Rifampcin-induced Thrombocytopaenia Purpura.

We report the case of a 28-year-old resident doctor with no past history of having taken rifampicin, who presented with thrombocytoapaenic purpura occurring after the initiation of anti-tuberculosis therapy (isoniazid, rifampicin, pyrazinamide and ethambutol) for tubercular lymphadenopathy.

Thrombocytopenic Purpura Associated with Dietary Supplements Containing Citrus Flavonoids.

We report a case of thrombocytopenic purpura associated with the intake of two dietary supplements containing mainly citrus flavonoids. This is the first case to be notified to the French Agency for Food, Environmental and Occupational Health Safety (ANSES). It addresses the importance of an accurate medication history interview for each patient.

Acquired amegakaryocytic thrombocytopenia in a patient with occupational chemical exposure.

Acquired amegakaryocytic thrombocytopenia (AAT) is a hematologic disorder that presents as thrombocytopenia with absent megakaryocytes in the bone marrow. Causes of AAT include toxins, drugs, viral infections, systemic lupus erythematosus, and cytokine deficiencies. Patients with AAT should be followed for possible progression to aplastic anemia or myelodysplastic syndrome. We present a case of a 61-year-old woman with AAT due to occupational chemical exposure.

Nonclinical Safety Profile of BMS-986001, a Nucleoside Transcriptase Inhibitor for Combination Retroviral Therapy.

Nucleoside reverse transcriptase inhibitors (NRTIs)/nucleotide reverse transcriptase inhibitors are key components of combination antiretroviral therapy for HIV infection. First-generation NRTIs are associated with mitochondrial toxicity in patients, mainly due to inhibition of human DNA polymerase γ (hDNA polγ) that manifests as adverse events such as lipodystrophy, lactic acidosis, myopathy, cardiomyopathy, or nephropathy in patients. In chronic nonclinical studies in rodents and nonrodents, eukaryotic (host) mitochondrial toxicity manifests as some drug-specific toxicities similar to human toxicity. BMS-986001, a novel thymidine analog with minimal hDNA polγ inhibition, has demonstrated antiretroviral activity in early clinical studies. The primary toxicity of BMS-986001 in rats and monkeys is bone marrow dyserythropoiesis with associated decreases in red blood cell mass. Additionally, at high doses, severe platelet reductions accompanied by cutaneous petechiae began during weeks 8 and 11 in 3 of 60 monkeys in chronic toxicity studies. In a 6-month study, platelet reductions required euthanasia of the 2 affected monkeys (300 mg/kg/d) at week 14, but with dose reduction (200 mg/kg/d) remaining monkeys had no platelet changes. One affected monkey (200 mg/kg/d) in a 9-month study completed dosing and its platelet counts recovered during a 1-month recovery. Formation of platelet-bound immunoglobulin in the presence of BMS-986001, together with rapid and complete platelet recovery in the absence of BMS-986001, suggested that platelet decreases in monkeys may be immune mediated. No findings indicative of mitochondrial toxicity were observed in rats or monkeys given BMS-986001, suggesting an improved safety profile compared to marketed NRTI or tenofovir disoproxil fumarate.

Severe haematological complications during treatment with natalizumab.

The safety profile of natalizumab has been widely discussed due to several cases of progressive multifocal leukoencephalopathy, reported worldwide. Since the launch of natalizumab, 32 patients have been treated at our centre. In this context, we describe two cases (6.25%), one of immune-mediated acute haemolytic anaemia (IAHA) and another of immune thrombocytopenic purpura during treatment with natalizumab. The temporal relationship between drug administration and the nature of the haematological complications, confirmed with the serological findings in the case of the IAHA, suggests that natalizumab is the most probable cause for these adverse events. Although very uncommon, the haematological complications are severe enough to justify a close and careful monitoring for all patients with multiple sclerosis treated with an immunosuppressant treatment.

Alemtuzumab vs. interferon beta-1a in early multiple sclerosis.

