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Universal Journal of Medicine and Dentistry Vol. 1(3) pp. 034-036, March, 2012 Available online http://www.universalresearchjournals.org/ujmd Copyright 2012 Transnational Research Journals
Case Report

Acute severe thrombocytopenia in a young male; Case
report and review of literature
Abhishek Ojha1, Nishtha Sareen2 Greg Savino3, and Manouchkathe Cassagnol4
1MBBS Ravindra Nath Tagore Medical College, India 2MBBS Long Island Jewish Medical Center (Department of Medicine 3 St. John’s University College of Pharmacy and Allied Health Professions 4 St. John’s University College of Pharmacy and Allied Health Professions (Clinical Pharmacy Practice Department); Long Island Jewish Medical Center (Department of Pharmacy Services) A 42 year old male presented to the emergency department (ED) complaining of progressive oral
mucosal bleeding, rectal bleeding and diffuse petechiae over 72 hours. He denied any other systemic
symptoms. On presentation to our ED, he had diffused multiple petechiae on his torso and bilateral
lower extremities. His medical history was significant for sarcoidosis diagnosed 3 years ago for which
he was not on any medications. 3 weeks prior to this presentation, he had noticed spots in his left
visual field and upon examination was found to have retinal hemorrhages. As a part of the work up,
serum IgM (Immunoglobulin M) was positive for toxoplasmosis and he was given a 2 week course of
trimethoprim/sulfamethoxazole (TMPSMX). His visual symptoms had resolved at the time of his
presentation to ED. His vital signs were stable. Initial blood work revealed a platelet count of 3,000
cells/µL. He always had normal platelet count before. Given both worsening toxoplasmosis and
sarcoidosis could have caused thrombocytopenia, a thorough work up was undertaken. A repeat serum
toxoplasmosis IgM was negative. His serum Angiotensin Converting Enzyme (ACE) level was elevated
to 87, serum Lactate Dehydrogenase (LDH) and Liver Function Tests (LFTs) were within goal. Human
Immunodeficiency Virus (HIV) and Hepatitis screen were both negative. Chest X ray revealed hilar
lymphadenopathy and patchy opacity right upper lobe, consistent with known sarcoid disease.
Computed Tomography (CT) Chest revealed numerous upper lobe peri-bronchial pulmonary nodules,
right paratracheal, bilateral hilar and subcarinal lymphadenopathy. On day 2 of hospitalization, the
platelet count further decreased to nadir of 1,000 cells/µL. Due to the worsening thrombocytopenia, the
patient was transferred to the Medical Intensive Care Unit (MICU) where he was given two doses of 70
mg intravenous immune globulin (IVIG) along with a single 40 mg dose of intravenous dexamethasone.
By day 4, his platelet count increased to 17,000 cells/µL. On day 5 of hospitalization the platelet count
increased to 78,000 cells/µL and he was discharged later that day. Two days after discharge the
platelets normalized to 285,000 cells/µL. No further complications were noted after discharge.
Key Words: bleeding, thrombocytopenia, sulfamethaxazole-trimethoprim, sarcoidosis

