Effects of delayed cord clamping at different time intervals in late preterm and term neonates: a randomized controlled trial.

Delayed cord clamping (DCC) at delivery has well-recognized benefits; however, current scientific guidelines lack uniformity in its definition. This parallel-group, three-arm assessor-blinded randomized controlled trial compared the effects of three different timings of DCC at 30, 60, and 120 s on venous hematocrit and serum ferritin levels in late preterm and term neonates not requiring resuscitation. Eligible newborns (n = 204) were randomized to DCC 30 (n = 65), DCC 60 (n = 70), and DCC 120 (n = 69) groups immediately after delivery. The primary outcome variable was venous hematocrit at 24 ± 2 h. Secondary outcome variables were respiratory support, axillary temperature, vital parameters, incidences of polycythemia, neonatal hyperbilirubinemia (NNH), need and duration of phototherapy, and postpartum hemorrhage (PPH). Additionally, serum ferritin levels, the incidence of iron deficiency, exclusive breastfeeding (EBF) rate, and anthropometric parameters were assessed during post-discharge follow-up at 12 ± 2 weeks. Over one-third of the included mothers were anemic. DCC 120 was associated with a significant increase in the mean hematocrit by 2%, incidence of polycythemia, and duration of phototherapy, compared to DCC30 and DCC60; though the incidence of NNH and need for phototherapy was similar. No other serious neonatal or maternal adverse events including PPH were observed. No significant difference was documented in serum ferritin, incidences of iron deficiency, and growth parameters at 3 months even in the presence of a high EBF rate.   Conclusion: The standard recommendation of DCC at 30-60 s may be considered a safe and effective intervention in the busy settings of low-middle-income countries with a high prevalence of maternal anemia.   Trial registration: Clinical trial registry of India (CTRI/2021/10/037070). What is Known: • The benefits of delayed cord clamping (DCC) makes it an increasingly well-accepted practice in the delivery room. • However, uncertainty continues regarding the optimal timing of clamping; this may be of concern both in the neonate and the mother. What is New: • DCC at 120 s led to higher hematocrit, polycythemia and longer duration of phototherapy, without any difference in serum ferritin, and incidence of iron deficiency. • DCC at 30-60 s may be considered a safe and effective intervention in LMICs.

Severe chronic Carboxyhemoglobinemia and polycythemia due to smoking hookah.

Acute carbon monoxide (CO) poisoning due to smoking hookah has been reported and may present similarly to other causes of acute carbon monoxide poisoning with nausea, headache, and loss of consciousness [1]. In the acute poisoned patient, immediate removal from the carbon monoxide source is paramount in addition to administration of oxygen and possible hyperbaric oxygen therapy (HBO) in certain situations. However, cases of chronic CO poisoning, treatment options, and long-term adverse health effects are far less reported but may include atherosclerosis and vague neurologic symptoms [2]. We present a case of a patient who chronically smoked hookah creating a condition of chronic carboxyhemoglobinemia which was discovered during work up for unexplained polycythemia. While being seen in the hematology clinic, he was found to have a blood carboxyhemoglobin of level 33.6% despite being asymptomatic. This is the highest recorded hookah-related carboxyhemoglobin concentration in the medical literature; and the significant chronic carboxyhemoglobinemia explained his polycythemia. This case illustrates that a social history is crucial when assessing the patient with severe carboxyhemoglobinemia as HBO is not indicated in chronic CO poisoning in an asymptomatic patient.

Use of intravenous iron in cyanotic patients with congenital heart disease and/or pulmonary hypertension.

