and the diagnosis was revised to EDTA-dependent pseudothrombocytopenia. Several laboratory test values, including those for prothrombin time, activated partial thromboplastin time, bleeding time, coagulation time, T3 level, T4 level, antinuclear antibody level, and levels of serum complement components C3 and C4, were normal, although the serum ion level was lower than normal (33 µg/dl). The platelet counts (data not shown) of blood samples anticoagulated with citrate or heparin were far higher than that of the EDTA-anticoagulated blood and were close to the "true" platelet counts (i.e., the counts obtained immediately after blood withdrawal and before adding any anticoagulant). The patient was given sulpiride from day 98 to day 121 for control of psychotic behaviors and then underwent an antipsychotic-free washout period for 19 days.
A rechallenge with olanzapine was made on day 140, at a dose of 5 mg at night initially, increasing to 10 mg/day. A similar course of change in platelet counts was observed. The phenomenon of EDTA-dependent pseudothrombocytopenia lasted for more than 6 months (Table 1). Throughout the 241 days of serial investigation, no steroid therapy or platelet transfusion was given.
Discussion
EDTA-dependent pseudothrombocytopenia is important in clinical practice because failure to recognize this phenomenon may lead to misdiagnosis and subsequent mismanagement of patients.8 In the case presented here, we initially misinterpreted the platelet clumping in the blood film as a presentation of drug-induced immune thrombocytopenia and attributed the absence of bleeding tendency to the immediate discontinuation of olanzapine. Yet the progressive decrease in platelet counts in the period between 10 minutes and 4 hours raised the possibility of pseudothrombocytopenia. The causes of pseudothrombocytopenia include improper blood sampling technique, giant platelet syndrome, platelet satellitosis, and in vitro platelet clumping9 and are related to treatment with various medications10–12 and to physical illness.9,13 The platelet clumping can be EDTA-dependent,9 as in the case of EDTA-dependent pseudothrombocytopenia described here.
EDTA-dependent pseudothrombocytopenia occurs in about one of 1,000 blood samples examined (i.e., incidence in the general population of about 0.1%)1,10 and is the second most common cause for low platelet count (the incidence was reported as 17% in patients with a platelet count less than 10 x 104/µl).8 It could be mediated by several types of platelet agglutinins (i.e., naturally occurring, antiplatelet autoantibodies) against the platelet membrane glycoprotein IIb/IIIa complex.1 Antibodies of the immunoglobulin G (IgG) class that react at room temperature are found most frequently in EDTA-dependent pseudothrombocytopenia; however, cold reactive IgA, IgM alone, the combination of IgG and IgM, and the combination of IgG and IgA have also been reported.9 The glycoprotein IIb/IIIa complex must dissociate to expose glycoprotein IIb, called the "cryptantigen" or "neoantigen," for antibody binding to occur.9
Various drugs, EDTA concentration, pH, and temperature may all affect this complex dissociation.9,14 Drugs such as mexiletine and abciximab have been reported to be related to pseudothrombocytopenia.10–12 To our knowledge, this case report is the first to describe olanzapine-induced EDTA-dependent pseudothrombocytopenia confirmed by rechallenge with olanzapine. During the first few days of rechallenge with olanzapine, a clear acceleration of platelet clumping was noted: the platelet counts at room temperature at time lapse of 10 minutes showed a sudden drop. We did not try to document the presence of autoantibodies because of the difficulty in availability of the specific assay. The correct platelet count can usually be determined by collecting the blood into sodium citrate or heparin or performing a count by using a nonanticoagulated fingerprick sample.1
The diagnosis of pseudothrombocytopenia can be achieved either by examining by light microscope the blood film from EDTA-anticoagulated blood withdrawn 10 minutes earlier (instead of many hours earlier, in which case the phenomenon "pseudo pseudothrombocytopenia" may occur15) and kept at room temperature, or by comparing the difference between the automated platelet counts obtained at time lapses of 10 minutes and 4 hours. The evidence for pseudothrombocytopenia will consist of significant platelet clumpings or significant decrease in platelet count, respectively.
Although pseudothrombocytopenia has no pathologic significance and will not increase thrombotic or hemorrhagic risk, failure to recognize it may potentially place a patient in jeopardy for inappropriate discontinuation of the needed drug, delay of therapies involving invasive procedures, or initiation of unnecessary therapies, such as platelet transfusion or use of steroids.1,10,12 In the case reported here, olanzapine would not have been discontinued if an early distinction between pseudothrombocytopenia and drug-induced immune thrombocytopenia had been made.
REFERENCES
- Hoffman R, Banz EJ Jr, Shattil SJ, Silberstein LE (eds): Hematology: Basic Principles and Practice, 3rd ed. New York, Churchill Livingstone, 2000, pp 2138-2141
- Cadario B: Olanzapine (Zyprexa): suspected serious reactions. CMAJ 2000; 163:85-86, 89-90
- Olanzapine: keep an eye on this neuroleptic. Can Fam Physician 2000; 46:322-326[Medline]
- Bogunovic O, Viswanathan R: Thrombocytopenia possibly associated with olanzapine and subsequently with benztropine mesylate. Psychosomatics 2000; 41:277-278[Free Full Text]
- Gajwani P, Tesar GE: Olanzapine-induced neutropenia. Psychosomatics 2000; 41:150-151[Free Full Text]
- Benedetti F, Cavallaro R, Smeraldi E: Olanzapine-induced neutropenia after clozapine-induced neutropenia (letter). Lancet 1999; 354:567[CrossRef][Medline]
- Bachmann S, Schroder J, Pantel J, Mundt C, Zorn M, Witzens M, Egerer G: Olanzapine-induced thrombocytopenia in association with idiopathic thrombocytopenic purpura (letter). Br J Psychiatry 1998; 173:352
- Cohen AM, Cycowitz Z, Mittelman M, Lewinski UH, Gardyn J: The incidence of pseudothrombocytopenia in automatic blood analyzers. Haematologia (Budap) 2000; 30:117-121[Medline]
- Berkman N, Michaeli Y, Or R, Eldor A: EDTA-dependent pseudothrombocytopenia: a clinical study of 18 patients and a review of the literature. Am J Hematol 1991; 36:195-201[Medline]
- Holmes MB, Kabbani S, Watkins MW, Battle RW, Schneider DJ: Images in cardiovascular medicine: abciximab-associated pseudothrombocytopenia. Circulation 2000; 101:938-939[Free Full Text]
- Girmann G, Pees H, Scheurlen PG: Pseudothrombocytopenia and mexiletine (letter). Ann Intern Med 1984; 100:767
- Moll S, Poepping I, Hauck S, Gulba D, Dietz R: Images in cardiovascular medicine: pseudothrombocytopenia after abciximab (ReoPro) treatment. Circulation 1999; 100:1460[Free Full Text]
- Matarazzo M, Conturso V, Di Martino M, Chiurazzi F, Guida G, Morante R: EDTA-dependent pseudothrombocytopenia in a case of liver cirrhosis. Panminerva Med 2000; 42:155-157[Medline]
- Berning H, Stilbo I: Pseudothrombocytopenia and the haematology laboratory (letter). Lancet 1982; 2:1469-1470[Medline]
- Jim RT. Case report: pseudo pseudothrombocytopenia. Hawaii Med J 2001; 60:108[Medline]
Get information about faster international access.
Privacy Policy
Copyright © 2002
Academy of Psychosomatic Medicine.
All rights reserved.
Home
| Search
| Current Issue
| Past Issues
| Subscribe
| All APPI Journals
| Help
| Contact Us
|
