Association between hypocalcemia and rivaroxaban in coagulation disorders: a case report / Associação entre hipocalcemia e rivaroxaban em distúrbios de coagulação: relato de caso

ABSTRACT We describe a patient with tertiary hyperparathyroidism with history of three episodes of deep vein thrombosis and on rivaroxaban. The patient underwent a subtotal parathyroidectomy, developing cervical hematoma with airway compression. Therefore, emergency surgical decompression was necessary. Later, on the ninth postoperative day, the serum ionized calcium levels were low. Medical team knowledge about preexisting diseases and their implication in the coagulation state are essential conditions to reduce morbidity and mortality of surgeries. However, no reports were found in literature about the association of hypocalcemia with the use of the new class of anticoagulants, which act as factor X inhibitors (Stuart-Prower factor), predisposing to increased bleeding in the immediate postoperative period.

RESUMO Descrevemos um paciente com hiperparatireoidismo terciário com história de três episódios de trombose venosa profunda e em uso de rivaroxabana. O paciente foi submetido a uma paratireoidectomia subtotal, desenvolvendo hematoma cervical com compressão das vias aéreas. Foi necessária descompressão cirúrgica de emergência. No nono dia de pós-operatório, os níveis séricos de cálcio iônico estavam baixos. O conhecimento da equipe médica sobre doenças preexistentes e de sua implicação no estado de coagulação é condição indispensável para a redução da morbimortalidade do procedimento cirúrgico. No entanto, não há relatos na literatura associando hipocalcemia com o uso da nova classe de anticoagulantes que atuam como inibidores do fator X (fator de Stuart-Prower), predispondo ao aumento do sangramento no pós-operatório imediato.

Uso inapropiado de diuréticos: Algunas características no tan conocidas / Diuretic misuse: Some not so well known characteristics

Entre las situaciones asociadas al uso inapropiado de diuréticos se encuentran los intentos por descencer rápidamente de peso, comunes en los desordenes de la alimentación, y los intentos por enmascarar el consumo de otras sustancias, en el caso de las competencias deportivas. El uso sin indicación ni supervisión médica de estos fármacos genera un desbalance electrolítico, que puede manifestarse con hiponatremia, hipocalemia, hipocalcemia e hipomagnesemia, hipercalemia, entre otras alteraciones. El objetivo de este trabajo fue investigar las caracteríscas del uso inapropiado de diuréticos a partir de la casuística del CENATOXA. Se realizó un estudio descriptivo restrospectivo sobre los análisis ingresados al CENATOXA con solicitud de investigación cualitativa de diuréticos en orina, entre los años 2002 y 2016. En dicho período ingresaron al CENATOXA 138 casos, de los cuales el 56 % resultó positivo para algún diurético. Del total de casos con resultado positivo, el 93,5 % fueron mujeres entre 25 y 55 años de edad y predominó la etiología intencional. Los diuréticos mayoritariamente encontrados fueron hidroclorotiazida y furosemida. El perfil de diuréticos hasta el año 2008 (hidroclorotiazida = 68% de los casos positivos) se diferenció del hallado entre 2009 y 2016 (furosemida + hidroclorotiazida = 60% de los casos positivos). Se observó recurrencia en el uso inapropiado en el 8% de los casos. El uso simultáneo de más de un diurético y la recurrencia son factores que pueden contribuir a la aparición de toxicidad. Estos resultados sugieren que el uso inapropiado de diuréticos es una situación que debería ser ob­servada más atentamente para establecer mejor su alcance y sus riesgos.

