Relative Polycythemia Research Articles

Polycythemia as an Uncommon Finding in 2 Children, One With Systemic Capillary Leak Syndrome and the Other With Protein-losing Enteropathy Caused by CD55 Deficiency.

We report 2 children with distinct causes of polycythemia, 1 from systemic capillary leak syndrome (SCLS) and the other from protein-losing enteropathy (PLE) caused by CD55 deficiency. There is only a single case series about polycythemia in children with SCLS, but none on polycythemia in children with PLE. We present a 10-year-old girl with hypoalbuminemia, polycythemia, and edema who died as a result of an SCLS attack and a 1-year-old girl with PLE who was successfully treated with eculizumab. Our experience suggests that hematologists should be alert for SCLS and PLE in children with relative polycythemia.

GAISBOCK'S SYNDROME: A CASE STUDY

Felix Gaisbock, MD, (1905) described a syndrome in patients with hypertension, increased hematocrit levels, plethoric appearances, and without splenomegaly. He hypothesized that this relative erythrocytosis was stress related. In this case report, a 38-year-old hypertensive male presented with constitutional symptoms along with new onset polycythemia. There was no splenomegaly. A workup did not show any evidence of polycythemia rubra vera (PRV) or some other secondary cause of his polycythemia. He was given appropriate supportive therapy for his constitutional symptoms. His hematocrit returned to normal levels over the next few days under observation. We concluded that this patient had Gaisbock's syndrome, a form of relative polycythemia that manifests when there is evidence of plasma contraction.

CASE STUDY: JAK2 V617F NEGATIVE POLYCYTHAEMIA CAUSING PORTAL VENOUS HYPERTENSION WITHOUT EVIDENT PORTAL VEIN THROMBOSIS.

Polycythaemia is dened as an increase in the haemoglobin above normal. This increase may be real or only apparent because of a decrease in plasma volume (spurious or relative polycythaemia). Often patients with polycythaemia are detected through an incidental nding of elevated haemoglobin or haematocrit level. Patients with polycythaemia may be asymptomatic or experience symptoms related to the increased red cell mass or the underlying disease process that leads to the increased red cell mass. The dominant symptoms from an increased red cell mass are related to hyper viscosity and thrombosis (both venous and arterial), because the blood viscosity increases logarithmically at haematocrits >55%. We are presenting a case of a patient aged 30 years presenting with fatigue, headaches, dizziness, recurrent multiple joint pain.

JAK2-Negative Polycythemia: Underlying Causes, Including Novel Variants of Uncertain Significance - Real Life Data of 10 Years from a Tertiary Reference Center

Background:Real life data of underlying causes of JAK2-negative polycythemia is sparse. We aimed to analyze clinical and laboratory data of patients at our tertiary referral hospital, in order to identify the most frequent underlying causes of JAK2-negative polycythemia. Particularly, we intended to analyze the prevalence and causes of hereditary erythrocytosis.Methods:The hospital database was searched to find patients ≥15 years of age with polycythemia (inpatients and outpatients) between 1 st Oct 2008 and 31 st Jul 2019. Using a stepwise process, we focused on patients in whom a JAK2 result was available. For the diagnosis of polycythemia, including reactive and relative, the diagnostic criteria of the 2016 WHO classification for polycythemia vera were used: hemoglobin >165 g/L in men and >160 g/L in women, or hematocrit >49% in men and >48% in women.Results:Files of 727,731 patients were screened, and in 4,391 polycythemia was mentioned as a diagnosis on the electronic record. Of these, polycythemia was confirmed in 1,483 based on laboratory values. From them, 391 were tested for JAK2 mutation, and 294 were negative, thus representing our study cohort.The median age at polycythemia diagnosis was 46 years (r 15 - 89), and the majority of patients were males (N=242, 82%). The median Hb and Hct value were 172 g/L (r 157 - 224) and 51% (r 45 - 68) respectively. The patients were followed up for a median time of 4 years (r 12 days - 21 years).In 61% of patients (179/294) reactive polycythemia was diagnosed, while in 4.8% (14/294) relative polycythemia was present.In 30% of patients (89/294) the cause of polycythemia was undetermined, whereas in 70% (205/294) an underlying cause explaining polycythemia was found (Table 1). In 12 patients (4.1%), a congenital cause was identified. Among them, hemoglobinopathy or high-oxygen affinity Hb (N=8, 2.7%) were the most common (Table 1). Sleep apnea confirmed through a polysomnography (N=55, 18.7%), followed by smoking (N=51, 17.3%), increased HbCO>5% (N=14, 4.8%), respiratory diseases (N=13, 4.4%), and non-cancer kidney disease, for instance renal cysts (N=12, 4.1%), were the most common associated causes. Polysomnographies were performed on 60 patients, of whom sleep apnea was confirmed in 92% (N=55), and a significant proportion of these patients were younger than 40 years old (N=18, 33%).From all patients with undetermined causes (N=89), we focused on those with persistent polycythemia for further investigations. Accordingly, 25 patients were identified, all male and 72% (N=18) younger than 40 years of age. In 12/25 patients a congenital erythrocytosis NGS panel was performed, and in 3/12 patients 4 different heterozygous mutations were found (two of which were in one patient). All mutations were characterized as variants of unknown significance (VUS). None of these mutations were previously described in the literature, and their finding in patients with polycythemia suggests a pathogenic likelihood (Table 2).Conclusion:In one third of JAK2-negative patients with polycythemia, despite extensive workup, no underlying cause was found. Sleep apnea was the main cause of secondary forms, even in young patients, underlining the importance of performing a polysomnography in the workup of such patients. The NGS erythrocytosis panel offers easy and accessible characterization of some idiopathic forms, however there is still a majority of these patients unable to be characterized. In this cohort the investigation with NGS showed 4 mutations which have not been reported in the literature. The presence of these in patients with polycythemia suggests the probability of a relationship in its pathogenesis. [Display omitted] DisclosuresJalowiec: Kite Pharma Gilead Sciences': Honoraria, Speakers Bureau. Rovo: AG Alexion: Research Funding; CSL Behring: Research Funding; Novartis: Research Funding; AG Alexion: Honoraria; BMS: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria; OrPhaSwiss GmbH: Honoraria; Swedish Orphan Biovitrum AG: Honoraria; Amgen: Other: Financial support for congresses and conference travel; AstraZeneca: Other; BMS: Other; Sanofi: Other; Roche: Other.