DISCUSSION

Thrombocytopenia is often defined as a platelet count
be attributed including, but not restricted to systemic ≤100,000cells/µL or a reduction from baseline of greater infections, alcohol intoxication, vitamin B 12 deficiency, than 50%. There are multiple etiologies, to which it can severe liver dysfunction, hereditary conditions (Fanconi’s/ Thrombocytopenic Purpura, Disseminated Intravascular *Corresponding author Email:cassagnm@sjtohns.edu, Tel: 718- Coagulopathy, Systemic Lupus Erythematosus, the hospital where he was found to have a platelet count of <5,000 cells /µL. He was administered 1mg/kg of oral prednisolone daily for 2 weeks, over which his thrombocytopenia associated with either sarcoidosis or thrombocytopenia resolved. He was discharged with an toxoplasmosis does exist and is typically accounted for additional four weeks of oral prednisolone to be tapered by case reports (Tuon et al., 2008 and Larner et al., 1990 and was said to remain well after treatment. and 2010). This patient had both of these conditions In a similar case, a 54 year old woman (Yamreudeewong, previously diagnosed, but was recently started on et al., 2002) developed blood blisters in her mouth and TMP/SMX. The chronology of events during his drug petechiae on her hands after 9 days of therapy with therapy provided the greatest indication that TMP/SMX TMP/SMX 160mg/800mg. A complete blood count was the most credible causative agent of his revealed a platelet count of 2,000cells/µL and TMP/SMX thrombocytopenia. The Naranjo Nomogram for Causality was discontinued. Treatment consisted of a transfusion of (Naranjo et al., 1981) yielded a score of 6, making two units of platelets along with oral prednisone 60mg TMP/SMX a probable cause of this adverse drug event. given twice daily. After 1 day of treatment (and TMP/SMX Hence, TMP/SMX was discontinued and he was discontinuation) the patient’s platelets increased to 7,000 The incidence of drug-induced thrombocytopenia, manifestations had gradually resolved over the hospital excluding heparin, has been estimated to be 10 cases course. By day 5 of hospitalization, platelets were per 1,000,000 persons, in the general population, per 110,000 cells/µL. The patient was discharged and 10 year (Dipiro et al. 2008). Well over 100 medications have days of oral prednisone was tapered to discontinuation. been found to induce thrombocytopenia and a number of Two weeks later her platelet count was 351,000 cells/µL. mechanisms have been proposed5 including 1) direct In a third report, a 40 year old male developed an toxicity reactions, 2) hapten-type immune reactions, 3) erythematous rash on his face after 5 days of TMP/SMX platelet-reactive autoantibodies and 4) drug-dependent 80mg/400mg treatment (Kocak et al 2006)., TMP/SMX was autoantibodies. Most commonly, an immunologic reaction withdrawn and levofloxacin was initiated to treat the is seen and occurs when the offending drug binds to condition, but the condition progressed to the oral certain platelet glycoproteins, forming an antigenic mucosa, trunk and extremities. Antihistamines and complex. Antibodies are then generated and bind to steroids did not work well in the patient. Platelet count these complexes. This results in an increased peripheral was 133,000 cells/dL and most other laboratory values lysis of platelets through complement activation or were below normal range. The patient was diagnosed circulating macrophages (Dipiro et al. 2008). Although with neutropenia (WBC, 700 cells/dL; ANC, 200 cells/dL) TMP/SMX is considered to be an effective and well and erythroderma. Despite continued steroid therapy, tolerated therapeutic antibiotic, rare and serious side whole blood, red cell concentrates, thrombocyte effects have been established even with normal dosages. transfusions and filgrastim, laboratory results on day 8 of hospitalization revealed a platelet count of 4,000 cells/dL. Three days later the patient died despite continued ther Review of literature
In our patient, platelet levels on admission were 3,000cells/µL. Platelet transfusions yielded no increase in To date, there have been 3 cases of thrombocytopenia the patient’s platelet count, but may have acted as a due to oral trimethoprim/sulfamethoxazole (MEDLINE supplement to counteract platelet lysis by drug search from January 1965 to July 2010). The three dependent antibodies. Platelet levels dropped to similar case reports of severe thrombocytopenia possibly 1,000cells/µL by day 2 of hospitalization and the patient precipitated by oral TMP/SMX administration are was administered dexamethasone. While corticosteroid summarized in tabular format (table 1) (DiPiro et al., 2008 therapy was also seen in the other three cases with beneficial outcomes, due to the severity of our patient’s Generally, TMP/SMX thrombocytopenia reactions occur thrombocytopenia, intravenous immune globulin (IVIG) approximately 5 to 9 days after exposure. The onset time was also initiated. IVIG is thought to exert its activity in seen in our patient was approximately 7 days, which the reticuloendothelial system through blockade of the Fc coincides with other reports. Primary treatment entails receptor on macrophages, disallowing antibody binding discontinuation of the offending agent and supplementary and thus platelet phagocytosis (Immune Globulin 2010) . treatment modalities should be utilized (DiPiro et al., Improvement in clinical manifestations and platelet count occurred over the next two days. By day 5, steroid Papaioannides et al. 2003, reported a case of a 58 year therapy was still in place and platelets reached 78,000 old male who discontinued TMP/SMX 160mg/800mg cells/µL. The patient was discharged on day 5 with no therapy 2 days before completion of a 10 day course due to easy bruising. The subsequent development of widespread purpuric lesions and rhinorrhagia led him to 036. Univers. J. Med. Dent.