Among the situations associated with diuretics misuse are the attempts to lose weight fast, frequently observed in eating disorders, and the attempts to mask the consumption of other substances, in the case of sports competitions. The use of these drugs with no medical indication or supervision generates an electrolyte imbalance, leading to hyponatremia, hypokalemia, hypocalcemia and hypomagnesemia, hyperkalemia, among other alterations. The objective of this work was to investigate the characteristics of diuretics misuse from the CENATOXA database, where the qualitative investigation of diuretics in urine is per­formed. A descriptive retrospective study was conducted on the cases admitted to the CENATOXA with a request for qualitative diuretic investigation, between 2002 and 2016. During this period, 138 urine samples were received at the CENATOXA and 56% were positive for at least one diuretic. Of all cases with positive results, 93.5% were women between 25 and 55 years of age, and intentional etiology predominated. The most detected diuretics were hydrochlorothiazide and furosemide. The diuretic misuse pattern detected up to 2008 (hydrochlorothiazide = 68% of positive cases) differed from that detected between 2009 and 2016 (furosemide + hydrochlorothiazide = 60% of positive cases). Recurrence in misuse was observed in 8% of the cases. The simul­taneous misuse of more than one diuretic and the recurrence are factors that can contribute to the onset of toxicity. These results suggest that diuretic misuse is a situation that should be observed more closely to better assess its consequences and its risks.

Electrolyte Imbalances and Nephrocalcinosis in Acute Phosphate Poisoning on Chronic Type 1 Renal Tubular Acidosis due to Sjogren's Syndrome

Although renal calcium crystal deposits (nephrocalcinosis) may occur in acute phosphate poisoning as well as type 1 renal tubular acidosis (RTA), hyperphosphatemic hypocalcemia is common in the former while normocalcemic hypokalemia is typical in the latter. Here, as a unique coexistence of these two seperated clinical entities, we report a 30-yr-old woman presenting with carpal spasm related to hypocalcemia (ionized calcium of 1.90 mM/L) due to acute phosphate poisoning after oral sodium phosphate bowel preparation, which resolved rapidly after calcium gluconate intravenously. Subsequently, type 1 RTA due to Sjogren's syndrome was unveiled by sustained hypokalemia (3.3 to 3.4 mEq/L), persistent alkaline urine pH (> 6.0) despite metabolic acidosis, and medullary nephrocalcinosis. Through this case report, the differential points of nephrocalcinosis and electrolyte imbalances between them are discussed, and focused more on diagnostic tests and managements of type 1 RTA.

Avaliação do quadro clínico e perfil bioquímico de bovinos durante indução e tratamento de hipocalcemia / Assessment of clinical and biochemical profile of cattle during induction and treatment of hypocalcemia

O presente trabalho objetivou estudar o quadro sintomatológico, algumas variáveis bioquímicas e a resposta ao tratamento com cálcio de bovinos com hipocalcemia induzida experimentalmente. Foram utilizadas 12 novilhas distribuídas nos grupos controle (n = 5) e tratado (n = 7). Foi infundida solução de EDTA a 5% até o animal apresentar sinais clínicos de hipocalcemia, quando então era iniciado o tratamento com solução contendo cálcio, fósforo, magnésio e glicose, na dose de 1 mL/kg/PV, em 30 minutos, enquanto que o grupo controle recebia apenas solução fisiológica na mesma dose. Exame clínico e coleta de amostras sanguíneas foram realizados nos tempos T0 (basal), T1 (Fase I, caracterizada por tremores musculares), T2 (ao final da infusão com EDTA), T3 (ao final do tratamento) e T4 (24 horas após o término do experimento). Todas as novilhas mostraram diminuição temporária da concentração de cálcio total e livre, fósforo, e apresentaram quadro clássico de hipocalcemia. A taquicardia, a hipofonese e a atonia ruminal desapareceram no decorrer do tratamento, sendo observado aumento no cálcio livre e total e fósforo. O medicamento usado no tratamento dos animais foi eficaz na recuperação do quadro clínico de hipocalcemia dentro de 30 minutos, promovendo retorno das principais variáveis do perfil bioquímico aos valores basais