BACKGROUND: Secondary erythrocytosis is common in patients with cyanosis secondary to congenital heart disease (CHD) and/or pulmonary hypertension (PH). This compensatory mechanism aims at increasing oxygen delivery to the tissues, but it requires adequate iron stores. Optimal methods of iron supplementation in this setting remain controversial, with fears of excessive erythropoiesis and hyperviscosity symptoms. We describe our experience using intravenous ferrous carboxymaltose. METHODS AND RESULTS: 142 consecutive cyanotic patients were treated over 5.7 years (201 administrations). Mean age was 51.3 ±â€¯17.6 years and 55 (38.7%) were male. Eisenmenger syndrome (ES) was present in 41 (28.8%), other pulmonary arterial hypertension (PAH) related to CHD (PAH-CHD) in 27 (19.0%), cyanotic CHD without PAH in 16 (11.3%) and PH without CHD in 58(40.8%). Baseline haemoglobin (Hb) concentration was 14.6 ±â€¯3.0 g/dL and haematocrit 0.45 ±â€¯0.09. A 500 mg dose of intravenous (IV) iron carboxymaltose was given in 163 (81.1%) of administrations and a 1000 mg dose in 37 (18.4%). A significant improvement in average Hb, haematocrit, ferritin and transferrin saturation was observed after a median follow-up of 100.0 [70.0-161.0] days (p ≤ 0.0001 for all). There were no cases of excessive erythropoiesis resulting in new hyperviscosity symptoms and/or requiring venesection. A minor transient rash was observed in 2 patients and one patient experienced an air embolus causing a transient ischemic attack. CONCLUSIONS: Intravenous ferrous carboxymaltose appears to be safe in iron deficient patients with cyanosis due to CHD and/or PH, as long as care is taken to avoid air emboli. Further randomised studies are needed to confirm the safety and efficacy of intravenous iron in this setting.

[Treatment by bloodletting in the past and present].

INTRODUCTION: Therapeutic bloodletting has been practiced at least 3000 years as one of the most frequent methods of treatment in general, whose value was not questioned until the 19th century, when it was gradually abandoned in Western medicine, while it is still practiced in Arabic and traditional Chinese medicine. CONTENT: In modern medicine bloodletting is practiced for very few indications. Its concept was modeled on the process of menstrual bleeding, for which it was believed to"purge women of bad humours. "Thus, bloodletting was based more on the belief that it helps in the reestablishment of proper balance of body "humours" than on the opinion that it serves to remove excessive amount of blood as well as to remove toxic "pneumas" that accumulate in human body. It was indicated for almost all known diseases, even in the presence of severe anemia. Bloodletting was carried out by scarification with cupping, by phlebotomies (venesections), rarely by arteriotomies, using specific instruments called lancets, as well as leeches. In different periods of history bloodletting was practiced by priests, doctors, barbers, and even by amateurs. In most cases, between one half of liter and two liters of blood used to be removed. Bloodletting was harmful to vast majority of patients and in some of them it is believed that it was either fatal or that it strongly contributed to such outcome. In the 20th century in the "Western"medicine bloodletting was still practiced in the treatment of hypertension and in severe cardiac insufficiency and pulmonary edema, but these indications were later abandoned. CONCLUSION: Bloodletting is still indicated for a few indications such as polycythemia, haemochromatosis, and porphyria cutanea tarda, while leeches are still used in plastic surgery, replantation and other reconstructive surgery, and very rarely for other specific indications.

Idiopathic erythrocytosis in dialysis patients: a case report and literature review.

Anemia is a common complication in end-stage renal disease (ESRD) patients. On the other hand, idiopathic erythrocytosis is extremely rare, with only a few cases reported in the literature. We present a case of erythrocytosis that developed after initiating hemodialysis. A 68-year-old male with a history of ESRD secondary to diabetes presented with erythrocytosis that started a few months after initiating dialysis in the absence of having received erythropoietin-stimulating agents or iron supplements. His erythropoietin level was elevated, with a negative JAK2 mutation. Blood gases showed normal oxygen and CO(2), with slightly elevated carboxyhemoglobin. Tiny foci in both kidneys were noted, representing vascular calcifications or renolithiasis. There was no radiological evidence of neoplasms or cysts. After excluding secondary causes, a diagnosis of idiopathic erythrocytosis was made. The patient underwent intermittent phlebotomies during dialysis, and his hemoglobin went from 18.5 to 14 mg/dl. Erythrocytosis in ESRD patients is very rare. So far, there is no complete understanding of the underlying pathophysiology; however, there seem to be multiple possible reasons for an increased erythropoietin level. Phlebotomy is a successful and easy way to control erythrocytosis in such patients. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, currently being used in posttransplant erythrocytosis, might also be considered.

[Middle-aged female presenting with headache, blurred vision and skin rash]. / Ei kvinne i 50-åra med hovudverk, uklart syn og utslett.

