Severe Thrombocytopenia Associated with Once-Daily Rifampin Therapy

1987 ◽  
Vol 21 (11) ◽  
pp. 882-884 ◽  
Author(s):  
Alice K. Pau ◽  
Melanie A. Fisher ◽  
Wanda Maldonado ◽  
Marc Lebel

Rifampin-induced thrombocytopenia has been recognized as an immunological reaction associated with intermittent high-dose therapy, and rarely seen with daily low-dose regimens. Our patient was a 33-year-old male with Marfan's syndrome who was given rifampin 600 mg/d po along with intravenous vancomycin for the treatment of Staphylococcus epidermidis endocarditis. His platelet count dropped from a baseline of 519000/mm3 to 4000/mm3 after four doses of rifampin. Petechiae were present on the lower extremities without the presence of other bleeding sites. Rifampin, low-dose aspirin, and dipyridamole were discontinued. His platelet count returned to normal nine days after discontinuation of therapy. With the increasing use of rifampin for the treatment of nontuberculosis infections, clinicians should recognize the possibility of this drug causing such serious immunological reactions as thrombocytopenia, hemolytic anemia, acute renal failure, and shock with daily or intermittent therapy. Extracto Rifampin es un agente antibacteriano el cual es utilizado ampliamente en el tratamiento de tuberculosis y de otras infecciones bacterianas. El fármaco puede causar reacciones inmunológicas severas que pueden resultar en trombocitopenia púrpura, anemia hemolítica, insuficiencia renal, y shock. Estas están usualmente asociadas a dosis altas administradas en una manera intermitente, y la descontinuación del fármaco usualmente resulta en resolución de la reacción. Los autores describen el caso de un hombre de 33 años de edad con el Síndrome de Marfan que desarrolla una trombocitopenia severa luego de la administración de 600 mg diarios de rifampin para el tratamiento de endocarditis causado por Staphylococcus epidermidis. El paciente recibió también conjuntamente con rifampin, vancomicina 1 gm iv q 12h, aspirina 600 mg po qd, dipyridamole 25 mg po tid, y propranolol 80 mg po q12h. Cuatro horas luego de la cuarta dosis de rifampin (Día numero 4) el paciente desarrolló petequias en las extremidades inferiores, y el contaje de plaquetas obtenido inmediatamente reveló una concentración de 4000/mm3, el cual refleja una disminución significativa en comparación con el contaje obtenido ocho días antes de 519000/mm3. Tanto rifampin como aspirina y dipyridamole fueron descontinuados. Una marcada trombocitopenia y petequias perduraron por una semana, otras fuentes de sangramiento fueron descartadas y no hubo ningún cambio significativo en el estado de coagulación o en el recuento sanguíneo. Las plaquetas regresaron a un nivel normal nueve días después de descontinuado el rifampin. Aunque las plaquetas aumentaron de 11000/mm3 a 36000/mm3 el día en que propranolol fue descontinuado, los autores expresan que esta respuesta es muy rápida para considerar a éste como el agente causante. Aunque no se puede establecer con certeza que la trombocitopenia fuera causada por rifampin o aspirina solamente, o por un efecto sinergístico de ambos, rifampin parece ser el agente causante más probable. Es importante reconocer el potencial que posee rifampin para causar reacciones adversas serias como trombocitopenia, anemia hemolítica, insuficiencia renal aguda, y shock. La terapia con rifampin debe de descontinuarse si alguna de estas ocurren y otras causas no se pueden identificar. Resume Les thrombocytopénies associées avec la rifampicine sont reconnues comme des réactions immunologiques rencontrées particulièrement avec des thérapies à hautes doses. Le cas décrit par les auteurs est celui d'un patient mâle agé de 33 ans présentant un syndrome de Marfan à qui on a administré 600 mg de rifampicine en dose unique quotidienne en combinaison avec vancomycine iv pour le traitement d'une endocardite à Staphylococcus epidermidis. Le décompte plaquettaire a chuté d'une valeur de 519000/ml à 4000/ml seulement quatre heures après la dose de rifampicine. Des pétéchies étaient apparentes au niveau des jambes en absence de saignements à d'autres sites. Rifampicine, acide acétylsalicylique à faible dose, et dipyridamole furent suspendus. Les plaquettes sont revenus a leur niveau normal neuf jours apres l'arrêt de la thérapie. Devant l'augmentation de l'utilisation de la rifampicine pour le traitement des infections non-tuberculeuses, les cliniciens devront reconnaître le potentiel de ce medicament à causer des réactions immunologiques sévères telles que thrombocytopénie, anémie hémolytique, insuffisance rénale et choc.

Blood ◽  
2012 ◽  
Vol 119 (15) ◽  
pp. 3595-3603 ◽  
Author(s):  
Silvia Pascale ◽  
Giovanna Petrucci ◽  
Alfredo Dragani ◽  
Aida Habib ◽  
Francesco Zaccardi ◽  
...  