The Impact of Iodine Exposure in Excess on Hormonal Aspects and Hemato-Biochemical Profile in Rats.

Excessive exposure of iodine over a time is well known to cause thyroid dysfunction, which may be followed by different effects on body organs. The present study aimed to illustrate the impacts of exposure of rats to excess iodine (above the tolerable range) and the reversibility of any negative impacts on hormonal profile related to thyroid besides cortisol and the hematological and biochemical parameters along with the histopathological alterations in the thyroid gland, liver, kidneys, and heart. Seventy-five rats were divided equally into three groups: Group 1 was control animals. Groups 2 and 3 received sodium iodide (NaI) orally at a dose of (35 and 70 mg/kg BW), which corresponded to (500 and 1000) times excess iodine from the physiological dose, respectively for 30 days, then the NaI administration stopped in the treated groups for 15 consecutive days. Blood and tissue samples were collected twice for various experimental tests after 30 and 15 days of exposure to excess iodine and stopping the exposure, respectively. Overall results revealed that excess iodine in both tested groups developed a hyperthyroid condition, hypercortisolism, relative polycythemia, neutropenia, elevation in serum liver and cardiac enzymes activities, hyperprotenemia, hyperglobulinemia, elevation in serum urea, and cardiac troponin I concentrations (p < 0.05). It was concluded that the excess iodine caused hyperthyroidism, which was associated with significant changes in erythrogram and leukogram and alterations in hepatic, renal, and cardiac functions in an iodine dose-dependent damage relationship and the most of negative impacts continued after stopping the administration.

Acute pancreatitis and relative polycythaemia: a case series

Relative polycythaemia is an apparent rise in erythrocyte level in the blood. However, the underlying cause is reduced blood plasma. Relative polycythaemia is often caused by loss of body fluids seen in conditions such as burns, dehydration and stress manifesting itself as a raised Haemoglobin or haematocrit. This case series presents a clinical summary of three patients with acute pancreatitis (AP) and relative polycythaemia due to reduction in plasma volume as a result of intravascular volume depletion as demonstrated by increase in haemoglobin and haematocrit. Haem concentration may be considered as a marker for acute severe pancreatitis and correcting the volume depletion by adequate fluid improves the outcome of AP as seen in all our three patients.

