0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

1
Letter   |    
Severe Normochrome and Normocytic Anemia After 19 Months on Ticlopidine
J. Finsterer, M.D., Ph.D.
The Journal of Neuropsychiatry and Clinical Neurosciences 1999;11:118-119.
View Author and Article Information

TiclopidineSide EffectsStroke

SIR: Ticlopidine (TPD), a powerful antiplatelet activator that inhibits adenosine diphosphate—induced platelet aggregation, is frequently given for secondary stroke prevention. A rare side effect of TPD is bone marrow suppression causing agranulocytosis and isolated aplastic anemia; this usually occurs shortly after the beginning of treatment.14 Consequently, blood cell counts are required within short intervals during the first 3 months of treatment. Late-onset aplastic anemia due to TPD therapy has not been reported before.

+

Case Report

In an 85-year-old woman, TPD was started as a secondary stroke prevention after a second stroke. She underwent hematologic monitoring every 2 weeks during the first 3 months. Immunoglobulin M-kappa paraproteinemia had been found after the first stroke, but repeated investigations gave no indication for plasmocytoma. Besides TPD, the patient had received lisinopril, nifedipine, and digoxin since the second stroke. One year after starting TPD, the patient was admitted because of acute heart failure. Laboratory investigations at that time already revealed a slight normocytic and normochrome anemia. After treatment, she regained her previous condition. She was additionally given furosemide, molsidomine, nitroglycerin, and allopurinol. TPD was continued.

Nineteen months after starting TPD, the patient was admitted because of increasing fatigability, dyspnea, and anemia. On her arrival, erythrocytes were 2.01, hemoglobin 5.6, and hematocrit 17.9. Median cell volume, median cell hemoglobin, and median cell hemoglobin concentration were normal, as were leukocytes, platelets, iron, transferrin, lactate-dehydrogenase, haptoglobin, and bilirubin. Reticulocytes were normal later on. Tests for occult blood in the feces were negative. Gastroscopy revealed chronic atrophic gastritis, and colonoscopy revealed melanosis coli and rare sigmoidal diverticles. Rectoscopy revealed internal hemorrhoids. Bone marrow aspiration was refused by the patient. TPD was changed to pentoxifylline; the other medications remained unchanged. After six red cell transfusions, the blood cell count became normal again. Three and 6 months after discharge the blood cell count was still normal, despite unchanged medication.

This case shows that TPD may cause severe isolated normochrome and normocytic anemia, even 19 months after starting medication. The patient's anemia was interpreted as aplastic and TPD-induced, since acute and chronic bleeding as well as hemolysis and vitamin B2, B6, and B12 deficiency were excluded. There was no indication for sideropenic or sideroachrestic anemia. Neither chronic infection nor tumor was found. There was no severe liver or kidney insufficiency or hemoglobinopathia.

Isolated aplastic anemia has been previously described as a rare side effect of TPD.25 In most of these cases, anemia occurred a few weeks after starting TPD. Why anemia in our patient did not become symptomatic until 19 months after initiation of treatment remains speculative; possibly the occurrence of anemia due to TPD decreases with age. Discontinuation of TPD led to an immediate improvement of the blood cell count and suggests TPD as the causative agent for the anemia in our patient. However, paraproteinemia predisposed for anemia cannot be definitively excluded.

An implication of the presented case is that controlled studies should be carried out dealing with the following questions: 1) should blood cell counts be conducted more frequently than recommended by the producing company, and 2) should TPD no longer be recommended as a stroke prophylaxis, especially in older patients.

Severe isolated aplastic anemia may be a late complication of TPD. The use of TPD as a secondary stroke prevention should be reconsidered, especially in older patients.

Marinella MA: Agranulocytosis associated with ticlopidine: a possible benefit with filgastrim. Ann Clin Lab Sci  1997; 27:418—421
[PubMed]
 
Su CC, Tseng CD, Hwang JJ, et al: Severe aplastic anemia induced by ticlopidine: report of a case. J Formos Med Assoc  1995; 94:689—691
[PubMed]
 
Mallet L, Mallet J: Ticlopidine and fatal aplastic anemia in an elderly woman. Ann Pharmacother  1994; 28:1169—1171
[PubMed]
 
DeJaureguiberry JP, Galzin M, Talard P, et al: Ticlopidine induced bone marrow aplasia. Rev Med Interne  1996; 17:1032—1036
[CrossRef] | [PubMed]
 
Shapiro CM, Walk D: Aplastic anemia associated with ticlopidine. Neurology  1996; 47:300
 
+

References

Marinella MA: Agranulocytosis associated with ticlopidine: a possible benefit with filgastrim. Ann Clin Lab Sci  1997; 27:418—421
[PubMed]
 
Su CC, Tseng CD, Hwang JJ, et al: Severe aplastic anemia induced by ticlopidine: report of a case. J Formos Med Assoc  1995; 94:689—691
[PubMed]
 
Mallet L, Mallet J: Ticlopidine and fatal aplastic anemia in an elderly woman. Ann Pharmacother  1994; 28:1169—1171
[PubMed]
 
DeJaureguiberry JP, Galzin M, Talard P, et al: Ticlopidine induced bone marrow aplasia. Rev Med Interne  1996; 17:1032—1036
[CrossRef] | [PubMed]
 
Shapiro CM, Walk D: Aplastic anemia associated with ticlopidine. Neurology  1996; 47:300
 
+
+

CME Activity

There is currently no quiz available for this resource. Please click here to go to the CME page to find another.
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 1

Related Content
Books
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 37.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 37.  >
Topic Collections