Absolute Polycythemia Research Articles

Germline JAK2 E846D Substitution as the Cause of Erythrocytosis?

The discovery in 2005 of the JAK2 V617F gain-of-function mutation in myeloproliferative neoplasms and more particularly in polycythemia vera has deeply changed the diagnostic and therapeutic approaches to polycythemia. More recently, the use of NGS in routine practice has revealed a large number of variants, although it is not always possible to classify them as pathogenic. This is notably the case for the JAK2 E846D variant for which for which questions remain unanswered. In a large French national cohort of 650 patients with well-characterized erythrocytosis, an isolated germline heterozygous JAK2 E846D substitution was observed in only two cases. For one of the patients, a family study could be performed, without segregation of the variant with the erythrocytosis phenotype. On the other hand, based on the large UK Biobank resource cohort including more than half a million UK participants, the JAK2 E846D variant was found in 760 individuals, associated with a moderate increase in hemoglobin and hematocrit values, but with no significant difference to the mean values of the rest of the studied population. Altogether, our data as well as UK Biobank cohort analyses suggest that the occurrence of an absolute polycythemia cannot be attributed to the sole demonstration of an isolated JAK2 E846D variant. However, it must be accompanied by other stimuli or favoring factors in order to generate absolute erythrocytosis.

Polycythemia vera: Gingival and periodontal manifestations and management – A case report

Polycythemia vera is a rare case confronted in dentistry with scarcely available case reports. Hence a scrupulous knowledge of it is inevitable. It is a myeloproliferative disorder characterized by excessive proliferation of erythroid elements, granulocytic and megakaryocytic cells. Here, the blood viscosity increases leading to menace of thrombosis. The medications often used include cytoreductive agents like hydroxyurea 500mg to reduce the leukemogenic risk and Ecospirin 75mg to lessen the thrombotic risk in artery.A 44-year-old male patient reported with a history of pain over the upper right back tooth region since two weeks. The pain was sudden in onset sharp intermittent non radiating aggravates on taking cold fluids and relieves by itself. He also complained of food lodgement around the same site. He is a known case of absolute polycythemia in the last 8 months, undergoing treatment with Ecospirin 75mg and frequently subjected to phlebotomy.A synchronized endeavour by hemato-oncologist and dentist is required for dental treatments, peculiarly invasive therapies, in such patients. Further, an awareness of the medication used for the treatment is unavoidable.

What determines blood viscosity at the highest city in the world?

What determines blood viscosity at the highest city in the world?

A suspected case of hypoxia-induced pre-renal azotemia in an old part-Arab stallion: case report and review of the literature

The kidneys maintain homeostasis and this function is compromised in hypoxic conditions. Hematology and serum biochemistry evaluations were performed on a 17-year old Nigerian part-Arab stallion, who was observed to be docile, cachexic, and has bilateral ocular mucus discharge. Ticks were seen attached around the inguinal region. The mucous membrane of the eyes was congested, animal was partially insensitive to its environment and had an abnormal posture and gait. Blood samples for hematology and clinical biochemistry analyses were collected from the jugular vein. Hematology and serum biochemistry determinations followed standard procedures. Hematological analysis revealed that the stallion had secondary absolute polycythemia, low erythrocyte sedimentation rate. The mean corpuscular volume, mean corpuscular hemoglobin concentration and total leukocyte count were within the respective reference ranges. The clinical biochemistry profile of the horse showed normal serum activity of alanine aminotransferase and elevated serum activities of aspartate aminotransferase and alkaline phosphatase, normal serum total protein, albumin, decreased serum globulin concentrations, with a high albumin: globulin (A/G) ratio. The stallion also had normal total cholesterol level and an abnormally high serum creatinine and blood urea nitrogen levels. These findings were suggestive of hypoxia-induced pre-renal azotemia.

A case of Polycythemia: diagnostic dilemma

Approach to a case of polycythemia is initially to distinguish relative from absolute polycythemia; then to distinguish Polycythemia Vera (PV) from secondary polycythemia. Finally, the etiology of secondary polycythemia has to be ascertained. A certain number of patients cannot be easily classified as having either PV or secondary polycythemia due to diagnostic difficulties. We present a case of 52-yearmale, chronic smoker, hypertensive and an asthamatic for whom a complete work up was attempted to rule out PV. There was a diagnostic difficulty as to consider this patient a case of secondary polycythemia or Gaisbock’s syndrome. We were unable to measure the red cell mass in this patient (which will be normal in Gaisbock’s syndrome and increased in secondary polycythemia). Patient underwent phlebotomy and was asymptomatic at discharge.

