Total Red Blood Cell Volume Research Articles

Early effects of acetazolamide on hemoglobin mass and plasma volume in chronic mountain sickness at 5100 m

Introduction and objectivesChronic Mountain Sickness (CMS) syndrome, combining excessive erythrocytosis and clinical symptoms in highlanders, remains a public health concern in high-altitude areas, especially in the Andes, with limited therapeutic approaches. The objectives of this study were to assess in CMS-highlanders permanently living in La Rinconada (5100–5300 m, Peru, the highest city in the world), the early efficacy of acetazolamide (ACZ) and atorvastatin to reduce hematocrit (Hct), as well as the underlying mechanisms focusing on intravascular volumes. Materials and methodsForty-one males (46±8 years of age) permanently living in La Rinconada for 15 [10–20] years and suffering from CMS were randomized between ACZ (250 mg once-daily; N = 13), atorvastatin (20 mg once-daily; N = 14) or placebo (N = 14) uptake in a double-blinded parallel study. Hematocrit (primary endpoint) as well as arterial blood gasses, total hemoglobin mass (Hbmass) and intravascular volumes were assessed at baseline and after a mean (±SD) treatment duration of 19±2 days. ResultsACZ increased PaO2 by +13.4% (95% CI: 4.3 to 22.5%) and decreased Hct by -5.2% (95% CI: -8.3 to -2.2%), whereas Hct remained unchanged with placebo or atorvastatin. ACZ tended to decrease Hbmass (-2.6%, 95% CI: -5.7 to 0.5%), decreased total red blood cell volume (RBCV, -5.3%, 95% CI: -10.3 to -0.3%) and increased plasma volume (PV, +17.6%, 95% CI: 4.9 to 30.3%). Atorvastatin had no effect on intravascular volumes, while Hbmass and RBCV increased in the placebo group (+6.1%, 95% CI: 4.2 to 7.9% and +7.0%, 95%CI: 2.7 to 11.4%, respectively). ConclusionsShort-term ACZ uptake was effective to reduce Hct in CMS-highlanders living at extreme altitude >5,000 m and was associated with both an increase in PV and a reduction in RBCV.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Excessive Erythrocytosis Is Not Associated With Altered Iron Homeostasis in Men From the World's Highest City.

Intravascular Volume Derangement and Value of Blood Volume Analysis in Stable Ambulatory Patients with Advanced Heart Failure Supported with Left Ventricular Assist Device

<h3>Purpose</h3> Heart failure is associated with elevated filling pressures and significant volume expansion. Durable left ventricular assist devices (LVAD) have been shown to improve survival and quality of life in patients with advanced heart failure. There is strong evidence suggesting structural, neurohormonal and hemodynamic improvement after LVAD implantation. The data on normalization of plasma volume is lacking. We sought to describe blood volume parameters in stable outpatient LVAD recipients. <h3>Methods</h3> We performed blood volume analysis (BVA) on 33 stable consecutive patients supported with LVADs in the outpatient setting. All BVAs were obtained as part of routine outpatient follow up. Results of the test were provided to clinicians for ongoing patient management. BVA is clinically approved and utilizes the Iodine131-tagged albumin tracer to provide quantitative measurement of total blood volume (TBV), plasma volume (PV) and red blood cell volume (RBC). The BVA-report provides absolute values (ml) and deviation from ideal TBV, PV, and RBC. A TBV deviation ≥±8% was considered to be either an excess or deficit of volume. <h3>Results</h3> Only 9% of stable ambulatory LVAD patients had normal blood volume results. 18/33 (54%) had significant anemia, 4/33 (12%) had polycythemia. Polycythemia in all of the patients was masked on complete blood count analysis, due to significant hypervolemia. One of the patients with masked polycythemia had fatal pump thrombosis. Plasma volume abnormality was found in 75% of patients (39% were hypervolemic, 36% were hypovolemic). 6 patients had repeat BVA after medical interventions and all of them were unsuccessful in normalizing plasma volume. <h3>Conclusion</h3> BVA is useful tool in outpatient management of patients with LVADs. As with advanced heart failure, correction of clinically unsuspected and undetected derangements in intravascular volume and red blood cell volumes likely have an impact on device and patient outcomes. These deviations may be recalcitrant to correction and further investigation is ongoing. Underdiagnosed polycythemia in LVAD patients may further contribute to hemo-compatibility issues and thrombosis. Measurement and treatment of derangements of intravascular volumes likely will improve performance and survival of patients and devices.

