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 Table of Contents  
CASE REPORT
Year : 2022  |  Volume : 2  |  Issue : 3  |  Page : 682-684

Dorzolamide-induced giant cell thrombocytopenia: A case report of a hitherto unreported condition


1 Department of Ophthalmology, Consultant Glaucoma and Pediatric Ophthalmology Services Priyamvada Birla Aravind Eye Hospital, Kolkata, India
2 Department of Ophthalmology, Consultant Cataract & Glaucoma Services Charak Hospital & Research Centre, Lucknow, India
3 Department of Pathology, Consultant Patologist, Woodlands Multispeciality Hospital, Kolkata, India

Date of Submission18-Jan-2022
Date of Acceptance15-Mar-2022
Date of Web Publication16-Jul-2022

Correspondence Address:
Dr. Komal Daljit Singh
Department of Ophthalmology, Consultant Cataract & Glaucoma Services Charak Hospital & Research Centre, Lucknow - 226 003
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_98_22

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  Abstract 


Carbonic anhydrase inhibitors are frequently prescribed in topical and oral forms in various types of glaucoma. Dorzolamide eye drops are frequently associated with ocular side effects but systemic side effects are rare with its use. We report a case of dorzolamide-induced giant cell thrombocytopenia in a patient with post uveitic angle-closure glaucoma. After discontinuation of dorzolamide eye drops, the thrombocytopenia reversed.

Keywords: Dorzolamide, giant cell thrombocytopenia, glaucoma, systemic absorption


How to cite this article:
Ganguly A, Singh KD, Chakraborty M. Dorzolamide-induced giant cell thrombocytopenia: A case report of a hitherto unreported condition. Indian J Ophthalmol Case Rep 2022;2:682-4

How to cite this URL:
Ganguly A, Singh KD, Chakraborty M. Dorzolamide-induced giant cell thrombocytopenia: A case report of a hitherto unreported condition. Indian J Ophthalmol Case Rep [serial online] 2022 [cited 2022 Aug 13];2:682-4. Available from: https://www.ijoreports.in/text.asp?2022/2/3/682/351222



Dorzolamide 2% is a commonly prescribed topical carbonic anhydrase inhibitor for treatment of various types of glaucoma. Ocular side effects like conjunctival hyperaemia, blepharitis, and sterile conjunctivitis are common with its use.[1] Although systemic side effects of topical dorzolamide are few, cases of thrombocytopenia have also been reported with dorzolamide previously.[2] We report a rare case of dorzolamide-induced giant cell thrombocytopenia which has so far not been reported in medical literature.


  Case Report Top


A 42-year-old man with post uveitic chronic angle-closure glaucoma with complicated cataract in left eye presented for a second opinion. On examination, his best corrected visual acuity (BCVA) was 6/6 in right eye and 1/60 in left eye with temporal fixation. Anterior segment of right eye was within normal limits. Left eye anterior segment showed old keratic precipitates and pigments on corneal endothelium along with iris bombe and seclusion pupillae and complicated cataract. Right eye fundus examination was within normal limits and left eye fundus could not be viewed. Applanation tonometry showed intraocular pressure (IOP) of 18 mmHg in right eye and 38 mmHg in left eye. Gonioscopy showed open angles in right eye and in left eye, there was appositional closure of 360 degrees with PAS on indentation noted in temporal quadrant 2 clock hours; rest of the angle was opening in all quadrants by indentation. Patient was started on eye drops pred acetate 1% two hourly, and timolol 0.5% and brimonidine 0.1% combination eye drops twice daily in left eye. Dorzolamide (2%) eye drops was added two weeks later to achieve better IOP control. Initially, a YAG peripheral iridotomy was attempted in the left eye but it failed due to thick iris; consequently, a surgical iridectomy was performed in the left eye three weeks later to control persistent uncontrolled IOP (26 mm Hg). Post-surgical iridectomy, the IOP in left eye came down to 20 mmHg, and patient was started on timolol (0.5%) eye drops twice daily along with prednisolone acetate eye drops once daily. Rest other antiglaucoma eye drops were stopped. Subsequently, after six months, the patient underwent phacoemulsification within the bag PCIOL implantation in left eye. His visual acuity improved to 6/36. IOP was 16 mmHg in right eye and 28 mmHg in left eye. Fundus examination of left eye showed an optic disc with C: D ratio of 0.9 with vitreous opacity. Dorzolamide (2%) and timolol (0.5%) eye drops combination was started again twice daily in the left eye along with pred acetate eye drops in tapering doses which was ultimately stopped. The patient was on regular follow-up, 3-monthly, and in all instances, his left eye IOP was between 12 and 16 mmHg. One year later, when the patient came for a routine follow-up, he produced a blood peripheral smear investigation done as a routine check-up for employment purposes, which showed giant cell thrombocytopenia as shown in [Figure 1] and [Figure 2]. Platelet count at diagnosis was 43 × 109 L, Hb was 13.6 mg/dl, TLC 8.8 × 109/L, PCV 0.42 L/L, MCV 91.2 FL, MCH 29.1 pg, MCHC 31.8 gm/dl, RDW 12.6%, and ESR 2 mm. Keeping the possibility of dorzolamide-induced thrombocytopenia in mind, eyedrop dorzolamide 2% and timolol 0.5% combination was stopped, and adequate control of IOP was subsequently established with a combination of timolol (0.5%), brimonidine (0.1%), and latanoprost (0.005%) eye drops. The patient had no other systemic symptoms and there was no history of any other systemic medications or viral infections. After three months of stopping dorzolamide topical eye drops, the platelet count was 153 × 109/L. For two previous years, his platelet counts were 166 × 109/L, and 170 × 109/L respectively, as noted from the yearly routine investigations done as part of his employment rules. For the next five years, his readings were 169 × 109/L; 157 × 109/L; 177 × 109/L; 151 × 109/L; 162 × 109/L as repeated every year according to employment requirements. So, after the withdrawal of dorzolamide (2%), the thrombocytopenia totally reversed and did not relapse over the last five years.
Figure 1: Enlarged view of giant cell in peripheral blood smear