BACKGROUND: Autoimmune hyperlipidemia (AIH) is a rare cause of secondary hyperlipidemia. A few cases of AIH have been reported in multiple myeloma. MATERIAL AND METHODS: A female in her fifties was referred to the outpatient clinic presenting with headache, blurred vision and skin rash. Physical examination with subsequent laboratory and histological examinations revealed severe hyperlipidemia secondary to secretory multiple myeloma with monoclonal IgG kappa protein and erythrocytosis secondary to a erythropoietin secreting adenoma in the liver. RESULTS AND INTERPRETATION: Treatment for multiple myeloma (induction treatment and autologous hematological stem cell transplantation) gained partial remission and was associated with normalization of serum lipids. There was no need for further medical treatment of the hyperlipidemia. Three years after the initial treatment, serum concentrations of triglycerides and total cholesterol increased in parallel with monoclonal IgG kappa protein. Total cholesterol and triglycerides decreased and remained within the reference ranges after retreatment with a second autologous stem cell transplantation. Surgical removal of the hepatic adenoma caused normalisation of the erythropoietin concentration and resolution of the erythrocytosis. The present case reports two rare complications (AIH and erythrocytosis) to multiple myeloma and hepatic adenoma, with regression of complaints and normalisation of laboratory tests after adequate treatment of underlying diseases.

Effect of delayed versus early umbilical cord clamping on neonatal outcomes and iron status at 4 months: a randomised controlled trial.

OBJECTIVE: To investigate the effects of delayed umbilical cord clamping, compared with early clamping, on infant iron status at 4 months of age in a European setting. DESIGN: Randomised controlled trial. SETTING: Swedish county hospital. PARTICIPANTS: 400 full term infants born after a low risk pregnancy. INTERVENTION: Infants were randomised to delayed umbilical cord clamping (≥ 180 seconds after delivery) or early clamping (≤ 10 seconds after delivery). MAIN OUTCOME MEASURES: Haemoglobin and iron status at 4 months of age with the power estimate based on serum ferritin levels. Secondary outcomes included neonatal anaemia, early respiratory symptoms, polycythaemia, and need for phototherapy. RESULTS: At 4 months of age, infants showed no significant differences in haemoglobin concentration between the groups, but infants subjected to delayed cord clamping had 45% (95% confidence interval 23% to 71%) higher mean ferritin concentration (117 µg/L v 81 µg/L, P < 0.001) and a lower prevalence of iron deficiency (1 (0.6%) v 10 (5.7%), P = 0.01, relative risk reduction 0.90; number needed to treat = 20 (17 to 67)). As for secondary outcomes, the delayed cord clamping group had lower prevalence of neonatal anaemia at 2 days of age (2 (1.2%) v 10 (6.3%), P = 0.02, relative risk reduction 0.80, number needed to treat 20 (15 to 111)). There were no significant differences between groups in postnatal respiratory symptoms, polycythaemia, or hyperbilirubinaemia requiring phototherapy. CONCLUSIONS: Delayed cord clamping, compared with early clamping, resulted in improved iron status and reduced prevalence of iron deficiency at 4 months of age, and reduced prevalence of neonatal anaemia, without demonstrable adverse effects. As iron deficiency in infants even without anaemia has been associated with impaired development, delayed cord clamping seems to benefit full term infants even in regions with a relatively low prevalence of iron deficiency anaemia. Trial registration Clinical Trials NCT01245296.

Partial exchange transfusion results in increased cerebral oxygenation and faster peripheral microcirculation in newborns with polycythemia.

