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| TOPIC OF THE ISSUE: LETTER TO EDITOR |
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| Year : 2011 | Volume
: 59
| Issue : 1 | Page : 69-70 |
Pure red cell aplasia with phenytoin following traumatic brain injury
G Paul1, P Sood1, A Berry2, BS Paul3
1 Critical Care Division, Dayanand Medical College and Hospital, Ludhiana, India
2 Department of Medicine, Dayanand Medical College and Hospital, Ludhiana, India
3 Department of Neurology, Dayanand Medical College and Hospital, Ludhiana, India
| Date of Submission | 28-Apr-2010 |
| Date of Decision | 28-Apr-2010 |
| Date of Acceptance | 31-Oct-2010 |
| Date of Web Publication | 18-Feb-2011 |
Correspondence Address:
G Paul
Critical Care Division, Dayanand Medical College and Hospital, Ludhiana
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0028-3886.76866
How to cite this article:
Paul G, Sood P, Berry A, Paul B S. Pure red cell aplasia with phenytoin following traumatic brain injury. Neurol India 2011;59:69-70 |
Sir,
The hematological, toxic effects of phenytoin therapy are well documented, but drug-induced, pure red cell aplasia is an uncommon disorder. We report the case of acute bone marrow suppression and pure red cell aplasia following prophylactic phenytoin after traumatic brain injury.
A 25-year-old male was admitted to Emergency Department after sustaining frontomaxillary injuries His past medical and family history were unremarkable. Neurologic examination showed Glasgow Coma Scale (GCS) score of 13. His hemoglobin was 9.6gm/dl. Computed tomography (CT) of head revealed frontal contusions. He was managed conservatively and discharged about three weeks later on phenytoin anticonvulsant prophylaxis. He was readmitted after one month with complaints of excessive weakness, fatigability, and dyspnea. On examination, significant pallor was noted, with a heart rate of 124/minute and respiratory rate of 30 breaths/minute. Cardiac auscultation revealed a Grade III/VI ejection systolic murmur and a soft S3. Laboratory investigations were: hemoglobulin 1.9 gm/dl; hematocrit 0.565; white blood cell count 13,500/ul, a platelet count of 4.49 lakhs/cumm, and a reticulocyte count of 0.7%. Peripheral blood smear showed moderate anisopoikilocytosis with microcytic hypochromic picture. Chest X-ray and ultrasonography (USG) abdomen were normal and stool for occult blood was also negative. A direct Coombs test was negative and hematinic profile was normal. Liver enzymes were not raised and tests for hepatitis B virus, cytomegalovirus, and parvovirus B19 were all negative. Bone marrow examination [Figure 1] showed acellular marrow with complete absence of erythropoiesis, adequate myelopoiesis, and megakaryopoiesis, with no malignant cells. Laboratory data supported the diagnosis of pure red cell aplasia. Phenytoin was considered the culprit and was withdrawn. Supportive treatment was given in the form of packed red cell transfusions. The response to phenytoin withdrawal was dramatic, within three weeks hemoglobin increased to 10.5 gm/dl and remained stable thereafter.[Figure 2] shows the evolution of laboratory data during the clinical course of the patient. | Figure 1: Bone marrow biopsy showing cellular marrow with marked depression of erythroid series myelopoiesis and megakaryopoiesis are adequate with no malignant cells or magaloblastic changes
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 | Figure 2: Graph showing Hb, complete blood count, platelets, and reticulocyte count during the patient's clinical course. The x-axis shows specific dates. Hb levels during discharge from first admission were 10.2 gm/dl. At admission four weeks later, the Hb had dropped to its lowest level of 1.9 gm/dl, while the WBC and platelet counts were normal. The bone marrow biopsy showed a depression of the erythroid series only. He was given a transfusion of packed cells. Each ¡õ depicts transfusion of packed cells. The reticulocyte count remained abnormally low throughout this period and only after stopping phenytoin the reticulocyte count and Hb started to rise
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Pure red cell aplasia (PRCA) is characterized by severe normochromic normocytic anemia, reticulocytopenia, and isolated erythroblastopenia in the bone marrow, which can be either primary or secondary. Drug-induced PRCA represents an acute and generally reversible form of isolated erythroid aplasia. Of the drugs, only phenytoin, azathioprine, and isoniazid have sufficient evidence of causal association. [1] Our patient had severe anemia, a fall from 9.6 gm/dl to 1.9 gm/dl after starting phenytoin. Hematological workup was suggestive of complete lack of erythropoiesis with normal value of other cell linage. Investigations ruled out other causes of acute bone marrow suppression, thus making phenytoin the most likely culprit. The quick return of counts on discontinuing phenytoin without any specific therapy was consistent with the previous reports of hematological toxicity due to this drug.
The association of phenytoin with PRCA has been well-documented. [2] The possible mechanisms of drug-induced PRCA are immune complex damage to the erythroid progenitor cells or beyond the stage of differentiation of the CFU-E, or antibodies against drug-modified antigens on the progenitors. [3] However, the fact that phenytoin is a membrane-active agent and its presence is necessary to induce suppression of erythropoiesis is in favor of its primary role as a hapten. Other possible mechanisms include direct inhibition of DNA synthesis in marrow erythroid cells. [4]
The interval between the initiation of therapy and onset of anemia varies widely from four months to four years. [2],[5] Our patients is unique in that the patient developed acute bone marrow suppression and PRCA within one month of phenytoin therapy. The recommended duration of prophylactic anticonvulsant therapy with phenytoin is only seven days in patients with traumatic brain injury. [6] It is prudent on the part of the clinicians to avoid phenytoin therapy beyond the specified period in patients with traumatic brain injury. Patients with drug induced PRCA require supportive care and discontinuation of the offending drugs and treatment of the associated infections. Our patient was managed accordingly.
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| 1. | Thompson DF, Gales MA. Drug-induced pure red cell aplasia. Pharmacotherapy 1996;16:1002-8. 
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| 2. | Brittinoham TE, Lutcher CL, Murphy DL. Reversible erythroid aplasia induced by diphenylhydantom. Arch Intern Med 1964;113:764-8.
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| 3. | Dessypris EN, Redline S, Harris JW, Krantz SB. Diphenylhydantoin induced pure red cell aplasia. Blood 1985;65:789-94.
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| 4. | Agrawal A, Parrott NR, Riad HN, Augustine T. Azathioprine-induced pure red cell aplasia: Case report and review. Transplant Proc 2004;36:2689-91.
[PUBMED] [FULLTEXT] |
| 5. | Pritchard KI, Quirt IC, Simpson WJ, Fleming JF. Phenytoin-associated reversible red cell aplasia. Can Med Assoc J 1979;121:1491-3.
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| 6. | Chang BS, Lowenstein DH. Practice parameter: Antiepileptic drug prophylaxis in severe traumatic brain injury: Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 2003;60:10-6.
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[Figure 1], [Figure 2]
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