The present work aims to study the clinical picture, biochemical profile and treatment response in cattle with induced hypocalcaemia. Were utilized 12 heifers randomly distributed in treated (n = 7) and control (n = 5) groups. The induction model was carried on by continuous EDTA infusion into jugular vein until the animals present clinical signs of hypocalcaemia. After that, the treated group received a calcium (Ca) solution enriched with phosphorus, magnesium and glucose with a dose of 1 mL/kg/BW in 30 minutes, meanwhile, the control group was treated with the same dose of physiologic solution. Clinical examination were performed and blood samples were obtained in times T0 (basal time), T1 (beginning of hypocalcaemia); T2 (end of EDTA infusion); T3 (end of treatment) and T4 (24 hours after the induction). All the heifers present temporary blood calcium and phosphorus reduction and demonstrated classical clinical picture of hypocalcaemia. The treated group present full clinical recovery and blood calcium and phosphorus increase. Most evident clinical signs were increasing heart beat, hypophonesis and rumenal atony. Those symptoms were reversed after calcium treatment. The solution used for treatment was efficient on clinical recovery within thirty minutes, promoting the return to basal levels of the most of biochemical's variables

Severe Hypocalcemia Caused by Absorption of Sorbitol-Mannitol Solution during Hysteroscopy

Hysteroscopic procedure can be complicated by intravascular absorption of irrigating fluid. The clinical features of this complication are similar to transurethral resection of the prostate (TURP) syndrome. There have been few reports on hypocalcemia during endoscopoic surgery and clinical implications of hypocalcemia in TURP syndrome have been underestimated. We report a case of TURP syndrome association with a decreased ionized calcium concentration of 0.53 mM/L after the absorption of a large amount of sorbitol-mannitol solution during hysteroscopy. The hypotension which occurred in TURP syndrome did not respond to vasopressor and inotropic agent but responded to the administration of calcium. This case was also accompanied by hyponatremia, hyperglycemia and lactic acidosis through the metabolism of sorbitol.

Calcium homeostasis in low and high calcium water acclimatized Oreochromis mossambicus exposed to ambient and dietary cadmium.

The effects of cadmium administered via ambient water (10 microg/l) or food (10 microgCd/fish/day) on plasma calcium, corpuscles of Stannius and bony tissues of Oreochromis mossambicus acclimated to low calcium (0.2 mM) and high calcium (0.8 mM) water were studied for 2, 4, 14 and 35 days. In low calcium water acclimated fish, ambient cadmium induced significant hypocalcemia, while the structure and morphometry of type-1 and type-2 cells of corpuscles of Stannius were not affected on day 2 and 4. Subsequently on day 14 and 35, recovery of plasma calcium to normal levels was observed followed by a decrease in corpuscles of Stannius index (CSI), cell size, volume of granular endoplasmic reticulum (p < 0.05) of type-1 cells in both, fish exposed to ambient or dietary cadmium. The type-2 cells were not affected. In high calcium water acclimated fish both, ambient and dietary cadmium caused a significant reduction of plasma calcium levels on day 2 and 4. In these fish, there was a significant transient increase in the size of corpuscles of Stannius on day 4, followed by recovery on day 14 and 35. Ultrastructural observations of corpuscles of Stannius revealed that cadmium did not cause any cellular damage on type- and type-2 cells during 35 days exposure. In low or high calcium water acclimatized tilapia exposed to ambient or dietary cadmium had no effect on the calcium and phosphate composition of the scales, operculum and vertebrae. Thus, it is unlikely that recovery of hypocalcemia was due to the dissolution of calcium from bony tissues. This study also revealed that cadmium does not mediate stimulation of the corpuscles of Stannius gland, and that high Ca2+ water had a protective effect against ambient and dietary cadmium.

Responses of serum calcium and inorganic phosphate levels as well as parathyroid gland and calcitonin producing C cells of Rattus norvegicus to Mipcin administration.

