RESUMEN
The case presented describes the combined onset of heparin-induced thrombocytopenia II (HIT) and post-transfusion purpura (PTP) 5-10 days following exposure to heparin and blood transfusion during aortic dissection repair. On day 4 the platelet count decreased by 40% and D-dimers started to increase again. Despite a low clinical probability for HIT-II at this time (4T score of 3) serological testing was done the next day and yielded a negative test result. Following a transient rise after platelet transfusion another 40% decrease in platelet count occurred on day 8. To increase precision of the 4T score, screening ultrasonography was performed and identified a clinically unapparent jugular vein thrombosis. As this increased the 4T score to 6 points, serological testing was repeated and now showed the presence of HIT-II antibodies. Despite switching from heparin to argatroban the platelet count continued to decrease to <5×10(3)/µl. Conventional clotting tests showed a prolonged prothrombin time and severe hypofibrinogenemia. Because of the female sex, age >50 years, history of pregnancy and transfusion 8 days before, PTP was suspected. The alteration of the plasmatic coagulation, however, could not be explained by PTP. Therefore, disseminated intravascular coagulation (DIC) and interference of argatroban with conventional clotting tests were considered as alternative diagnoses. In order to differentiate between the two alternatives rotational thrombelastometry (ROTEM®) was performed and revealed an increased functional fibrinogen level without signs of hyperfibrinolysis. This argued for an interference of argatroban with the Clauss method of fibrinogen measurement and rendered DIC unlikely. Under suspicion of PTP, treatment with immunoglobulin was initiated and blood transfusions were avoided. Detection of PTP antibodies 1 day later confirmed the combined presence of PTP and HIT-II. As hyperfibrinogenemia compensated for the effects of thrombocytopenia on clot firmness in ROTEM®, anticoagulation with lepirudin was started at 9×10(3) platelets/µl only. The next day the platelet count increased to 32×10(3)/µl and clot firmness returned to normal. No thromboembolic complications and no relevant bleeding were observed. In summary, this case shows for the first time that HIT-II and PTP can occur in parallel in patients with simultaneous exposure to heparin and blood transfusions. Confounding effects of argatroban on conventional clotting tests may mimic DIC under these circumstances and make diagnosis difficult. Careful evaluation of the time-related magnitude in platelet decrease, patient history, course of D-dimers, screening ultrasonography and ROTEM® seem to be helpful to initiate early appropriate therapy before serological test results become available. In contrast to the Clauss method of fibrinogen measurement, assessment of clot firmness in ROTEM® is not influenced by argatroban. Moreover, ROTEM® reveals the compensatory effects of increased functional fibrinogen on clot firmness during severe thrombocytopenia as an important variable for anticoagulation therapy during thrombocytopenia with increased thromboembolic risk.
Asunto(s)
Anticoagulantes/efectos adversos , Heparina/efectos adversos , Púrpura Trombocitopénica/terapia , Tromboelastografía , Trombocitopenia/terapia , Terapia Trombolítica/métodos , Reacción a la Transfusión , Antitrombina III/análisis , Aneurisma de la Aorta/cirugía , Recuento de Células Sanguíneas , Femenino , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Tiempo de Tromboplastina Parcial , Púrpura Trombocitopénica/etiología , Síncope/complicaciones , Trombocitopenia/inducido químicamente , Trombocitopenia/etiologíaRESUMEN
BACKGROUND AND OBJECTIVE: Isoflurane is a chiral volatile anaesthetic, routinely administered as racemate. It has a low metabolic rate and is mostly eliminated via respiration. In blood samples, S(+) enantiomers are found in greater proportion in the days immediately after administration of isoflurane racemate whereas the ratio in breath samples is unknown. METHODS: Breath and blood samples were drawn immediately after recovery and daily up to 19 days after operation from patients undergoing anaesthesia with isoflurane racemate. The percentage of isoflurane enantiomer was determined by gas chromatography mass spectrometry in blood and thermodesorption gas chromatography mass spectrometry in breath samples. RESULTS: In breath samples, there were significant differences in S(+) enantiomers at all time points compared to the racemate. During the early postoperative phase, the percentage of S(+) enantiomers were significantly enhanced whereas 5 days after surgery predominantly R(-) enantiomers (50.41%) were detected in the breath samples. Also in blood samples a statistical significant accumulation of the S(+) enantiomer was noted between days 1 and 5 compared to isoflurane racemate blood control. S(+) enantiomers were significantly higher in blood compared to breath samples and was most evident on the third day after surgery (51.43%). CONCLUSIONS: During the first days after application of isoflurane racemate, the percentage of S(+) enantiomers are higher in breath and blood samples of patients. We suggest that resorption and/or redistribution of enantiomers are responsible for the different kinetics of isoflurane enantiomers.