AIM: The aim of this study was to assess cerebral and peripheral oxygenation, by using near infrared spectroscopy (NIRS) and microcirculation by using side stream dark field (SDF) imaging in newborns with polycythemia before and after partial exchange transfusion (PET) therapy to investigate treatment effect on tissue oxygenation and microcirculation. METHODS: Polycythemic newborns with venous haematocrit (Htc) >70% or ≥65% with symptoms were included. NIRS measurements for cerebral and peripheral oxygenation and SDF recordings for microcirculatory flow assessment were obtained before and after PET. Fractional tissue oxygen extraction (FTOE) was calculated based on tissue oxygenation index and oxygen saturation. Wilcoxon test was used for statistical analysis. RESULTS: Fifteen newborns were included. Cerebral tissue oxygenation index, microvascular flow index and % of vessels with hyperdynamic flow increased after PET; median (range): 61.27 (51.36-61.87) versus 64.54 (54.1-74.38), 2.74 (2.46-3) versus 3.22 (2.64-3.75) and 0 (0-2.8) versus 3 (0-99.3), respectively. Whereas cerebral fractional tissue oxygen extraction (CFTOE), % of vessels with sluggish flow decreased after treatment; 0.36 (0.22-0.44) versus 0.31 (0.17-0.46), 1.4 (0-69) versus 0 (0-0.9), respectively. Peripheral oxygenation was unchanged. CONCLUSION: Partial exchange transfusion improves microcirculation in polycythemic newborns. Cerebral oxygenation increases and cFTOE decreases suggesting increased blood flow. Microvascular flow increases possibly representing reactive hyperperfusion after hemodilution. Whether these effects are beneficial require further research.

[Clinical implications of high blood viscosity and its reduction bu photo-hemotherapy]. / Klinicheskoe znachenie vysokoí viazkosti krovi i vozmozhnosti ee snizheniia metodami fotogemoterapii.

The paper is concerned with an essential blood characteristic--viscosity which is considered in relation of mechanisms responsible for its normal and abnormal characteristics, its role in the onset of circulatory disorders. High blood viscosity may contribute to development of vascular disturbances. Efficient methods of normalizing high blood viscosity are analyzed with special emphasis on photochemotherapy. Effects of ultraviolet, blue and red laser radiation on blood viscosity are outlined.

Inadequate treatment of excessive erythrocytosis / Tratamiento inadecuado en la eritrocitosis excesiva

Los pacientes con el mal de montaña crónico o eritrocitosis excesiva (EE) son residentes de la altura (3600 m), con mayor o igual 6.5 x 10 a la sexta glóbulos rojos (GR) que presentan cianosis.Esto ocasiona problemas estéticos y psicológicos en su vida ya que las demás personas creen que son alcohólicos. Cuando hay aumento de los GR, ellos buscan una cura milagrosa. De acuerdo a los conceptos evolutivos de la EE, los tratamientos han incluído; sanguijuelas, radioterapia de la médula ósea mediante administración de substancias radiactivas como el fósforo, y más recientemente, flebotomías, infusiuones de té, tabletas de ajo y la más peligrosa la administración de la fenilhidrazina, agente citotóxico prohibido. Encontramos que la mayoría de los pacientes con EE tienen placas radiográficas de tórax anormales. El concepto de los tratamientos es el de disminuir los GR. Sin embargo, la fenilhidrazina es tóxica para la médula ósea, el hígado y otros tejidos, cambiando el color de la piel de cianótica a icterica. Las conjuntivas se tornan ictéricas y la harina de café oscura. Una vez iniciado el tratamiento, la sangre de los pacientes es analizada periódicamente y el recuento de GR disminuyue, con lo que quedan satisfechos. Sin embargo, este medicamento tóxico puede producir la muerte. Al reducir los GR, el contenido arterial de oxígeno (CaO2) en la sangre disminuye. Las pruebas ergométricas en estos pacientes durante el tratamiento producen gran débito de oxígeno. En el paciente descrito, en el 4to nivel del protocolo de Bruce,m el dolor intenso de ambasd pantorrillas se hizo intolerable y requirió oxígeno post ejercicio. Al interrumpirse la fenilhidrazina, el, CaO2 retorna a niveles normales en aproximadamente 60 días, con una elevación de los GR por encima de los valores iniciales, y mejoría de la capacidad de ejercicio. Este y muchos otros casos nos llevan a creer que la EE es un mecanismo de compensación de la enfermedad pulmonar en la altura y que la cantidad de GR no debe ser disminuída.

[Blood viscosity and cerebral blood flow in aged].