A Comparison of Oral vs Intravenous Tranexamic Acid in Patients Undergoing Staggered Bilateral Total Knee Arthroplasty.

All previous studies comparing the blood sparing efficacy oral and intravenous tranexamic acid (TXA) in total knee arthroplasty have involved two or more patient cohorts, outcomes of which may be limited by inter-individual variability in human drug response. The purpose of this study was to evaluate if both oral and intravenous preparations of TXA are equivalent at reducing blood loss in the same patients undergoing staggered bilateral total knee arthroplasty. 40 patients undergoing staggered bilateral total knee replacement were recruited. They received 2 g of oral TXA 2 hours preoperatively for the first knee and 1 g of bolus intravenous TXA 15 minutes before skin incision for the second knee. 7 patients were excluded for protocol deviation, leaving 33 participants for the study. The second knee was operated within 5-6 days of the first knee. The primary outcome was reduction in hemoglobin. Equivalence was tested with a two one-sided test (TOST) and a P < 0.05 indicated equivalence between oral and intravenous modes of TXA administration. The mean reduction in hemoglobin was similar between oral and intravenous mode of TXA administration (2.18 and 2.16 g/dl respectively, P<0.0001, equivalence). There was no significant difference in the total hemoglobin loss and total red blood cell volume loss {(104 and 102 g, P=0.86) and (865 and 863 ml, P=0.53) respectively}. Oral and intra venous TXA have equal blood sparing properties in patients undergoing staggered bilateral total knee arthroplasty.

Transfusion-associated hyperkalemia in pediatric population: Prevalence, risk factors, survival, infusion rate, and RBC unit features.

Hyperkalemia is a rare life-threatening complication of red blood cell (RBC) transfusion. Stored RBCs leak intracellular potassium (K+) into the supernatant; irradiation potentiates the K+ leak. As the characteristics of patients and implicated RBCs have not been studied systematically, a multicenter study of transfusion-associated hyperkalemia (TAH) in the pediatric population was conducted through the AABB Pediatric Transfusion Medicine Subsection. The medical records of patients <18 years old were retrospectively queried for hyperkalemia occurrence during or ≤12 h after the completion of RBC transfusion in a 1-year period. Collected data included patient demographics, diagnosis, medical history, timing of hyperkalemia and transfusion, mortality, and RBC unit characteristics. A total of 3777 patients received 19,649 RBC units during the study period in four facilities. TAH was found in 35 patients (0.93%) in 37 occurrences. The patient median age and weight were 1.28 years and 9.80 kg, respectively. All patients had multiple serious comorbidities. There were 79 RBC units transfused in the TAH events; 62% were irradiated, and the median age of the units was 10 days. The median total RBC volume transfused ≤12 h before TAH was 24% of patient estimated total blood volume, and the median infusion rate (IR) was19.6 ml/kg/h. Mortality rate within 1 day after the TAH event was 20%. The prevalence of TAH in children was low; however, the 1-day mortality rate was 20%. Patients with multiple comorbidities may be at higher risk for TAH. The IR was higher for patients who had TAH than the IR threshold for safe transfusion.

Correlation of Quantitated Intravascular Volume with Blood Pressure in Patients with Systemic Hypertension.

