The In Vitro Platelet Toxicity Assay (iPTA): A Novel Approach for Assessment of Drug Hypersensitivity Syndrome

Elzagallaai, Abdelbaset A.; Rieder, Michael J.; Koren, Gideon

doi:10.1177/0091270010365554

Cited by 13 publications

(24 citation statements)

References 36 publications

(73 reference statements)

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“…This phenomenon has been observed using PBMCs as a surrogate cell model to test for patient susceptibility for DHRs . In addition, our data show that the degrees of cell death in platelets are higher than in PBMCs from the same patients (Figure ) . This may be attributed to two factors: (1) platelets are un‐nucleated cell fragments originated from megakaryocytes and they have limited defense capacity against in vitro chemical and oxidative insult due to their lack of inducible protein expression mechanisms and their exhaustible reservoir of glutathione and other antioxidant.…”

Section: Discussionsupporting

confidence: 53%

“…Adding other available tests such as the lymphocyte transformation test, which detect drug specific T‐cells in the patient periphery, the skin patch test and drug re‐challenge can provide a better evaluation and superior patient care service. The multi‐mechanistic pathophysiology underlying DHRs may also necessitate combining more than one approach to solve the diagnosis puzzle . These approaches can include genetic testing for high‐risk alleles such as mutations in the HLA gene region, which have been found to have a strong association with DHRs to many drugs …”

Section: Discussionmentioning

confidence: 99%

“…We have recently developed a novel test for the diagnosis of drug hypersensitivity reactions (DHRs), the in vitro platelet toxicity assay (iPTA) . This test promises to be a useful tool in DHRs evaluation and management.…”

mentioning

confidence: 99%

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The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

Elzagallaai

Koren

Rieder

2013

The Journal of Clinical Pharma

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Drug hypersensitivity reactions (DHRs) are rare but potentially fatal adverse drug reactions (ADRs). A reliable test to diagnose DHRs would be a major advance in the clinical care for patients and in the evaluation of ADRs during drug development as well as for mechanistic studies of drug hypersensitivity. Available in vitro tests including the lymphocyte toxicity assay (LTA) have been used but are time-consuming, cumbersome, and expensive. We have developed a novel diagnostic test for DHRs, the in vitro platelet toxicity assay (iPTA). The aim of this study was to evaluate the predictive value of the iPTA in diagnosis of DHRs to sulfonamides. We recruited 66 individuals (36 DHS-sulfa patients and 30 healthy controls) to participate in the study. Blood samples were obtained and LTA and iPTA were performed in parallel. There was concentration-dependent toxicity in the cells of patients when incubated with the reactive hydroxylamine metabolite of sulfamethoxazole for both the LTA and iPTA (P < .05). The iPTA was more sensitive than conventional LTA test in detecting susceptibility of patient cells to in vitro toxicity (P < .05). The novel iPTA has considerable potential as an investigative tool for DHS as it is more sensitive and cheaper, requiring no special reagents.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

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The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

Elzagallaai

Koren

Rieder

2013

The Journal of Clinical Pharma

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“…[23] The diagnosis of DHS is mainly clinical, though currently in vitro tests on isolated peripheral blood lymphocytes and platelets have been introduced, which have a predictive value between 80% and 90% in a population of highly suspected DHS patients. [4]…”

Section: Introductionmentioning

confidence: 99%

Pregabalin hypersensitivity in a patient treated for postherpetic neuralgia

2013

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“…The first category includes tests that measure drug‐specific immunoglobulin E (IgE) (such as the radioallergosorbent test), activation of basophils, or T lymphocytes (e.g., the lymphocyte transformation test, LTT). The second category includes the lymphocyte toxicity assay (LTA) and the recently described in vitro platelet toxicity assay (iPTA) 7 . This article focuses on the current status of the in vitro diagnosis of immune‐mediated DHRs; we describe these tests and their strengths and weaknesses as well as possible future directions for this quickly evolving field.…”

Section: Classification Of (A) Immune‐mediated Hypersensitivity Reactmentioning

confidence: 99%

In Vitro Testing for Hypersensitivity-Mediated Adverse Drug Reactions: Challenges and Future Directions

Elzagallaai

Koren

Bend

et al. 2011

Clin Pharmacol Ther

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Drug hypersensitivity reactions (DHRs) are uncommon but potentially fatal adverse events. Their diagnosis and prediction are difficult given their variable presentation and the overlap of symptoms with those of other clinical conditions. Systemic rechallenge is considered the gold standard for the diagnosis of DHRs; however, this may have severe consequences. In vitro tests are currently not sufficiently reliable to provide the basis for clinical decisions. This article summarizes the challenges associated with in vitro testing for DHRs. Clinical Pharmacology & Therapeutics (2011) 90 3, 455–460. doi:

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The In Vitro Platelet Toxicity Assay (iPTA): A Novel Approach for Assessment of Drug Hypersensitivity Syndrome

Cited by 13 publications

References 36 publications

The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

The Predictive Value of the In Vitro Platelet Toxicity Assay (iPTA) for the Diagnosis of Hypersensitivity Reactions to Sulfonamides

Pregabalin hypersensitivity in a patient treated for postherpetic neuralgia

In Vitro Testing for Hypersensitivity-Mediated Adverse Drug Reactions: Challenges and Future Directions

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