Asunto(s)
Anestésicos por Inhalación/metabolismo , Isoflurano/metabolismo , Anestésicos por Inhalación/sangre , Anestésicos por Inhalación/química , Pruebas Respiratorias , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Isoflurano/sangre , Isoflurano/química , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Intercambio Gaseoso Pulmonar/fisiología , Estadísticas no Paramétricas , Estereoisomerismo , Factores de TiempoRESUMEN
BACKGROUND AND OBJECTIVE: Isoflurane is a chiral, volatile anaesthetic with low metabolic rate (0.17%) that is routinely administered in its racemic form. Knowledge about the distribution of the enantiomers in human beings may give some important information about the understanding of the mechanisms of volatile anaesthetics. METHODS: Blood samples were drawn immediately after tracheal extubation and daily up to 8 days postoperatively from patients undergoing general anaesthesia with isoflurane racemate. The enantiomer enrichment of isoflurane was determined by headspace gas chromatography-mass spectrometry. RESULTS: At all time points, there was a statistically significant accumulation of the S(+) enantiomer in blood, especially at days 2 (52.01%) and 7 (52.1%). Separate analysis of obese patients or in a small group of patients with co-existing lung disease did not show any difference to the total population. In addition, duration of anaesthesia did not influence the enantiomer concentrations. CONCLUSIONS: We suggest that a slower association and dissociation rate is responsible for the S(+) enrichment.
Asunto(s)
Anestesia General , Anestésicos por Inhalación/sangre , Anestésicos por Inhalación/química , Isoflurano/sangre , Isoflurano/química , Anciano , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Intubación Intratraqueal , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , EstereoisomerismoRESUMEN
Lower respiratory tract disease caused by respiratory syncytial virus (RSV) is characterized by profound airway mucosa inflammation, both in infants with naturally acquired infection and in experimentally inoculated animal models. Chemokines are central regulatory molecules in inflammatory, immune, and infectious processes of the lung. In this study, we demonstrate that intranasal infection of BALB/c mice with RSV A results in inducible expression of lung chemokines belonging to the CXC (MIP-2 and IP-10), CC (RANTES, eotaxin, MIP-1beta, MIP-1alpha, MCP-1, TCA-3) and C (lymphotactin) families. Chemokine mRNA expression occurred as early as 24 h following inoculation and persisted for at least 5 days in mice inoculated with the highest dose of virus (10(7) PFU). In general, levels of chemokine mRNA and protein were dependent on the dose of RSV inoculum and paralleled the intensity of lung cellular inflammation. Immunohisthochemical studies indicated that RSV-induced expression of MIP-1alpha, one of the most abundantly expressed chemokines, was primarily localized in epithelial cells of the alveoli and bronchioles, as well as in adjoining capillary endothelium. Genetically altered mice with a selective deletion of the MIP-1alpha gene (-/- mice) demonstrated a significant reduction in lung inflammation following RSV infection, compared to control littermates (+/+ mice). Despite the paucity of infiltrating cells, the peak RSV titer in the lung of -/- mice was not significantly different from that observed in +/+ mice. These results provide the first direct evidence that RSV infection may induce lung inflammation via the early production of inflammatory chemokines.
Asunto(s)
Pulmón/patología , Proteínas Inflamatorias de Macrófagos/fisiología , Infecciones por Virus Sincitial Respiratorio/patología , Virus Sincitiales Respiratorios/inmunología , Animales , Quimiocina CCL3 , Quimiocina CCL4 , Femenino , Humanos , Inmunohistoquímica , Inflamación , Pulmón/metabolismo , Pulmón/virología , Proteínas Inflamatorias de Macrófagos/genética , Ratones , Ratones Endogámicos BALB C , Infecciones por Virus Sincitial Respiratorio/inmunología , Infecciones por Virus Sincitial Respiratorio/virología , Replicación ViralRESUMEN
The objective of these experiments was to examine the ability of Helicobacter pylori to stimulate interleukin-10 (IL-10) or IL-12 and select for either Th1 or Th2 cells. Gastric biopsy specimens were collected from patients who were categorized with respect to the presence of H. pylori and gastric disease as well as their age, gender, medications, and other factors. As Th1 and Th2 cells are selected by IL-12 and IL-10, respectively, biopsy specimens were screened for mRNA and protein for these cytokines. Although mRNA for IL-12 and IL-10 was detected in biopsy specimens obtained from both infected and uninfected patients, IL-12 protein predominated. Levels of IL-10 and IL-12 in gastric tissue did not change in response to infection. Moreover, gamma interferon (IFN-gamma)-producing T cells were found in both the infected and the uninfected gastric mucosa. Stimulation of peripheral blood leukocytes from either infected or uninfected donors with various concentrations of live or killed H. pylori induced immunoreactive IL-12 and IL-10. After stimulation with live H. pylori, IL-12 levels increased more than 30-fold, whereas IL-10 levels increased only 2- to 5-fold, compared to cells stimulated with medium alone. Interestingly, killed H. pylori induced significantly more IL-10 (P < 0.05) than live H. pylori, while recombinant urease only induced IL-10. These results demonstrate that live H. pylori selectively stimulates the induction of IL-12 and Th1 cells that produce IFN-gamma, whereas preparations used in oral vaccines induce more IL-10 and may favor Th2 cell responses.