Secondary polycythaemia associated with high plasma erythropoietin concentrations in a dog with a necrotising pyelonephritis

An 11-year-old mixed breed dog was presented with anorexia, apathy and intermittent macrohaematuria, absolute polycythaemia (packed cell volume, 80 per cent; red blood cell, 12.2 x 10(6)/microl) and elevated erythropoietin concentrations. A renal mass was detected by ultrasonography and, following total nephrectomy, diagnosed as necrotising pyelonephritis. After surgery, the haematological parameters and erythropoietin values returned to normal, suggesting that the pyelonephritis was the cause of the polycythaemia. While secondary polycythaemia because of a non-neoplastic condition of the kidneys occasionally occurs in human beings, it has only extremely rarely been reported in dogs. This is the first case report of a unilateral pyelonephritis causing secondary polycythaemia in a dog.

The interpretation of measured red cell mass and plasma volume in patients with elevated PCV values.

Various formulae using both height and weight have been proposed to interpret measured red cell mass (RCM) and plasma volume (PV). This paper compares four different methods for evaluating these measurements in 50 males with PCV values above 0.51 and three different methods for evaluating results in 50 females with PCV values above 0.49. Overall there was close agreement in the RCM result expressions by all methods for both males and females except at extremes of height and/or weight. The incidence of absolute polycythaemia in both sexes was influenced by the width of the normal range. When this was taken into account overall the incidence of polycythaemia was similar, but in a small number of individuals there were discrepancies of interpretation. These individual patient differences establish that decisions regarding further investigations of a patient must not rest on a strict interpretation of a measured RCM. The various methods of measured PV interpretation gave dissimilar results--in particular by one of the male PV interpretation methods. The differences in the methods almost certainly reflect methodological discrepancies in the original techniques used to establish the normal values. The differences in result expression for PV would however lead to a different incidence of relative, low plasma volume, polycythaemia by the various techniques.

Analysis of Red Cell Mass and Plasma Volume in Patients With Polycythemia

Polycythemia describes an increased proportion of red blood cells in the peripheral blood. In absolute polycythemia, there is increased red cell mass (RCM) with normal plasma volume, in contrast with apparent polycythemia, in which there is increased or normal RCM and decreased plasma volume. In order to deliver the appropriate treatment it is necessary to differentiate between the two. A retrospective analysis of RCM and plasma volume data are presented, with special attention to different methods of RCM interpretation. The measurements of RCM and plasma volume in 64 patients were compared with the venous and whole-body packed cell volume, and the incidence of absolute and apparent polycythemia was determined for increasing hematocrit levels. Measurements of RCM and plasma volume were performed using chromium 51-labeled red cells and iodine 125-labeled albumin, respectively. The measured RCM of each patient was expressed as a percentage of the mean expected RCM and was also defined as being within or outside the range of 2 SD of the mean. The results were also expressed in the traditional manner of mL/kg body weight. Twenty-one patients (13 women and 8 men) had absolute polycythemia. None of them had an increased plasma volume beyond 2 SD of the mean. When expressed according to the criteria of mL/kg body weight, 17 of the 21 patients had abnormally increased RCM, but 4 patients (19%) had a normal RCM value. Twenty-eight patients had apparent polycythemia. The remaining 15 patients had normal RCM and plasma volume. The measurement of RCM and plasma volume is a simple and necessary procedure in the evaluation of polycythemia. In obese patients, the expression of RCM in mL/kg body weight lacks precision, considering that adipose tissue is hypovascular. The results of RCM are best described as being within or beyond 2 SD of the mean value.

Congenital and inherited polycythemia.

Absolute polycythemia is a condition with increased red blood cell mass. There are a number of primary and secondary polycythemic disorders leading to absolute polycythemia. Primary polycythemias are caused by a defect intrinsic to the erythroid progenitor cells. The best characterized primary polycythemia is the autosomal dominant primary familial and congenital polycythemia (PFCP). Familial or childhood occurrence of the myeloproliferative disorder polycythemia vera are also discussed, emphasizing the importance of distinction between polycythemia vera and PFCP. Congenital or familial secondary polycythemic conditions are characterized by increased red cell mass, which is caused by circulating serum factors, typically erythropoietin.