Abstract Essential thrombocythemia (ET) is characterized by enhanced platelet generation and thrombotic complications. Once-daily low-dose aspirin incompletely inhibits platelet thromboxane A2 (TXA2) in the majority of ET patients. In the present study, we investigated the determinants of aspirin-insensitive platelet TXA2 biosynthesis and whether it could be further suppressed by changing the aspirin dose, formulation, or dosing interval. In 41 aspirin-treated ET patients, the immature platelet count predicted serum TXB2 independently of platelet count, age, JAK-2 V617F mutation, or cytoreduction (β = 3.53, P = .001). Twenty-one aspirin-treated patients with serum TXB2 ≥ 4 ng/mL at 24 hours after dosing were randomized to the following 7-day regimens in a crossover design: enteric-coated aspirin 100 mg twice daily, enteric-coated aspirin 200 mg once daily, or plain aspirin 100 mg once daily. A twice-daily regimen caused a further 88% median (IQR, 78%-92%, P < .001) TXB2 reduction and normalized the functional platelet response to aspirin, as assessed by urinary 11-dehydro-TXB2 excretion and the VerifyNow Aspirin assay. Doubling the aspirin dose reduced serum TXB2 only partially by 39% median (IQR, 29%-54%, P < .05). We conclude that the abnormal megakaryopoiesis characterizing ET accounts for a shorter-lasting antiplatelet effect of low-dose aspirin through faster renewal of platelet cyclooxygenase-1, and impaired platelet inhibition can be rescued by modulating the aspirin dosing interval rather than the dose.


1995 ◽  
Vol 74 (05) ◽  
pp. 1225-1230 ◽  
Author(s):  
Bianca Rocca ◽  
Giovanni Ciabattoni ◽  
Raffaele Tartaglione ◽  
Sergio Cortelazzo ◽  
Tiziano Barbui ◽  
...  

SummaryIn order to investigate the in vivo thromboxane (TX) biosynthesis in essential thromboeythemia (ET), we measured the urinary exeretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p <0.001) in thrombocythemic patients (4,063 ± 3,408 pg/mg creatinine; mean ± SD) than in controls (504 ± 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 >2 SD above the control mean. Patients with platelet number <1,000 × 109/1 (n = 25) had significantly higher (p <0.05) 11 -dehydro-TXB2 excretion than patients with higher platelet count (4,765 ± 3,870 pg/mg creatinine, n = 25, versus 2,279 ± 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging >55 was significantly higher than in the younger group (4,784 ± 3,948 pg/mg creatinine, n = 24, versus 2,405 ± 1,885 pg/mg creatinine, n = 16, p <0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p <0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p <0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age >55 and platelet count <1,000 × 1099/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo;2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yong Xie ◽  
Meng Pan ◽  
Yanpan Gao ◽  
Licheng Zhang ◽  
Wei Ge ◽  
...  

AbstractThe failure of remodeling process that constantly regenerates effete, aged bone is highly associated with bone nonunion and degenerative bone diseases. Numerous studies have demonstrated that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) activate cytokines and mediators on osteoclasts, osteoblasts and their constituent progenitor cells located around the remodeling area. These cells contribute to a complex metabolic scenario, resulting in degradative or synthetic functions for bone mineral tissues. The spatiotemporal effects of aspirin and NSAIDs in the bone remodeling are controversial according the specific therapeutic doses used for different clinical conditions. Herein, we review in vitro, in vivo, and clinical studies on the dose-dependent roles of aspirin and NSAIDs in bone remodeling. Our results show that low-dose aspirin (< 100 μg/mL), which is widely recommended for prevention of thrombosis, is very likely to be benefit for maintaining bone mass and qualities by activation of osteoblastic bone formation and inhibition of osteoclast activities via cyclooxygenase-independent manner. While, the roles of high-dose aspirin (150–300 μg/mL) and other NSAIDs in bone self-regeneration and fracture-healing process are difficult to elucidate owing to their dual effects on osteoclast activity and bone formation of osteoblast. In conclusion, this study highlighted the potential clinical applications of low-dose aspirin in abnormal bone remodeling as well as the risks of high-dose aspirin and other NSAIDs for relieving pain and anti-inflammation in fractures and orthopedic operations.


Rheumatology ◽  
2020 ◽  
Vol 59 (8) ◽  
pp. 1826-1833
Author(s):  
Xinyi Jia ◽  
Xiao Du ◽  
Shuxian Bie ◽  
Xiaobing Li ◽  
Yunguang Bao ◽  
...  