Volume management is an essential component of anti-hypertensive therapy. Different volume phenotypes have been proposed. We sought to study the total blood volume (TBV), plasma volume (PV), and red blood cell volume (RBV) in hypertensive patients. We included patients followed in an outpatient cardiology clinic from 1998 to 2003. Blood volume (BV) parameters were measured using radioisotope iodine-131-labeled albumin dilution technique. Values were expressed as percentage (%) deviation from ideal volumes. A total of 95 patients were included. The intravascular volume distribution as percent deviation from normal volume ranged from - 23 to + 28% for TBV, - 22 to + 36% for PV and - 29 to + 37% for RBV. There was no significant correlation between systolic BP and any of the BV parameters (TBV and SBP, r = - 0.03; PV and SBP, r = - 0.12; RBV and SBP, r = - 0.08). Patients with hypertension have a wide variation in BV parameters. BV does not correlate with SBP.

Impact of red blood cell transfusions on intestinal barrier function in preterm infants.

To determine the relationships of red blood cell (RBC) transfusion and enteral feeding to changes in intestinal permeability (IP) measured by the relative intestinal uptake of lactulose (La) and rhamnose (Rh) in preterm infants <33 wk gestation. Infants 240-326wk gestation received La/Rh solution enterally on study days 1, 8 and 15.Urinary La/Rh ratio was measured by HPLC. Hematocrit preceding transfusion, total RBC transfusion volume, volume/kg, and feeding status during each study interval (birth-d1; d1-d8, and d8-d15) were determined. Of the seventeen (40.5%) subjects who received≥1 transfusion during the study period, 12 (70.6%) infants were <28 wk gestation and 5 (29.4%) infants were≥28 wk gestation, p < 0.0001. Lower pre-transfusion hematocrit was observed in intervals preceding high IP (La/Rh > 0.05) than in intervals preceding low IP (La/Rh≤0.05) measurements (33 vs 35.8, p = 0.1051). RBC transfusions occurred more frequently in intervals preceding high IP than in intervals preceding low IP (26.8%; vs 8.3%, p = 0.0275) with 5-fold higher total RBC volume and volume/kg in intervals preceding any time point with high IP. RBC transfusion during an interval was associated with a three-fold increased risk of high IP (aOR 2.7; 95% C.I 0.564-12.814; p = 0.2143). Exclusive breast milk exposure and post-menstrual age reduced the risk for high IP following RBC transfusion. Both RBC transfusion number and volume was associated with subsequent high IP measurements in preterm infants <33 weeks gestation and potentially may contribute to impairment of the preterm intestinal barrier.

An intensified training schedule in recreational male runners is associated with increases in erythropoiesis and inflammation and a net reduction in plasma hepcidin

Iron status is a determinant of physical performance, but training may induce both low-grade inflammation and erythropoiesis, exerting opposing influences on hepcidin and iron metabolism. To our knowledge, the combined effects on iron absorption and utilization during training have not been examined directly in humans. We hypothesized that 3 wk of exercise training in recreational male runners would decrease oral iron bioavailability by increasing inflammation and hepcidin concentrations. In a prospective intervention, nonanemic, iron-sufficient men (n=10) completed a 34-d study consisting of a 16-d control phase and a 22-d exercise-training phase of 8 km running every second day. We measured oral iron absorption and erythroid iron utilization using oral 57Fe and intravenous 58Fe tracers administered before and during training. We measured hemoglobin mass (mHb) and total red blood cell volume (RCV) by carbon monoxide rebreathing. Iron status, interleukin-6 (IL-6), plasma hepcidin (PHep), erythropoietin (EPO), and erythroferrone were measured before, during, and after training. Exercise training induced inflammation, as indicated by an increased mean ± SD IL-6 (0.87 ± 1.1 to 5.17 ± 2.2 pg/mL; P<0.01), while also enhancing erythropoiesis, as indicated by an increase in mean EPO (0.66 ± 0.42 to 2.06 ± 1.6 IU/L), mHb (10.5 ± 1.6 to 10.8 ± 1.8 g/kg body weight), and mean RCV (30.7 ± 4.3 to 32.7 ± 4.6 mL/kg) (all P<0.05). Training tended to increase geometric mean iron absorption by 24% (P=0.083), consistent with a decreased mean ± SD PHep (7.25 ± 2.14 to 5.17 ± 2.24 nM; P<0.05). The increase in mHb and erythroid iron utilization were associated with the decrease in PHep (P<0.05). Compartmental modeling indicated that iron for the increase in mHb was obtained predominantly (>80%) from stores mobilization rather than from increased dietary absorption. In iron-sufficient men, mild intensification of exercise intensity increases both inflammation and erythropoiesis. The net effect is to decrease hepcidin concentrations and to tend to increase oral iron absorption. This trial was registered at clinicaltrials.gov as NCT01730521.

