8
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Transient hypofibrinogenemia due to allopurinol

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          This study reports a case of an 80-year-old male who suffered from drug eruption due to oral allopurinol for the treatment of gout. This patient complained of widespread erythema and maculopapule with itch, and small quantities of purplish-red rash with diffused distribution on four limbs were noted. After he was hospitalized, the area with purpuric rash increased in size, and hypofibrinogenemia was found. After treatment with intravenous infusion of fibrinogen and cryoprecipitate, and continued treatment with high-dose methylprednisolone, the skin rash gradually went away. This is the first report of purpura and hypofibrinogenemia induced by allopurinol and the pathophysiology underlying this reaction remained unknown.

          Related collections

          Most cited references 13

          • Record: found
          • Abstract: found
          • Article: not found

          Allopurinol hypersensitivity: a systematic review of all published cases, 1950-2012.

          Allopurinol is the primary therapy for the management of chronic gout. Utilization of allopurinol has increased in tandem with the growing prevalence of gout globally. This exposes more patients to the risk of allopurinol hypersensitivity (AH), a rare adverse reaction characterised by a spectrum of cutaneous reactions and systemic manifestations. Severe forms of AH have been associated with high mortality. The pathophysiology underlying this reaction remains unknown, but several risk factors have been proposed. The aim of this study was to review all published cases of AH documented in the literature in order to better understand the constellation of factors predisposing to this reaction, building on previous reviews by Lupton and Odom, Singer and Wallace and Arellano and Sacristan. A literature search was conducted in MEDLINE and EMBASE to identify relevant articles published between January 1950 and December 2012, with no language restrictions imposed. Articles that were included reported either allopurinol-induced cutaneous manifestations alone or satisfied the diagnostic criteria for AH as defined by Singer and Wallace. Nine hundred and one patients (overall AH cohort) were identified from 320 publications. Of these patients, 802 satisfied the Singer and Wallace criteria ('Singer and Wallace' cohort) while 99 patients had only mild cutaneous manifestations ('non-Singer and Wallace' cohort). Data were often incomplete; hence the results reported reflect the fractions of the subsets of the cohort where the data in question were available. In the overall AH cohort, 58 % (416/722) were male. The majority (73 %; 430/590) of patients were Asian. Renal impairment (48 %; 182/376) and hypertension (42 %; 160/376) were the most common chronic conditions; accordingly, diuretics (45 %; 114/252) and antihypertensives (39 %; 99/252) were the most prevalent concomitant medications. Allopurinol was prescribed for approved indications (chronic gout and chemoprophylaxis) in only 40 % (186/464) of patients. The median allopurinol dose was 300 mg/day (range 10-1,000 mg/day) and was taken by 50 % (168/338). There was no significant association between a higher dose (>300 mg/day) and an increased risk of severe cutaneous manifestations [odds ratio (OR) 1.76; 95 % CI 0.73-4.22; p = 0.23]. Approximately 90 % (489/538) of patients developed AH within 60 days of initiating allopurinol therapy. Serum oxypurinol (the active metabolite of allopurinol) concentration was only recorded in six patients, four of whom had levels within the putative therapeutic range of 30-100 μmol/L. The HLA-B*5801 allele was present in 99 % (166/167) of patients tested, with the majority (147/166) being of Asian ancestry. The all-cause mortality rate was 14 % (109/788) with 94 AH-related deaths, all of which occurred in the cohort meeting the Singer and Wallace criteria. The publications included in this review utilized different laboratory reference ranges to classify the non-cutaneous manifestations of AH; this may have introduced some variation in the cases identified as AH. A majority of the articles included in this analysis consisted of case reports and series--publication types that are not recognized as best-quality evidence; this thus limited the conclusions we could draw about the many risk factors we were interested in evaluating. Risk factors associated with AH, such as concomitant diuretic use, pre-existing renal impairment and recent initiation of allopurinol, were commonly present in AH patients; however, their role in the mechanism of AH remains to be established. A clear risk factor was the HLA-B*5801 status; this was especially relevant in Asian populations where there is a higher carriage rate of the allele. High allopurinol dose, previously suggested to be a risk factor, was not confirmed as such. The paucity of well-documented case reports and studies of AH render it difficult to draw more concrete conclusions or construct a meticulous profile of patients at risk of AH. Future case reports of AH need to be better documented to contribute to understanding the risks for, and mechanisms of, AH.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Adverse drug reaction and causality assessment scales