Abstract Objective The use of IVIG plus high- or low-dose aspirin for the initial treatment of Kawasaki disease remains controversial. The aim of this study was to evaluate the efficacy of IVIG plus high-dose aspirin compared with IVIG plus low-dose aspirin in the treatment of Kawasaki disease. Methods Studies related to aspirin therapy for Kawasaki disease were selected by searching the databases of Medline (PubMed), Embase and the Cochrane Library before March 2019. Statistical analyses were performed by using a Review Manager Software package and STATA v.15.1. Results Eight retrospective cohort studies, characterizing 12 176 patients, were analysed. Overall, no significant difference was found in the incidence of coronary artery abnormalities between the high- and low-dose aspirin groups [relative risk (RR) 1.15; 95% CI: 0.93, 1.43; P = 0.19; random-effects model]. The patients treated with high-dose aspirin had slightly faster resolution of fever [mean difference (MD) −0.30; 95% CI: −0.58, −0.02; P = 0.04; random-effects model]. but the rates of IVIG resistance (RR, 1.26; 95% CI: 0.55, 2.92; P = 0.59; random-effects model) and days in hospital (MD, 0.22; 95% CI: −0.93, 1.37; P = 0.71; random-effects model) were similar between the two groups. Conclusion Low-dose aspirin plus IVIG might be as effective as high-dose aspirin plus IVIG for the initial treatment of Kawasaki disease. Considering that high-dose aspirin may cause more adverse reactions than low-dose aspirin, low-dose aspirin plus IVIG should be recommended as the first-line therapy in the initial treatment of Kawasaki disease.


1979 ◽  
Author(s):  
S. Moore ◽  
L.W. Belbeck ◽  
S.A. Pineau

Previous work in this laboratory has shown that an occlusive thrombus (O.T.) induced. the left anterior descending coronary artery (L.A.D.) of dogs, by the placement of a segment of magnesium-aluminum wire (M.A.W.) in the lumen of the artery, is associated with the development of full thickness infarct (F.T.I.). Incomplete (mural) thrombus is associated with focal areas of ischaemic damage, mainly sub-endocardial, in the myocardium of the antero-lateral left ventricle. A 1.0 cm. length of M.A.W., shaped in the form of a tennis racquet, was placed by cardiac catheterization in the proximal L.A.D. of 30 mongrel dogs. Ten dogs received low dose aspirin (L.D.A.); (14 or 29 mgm/Kg daily in a single dose). Ten dogs received high dose aspirin (H.D.A.); (100 mgm/Kg daily in divided doses). Treatment was begun one day before operation and continued until death or killing. Ten control dogs received no drug. All control dogs died within 3 days of operation. Five had O.T. and F.T.I. The remainder showed focal ischaemic myocardial damage. None of the L.D.A. group died. At autopsy 3 or 4 days after operation, none had O.T. or F.T.I. In the H.D.A. group 3 died; 4 had O.T. and F.T.I. Thus L.D.A. provided significant protection from death, O.T., and F.T.I. H.D.A. provided some (P <0.005) but less protection from death but did not significantly affect the incidence of O.T. or F.T.I. Supported by Ontario Heart Foundation Grant T15-7.


2015 ◽  
Vol 114 (09) ◽  
pp. 645-650 ◽  
Author(s):  
Rupert Bauersachs ◽  
Jan Beyer-Westendorf ◽  
Henri Bounameaux ◽  
Timothy Brighton ◽  
Alexander Cohen ◽  
...  

SummaryPatients with unprovoked venous thromboembolism (VTE) are at high risk for recurrence. Although rivaroxaban is effective for extended VTE treatment at a dose of 20 mg once daily, use of the 10 mg dose may further improve its benefit-to-risk ratio. Low-dose aspirin also reduces rates of recurrent VTE, but has not been compared with anticoagulant therapy. The EINSTEIN CHOICE study is a multicentre, randomised, double-blind, active-controlled, event-driven study comparing the efficacy and safety of two once daily doses of rivaroxaban (20 and 10 mg) with aspirin (100 mg daily) for the prevention of recurrent VTE in patients who completed 6–12 months of anticoagulant therapy for their index acute VTE event. All treatments will be given for 12 months. The primary efficacy objective is to determine whether both doses of rivaroxaban are superior to aspirin for the prevention of symptomatic recurrent VTE, while the principal safety outcome is the incidence of major bleeding. The trial is anticipated to enrol 2,850 patients from 230 sites in 31 countries over a period of 27 months. In conclusion, the EINSTEIN CHOICE study will provide new insights into the optimal antithrombotic strategy for extended VTE treatment by comparing two doses of rivaroxaban with aspirin (clinicaltrials.gov NCT02064439).


Circulation ◽  
1996 ◽  
Vol 94 (9) ◽  
pp. 2113-2116 ◽  
Author(s):  
Rau´l Altman ◽  
Jorge Rouvier ◽  
Enrique Gurfinkel ◽  
Alejandra Scazziota ◽  
Alexander G.G. Turpie

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