Serum calcium (Ca) level of Rattus norvegicus ranged between 13.08 +/- 0.41 - 13.25 +/- 0.39 mg/100 ml whereas serum inorganic phosphate (Pi) concentration varied between 4.21 +/- 0.28 - 4.33 +/- 0.26 mg/100 ml. Sublethal (0.50 LD50 and 0.75 LD50) administration of Mipcin induced a progressive dose-dependent decline in serum Ca level in the rat which was statistically significant at 7 and 14 days. Serum inorganic phosphate level of the treated rats did not exhibit significant fluctuation during the entire course of investigation. Parathyroid chief cells of the experimental rats exhibited degranulation, vacuolation, loss of secretory (hormone) granules and lipid droplets, decreased chromatin in nuclei and damages in the endoplasmic reticulum as well as cristae of mitochondria at 14 days of the treatment. Not much of changes could be seen in the oxyphil cells of parathyroid as well as thyroid C cells of the Mipcin-treated rats.

Effects of diazinon on serum calcium and inorganic phosphate levels as well as ultrastructures of parathyroid and calcitonin cells of Rattus norvegicus.

Daily intramuscular administration of two doses--0.50 LD550 (150 mg/kg b w) and 0.75 LD50 (225 mg/kg b w) of diazinon for 14 days induced progressive hypocalcemia without altering serum inorganic phosphate value in Rattus norvegicus. Hypocalcemic response of the pesticide was dose- as well as time-dependent. Parathyroid chief cells of the experimental rats exhibited degranulation, vacuolation, loss of secretory granules and lipid droplets, decreased chromatin, and degenerative changes in endoplasmic reticulum, Golgi complex as well as cristae of the mitochondria. Not much of ultrastructural changes could be seen in the C cells of the rats treated with diazinon.

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH) secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 + or - 0.2 percent; range = 3.5-5.0 percent), 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 + or - 0.4 percent; range = 6.0-8.5 percent), and 8 patients with poor metabolic control (group P: HbA1C = 12.5 + or - 1.0 percent; range: 10.0-18.8 percent). Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight) and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 + or - 0.01 mmol/l) than in group N (1.21 + or - 0.01 mmol/l) and group G-R (1.22 + or - 0.01 mmol/l). After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01) in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 + or - 2.1 vs G-R = 13.7 + or - 1.6 vs P = 7.5 + or - 0.7 pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion is impaired in patients with poorly controlled diabetes

Toxicología preclínica de bisfosfonatos / Preclinical toxicology of bisphosphonates

Los bisfosfonatos regulan el recambio óseo por inhibición de la reabsorción óssea osteoclástica. Sus características farmacodinémicas y farmacocinéticas les confieren un particular perfil fármaco-toxicológico, determinado en gran parte por su alto grado de especialidad escasa o nula distribución en tejidos blandos, fuerte afinidad por tejidos calcificados. Los estudios de toxicología preclínica, cuyo objetivo principal es localizar el o los órganos blanco de toxicidad y estimar el margen de seguridad de un "candidato a agente terapéutico" en animales de experimentación, permiten extraer conclusiones generales que, en el caso de los bisfosfonatos, se avalan con resultados propios y obtenidos en la literatura. Se consideran distintos integrantes de este grupo farmacológico: Alendronato, Clodronato, Etidronato, Olpadronato, Pamidronato. En general, deben administrarse dosis muy altas de bisfosfonatos para la observación, en grado e incidencia variable, de efectos tóxicos extraesqueléticos: reacción local, hipocalcemia- y sus consecuencias sobre el sistema cardiovascular y la posibilidad de tetania-, afectación de las estructuras dentarias y disfunción renal. La mayoría de estos efectos pueden atribuirse a la escasa solubilidad en fluídos biológicos, a la formación de complejos con el ión calcio, a su potente efecto inhibitorio de la reabsorción ósea endógena o inducida y a su principal vía de excreción. Otros efectos tóxicos (oculares, pulmonares, hepáticos), pueden relacionarse con excesivas dosis reiteradas. Si se considera la cantidad total de Olpadronato administrada a distintas especies animales en estudios toxicológicos y en modelos experimentales farmacodinámicos (osteopenias por deprivación estrogénica e inmovilización, hipercalcemia inducida por retinoides), se puede estimar un margen de seguridad de 200-300:1 entre las dosis "tóxicas" y "farmacológicas". Si las dosis tóxicas en animales se relacionan con las máximas propuestas para humanos, la relación asciende a 300 - 1000:1 dependiendo de la patología y la vía de administración consideradas. Con respecto a su efecto óseo, los datos experimentales con los nuevos bisfosfonatos sugieren un marcado alejamiento entre dosis activas farmacológicamente y aquellas que producen defectos en la mineralización ósea. La exagerada inhibición del remodelamiento óseo, producto del empleo de altas dosis en animales normales, es la natural consecuencia del efecto farmacológico de este tipo de compuestos. ...