Red blood cell volume is not decreased in ESA-naive anemic chronic kidney disease patients.

Anemia is defined according to decreased blood hemoglobin concentration ([Hb]), which is considered a marker of low total red blood cell volume (RBCV). Alterations of plasma volume (PV) may also modify [Hb] without concomitant changes in RBCV. Since anemia and fluid retention are frequent complications of chronic kidney disease (CKD), we hypothesized that anemia during CKD may in part be related to expanded PV without a simultaneous decrease in RBCV. We quantified hemoglobin mass, RBCV, PV, and total blood volume (BV) using an automated carbon monoxide device in 40 consecutive stage 3–5 CKD patients not on dialysis and in seven healthy male controls of the same age range. These were compared within and to predicted volumes according to Nadler's formula. Arterial stiffness and NT‐proBNP were measured. RBCV was similar to predicted values range in anemic CKD patients 2073 (1818–2704) versus, 2061 (1725–2473) mL, P > 0.05. In contrast, PV was largely increased in anemic CKD patients (3881 (3212–4352) vs. 2916 (2851–3201)), P = 0.01. Of 26 anemic patients, only six had a >20% decrease in RBCV as the cause for their anemia, whereas 14 had a >20% increase of PV as a cause for their anemia. NT‐pro BNP correlated with eGFR but neither with PV nor BV, whereas arterial stiffness was not correlated to blood volumes. Anemia in CKD as diagnosed by low [Hb] is not necessarily associated to low RBCV but may reflect increased PV. This finding has implications for the treatment of CKD patients and may refrain from normalizing [Hb] levels in all CKD patients.

Regulation of blood volume in lowlanders exposed to high altitude.

Humans ascending to high altitude (HA) experience a reduction in arterial oxyhemoglobin saturation and, as a result, arterial O2 content ([Formula: see text]). As HA exposure extends, this reduction in [Formula: see text] is counteracted by an increase in arterial hemoglobin concentration. Initially, hemoconcentration is exclusively related to a reduction in plasma volume (PV), whereas after several weeks a progressive expansion in total red blood cell volume (RCV) contributes, although often to a modest extent. Since the decrease in PV is more rapid and usually more pronounced than the expansion in RCV, at least during the first weeks of exposure, a reduction in circulating blood volume is common at HA. Although the regulation of hematological responses to HA has been investigated for decades, it remains incompletely understood. This is not only related to the large number of mechanisms that could be involved and the complexity of their interplay but also to the difficulty of conducting comprehensive experiments in the often secluded HA environment. In this review, we present our understanding of the kinetics, the mechanisms and the physiological relevance of the HA-induced reduction in PV and expansion in RCV.

Exercise intolerance in heart failure with preserved ejection fraction: time to scrutinize diuretic therapy?

Exercise intolerance in heart failure with preserved ejection fraction: time to scrutinize diuretic therapy?

A retrospective study about cerebral near-infrared spectroscopy monitoring during paediatric cardiac surgery and intra-operative patient blood management