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

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

Polycythemia

Polycythemia is a disease state in which the red blood cell numbers are increased in the blood (erythrocytosis), which in turn makes blood thicker and can cause circulatory problems. Polycythemia Vera is a stem cell disease belonged to a group of myeloproliferative neoplasm in which the erythroid progenitors are overly proliferated by acquired mutation of the JAK2 gene, resulting in excessive erythrocytosis. Secondary Polycythemia refers erythrocytosis due to underlying conditions. It is usually associated with increased blood erythropoietin levels as a compensatory reaction to tissue hypoxia, which can be seen in patients with chronic lung disease or sleep apnea or living at high altitudes. Certain tumors produce the erythropoiet ©Win and testosterestern University of Heone incralth Scienceseases the blood erythropoietin level, resulting in secondary polycythemia. Relative polycythemia is the consequence of plasma volume contraction, falsely raising the RBC count and hemoglobin/hematocrit level in CBC. Two cases of polycythemia are presented: 1) a patient with polycythemia vera and 2) a patient with secondary polycythemia. Various types of polycythemia are discussed with an updated review covering the etiology, clinical manifestation, diagnostic approach and treatment.

Hypodipsic-hypernatremia syndrome in an adult with polycythemia: a case report

BackgroundHypernatremia is a very common electrolyte disorder and is frequently encountered in out-patient as well as in-hospital settings. We describe an adult who was found to have unexplained relative polycythemia and episodic hypernatremia. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and the patient was managed with a water-drinking schedule.Case presentationA 24-year-old South African-Indian man was found to have polycythemia in association with episodes of hypernatremia. Investigations indicated that he had relative polycythemia. He experienced no thirst at a time when his serum sodium concentration was found to be 151 mmol/L. Further testing indicated that his renal response to arginine vasopressin was intact and magnetic resonance imaging of his brain revealed no hypothalamic lesions. A diagnosis of idiopathic hypodipsic-hypernatremia syndrome was made and he was managed with a water-drinking schedule that corrected his hypernatremia.ConclusionHypodipsia should always be considered when a patient without physical or cognitive disability presents with unexplained episodic hypernatremia or with relative polycythemia.

An unusual case of relative polycythemia with complication of pseudocyst of pancreas

Relative polycythemia is a term used to describe an elevation of the hematocrit level either caused by an acute transient state of hemoconcentration associated with intravascular fluid depletion or a chronic sustained relative polycythemia caused by contraction of the plasma volume. Relative polycythemia can occur when the plasma volume is reduced due to intravascular volume depletion during acute pancreatitis episode, complicating as pseudocyst of pancreas. We report a case of Relative Polycythemia with pseudocyst of Pancreas a secondary complication of pancreatitis.

Retrospective Study of High Hemoglobin Levels in 56 Young Adults

▪Introduction. Erythrocytosis is a common reason for a hematology consultation. Most of the patients are over 50 years of age. The diagnostic approach is already well established, but determining the etiology of erythrocytosis in the young adult may be a real diagnostic challenge. Hereditary causes are often first suspected, but the real etiologic panorama of erythrocytosis in this population is still poorly understood.Methods. This Canadian single-center retrospective observational study was conducted in a Québec university hospital over a period of 20 years (1995 - 2015). Data were collected by a single investigator in a standardized database. From a computer-generated query over a chosen period of time, all patients between 16 and 35 years of age with high levels of hemoglobin or hematocrit were selected (hemoglobin > 185 g/L and/or hematocrit > 0.52 in men; hemoglobin > 165 g/L and/or hematocrit > 0.48 in women). Files were analyzed after approval from the scientific and ethical committees.Results. 426 patients fulfilled the above criteria (on a total of 113 453 complete blood counts conducted in the same age range during the analysis period), but only 56 benefitted from further investigations. Only those cases were included in the study. The male-to-female ratio was 5 : 3. Among them, 59% were smokers, 11% had a high alcohol intake and 27% were using drugs on a regular basis. Obesity was present in 43% of patients (morbid obesity in nearly one third of cases). More than half of the patients had one visit or less with a specialist for investigation of their erythrocytosis. Among those who had a medical follow-up, the median length is 42 months. Erythropoietin was measured in 23% of cases and the JAK2 mutation was screened in 18% of cases. The diagnosis of an acquired polycythemia was made in 41% of cases: hypoxemia (n= 13), renal disorders (n = 6) and drug-induced (n= 4). No case of myeloproliferative syndrome was identified. Two cases were associated with congenital polycythemia (high oxygen affinity hemoglobinopathy). Diagnosis of relative polycythemia was made in slightly over 10% of cases (n= 7). In 24 patients, no conclusive cause could be identified. One third of those patients (n= 8) were hospitalised for mental health decompensation or self-induced intoxication when high hemoglobin levels were detected. When JAK2 mutation testing was not available, the complete blood count was further analyzed and it did not provide any evidence for myeloproliferative syndrome. One in five patients received treatment for their polycythemia, whatever the cause: aspirin (n= 7) and phlebotomy (n= 5). There has been no reported patient death associated with polycythemia or its treatment. Only two major complications occurred: thrombosis (n =1) and bleeding (n= 1).Conclusion. This is the first study to specifically analyze erythrocytosis in young adults. Despite the retrospective design, it demonstrates patient management often inconsistent with the actual recommendations and a lack of follow-up after initial investigations. Congenital polycythemia deserves to be systematically evoked in this age range, but represents only a small part of cases. Acquired polycythemia dominates the etiologies whereas myeloproliferative syndromes were not depicted in this study. Harmonisation of patient care for young adults with erythrocytosis is therefore highly desirable. DisclosuresNo relevant conflicts of interest to declare.

