A rare case of absolute thrombocytopaenia in a COVID-19 patient: Case report.

INTRODUCTION: Thrombocytopaenia, one of the most common haematological disorders worldwide, is characterised by platelet counts <150,000/mm3. Patients with coronavirus disease (COVID-19) were found to commonly exhibit haematological abnormalities, often with mild forms of thrombocytopaenia. Absolute thrombocytopaenia tends to be rare among these patients and is believed to be secondary to immune-induced thrombocytopaenia. CASE PRESENTATION: A 53-y-old man presented with fever and generalised body ache that persisted for a few days. His polymerase chain reaction test was positive for COVID-19, for which he was treated with acetaminophen, levofloxacin, and favipiravir. On the third day of treatment, he noticed bruising and bleeding, mainly in the oral cavity, with clot formation. A complete blood picture (CBP) revealed severe thrombocytopaenia with an almost-zero count. Prednisone 1 mg/kg/d and frequent doses of intravenous platelet transfusion were administered as rescue therapy to prevent fatal bleeding. The patient was able to recover. CLINICAL DISCUSSION: Immune thrombocytopaenia should be considered in patients presenting with bleeding tendencies after severe acute respiratory syndrome coronavirus 2 infection. Serial CBP is recommended for vulnerable patients, especially during the second and third weeks of hospitalisation, for the early detection and prevention of life-threatening COVID-19 complications. CONCLUSIONS: Absolute thrombocytopaenia is a rare condition. Such a condition should be considered in patients presenting with bleeding tendencies with severe Covid-19 infection. With early diagnosis and appropriate treatment, patients' lives can be saved.

Influence of 16S ribosomal RNA gene polymerase chain reaction and sequencing on antibiotic management of bone and joint infections.

INTRODUCTION: Amplification of the 16S ribosomal RNA gene by polymerase chain reaction (PCR) followed by analysis of generated sequences can be an important adjunct to conventional cultures. OBJECTIVE: To determine how the results of this approach influence physicians' decisions regarding the management of bone and joint infections. METHOD: Clinical and laboratory findings of patients seen at the Queen Elizabeth II Health Sciences Centre (Halifax, Nova Scotia) between December 2005 and September 2009 were reviewed. Patients who had negative cultures but likely or possible bone and joint infections were further evaluated using 16S rRNA PCR. The impact of the 16S rRNA PCR result on antibiotic management was evaluated and it was assessed whether untreated patients with negative 16S rRNA PCR subsequently presented with infections, suggesting a false-negative result. RESULT: A total of 36 patients (mean age 62 years) were reviewed. Thirty-two patients were evaluated by infectious disease consultants; of these, 20 were considered likely to have infections. Seventeen patients were admitted with suspected prosthetic joint infections. Twenty-nine patients received antimicrobial treatment before the sample for the 16S rRNA PCR assay was obtained. Of the 36 patients, 26 (72.2%) were treated appropriately with modifications to their antibiotic regimen in response to the 16S rRNA PCR assay results. Antimicrobials were discontinued for 19 patients based on negative PCR assay and, in seven patients, antibiotics were changed based on a positive result. There were no relapses among patients with negative PCR assay in whom antibiotics were discontinued. CONCLUSION: 16S ribosomal RNA gene PCR and sequencing is a valuable tool in the guidance of antimicrobial therapy for bone and joint infections.

HISTORIQUE: L'amplification de la réaction en chaîne de la polymérase (PCR) du gène de l'ARN ribosomique 16S, suivie de l'analyse des séquences générées, peut être un ajout important aux cultures habituelles. OBJECTIF: Déterminer en quoi les résultats de cette approche influent sur les décisions des médecins à l'égard de la prise en charge des infections osseuses et articulaires. MÉTHODOLOGIE: Les chercheurs ont analysé les résultats cliniques et de laboratoire des patients vus au Queen Elizabeth II Health Sciences Centre de Halifax, en Nouvelle-Écosse,entre décembre 2005 et septembre 2009. Les patients dont les cultures étaient négatives, mais qui présentaient une infection osseuse ou articulaire probable ou possible, subissaient une évaluation plus approfondie au moyen de la PCR de l'ARNr 16S. Les chercheurs ont évalué les répercussions du résultat de la PCR de l'ARNr 16S sur la prise en charge des antibiotiques et ont déterminé si les patients non traités dont la PCR de l'ARNr 16S était négative ont ensuite souffert d'infections, laissant ainsi supposer un résultat faux négatif. RÉSULTAT: Au total, les chercheurs ont analysé le dossier de 36 patients (d'un âge moyen de 62 ans). Trente-deux patients ont été évalués par des consultants en infectiologie, et de ce nombre, 20 ont été considérés comme susceptibles d'avoir une infection. Dix-sept patients ont été hospitalisés en raison d'une présomption d'infection articulaire prosthétique. Vingt-neuf patients ont reçu un traitement antimicrobien avant l'obtention de l'échantillon en vue de la PCR de l'ARNr 16S. Des 36 patients, 26 (72,2 %) ont été traités correctement par des modifications au régime antibiotique après l'obtention des résultats de la PCR de l'ARNr 16S. Le traitement aux antimicrobiens a été interrompu chez 19 patients en raison d'une PCR négative et chez sept patients, on l'a remplacé par un autre en raison d'un résultat positif. Les chercheurs n'ont constaté aucune rechute chez les patients dont la PCR était négative et à qui on avait arrêté d'administrer des antibiotiques. CONCLUSION: La PCR et le séquençage du gène de l'ARN ribosomique 16S est un outil précieux pour orienter le traitement antimicrobien des infections osseuses et articulaires.