ObjectivesCerebral non-invasive monitoring of oxygen saturation by near-infrared spectroscopy (rSO2) during paediatric cardiac surgery is supposed to decrease the risk of neurological complications. Since haemoglobin level is one of the factors changing rSO2, we aimed to explore if rSO2 monitoring influences intra-operative RBC (red blood cell) transfusion threshold and volumes, as well as the duration of ICU stay. MethodsThe design was a retrospective analysis involving 91 children less than 2 years of age (including 16 neonates) with a congenital heart disease requiring surgical treatment with or without cardiopulmonary bypass from January 2006 to August 2009. Systematic rSO2 monitoring was introduced after September 2007 (n=56). The independent factors associated with the intra-operative transfusion threshold haemoglobin (Hb) level>9.5g/dL, total volume of intra-operative RBC transfusion<30mL/kg and ICU stay<6 days were identified by multivariate analysis logistic regression. Data were expressed as medians (25–75%). ResultsCardiac malformations and demographic characteristics were similar in both periods. Two independent factors, weight and rSO2 monitoring, were identified as independent factors associated with the three end-points. The transfusion threshold, total transfusion volume and ICU stay with and without rSO2 were 9.8 (8.9 to 10.3) versus 8.7 (8.2 to 9.6) g/dL (P<0.0001), 20 (14–49) versus 36 (22.5–51.5) mL/kg (P=0.0165) and 5 (3–8) versus 7 (5–10.7) days (P=0.0084), respectively. ConclusionrSO2 monitoring changed our transfusion strategy with an earlier transfusion but a reduced total RBC volume and decreased the length of ICU stay.

Congenital familial erythrocytosis: A case report with literature review

Familial erythrocytosis is a heterogeneous group of hereditary conditions with an increased total red blood cell volume. The disease occurs in a familial pattern and follows a relatively benign course. The absence of leukocytosis and thrombocytosis differentiates it from polycythemia vera. The best characterized primary erythrocytosis is the autosomal dominant primary familial and congenital polycythemia. In most families, erythrocytosis is due to abnormal hemoglobin with increased oxygen affinity. In other families, erythrocytosis is caused by an autonomous production of erythropoietin (EPO). EPO receptor gene mutations are also responsible for erythrocytosis when no secondary causes are apparent. Presented herein is a family with familial erythrocytosis possibly due to high autonomous production of EPO, which as per the literature is the first of its kind in the Indian context.

Certification of apheresis nurses in Indonesia

25/31 (81%) had a diagnosis of oncological malignancy, four (13%) with immunological conditions, and two (6%) with acute leukaemia. The most common mobilisation protocol used was chemotherapy/G-CSF in 24/31 (77%) patients, supplemented with plerixafor in three cases, and G-CSF alone in 7/31 (23%), five cases with addition of plerixafor. Spectra Optia settings; total blood volumes processed – 2.5, Whole Blood:AC ratio – 12:1, maximum AC rate 0.9ml/min/L TBV, initial flush volume of 16ml, and chase volume of 4ml. Custom prime recommendation was triggered if extracorporeal volume >10% of either total blood volume or red blood cell volume. Final flush volume was increased to 26ml in all procedures. For the first 10 procedures at least 2 chamber flushes were performed, and for the subsequent 40 at least 3. For children below 25kg a blood volume of 80ml/kg was used. In very small children the procedure ran in caution mode, as the AC rate was >1.2ml/min/ /L TBV. Prophylactic calcium gluconate infusions were given throughout procedures running in caution mode. There were no patient adverse events due the apheresis procedure. Data were collected to validate the efficiency of the machine to collect CD34 cells, red cell, platelet and neutrophil contamination, and changes to patient haemoglobin, platelet count, and serum electrolyte levels. CD34 doses, median (range) 4.8×106/kg (0.54–75.1×106/kg), and collection efficiency per blood volume processed (CE2) median (range) 47.4% (24.0–88.6%) were calculated. More than 2.0×106/kg CD34 cells were obtained in 43/50 (86%) procedures, and a CD34 dose of >3.0×106/kg was obtained in 29/31 (94%) children. Changes to patient haemoglobin and platelet counts were recorded. Due to custom prime requirements in 42/50 (84%) procedures, haemoglobin increased, median (range) +11% (−4% to +24%). Platelets were reduced, median (range) −39% (−66% to +26%). No significant changes to serum electrolyte levels were noted.