Relative polycythemia in acute pancreatitis: a series of case report

Polycythemia is an unusual manifestation of acute pancreatitis. When polycythemia does occur, it is almost invariably due to intravascular fluid depletion, contraction of Plasma volume, Gaisbock’s Syndrome, Primary congenital and familial polycythemia, polycythemia vera, Hypoxia as in high altitude, pulmonary cyanotic congenital heart diseases, hypoventilation syndromes like sleep apnea, Smoker’s Polycythemia, carbonmonoxide intoxication caused by industrial exposure, Erythropoietin secreting tumors, post renal transplantation erythrocytosis and congenital polycythemias. This case series report presents four patients with acute pancreatitis and relative polycythemia due to reduction in plasma volume as a result of intravascular volume depletion, as demonstrated by Haemoglobin and Hematocrit during acute pancreatitis and the significance of this association is discussed. Among the case series, the case 1 was relative polycythemia with acute pancreatitis presented as pseudocyst, whereas the case 2, 3 and 4 presented as relative polycythemia with necrotizing pancreatitis. The clinical course of the patient suggested that the relative polycythemia developed subsequent to the clinical onset of acute pancreatitis. It is believed that this represents the first recorded case series in the English Literature of acute pancreatitis with Relative Polycythemia due to reduction in plasma volume as a result of intravascular volume depletion. Four Patients presented with Relative polycythemia during acute pancreatitis was found.

Polycythemias

Polycythemia, also called erythrocytosis, is an increase in the number of circulating red blood cells per volume of blood, as reflected by an elevated hematocrit or hemoglobin level. The three major categories of polycythemia are relative polycythemia, secondary polycythemia, and polycythemia vera. Included in this chapter are discussions on initial evaluation; familial polycythemia; and polycythemia caused by renal and hepatic disorders, drug use, and appropriate increases in erythropoietin production. A flowchart depicts an approach to the evaluation of a patient with polycythemia. Other figures depict the oxygen-hemoglobin dissociation curve characteristic of various polycythemias and a gene mutation associated with familial polycythemia. This review contains 3 highly rendered figures and 27 references.

Perfis clínico e hematológico de camundongos submetidos ao envenenamento escorpiônico experimental por Tityus fasciolatus

Estudou-se o quadro clínico do veneno decorrente do envenenamento por Tityus fasciolatus e sua ação refletida nos componentes hematológicos no modelo murino. Para o estudo do perfil hematológico, foram utilizados 54 camundongos Swiss CF1, machos, com 30g, distribuídos em três grupos (G) (n=18) inoculados via subcutânea com: 50µL de PBS (G1); 24µg de veneno de T. fasciolatus (G2) e 8µg de veneno de T. serrulatus (G3). Cada grupo foi subdividido em três subgrupos (n=6) de acordo com o momento da coleta de sangue que foi estipulada em uma, oito e 24h após a inoculação do veneno, e foram realizados o hemograma e a dosagem de proteínas totais e fracionadas. O veneno de T. fasciolatus na dose de 24µg causou piloereção, comportamento nociceptivo, secreção nasal e oral acentuada, dispneia, prurido na face e reflexos exacerbados. No exame hematológico, foram observadas policitemia relativa e leucocitose com linfocitose.

Hematological values and their assessment as risk factor in Saudi patients with stroke.