Investigation of patients with polycythaemia.

Polycythaemia may complicate or be the presenting feature of a wide variety of different pathologies. Early diagnosis and treatment of primary polycythaemia will significantly reduce the morbidity and mortality associated with this condition. Patients with a raised packed cell volume are divided into those with a raised red cell mass (absolute polycythaemia), and those with a red cell mass within their normal range (apparent polycythaemia). A standard investigative approach of an absolute polycythaemia enables patients with primary and secondary polycythaemia to be identified, leaving a group termed idiopathic erythrocytosis. There are a number of physiological situations and pathological events associated with idiopathic erythrocytosis and apparent polycythaemia. Careful follow-up of both groups of these patients is essential to identify possible causative mechanisms.

Serum erythropoietin values in polycythemic cats.

Serum erythropoietin (EPO) concentrations and clinicopathological features were evaluated in 31 cats with absolute polycythemia (i.e., packed cell volume [PCV], 52% to 84%). Five cats had high serum EPO values and were classified as having secondary polycythemia. The remaining 26 cats had EPO values in the low or normal range. Four of these 26 cats had clinical evidence of secondary polycythemia and therefore were classified as having secondary polycythemia. In the remaining 22 cases, no signs of secondary polycythemia could be found, and primary polycythemia was diagnosed. A low or normal serum EPO value in a polycythemic cat is consistent with primary polycythemia, but does not exclude secondary polycythemia.

Apparent polycythaemia: diagnosis, pathogenesis and management

The term "apparent polycythaemia" is applied to a group of patients who have a raised PCV (> 0.51 in males, > 0.48 in females) but a normal red cell mass (less than 25% above their predicted mean normal value). Some have additionally a marked reduction in plasma volume and can be defined as a subgroup: relative polycythaemia. Smoking, hypertension and to a lesser extent obesity, excessive alcohol, low-dose diuretic therapy and hypoxaemia have all been associated with apparent polycythaemia but the mechanism is both uncertain and likely to be complex. This group of patients is unlikely to be uniform in pathogenesis and may well include some normal individuals. Investigation requires exclusion of factors associated with other types of polycythaemia. The possibility of an increased vascular occlusive risk is uncertain in these patients except at the higher PCV values. Reduction of PCV by venesection is sensible at PCV > 0.54 or where there is perceived to be an increased risk of vascular occlusion. The remaining patients should be managed by regular observation to detect further rise in PCV or evolution to absolute polycythaemia (raised red cell mass). In some, the PCV returns to normal.

Polycythemia and steroid overproduction in a gonadotropin‐secreting seminoma of the testis

While investigating the cause of mild polycythemia in a young man, a testicular seminoma was discovered with unusual and tumor-dependent features: an absolute polycythemia with high plasma erythropoietin (EPO) levels, an overproduction of estradiol and testosterone, and a dramatic Leydig cell hyperplasia surrounding the tumor tissue. The authors attempted to gain insight into the relationship between this testicular tumor and the hormonal overproduction, i.e., of EPO, estradiol, and testosterone. Their results favored the conclusion that the high EPO levels and the polycythemia were an indirect effect secondary to the steroid overproduction rather than a direct EPO-producing activity. Moreover, the steroid overproduction by the testis could be caused by a paracrine mechanism through human chorionic gonadotropin activity on the Leydig cells.

Effect of absolute and relative changes of hematocrit on erythropoiesis in mice.

The serial changes of peripheral reticulocytes and marrow erythroid progenitor cells (CFU-e) in mice were monitored under the conditions of absolute or relative changes in red cell mass to study the regulatory mechanism of erythropoiesis. A decreased number of marrow CFU-e and peripheral reticulocytes was observed in the mice with relative polycythemia induced by dehydration as well as in the mice with absolute polycythemia induced by hypertransfusion. On the other hand, a transient increase in the number of marrow CFU-e followed by a gradual increase in the number of peripheral reticulocytes was seen after a considerable amount of exsanguination. Similar stimulatory effects on marrow CFU-e were also observed either by rehydrating the dehydrated mice or by overhydrating the untreated mice to relatively decrease the level of hematocrit. The results suggested that in addition to factors relating to the balance between oxygen supply and requirement, which has been well known, erythropoiesis is greatly affected by hematocrit.

Polycythemia: erythrocytosis and erythremia.