BACKGROUND: Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis. METHODS: In this phase 2, randomized, blinded trial involving previously untreated, early, relapsing-remitting multiple sclerosis, we assigned 334 patients with scores of 3.0 or less on the Expanded Disability Status Scale and a disease duration of 3 years or less to receive either subcutaneous interferon beta-1a (at a dose of 44 microg) three times per week or annual intravenous cycles of alemtuzumab (at a dose of either 12 mg or 24 mg per day) for 36 months. In September 2005, alemtuzumab therapy was suspended after immune thrombocytopenic purpura developed in three patients, one of whom died. Treatment with interferon beta-1a continued throughout the study. RESULTS: Alemtuzumab significantly reduced the rate of sustained accumulation of disability, as compared with interferon beta-1a (9.0% vs. 26.2%; hazard ratio, 0.29; 95% confidence interval [CI], 0.16 to 0.54; P<0.001) and the annualized rate of relapse (0.10 vs. 0.36; hazard ratio, 0.26; 95% CI, 0.16 to 0.41; P<0.001). The mean disability score on a 10-point scale improved by 0.39 point in the alemtuzumab group and worsened by 0.38 point in the interferon beta-1a group (P<0.001). In the alemtuzumab group, the lesion burden (as seen on T(2)-weighted magnetic resonance imaging) was reduced, as compared with that in the interferon beta-1a group (P=0.005). From month 12 to month 36, brain volume (as seen on T(1)-weighted magnetic resonance imaging) increased in the alemtuzumab group but decreased in the interferon beta-1a group (P=0.02). Adverse events in the alemtuzumab group, as compared with the interferon beta-1a group, included autoimmunity (thyroid disorders [23% vs. 3%] and immune thrombocytopenic purpura [3% vs. 1%]) and infections (66% vs. 47%). There were no significant differences in outcomes between the 12-mg dose and the 24-mg dose of alemtuzumab. CONCLUSIONS: In patients with early, relapsing-remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura. The study was not powered to identify uncommon adverse events. (ClinicalTrials.gov number, NCT00050778.)

Thrombocytopenic purpura after measles-mumps-rubella vaccination: a systematic review of the literature and guidance for management.

OBJECTIVE: To determine the incidence of immune thrombocytopenic purpura (ITP) after measles-mumps-rubella (MMR) immunization compared with natural measles and rubella, its clinical course and outcome, and the risk of recurrence after repeat MMR vaccination. STUDY DESIGN: We performed a systematic review of the Ovid MEDLINE (1950 to present) bibliographic database. We selected studies that reported cases of thrombocytopenia in a known number of children who were immunized with MMR vaccine before development of ITP. We also extracted data from the same and other studies regarding bleeding manifestations and the resolution of MMR-associated thrombocytopenia or thrombocytopenic purpura within 6 months. Finally, we studied the risk of ITP recurrence after MMR immunization or reimmunization. RESULTS: On the basis of 12 studies, the incidence of MMR-associated ITP ranged from 0.087 to 4 (median 2.6) cases per 100,000 vaccine doses. Severe bleeding manifestations were rare, and MMR-associated thrombocytopenia resolved within 6 months from diagnosis in 93% of the children. MMR vaccination of unimmunized patients with ITP and revaccination of patients with prior ITP did not lead to recurrence of thrombocytopenia. CONCLUSIONS: MMR-associated ITP is rare, self-limited, and non-life threatening, and susceptible children with ITP should be immunized with MMR at the recommended ages.

[Acute secondary iatrogenic thrombocytopenia in middle-aged patients].

Iatrogenic blood diseases are a primary concern for both patients and physicians. Pathology of blood coagulation system associated with pharmacotherapy has been studied in Samara regional Hemostasiological Centre during the last 30 years. A clinical case of secondary iatrogenic thrombopenic purpura is reported in a patient with a history of uncomplicated allergologic disorder. The disease developed after intake of several drugs at non-toxic doses.

[Severe Thrombocitopenia Induced by Fenofibrate]. / Trombocitopenia Grave Induzida por Fenofibrato.

Drug-induced thrombocytopenia is a common entity in clinical practice. However, having in consideration the severity of the case, it becomes imperative to distinguish non-immune thrombocytopenia from the po-tentially life-threatening immune-mediated forms. The authors report a rare clinical case of a 79-year-old man presenting with purpuric rash and gingival hemorrhage while on fenofibrate treatment (sixth day). The evolu-tion was favorable after drug removal and corticosteroid administration. Drug-associated thrombocytopenia is reported by manufacturers as an extremely rare event. This is the second case report of immune throm-bocytopenia to fenofibrate. The first event was reported for publication in 2015.

A trombocitopenia induzida por fármacos é uma entidade frequente na prática clínica. No entanto, pela sua gravidade torna-se imperativo distinguir a trombocitopenia não-imune das formas imunomediadas potenci-almente ameaçadoras da vida. Os autores descrevem o caso clínico raro de um homem de 79 anos que se apresentou com púrpura trombocitopénica grave não-trombótica e gengivorragia ao sexto dia de introdu-ção diária de fenofibrato na sua medicação habitual. Foi feita exclusão do fármaco e administrada metilprednisolona 125 mg endovenoso durante três dias com resolução completa do quadro estabelecendo uma probabilidade elevada de diagnóstico. A trombocitopenia associada ao fármaco é reportada pelos fabricantes como um evento extremamente raro. Este é o segundo caso reportado de trombocitopenia imune ao fenofibrato, tendo o primeiro caso sido publicado em 2015.

Safety of pentavalent DTaP-IPV/Hib combination vaccine in post-marketing surveillance in Guangzhou, China, from 2011 to 2017.