            Sir, I read with interest the articles by Gupta et al and Gulati et al on adverse drug reactions of antituberculous drugs.[1 2] I would like to make the following comments. Adverse drug reactions (ADRs) are a major cause of morbidity, hospital admission, and even death. Hence it is essential to recognise ADRs and to establish a causal relationship between the drug and the adverse event. It is desirable that ADRs should be objectively assessed and presented based on an acceptable “Probability Scale.” Many causality methods have been proposed to assess the relationship between a drug and an adverse event in a given patient, ranging from short questionnaires to comprehensive algorithms. The idea of creating a standardized assessment for the relationship-likelihood of case reports of suspected ADRs was in the hope that this would, in a structured way, lead to a reliable reproducible measurement of causality. The causality assessment system proposed by the World Health Organization Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre (WHO–UMC), and the Naranjo Probability Scale are the generally accepted and most widely used methods for causality assessment in clinical practice as they offer a simple methodology.[3 4] The above scales are structured, transparent, consistent, and easy to apply assessment methods. Table 1 summarizes the “Naranjo ADR Probability Scale,” which has gained popularity among clinicians because of its simplicity.[3] The WHO–UMC causality system takes into account the clinical-pharmacologic aspects, whereas previous knowledge of the ADR plays a less prominent role. Table 2 summarizes the WHO–UMC Probability Scale.[4] Table 1 Naranjo ADR probability scale—items and score Question Yes No Don’t know Are there previous conclusion reports on this reaction? +1 0 0 Did the adverse event appear after the suspect drug was administered? +2 –1 0 Did the AR improve when the drug was discontinued or a specific antagonist was administered? +1 0 0 Did the AR reappear when drug was re-administered? +2 –1 0 Are there alternate causes [other than the drug] that could solely have caused the reaction? –1 +2 0 Did the reaction reappear when a placebo was given? –1 +1 0 Was the drug detected in the blood [or other fluids] in a concentration known to be toxic? +1 0 0 Was the reaction more severe when the dose was increased or less severe when the dose was decreased? +1 0 0 Did the patient have a similar reaction to the same or similar drugs in any previous exposure? +1 0 0 Was the adverse event confirmed by objective evidence? +1 0 0 Scoring for Naranjo algorithm: >9 = definite ADR; 5–8 = probable ADR; 1–4 = possible ADR; 0 = doubtful ADR. Table 2 WHO–UMC causality categories Causality term Assessment criteria (all points should be reasonably complied) Certain Event or laboratory test abnormality, with plausible time relationship to drug intake Cannot be explained by disease or other drugs Response to withdrawal plausible (pharmacologically, pathologically) Event definitive pharmacologically or phenomenologically (ie, an objective and specific medical disorder or a recognized pharmacologic phenomenon) Rechallenge satisfactory, if necessary Probable/likely Event or laboratory test abnormality, with reasonable time relationship to drug intake Unlikely to be attributed to disease or other drugs Response to withdrawal clinically reasonable Rechallenge not required Possible Event or laboratory test abnormality, with reasonable time relationship to drug intake Could also be explained by disease or other drugs Information on drug withdrawal may be lacking or unclear Unlikely Event or laboratory test abnormality, with a time to drug intake that makes a relationship improbable (but not impossible) Disease or other drugs provide plausible explanation Conditional/unclassified Event or laboratory test abnormality More data for proper assessment needed, or Additional data under examination Unassessable/unclassifiable Report suggesting an adverse reaction Cannot be judged because information is insufficient or contradictory Data cannot be supplemented or verified I humbly request the Editors that Lung India should use either of the above two scales while reviewing articles related to ADRs.
              Bookmark
              • Record: found
              • Abstract: not found
              • Article: not found

              Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia.

                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2014
                02 September 2014
                : 8
                : 1231-1233
                Affiliations
                [1 ]Department of Dermatology The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
                [2 ]Department of Oncology The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
                [3 ]Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China
                Author notes
                Correspondence: Dan Luo, Department of Dermatology, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu 210029, People’s Republic of China, Tel +86 136 5518 7928, Fax +86 25 8371 6602, Email daniluo2005@ 123456sina.com

                *These authors contributed equally to this work

                Article
                dddt-8-1231
                10.2147/DDDT.S66868
                4159221
                © 2014 Yin et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Case Report

                Pharmacology & Pharmaceutical medicine

                purpura, fibrinogen, drug eruption, gout

                Comments

                Comment on this article