Drug-Induced Thrombotic Microangiopathy

Zakarija, Anaadriana; Bennett, Charles L.

doi:10.1055/s-2005-925474

Cited by 122 publications

(94 citation statements)

References 71 publications

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“…Antibiotics like cephalosporins, ampicillin, clarithromycin, metronidazole, oxytetracycline, penicillin, rifampicin, sulfisoxazole, and trimethoprimsulfamethoxazole have been also linked to the development of TTP. [8][9][10][11][12][13][14][15][16][17][18][19] Drugs may cause TTP via two mechanisms: a dose related toxicity and/or an immune mediated reaction. 9,10,18 In the particular association between TMP-SMX and TTP, very limited data is available to explain the possible mechanism by which TMP-SMX might be a trigger for TTP.…”

Section: Discussionmentioning

confidence: 99%

ADAMTS13 Deficiency and Thrombotic Thrombocytopenic Purpura Associated with Trimethoprim-Sulfamethoxazole

Bapani

Epperla

Kasirye

et al. 2012

Clinical Medicine & Research

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Case PresentationA previously healthy woman, age 26 years, presented with abdominal pain, progressive fatigue, and purpuric skin rash over the extremities that began 7 days after beginning a treatment with trimethoprim-sulfamethoxazole (TMP-SMX) for a Klebsiella pneumoniae urinary tract infection. She also complained of exertional shortness of breath with no cough, hemoptysis, or other cardiopulmonary symptoms. No history of bleeding gums or hematochezia was present. A detailed interrogation did not demonstrate any other recent clinical complaints or the administration of any other type of medication beyond TMP-SMX. Physical examination revealed a young woman in no obvious distress, with a body mass index of 27 and stable vital signs. She had pallor and icterus of the mucus membranes but had no bleeding gums or rectal bleeding. She had a non-itchy, purpuric skin rash over her extremities, as well as petechiae. The rest of her physical examination was unremarkable. Thrombotic thrombocytopenic purpura (TTP) is a hematological disease characterized by microangiopathic hemolytic anemia and thrombocytopenia. Although the link between ADAMTS13 deficiency and idiopathic TTP has been well-established, the role of trimethoprimsulfamethoxazole (TMP-SMX) in the pathogenesis of TTP is not yet well elucidated. To the best of our knowledge, there have been only two previous reports linking this medication with the development of TTP. We present the case of a healthy woman, age 26 years, who developed TTP during TMP-SMX therapy for urinary tract infection. She was found to have ADAMTS13 deficiency with anti-ADAMTS13 antibodies. Her condition responded to discontinuation of the TMP-SMX, plasmapheresis, and rituximab therapy. We speculate that the acquired ADAMTS13 deficiency might have been triggered by the TMP-SMX therapy.

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Section: Discussionmentioning

confidence: 99%

ADAMTS13 Deficiency and Thrombotic Thrombocytopenic Purpura Associated with Trimethoprim-Sulfamethoxazole

Bapani

Epperla

Kasirye

et al. 2012

Clinical Medicine & Research

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“…Adverse reactions to drugs are increasingly reported as probable causes of TTP-HUS. Recognition of a drugassociated etiology in patients with TTP-HUS is critical to avoid re-exposure and recurrent events (1,2). Chemotherapeutic agents have also been implicated in causing TTP-HUS, such as mitomycin C, cisplatin, bleomycin, doxorubicin, 5-fluorouracil, interferon-alfa, carboplatin, daunorubicin, dacarbazine, oxaliplatin, lomustine, vinblastine, tamoxifen, carmustine, tretinoin, cytarabine, and gemcitabine (3).…”

Section: Introductionmentioning

confidence: 99%

TTP-HUS Associated with Sunitinib

et al. 2008

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“…The mechanism of renal failure due to VNP40101M is unclear but is likely to be similar to what has been observed with other alkylating agents (17,18). This complication has not been observed in adult patients treated with this agent thus far (3 -5, 7 -9).…”

Section: Discussionmentioning

confidence: 85%

Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study

Gururangan

Turner

Stewart

et al. 2008

Clinical Cancer Research

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Purpose: VNP40101M (Cloretazine), a novel DNA alkylating agent, was evaluated in a phase I study in children with recurrent brain tumors. Experimental Design: VNP40101M was given i.v. daily for 5 consecutive days every 6 weeks for up to eight cycles. Dose escalation was done independently in patients stratified based on intensity of prior therapy (moderately pretreated, stratum I; heavily pretreated, stratum II). Correlative studies included pharmacokinetics and measurement of O 6 -alkylguanine-DNA alkyl transferase levels in peripheral blood mononuclear cells before and after treatment. Results: Forty-one eligible patients (stratum I, 19; stratum II, 22) were enrolled on this study. The dose-limiting toxicity in 35 evaluable patients was myelosuppression, which occurred in 4 of 16 patients in stratum I and 3 of 19 patients in stratum II. Pharmacokinetic studies showed a median terminal half-life of 30 min (range, 14-39.5). The maximum tolerated dose in stratum I and II were 45 and 30 mg/m 2 /d daily for 5 days every 6 weeks, respectively. Peripheral blood mononuclear cells alkylguanine alkyl transferase levels did not decrease significantly after VNP40101M treatment. Central imaging review confirmed that three patients had stable disease for a median of 45 weeks (range, 37-61+) after therapy.

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Drug-Induced Thrombotic Microangiopathy

Cited by 122 publications

References 71 publications

ADAMTS13 Deficiency and Thrombotic Thrombocytopenic Purpura Associated with Trimethoprim-Sulfamethoxazole

ADAMTS13 Deficiency and Thrombotic Thrombocytopenic Purpura Associated with Trimethoprim-Sulfamethoxazole

TTP-HUS Associated with Sunitinib

Phase I Trial of VNP40101M (Cloretazine) in Children with Recurrent Brain Tumors: A Pediatric Brain Tumor Consortium Study

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