A classification of polycythemia and three cases of demonstrating increased red cell mass are presented. Polycythemia may be relative or absolute, secondary to underlying disease, or an idiopathic dyscrasia of hematopoiesis. Accurate measurement of blood, red cell, and plasma volumes are essential to differentiate relative and absolute polycythemia. Dilution techniques may be misleading, due to escape of label from vascular spaces or differences between whole-body and venous hematocrits. Red-cell labeling offers a more precise method to differentiate between relative and absolute polycythemia but is not helpful in distinguishing primary from secondary causes. Hypoxia-sensitive receptors may mediate erythropoietin production where relative tissue anoxia exists for any reason. Certain tumors (benign and malignant), chemical agents, and physical factors also stimulate an increase in red cell mass, often through increasing elevation of erythropoietin. Erythropoietin levels (bioassay) are usually not demonstrably elevated in polycythemic states, since erythropoietin is constantly utilized in erythropoiesis. High levels are often seen with marrow aplasia and may be demonstrable in cyst fluid of erythropoietin-producing tumors. In addition to existing erythropoietin assay procedures, methods for determining turnover are badly needed. Biochemical, electrophoretic, molecular weight, and antibody neutralization studies suggest the similarity or sameness of tumor-produced and naturally occurring erythropoietin. Polycythemia rubra vera erythremia occurs more commonly in Caucasians and especially among Jewish peoples of Eastern European origin. Frequent symptoms are fatigue, dizziness, headache, and pruritus. Patients often seek care with symptoms related to peptic ulcer, varicose veins, gouty arthritis, and thrombotic episodes. Physical findings include plethora, splenomegaly, and, in 25% of cases, hepatomegaly as well as those associated with the complications. Elevation of packed cell volume, white cell and platelet counts, as well as elevated red cell mass are usual in erythremia. Proper hematologic control, with lessening of symptoms and complications, depends upon on-going evaluation as well as on phlebotomy and myelosuppression, as indicated. Controversy still exists as to optimal mode of myelosuppression.

Increased Erythropoietin Levels in Serum of Rats with Transplants of an Adrenal Cortical Carcinoma

SummaryExperiments on rats bearing a transplant of an adrenal cortical carcinoma show: that there is a significant increase in the reticulocyte count 2 weeks after transplants are made as well as increases in other peripheral red cell parameters; that there is an absolute polycythemia, as indicated by significant increases in total blood volume and total red cell volume with simultaneous normal plasma volumes at 4 weeks after transplantation; that there is no significant change in total white cell or differential counts up to 4 weeks but a significant decrease in total circulating esinophils at 3 weeks posttransplantation; and that there is an erythropoietic stimulating factor, presumed to be erythropoietin, in the serum 17 days after tumor transplantation.

POLYCYTHEMIA ASSOCIATED WITH DISTURBED FUNCTION OF THE RESPIRATORY CENTER

1. An unusual case of absolute polycythemia associated with hypoxemia, probably resulting from abnormal function of the respiratory center has been presented. 2. The mechanism of development of this type of polycythemia has been discussed. 3. A classification of polycythemia on the basis of blood volume and arterial oxygen saturation has been suggested.

Polycythemia Associated with Disturbed Function of the Respiratory Center

Abstract 1. An unusual case of absolute polycythemia associated with hypoxemia, probably resulting from abnormal function of the respiratory center has been presented. 2. The mechanism of development of this type of polycythemia has been discussed. 3. A classification of polycythemia on the basis of blood volume and arterial oxygen saturation has been suggested.

POLYCYTHEMIA VERA AND CHRONIC PULMONARY DISEASE

Weber1divided cases of polycythemia into three groups: (1) relative polycythemia due simply to concentration of the blood; (2) secondary polycythemia due to high altitude, cardiopulmonary disease, blood stasis in other organs or toxemia, such as poisoning by phosphorus, and infectious diseases and (3) true erythremia due to primary idiopathic excessive erythroblastic activity in the bone marrow. Polycythemia vera (erythremia, Vaquez' disease or Osler's disease) has been defined as a condition, characterized by a well marked, persistent relative and absolute polycythemia, due to an excessive erythroblastic activity of the bone marrow which appears to be the primary morbid factor. As to the agent or mechanism responsible for this disturbed function of the bone marrow, there is only speculation. Osler suggested that eventually all types of polycythemia would be found to be secondary. Even if this proves to be correct, it may be assumed that the polycythemia in some cases