Hemolysis induced by an extreme mountain ultra‐marathon is not associated with a decrease in total red blood cell volume

Prolonged running is known to induce hemolysis. It has been suggested that hemolysis may lead to a significant loss of red blood cells; however, its actual impact on the erythrocyte pool is unknown. Here, we test the hypothesis that prolonged running with high hemolytic potential decreases total red blood cell volume (RCV). Hemolysis (n = 22) and RCV (n = 19) were quantified in ultra-marathon runners before and after a 166-km long mountain ultra-endurance marathon (RUN) with 9500 m of altitude gain/loss. Assessment of total hemoglobin mass (Hbmass) and RCV was performed using a carbon monoxide rebreathing technique. RUN induced a marked acute-phase response and promoted hemolysis, as shown by a decrease in serum haptoglobin (P < 0.05). Elevated serum erythropoietin concentration and reticulocyte count after RUN were indicative of erythropoietic stimulation. Following RUN, runners experienced hemodilution, mediated by a large plasma volume expansion and associated with a large increase in plasma aldosterone. However, neither Hbmass nor RCV were found to be altered after RUN. Our findings indicate that mechanical/physiological stress associated with RUN promotes hemolysis but this has no impact on total erythrocyte volume. We therefore suggest that exercise 'anemia' is entirely due to plasma volume expansion and not to a concomitant decrease in RCV.

Heart rate and blood lactate responses to submaximal treadmill exercise in the normally performing standardbred trotter--age and sex variations and predictability from the total red blood cell volume.

The purposes of this study were to elucidate the influences of age and sex on the heart rate (HR, bpm) and blood lactate (LA, mmol/l) related exercise tolerance parameters V2000 (tread ill velocity at HR 200), VLA4 (velocity at LA 4), W200 (power output at V2000), and WLA4 (power output at VLA4), and to establish reference values for these in normally performing Standardbred trotting race horses. A further aim was to improve the predictability of individual normal values by correlating them with the total red blood cell volume (CV) alone or in combination with the blood lactate response at V200 (LA200). In total 205 horses were included in the study. According to their owners and/or trainers they were all performing satisfactorily (in racing or training) for shortly impending racing. The exercise test was performed on an inclined (3.5 degrees) high speed treadmill and consisted of four sequentially increasing speeds, each of 2 min duration, aiming at a final HR at or exceeding 200 bpm. HR was monitored continuously and recorded in parallel with blood sampling during the last 15 s of each speed. Blood volume determination was done with the Evans blue dye dilution technique immediately after the exercise test to ensure complete emptying of the splenic red cell reservoir. Both age and sex influenced significantly on all parameters. These were also all strongly dependent on the total red cell volume. Consequently, it was concluded that markers for work tolerance based on heart rate and blood lactate responses to submaximal treadmill exercise reliably reflect circulatory and muscle metabolic capacities. Further, individual normal values are predictable from the red cell volume alone with variation coefficients between 5 and 9.1%, or, in combination with LA200, between 4.4 and 62%. Disregarding the regression with CV, predictability of normal values is improved by considering age and sex variations.

Acute Preoperative Hemodilution in Patients Undergoing Radical Prostatectomy

Despite published guideline and consensus conference recommendations, the role of acute preoperative hemodilution in elective surgery has not been defined. We performed a case study analysis of this technique in a large surgical program in order to estimate its degree of efficacy as practiced routinely, and to better define its role as a blood conservation strategy. Patients undergoing elective radical prostatectomy by one surgeon during a 3-yr period were analyzed retrospectively for blood loss, hematocrit levels, records of acute hemodilution, and transfusion outcomes. Patient blood volumes were determined by nomogram; final hematocrits after discrete blood volumes lost by surgery or by hemodilution were estimated. Sixteen (4.4%) of 410 total patients reviewed underwent hemodilution, representing 0 (0%), 4 (3%), and 12 (8%) of the 112, 146, and 152 patients undergoing surgery in years 1, 2, and 3, respectively. Median whole blood volume and mean red blood cell (RBC) volume removed by hemodilution was 1000 mL (range, 400-1500 mL) and 338 mL (range, 156-585 mL), respectively, representing 15% of patients' admission RBC volume. Net intraoperative RBC volume "saved" in losses by this technique was 95 mL (range, 25-204 mL), representing only 9.3% (range, 4%-17%) of total RBC volume lost during hospitalization. RBC volume removed by hemodilution constituted 34% (95-283 mL) of the total RBC volume transfused. We conclude that use of acute preoperative hemodilution remains in evolution and, as a single blood conservation intervention, contributes only modestly to blood conservation.

