Acquired thrombotic thrombocytopenic purpura: puzzles, curiosities and conundrums

Abstract

We report a case of acquired thrombotic thrombocytopenic purpura (TTP) in a 34-year old patient with a prior diagnosis of systemic lupus erythematosis (SLE) who was recently started on hydroxychloroquine. Presenting symptoms included fevers, sore throat and productive cough with progressive weakness, dyspnea on exertion, hemoptysis and dark urine. Initial laboratory abnormalities were consistent with an acute microangiopathic hemolytic anemia and severe thrombocytopenia. At the time of admission, the patient's lupus was highly active as evident by his high SLE Disease Activity Index (SLEDAI) score. He was later also found to have severely reduced ADAMTS-13 levels and a positive antibody assay. This case highlights the occasional difficulty in pinpointing the exact etiology of TTP as well as establishes a possible novel drug association between hydroxychloroquine and TTP development.

Suspected hydroxychloroquine‐induced thrombotic thrombocytopaenic purpura

“…The literature on this subject is sparse and consists of one case report of TTP, three case reports of thrombocytopaenia secondary to HCQ, a fourth case report published in Spanish, and a case series of seven patients which did not clarify chloroquine or HCQ as the inducing agent . The manufacturer lists thrombocytopaenia as ‘rare’ (incidence of <0.01–0.1%) and the Medicines and Healthcare Products Regulatory Agency Drug Analysis Print lists two reports of thrombocytopaenic purpura (neither fatal) and 11 reports of thrombocytopaenia to HCQ from 1 July 1963 to 26 May 2015 .…”

“…The published case reports occurred on a background of RA, systemic lupus erythematosus or unknown pain aetiologies . The TTP case report showed recovery after cessation of the drug and daily TPE.…”

“…While TTP is a known adverse reaction to quinine, similar reports to HCQ are extremely rare in the literature. The available literature includes case reports from the Netherlands, USA, Spain and Turkey …”

The authors reply

“…The findings of hemolysis and TMA developed on day 17 of the admission which was 2 weeks after the drug had been discontinued. Both in the Fromm et al ( 3 ) and Mar et al ( 4 ) reports that were mentioned, TMA developed during the duration of treatment with HCQ. In addition, the most commonly used indication for HCQ is systemic lupus erythematosus (SLE); and we have to keep in mind that SLE can also lead to systemic TMA ( 5 ).…”

Thrombotic microangiopathy: COVID-19 or hydroxychloroquine?

“…In another case report, Mar et al described a patient with systemic lupus erythematosus who developed thrombotic thrombocytopenic purpura shortly after commencing on hydroxychloroquine. 4 …”