BACKGROUND: The DTaP-IPV/Hib combination vaccine can replace the acellular tetanus vaccine, polio vaccine, and the Haemophilus influenzae type B vaccine. Data on the safety of DTaP-IPV/Hib vaccines are required. We aimed to evaluate the safety of the vaccination program. METHODS: Using the National Adverse Events Following Immunization (AEFI) surveillance system (CNAEFIS) in Guangzhou, China, a retrospective study was performed from May 11, 2011, to December 31, 2017. There were 376 cases of adverse events after vaccination with the DTaP IPV/Hib vaccine. The primary analysis indicators were the number of vaccines used, the number of AEFI reports received, and the reporting rate (per 100,000). RESULTS: From May 1, 2011, to December 31, 2017, 516,000 doses of vaccine were inoculated, and 376 cases of adverse reactions were reported; the reporting rate was 72.8 per 100,000 vaccines. There were eight cases of serious AEFIs (1.5 per 100,000), with four cases of thrombocytopenic purpura (0.8 per 100,000); three cases of cyanosis of the lips, stiffness, and flexion of limbs, and convulsions (0.6 per 100,000); and one case of a high fever (0.2 per 100,000). The highest incidence of AEFIs occurred after the fourth dose (n = 207, 55.0%, 40.1 per 100,000), followed by the first dose (n = 81, 21.5%, 15.7 per 100,000), second dose (n = 48, 12.8%, 9.3 per 100,000) and third dose (n = 40, 10.6%, 7.7 per 100,000). The AEFI incidence was higher after injection of the vaccine into the deltoid muscle of the upper arm (n = 276, 73.4%, 53.5 per 100,000) than after injection of the vaccine into the thigh (n = 100, 26.6%, 19.4 per 100,000). There was a significant difference between AEFIs after injection into the deltoid of the upper arm deltoid and the thigh (x2 = 164.8, P < 0.05). CONCLUSIONS: Most of the reported AEFIs after DTaP-IPV/Hib vaccination are not serious. There were four cases of TP in this study; vaccination may be a rare cause of thrombocytopenic purpura.

Methotrexate intoxication: Beyond the adverse events.

AIM: Methotrexate (MTX) is the first-line disease-modifying antirheumatic drug in rheumatoid arthritis (RA). However, this anchor may cause some side effects that may range from nausea to mortality. The clinical features of MTX toxicity are under-researched. In this study, we aimed to find out the potential predisposing factors and outcomes of the MTX toxicity (n = 31). METHODS: The data were collected from 31 patients whose ages ranged from 25 to 81 years, who were suffering from immune-mediated inflammatory diseases and major MTX-related toxicity. RESULTS: Out of 31 patients, six (19.4%) used MTX every day, and 13 (41.9%) patients had renal insufficiency who were admitted to the hospital because of mucositis (90.3%) and fever (71%). While using MTX, 27 patients (87.1%) were discharged after the treatment and four patients (12.9%) died. CONCLUSIONS: Although MTX has high efficacy for the toxicity ratio, wrong use and dosage of MTX may be harmful to patients. Thus, patients should be informed about the proper use of MTX.

Study of the factors that cause specific transformation in cultures of lymphocytes from patients with quinine- and quinidine-induced immune thrombocytopenia.

Quinine- or quinidine-induced thrombocytopenic purpura is caused by synthesis of an immunoglobulin (Ig)G antibody, which caused platelet damage in the presence of the offending drug. The nature of the antigenic stimulus has been examined by measuring incorporation of [3H]thymidine into DNA during lymphocyte transformation to blast cells in the presence of the drug. Although patients' lymphocytes responded normally to the nonspecific mitogen, phytohemagglutinin P, they did not respond to either drug or platelets alone. However, significant transformation occurred when patients' lymphocytes were cultured for 7 d with homologous or autologous platelets in the presence of therapeutic concentrations of the drugs (0.39-39 microM). Platelet membranes were more active than intact platelets on the basis of protein content, whereas platelets from a patient with Bernard-Soulier syndrome were inactive. Washed platelets pretreated with the drugs were inactive when cultured with lymphocytes in the absence of the drugs, whereas platelets pretreated similarly in plasma caused transformation. Control lymphocytes from 20 normal patients and 6 patients with nondrug-induced thrombocytopenia were not transformed by drugs and platelets in the presence of normal serum or serum containing drug-dependent antibody, showing that the observed response was specific for presensitized lymphocytes. Thus lymphocytes of patients with drug-induced thrombocytopenia are transformed by an antigen that forms after interaction of plasma, specific platelet membrane components and the drug.

Tosufloxacin tosilate-induced thrombocytopenic purpura.

Tosufloxacin tosilate, a member of the naphthyridine group, was developed in Japan and became commercially available in 1990. We experienced a 69-year-old male who developed thrombocytopenic purpura due to tosufloxacin tosilate. The diagnosis was made when similar symptoms (petechiae and thrombocytopenia) were induced by inadvertent challenge with tosufloxacin tosilate. In this paper, we report the first case of tosufloxacin tosilate-induced thrombocytopenic purpura and present a brief published work review.