Prospective study of changes in serum calcium after diethyl-ether anaesthesia.

Changes in serum calcium after diethyl-ether anaesthesia given for various routine surgical operations, were studied in 30 patients. Mean (+/- SD) concentration (mg%) of serum calcium before induction of anaesthesia was 10.37 +/- 0.77. Serum calcium decreased by 0.05 per cent after 10 min of induction and by 3.33 per cent at the end of anaesthesia which was highly significant (P less than 0.001). There was a correlation (r = 0.63; P less than 0.01) between decline in serum calcium and duration of ether anaesthesia. Serum calcium returned to near normal levels after 24 h of ether anaesthesia. In view of the fall in serum calcium, it is emphasized that ether should be either avoided in patients with known or suspected hypocalcaemia or be used for as short a time as possible with due precaution and calcium supplementation.

A case of hypomagnesemia hypocalcemia as a complication of aminoglycoside and review of the literature.

A 28-year-old woman was admitted to the ENT Department of the Faculty of Medicine, Chiang Mai University because of left otitis externa, chronic mastoiditis and facial nerve palsy (lower motor neurone). Left radical mastoidectomy with wide debridement of granulation and necrotic tissue at ear canal, dura, sigmoid sinus, ossicle and facial nerve were done two weeks after admission. Multiple pus culture from the lesion revealed different types of organisms e.g. proteus mirabilis, beta strep non group A, and enterococci beta type. Several aminoglycosides were alternately given for two months without improvement of ear infection. She developed carpopedal spasm with hypocalcemia after three weeks of such treatment. Hypomagnesemia was recognized. Calcium and milk supplement gave temporary relief, but permanent relief was obtained after aminoglycoside was discontinued. Serum electrolyte had reversed to normal on follow-up.

Hipocalcemia en el período neonatal inducida por fototerapia / Hypocalcemia in the neonatal period induced by phototherapy

El autor de la presente Tesis estudia el comportamiento evolutivo a las 6,24 y 48 horas de vida de los minerales de calcio en sangre, mediante el empleo del método espectrofométrico por absorción atómica. Se seleccionaron dos grupos de recién nacidos, en el grupo A constituido por: 212 recién nacidos a términos adecuados para sus edades gestacionales, siendo subdivido en A1 (que representan 116 recién nacidos normales) y A2 (96 recién nacidos que presentaron icteria precoz después de la sexta hora de vida, sin reonocer procesos inmunológicos ni otra etiología). El grupo B integrado por: 98 recién nacidos pretérminos de bajo peso al nacer distribuidos en B1 por (50 recién nacidos pretérminos normales) y B2 (48 recién nacidos pretérminos ictericos con hiperbilirrubinemia); tanto éstos últimos como los a términos del subgrupo A2, fueron sometidos a la acción fotónica hasta el lapso ya mensionado. Se reportan los efectos de dicho tratamiento sobre los valores de calcio, registrándose tanto individualemnte como en sus valores promedio ninguna diferencia estadísticamente significativa entre la sexta y vigésima cuarta horas, pero sí un P < 0.01 evidente entre las 24 y 48 horas, por descensos acentuados de los valores en ambos grupos mientras que, en los normales (A1 y B1) se observaron valores individuales y promendio similares a la sexta y vigésima cuarta horas, con un P > 0,05, siendo inferior a los encontrados a las 48 horas (P < 0,01). Se aplica el test Students mediante el índice P, estudiando comparativamente los valores promedio de calcio en sangre de los subgrupos con los grupos entre sí..