Further examination of the selective toxicity of CCl4 in rat liver slices.

Lipid peroxidation and loss of enzymes located predominantly in either periportal or centrilobular hepatocytes were investigated in precision-cut liver slices from male Sprague-Dawley rats. Pretreatment of animals with 80 mg/kg phenobarbital for the site-specific enzyme studies enhanced and accelerated CCl4 toxicity in slices resulting from increased radical formation. Liver slices were exposed to 0.57 mM CCl4 by vaporization using a roller incubation system at 37 degrees C for a total of 9 hr. Conjugated diene formation, an index of lipid peroxidation, was detected 15 min following CCl4 administration and increased over time. Loss of cytochrome P450 occurred in a time-dependent manner relative to controls where levels in treated slices were 42% of controls at 9 hr. A 48-hr fast prior to termination increased intracellular K+ leakage relative to that present in slices from fed animals. Significant leakage of glucose-6-phosphate dehydrogenase and beta-glucuronidase from centrilobular hepatocytes occurred 9 hr following CCl4 administration. The content of the periportal enzymes (lactate dehydrogenase and sorbitol dehydrogenase) was unchanged in the same slices over the duration of the experiment. Reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide, a mitochondrial selective dye and indicator of viability, was significantly lower in treated slices from phenobarbital-treated animals at 9 hr relative to controls. These studies demonstrate that precision-cut slices are an ideal in vitro system for mechanistic studies and the investigation of site-specific toxicants since the integral architecture of the liver and cellular identity are maintained.

Factors involved in the depression of hepatic mixed function oxidase during infections with Listeria monocytogenes.

A number of infections are capable of depressing the capacity of the liver to metabolize drugs. We have studied a number of factors which could be involved in the depression of cytochrome P-450 and related drug biotransformation enzymes during infections with Listeria monocytogenes. During the course of the infection, drug metabolism and heme content of hepatic microsomes were depressed but heme oxygenase was elevated. A free radical scavenger alpha-tocopherol did not prevent the loss and xanthine oxidase activities did not correlate with the time course of the loss. Infections in susceptible (balb/c) mice produced a larger loss in drug metabolism than in resistant (C57BL/6) mice, and an avirulent strain of the bacteria was without effect. A preparation of hemolysin isolated from Listeria monocytogenes produced a dose-dependent loss of cytochrome P-450 in isolated hepatocytes. These experiments indicate that the loss of drug metabolism during Listeria infections is most likely due to hemolysin released by the bacteria.

Metabolism and alkylating activity of thio-TEPA in rat liver slice incubation.

Precision-cut rat-liver slices were used to study the metabolism of the alkylating agent N,N',N''-triethylenethiophosphoramide (thio-TEPA). Exposure to high concentrations (1-10 mM) of thio-TEPA for 6 h did not prove to be toxic to the liver slices as indicated by insignificant leakage of potassium from the cells. The time course of the disappearance of thio-TEPA (initial concentration, 5.2 microM) from the buffer during incubation followed first-order kinetics. Formation of N,N'N''-triethylenephosphoramide (TEPA) apparently accounted for the elimination of thio-TEPA. Pretreatment of the rats with phenobarbital significantly increased the reaction rate. Conversely, pretreatment with the cytochrome P-450 inhibitor allylisopropylacetamide significantly reduced the metabolic rate. The elimination of thio-TEPA and formation of TEPA occurred independently of thio-TEPA concentration, which ranged from 5.2 to 104 microM. Thio-TEPA's oxo-analogue TEPA, which was not further metabolized, was the only metabolite identified. However, a significantly time-related increase in 4-(nitrobenzyl)-pyridine (NBP) alkylating activity was observed following incubation of liver slices with thio-TEPA but not after their incubation with TEPA. This may possibly indicate the formation of unknown active metabolites.

Depression of murine hepatic mixed function oxidase during infection with Listeria monocytogenes.

The level of cytochrome P-450 and the oxidation of aminopyrine and benzo(a)pyrene hydroxylase were depressed in hepatic microsomes prepared from mice infected with the gram positive bacteria Listeria monocytogenes. Maximum depression of mixed function oxidase occurred on the 2nd day of infection. This loss in drug biotransformation capacity in the liver was correlated directly with the number of organisms found in that organ. The ability of mice to metabolize drugs in vivo also was impaired during Listeria monocytogenes infection. During the infective period the half-life of theophylline was significantly prolonged and the N-demethylation of aminopyrine as measured by the expiration of 14CO2 from radiolabeled aminopyrine was diminished. The loss of drug metabolism was not due to interferon production, fever or morphological damage to the liver. These results indicate that certain bacterial infections can depress drug biotransformation and elimination in a similar manner to that already reported in viral and parasitic infections. This finding may be of significance to patients receiving drugs which are metabolized by the mixed function oxidase system during episodes of infection with some bacteria.