Erythropoietin Synthesis by Tumor Cells in a Case of Meningioma Associated With Erythrocytosis

AbstractWhile secondary erythrocytosis is often associated with tumors arising from the kidney, other tumors have been described to originate in the liver, uterus, ovary, adrenal gland, and central nervous system, among which cerebellar hemangioblastomas are involved in most instances. Two cases of meningioma associated with erythrocytosis have already been reported. We observed a 59-year-old female patient who had developed a frontal meningioma associated with erythrocytosis. Before surgery, she had a significantly elevated total red blood cell volume with a normal plasma volume. Serum erythropoietin (Epo) dosage assessed by radioimmunoassay was within the normal range. The tumor was removed and the pathologic study found a meningotheliomatous meningioma. Total RNA from the tumor was hybridized to a monkey cDNA Epo probe. A strong 1.6- kb messenger RNA (mRNA) signal was observed, which is the expected size of human Epo mRNA. In situ hybridization with the 35S-labeled Epo probe was performed on frozen tumor tissue sections. A significant hybridization was observed in all the tumor cells, whereas the stroma was negative. Therefore, in this meningioma associated with erythrocytosis, Epo was produced by the tumor cells themselves.

Erythropoietin synthesis by tumor cells in a case of meningioma associated with erythrocytosis

While secondary erythrocytosis is often associated with tumors arising from the kidney, other tumors have been described to originate in the liver, uterus, ovary, adrenal gland, and central nervous system, among which cerebellar hemangioblastomas are involved in most instances. Two cases of meningioma associated with erythrocytosis have already been reported. We observed a 59-year-old female patient who had developed a frontal meningioma associated with erythrocytosis. Before surgery, she had a significantly elevated total red blood cell volume with a normal plasma volume. Serum erythropoietin (Epo) dosage assessed by radioimmunoassay was within the normal range. The tumor was removed and the pathologic study found a meningotheliomatous meningioma. Total RNA from the tumor was hybridized to a monkey cDNA Epo probe. A strong 1.6- kb messenger RNA (mRNA) signal was observed, which is the expected size of human Epo mRNA. In situ hybridization with the 35S-labeled Epo probe was performed on frozen tumor tissue sections. A significant hybridization was observed in all the tumor cells, whereas the stroma was negative. Therefore, in this meningioma associated with erythrocytosis, Epo was produced by the tumor cells themselves.

Thromboembolic complications of polycythemia: Polycythemia vera versus smokers' polycythemia

Purpose: This report compares patients with the hypercoagulable state of polycythemia vera to patients with secondary polycythemia caused by tobacco use to determine whether the incidence of thromboembolic events is equivalent.Methods: The medical records of 146 patients with the diagnosis of polycythemia between 1977 to 1990 were reviewed. Patients with transient, relative, or stress polycythemia were excluded from this study as were patients with polycythemia as a result of cardiac or pulmonary anomalies or both. The diagnosis of polycythemia vera (n = 43) was verified by use of the guidelines of the Polycythemia Vera Study Group. The diagnosis of polycythemia caused by smoking (n = 27) was based on an elevated total red blood cell volume, decreased oxygen saturation on arterial blood gas measurement, evidence of chronic obstructive pulmonary disease, and elevated carboxyhemoglobin levels.Results: Twenty-six patients (60%) with polycythemia vera and 11 patients (41%) with smoker's polycythemia had at least one thromboembolic problem. No significant differences existed between the groups with regard to age, hematocrit, or number of cardiac and cerebrovascular events. Overall, patients with polycythemia vera had a greater number of thromboembolic events per patient (p < 0.05) and more peripheral arterial thromboemboli (p < 0.005) than did patients with polycythemia as a result of smoking (Fisher's Exact Test).Conclusions: Thus the results of this study demonstrate that smokers' polycythemia does not represent a hypercoagulable state equivalent to that of polycythemia vera.