Table (1): Case Reports of Trimethoprim/Sulfamethoxazole Induced Severe Thrombocytopenia
Age/ Gender
TMP/SMX Dose
Initial Clinical
Platelet
Frequency
Signs/Symptoms
Manifestation
Co-trimoxazole Induced Acute 58/Male
Thrombocytopenic Purpura 12
Thromboctopenia 54/Female
Possibly
Associated
TMP/SMX Therapy 13
Trimethoprim-Sulfamethoxazole
Hematologic Disorders 14

CONCLUSION
Koda-Kimble et al (2008). "Drug-Induced Thrombocytopenia." Applied Therapeutics: The Clinical Use of Drugs. 9th ed. Philadelphia: Lippincott Williams and Wilkins. 87(7): 9-87 Presentation with thrombocytopenia has a very broad Toxoplasmosis (2009)." Division of Parasitic Diseases. Centers for differential and could pose a diagnostic dilemma in a patient with underlying multiple comorbidities. Medication 2009.Web.21June2010.<http://www.dpd.cdc.gov/dpdx/HTML/Frames induced thrombocytopenia should always be considered /SZ/Toxoplasmosis/body_Toxoplasmosis_serol1.htm> Tuon et al. (2008). "Acute Immune-mediated Thrombocytopenic carefully in any young patient presenting with low Purpura Related to Toxoplasma Gondii Infection." International platelets. Also, practitioners should educate patients on Journal of Infectious Diseases 12(6 ): 671-72 the side effects of prescribed medications and monitor Gurkan et al.(2003). "Immune Thrombocytopenic Purpura Associated their blood levels routinely for any life threatening with Brucella and Toxoplasma Infections." Am. J. Hematol. 74(1): 52-54. complication as thrombocytopenia. Continual self monitoring in combination with the monitoring of platelets <http://www3.interscience.wiley.com/cgi- when indicated may aid in early recognition of thrombocytopenia and can reduce more serious Larner et al(1990). "Life Threatening Thrombocytopenia in Sarcoidosis." complications. It’s often not possible to determine the (1990):31719.PubMedCentral.3Feb.1990.Web.23June2010.<http://w underlying mechanism responsible for drug-induced ww.ncbi.nlm.nih.gov/pmc/articles/PMC1661928/?tool=pubmed>. thrombocytopenia, especially in patients receiving various Naranjo et al.(1981). “A Method for Estimating the Probability of Adverse Drug reactions.” Clinical Pharmacology and Therapeutics 30 (1981): medications.2,4 Clinicians should use laboratory findings, <http://www.nature.com/clpt/journal/v30/n2/pdf/clpt1981154a.pdf>. evidence from recent reports and the temporal DiPiro et al (2008). "Treatment: Drug-Induced Thrombocytopenia." relationship to aid in causal determination of such events. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York: Papaioannides et al(2003). "Co-trimoxazole Induced Acute Thrombocytopenic Purpura." Emerge. Med. J. 20:3. REFERENCES
Yamreudeewong, et al (2002). "Severe Thrombocytopenia Possibly "Sulfamethoxazole and Trimethoprim." Lexi-Drugs Online. Lexi-Comp, 8 Kocak et al (2006). "Trimethoprim-sulfamethoxazole Induced Rash and <http://crlonline.com/crlsql/servlet/crlonline>. Fatal Hematologic Disorders." The J. Infect. 52 :49-52. “Immune Globulin (2010).” Micromedex. Thomson Reuters Healthcare, Gilman's the Pharmacological Basis of Therapeutics. 11th ed. United http://www.thomsonhc.com/hcs/librarian/ND_T/HCS/ND_PR/Main/CS /BB3D1B/DUPLICATIONSHIELDSYNC/C69B2F/ND_PG/PRIH/ND_B "SULFAMETHOXAZOLE/TRIMETHOPRIM." /HCS/SBK/3/ND_P/Main/PFActionId/hcs.common.RetrieveDocument Common/DocId/0693/ContentSetId/31#secN125DE Web.22June2010.<http://www.thomsonhc.com/hcs/librarian/ND_T/H CS/ND_PR/Main/CS/6510C4/DUPLICATIONSHIELDSYNC/4A13AD/ ND_PG/PRIH/ND_B/HCS/SBK/2/ND_P/Main/PFActionId/hcs.common.RetrieveDocumentCommon/DocId/0324/ContentSetId/31#mechanismOfActionPharmacologySection> DiPiro JT, Matzke B, Wells G, Posey LM (2008). "Drug-Induced Approach. 7th ed. New York: McGraw-Hill Medical. Pp. 1711

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