It is well known that there is a close correlation between blood viscosity and blood flow. To clarify any relationship between blood viscosity and regional cerebral blood flow (rCBF) in the elderly, we simultaneously studied both CBF with PET (positron emission tomography) and blood viscosity with viscosimeter before and after phlebotomy in the elderly with various kinds of polycythemia. These subjects consisted of five male cases of secondary polycythemia due to pulmonary fibrosis, one male case of essential erythrocytosis (average age 66.6 +/- 4.6 years old) and one female case of stress polycythemia (47 years old). Before phlebotomy an increase in blood viscosity, decrease in rCBF and regional cerebral metabolic rate of oxygen (rCMRO2) were observed in all cases. After phlebotomy (total amount of 800 to 1,000 ml) blood viscosity rapidly decreased, and both rCBF and rCMRO2 tended to increase. There was a significant negative or positive correlation between CBF and blood viscosity or rCMRO2, respectively. However, no increase in cerebral oxygen transport was observed in any subject after phlebotomy. It was noted that cerebral infarction is not infrequent among elderly visitors to Kusatsu spa, which is characterized by high temperature hot spring water. From the authors' observation of 23 cases of cerebral infarction encountered during the last five years, it is noteworthy that the disease tended to occur more frequently during midnight to morning, specially 3:00 to 6:00. Thus, to clarify the pathogenetic mechanism of the cerebral infarction occurring after bathing in hot spring water, we studied the changes in blood viscosity, blood pressure and coagulation-fibrinolytic system after bathing in hot spring water.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of recombinant human macrophage colony-stimulating factor in combination with whole-body hyperthermia in the treatment of mice infected with the polycythemia-inducing strain of the Friend virus complex.

Macrophage colony-stimulating factor (M-CSF, CSF-1) and whole-body hyperthermia (WBH) were evaluated, alone or in combination, for their capability to influence disease progression in mice inoculated with the polycythemia-inducing strain of the Friend virus complex (FVC-P). DBA/2 mice were injected i.v. with FVC-P and were treated with 20 micrograms/dose M-CSF s.c. twice a day for 5 days beginning 6 days after injection of FVC-P and/or with WBH (between 38.8 degrees C and 40.2 degrees C) given on days 5 and 12 after FVC-P injection. Fourteen days after viral inoculation, mice were sacrificed and spleen cells evaluated for: 1) spleen focus-forming virus (SFFV), by the spleen focus-forming unit assay (SFFU); 2) SFFV mRNA and genomic DNA using, respectively, Northern and Southern analysis with a B-E-SFFV DNA probe; and 3) natural killer (NK) cell activity, by 51Cr-release assay. Treatment with M-CSF or WBH alone had a small effect on SFFU numbers but little or no effect on SFFV mRNA expression and SFFV-specific DNA. However, dramatically decreased levels of SFFU and SFFV mRNA and specific DNA fragments were observed in mice treated with M-CSF in combination with WBH, and NK cell activity was restored to normal. These results suggest the possibility that M-CSF may have a therapeutic effect in combination with WBH in the in vivo treatment of certain hematologic malignancies and/or retroviral infections.

Hemodilution.

The dilution of whole blood leads to a significant improvement of its rheologic properties based on a decrease in hematocrit and, hence, blood viscosity. Under conditions of normovolemia and an adequate response of the cardiorespiratory system, the acute dilution of blood will enhance the venous return to the heart and thereby improve total and capillary blood flow significantly. In the hematocrit range of 25 to 30 per cent (limited hemodilution), this increase in flow rate is able to compensate fully for the diminished oxygen content of the blood. Changes in oxygen extraction or in oxygenhemoglobin affinity are only encountered at hematocrits below 20 per cent or if hemodilution is associated with hypovolemia. Since normovolemia is the condition sine qua non for the heart to increase its output compensatorily, intentional hemodilution should preferably be performed with colloid solutions which are capable of maintaining the colloid osmotic pressure of plasma and the circulating volume in normal limits. Limited normovolemic hemodilution with its beneficial effects on microcirculatory flow and tissue nutrition is emphasized for the treatment of impaired microcirculation as occurring in shock and low flow states, polycythemia, and high viscosity syndromes. Acute preoperative hemodilution is a means of reducing the use of bank blood and of avoiding the risks of blld transfusions in patients undergoing major elective surgery. Extreme hemodilution and total body washout in hypothermia appear to be effective clinical tools.