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Figure 2: Peripheral blood smear

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  Discussion Top


The incidence of drug-induced thrombocytopenia is approximately 10 cases per 10,00,000 population per year.[3] Topical carbonic anhydrase inhibitors are generally regarded as safe, especially compared with their oral forms which have numerous adverse effects like nephrolithiasis, blood dyscrasias, and fatigue.[4] However, there is little information regarding systemic side effects of topical carbonic anhydrase inhibitors.[2],[3] After ophthalmic instillation, some amount of the drug enters systemic circulation via absorption from nasal mucosa or directly via conjunctival blood vessels.[5] Systemic side effects of topical carbonic anhydrase inhibitors are based on their ability to inhibit CA-II isoenzyme in red blood cells and kidneys.[6] Topical carbonic anhydrase inhibitors have also been seen to cause non-anion gap metabolic acidosis in adults as well as in neonates and in patients with impaired renal function.[3],[6],[7] Being sulphonamides, they induce thrombocytopenia by eliciting an immunologic platelet destruction.[8] The drug, after systemic absorption, induces antibodies that bind to the normal platelets only in the presence of the drug. The epitopes targeted by these antibodies usually reside on glycoprotein IIb/IIIa or Ib/V/IX complexes.[9],[10],[11] Giant cell thrombocytopenia may most probably not be related to immune mechanisms as described earlier. In fact a platelet membrane defect induced by dorzolamide may be the cause; but the exact mechanism is yet to be identified.[11],[12] Thrombocytopenia with use of 2% dorzolamide has been previously reported[3],[10]; however, no case of sulfonamide-induced giant cell thrombocytopenia has been reported till now, either with oral or topical use. Giant platelets have a diameter greater than 7 microns (larger than a normal red blood cell). Giant platelets are seen in various conditions like myeloproliferative neoplasms, myelodysplasia, and congenital thrombocytopenia syndromes like Bernard–Soulier syndrome and MYH9-related disorders with clinical spectrum ranging from severe bleeding diathesis to asymptomatic conditions which may remain undetected even in adulthood.[13] Though ITP could have been a potential differential diagnosis, no symptoms of past or intercurrent viral infections/systemic disease were identified; the uveitis was inactive for almost a decade.

Giant cell thrombocytopenia with more than five times the RBC size have not been reported in literature. In fact, raised MPV values are considered against a diagnosis of ITP.[14]

To establish a causal relationship between the thrombocytopenia and eye drop dorzolamide, the Naranjo Algorithm or ADR probability score was computed as follows and the total score in our case was 7, which implied that there was probable or very likely causality between topical dorzolamide and giant cell thrombocytopenia.[15]

The ADR Probability Scale consists of 10 questions that are answered as either “Yes”, “No”, or “Do not know”. Different point values (−1, 0, +1 or +2) are assigned to each answer. A simplified version of the 10 questions is provided below:

  • Are there previous conclusive reports of this reaction? Yes +1
  • Did the adverse event appear after the drug was given? Yes +2
  • Did the adverse reaction improve when the drug was discontinued or a specific antagonist was given? +1
  • Did the adverse reaction reappear upon readministering the drug? 0 (In presence of a viable alternative topical drop, it was not ethical to put the patient through this challenge test)
  • Were there other possible causes for the reaction? Yes; but none identifiable in this case 0
  • Did the adverse reaction reappear upon administration of placebo? No. +1 (Considering alternative eye drop as placebo)
  • Was the drug detected in the blood or other fluids in toxic concentrations? Not Known 0
  • Was the reaction worsened upon increasing the dose? Or, was the reaction lessened upon decreasing the dose? Yes +1
  • Did the patient have a similar reaction to the drug or a related agent in the past? Not known 0
  • Was the adverse event confirmed by any other objective evidence? Yes + 1 (By Peripheral Blood Smear and Platelet Count.)
  • Total ADR probability score = 7; The score is probable.


The reaction (1) followed a reasonable temporal sequence after a drug, (2) followed a recognized response to the suspected drug, (3) was confirmed by withdrawal but not by exposure to the drug, and (4) could not be reasonably explained by the known characteristics of the patient's clinical state.


  Conclusion Top


This case report highlights the potential side effects of dorzolamide eye drops due to systemic absorption. Dorzolamide-induced giant cell thrombocytopenia is rare, but can occur in patients being treated with it. This thrombocytopenia can occur without any systemic manifestations as happened in our case. Patients should be made aware of this potential complication and should be screened by hemograms at regular intervals on follow-up. Also, regular punctal occlusion should be taught to the patients when they are started on dorzolamide topical formulations as with any other glaucoma drops. We suggest a complete hemogram every six months of topical carbonic anhydrase inhibitor use.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Hutzelmann JE, Polis AB, Michael AJ, Adamsons IA. A comparison of the efficacy and tolerability of dorzolamide and acetazolamide as adjunctive therapy to timolol. Oral to Topical CAI Study Group. Acta Ophthalmol Scand 1998;76:717-22.  Back to cited text no. 1
    
2.
Martin XD, Danese M. Dorzolamide-induced immune thrombocytopenia: A case report and literature review. J Glaucoma 2001;10:133-5.  Back to cited text no. 2
    
3.
George JN, Aster RH. Drug-induced thrombocytopenia: Pathogenesis, evaluation, and management. Hematology Am Soc Hematol Educ Program 2009;2009:153-8.  Back to cited text no. 3
    
4.
Swenson ER. Safety of carbonic anhydrase inhibitors. Expert Opin Drug Saf 2014;13:459-72.  Back to cited text no. 4
    
5.
Hoffmanová I, Sánchez D. Metabolic acidosis and anaemia associated with dorzolamide in a patient with impaired renal function. Br J Clin Pharmacol 2018;84:796-9.  Back to cited text no. 5
    
6.
Morris S, Geh V, Nischal KK, Sahi S, Ahmed MA. Topical dorzolamide and metabolic acidosis in a neonate. Br J Ophthalmol 2003;87:1052-3.  Back to cited text no. 6
    
7.
Santos VM, Castro RA, Lima CC, Moraes MB, Sugai TA. Skin eruption and thrombocytopaenia in a woman with glaucoma: A case report. West Indian Med J 2010;59:102.  Back to cited text no. 7
    
8.
Visentin GP, Newman PJ, Aster RH. Characteristics of quinine-and quinidine-induced antibodies specific for platelet glycoproteins IIb and IIIa. Blood 1991;77:2668-76.  Back to cited text no. 8
    
9.
Asvadi P, Ahmadi Z, Chong BH. Drug-induced thrombocytopenia: Localization of the binding site of GPIX-specific quinine-dependent antibodies. Blood 2003;102:1670-7.  Back to cited text no. 9
    
10.
Mhawech P, Saleem A. Inherited giant platelet disorders: Classification and literature review. Am J Clin Pathol 2000;113:176-90.  Back to cited text no. 10
    
11.
Greinacher A, Mueller-Eckhardt C. Hereditary types of thrombocytopenia with giant platelets and inclusion bodies in the leukocytes. Blut 1990;60:53-60.  Back to cited text no. 11
    
12.
Gröttum KA, Solum NO. Congenital thrombocytopenia with giant platelets: A defect in the platelet membrane. Br J Haematol 1969;16:277-90.  Back to cited text no. 12
    
13.
Drachman JG. Inherited thrombocytopenia: When a low platelet count does not mean ITP. Blood 2004;103:390-8.  Back to cited text no. 13
    
14.
Noris P, Klersy C, Gresele P, Giona F, Giordano P, Minuz P, et al. Platelet size for distinguishing between inherited thrombocytopenias and immune thrombocytopenia: A multicentric, real life study. Br J Haematol 2013;162:112-9.  Back to cited text no. 14
    
15.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 15
    


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