The retrospective analysis of hematological data on 500 consecutive Saudi patients (342;158F) (mean age 63 +/- 17 yrs) with stroke whose composition was: large infarctions 260 (52%); lacunar infarctions 121 (24.2%), intracerebral hemorrhage 107 (21.2%) and subarachnoid hemorrhage 12 (2.4%), showed that RBC (5.2 +/- 1.9 x 10(12)/L), Hb (143 +/- 21 g/l) and Hct (0.43 +/- 0.07 1/1) values were significantly higher (P < 0.001) in patients with large infarctions as compared to other types of strokes. In both male and female groups of patients, the most likely stroke prone age was 61 to 70 years and interestingly the levels of above three parameters increased or dropped after a certain age. The highest values were in the 61-70 yr age group with men being higher than women (P < 0.001). The overall mortality rate was about 20%, but it was higher in the group of patients with large infarction (63/260; 24.3%). Of these 13 were below the age of 60 years and the remaining 50 aged > 60 included 28 patients (20M;8F) who had Hb > 140 g/l suggesting that Hb > 150 g/L or Hct > 0.44 in men and > 140 g/l or Hct > 0.42 in women is probably a risk factor for having cerebral infarctions and increased mortality. Since this study is neither a cohort nor prospective and was not performed in the acute phase, it was difficult to ascertain if relative polycythemia was a primary event for stroke or was secondary to dehydration in which Saudi hot weather may be a contributory factor.

What is your diagnosis? Particulate material in peritoneal fluid from a dog

9-year-old castrated male Greyhound dog was presented for evaluation of vomiting and lethargy of 1-week duration. On physical examination, the dog was febrile and dehydrated with a tense abdomen and petechial hemorrhages. Clinicopathologic abnormalities included relative polycythemia, mild lymphopenia with reactive lymphocytes, hypoalbuminemia, hypocholesterolemia, hyperbilirubinemia, increased ALP, mild hypokalemia, hyperamylasemia, hyperlipasemia, increased D-dimer concentration, and hyperfibrinogenemia. Cytologic evaluation of peritoneal fluid revealed marked suppurative inflammation with intracellular barium sulfate particles. The day before presentation, the referring veterinarian had administered oral barium sulfate in an upper gastrointestinal contrast study. Radiographs revealed free contrast material in the peritoneal cavity, consistent with gastrointestinal perforation, and leakage of contrast material. Abdominal exploratory surgery revealed a mid-jejunal perforation and a hepatic nodule. Histopathologic diagnosis of the jejunal and liver lesions was T-cell lymphoma. The patient recovered well postoperatively and received chemotherapy for treatment of lymphoma. Most commercial barium sulfate preparations contain relatively uniform, weakly birefringent, pale yellow particles <1 microm in diameter. Because barium sulfate is found occasionally in clinical specimens, cytopathologists should be familiar with its cytologic appearance.

Effect of Renin Angiotensin System (RAS) Blockade on Hematological Parameters in Patients with Secondary Polycythemia (SP) Associated with Chronic Obstructive Pulmonary Disease (COPD) and Sleep Apnea (SA).

Introduction: Erythrocytosis secondary to hypoxia is an erythropoeitin (EPO) driven physiologic mechanism to sustain tissue oxygenation. Phlebotomy is indicated to relief symptoms of hyperviscosity that occur at very high hemoglobin (Hb)/hematocrit (Hct) levels. Recent evidence suggests a causal relationship between RAS and hematopoesis in SP through either EPO related or non-EPO-related mechanisms. On that premise, angiotensin converting enzyme inhibitors (ACEI) used to treat post-transplant erythrocytosis in kidney recipients may have a beneficial effect in lowering hct levels in SP patients.Objective: To study the effect of RAS blockade with ACEIs on Hb, Hct and EPO levels in patients with SP due to COPD/SA.Material and methods: We retrospectively identified patients with SP or erythocytosis treated at our Institutions using the ICD code system. Search involved patients evaluated/treated between 1999 and 2006. Only patients with documented hypoxemia (diagnosis of COPD or sleep apnea), normal to elevated EPO levels, absent splenomegaly and elevated red cell mass in nuclear studies when available were included in the analysis. Demographic characteristics, pulmonary function tests results, baseline, peak Hb, Hct, serum creatinine (Cr), EPO levels at initial diagnoses and history of ACE inhibitors use were obtained. Subsequently, patients were divided into two groups based on whether or not they were on ACE inhibition for at least 2–3 months prior to the peak HgB/Hct values. Patients without documented hypoxemia were excluded as well as those with features suggestive of myeloproliferative disorder or relative polycythemia. Chi-square test was used to evaluate differences in Hct levels between groups before and after ACEI or placebo.Results: A total of 44 patients were identified with median age 60.5 years. There were 22 patients who had received ACEIs for other co-morbid conditions, for at least 3 months prior to peak hematocrit/hemoglobin values. Serum creatinine (median 1.0 mg/dl) levels were equally balanced between two groups. About half of patients in each group had moderate to severe COPD/SA base on PFTs and sleep studies. The median peak Hct and HgB in patients receiving ACEI were 57.45% and 18.65 gr/dl (Mean peak values 56.92% and 18.96 grs/dl; range 51.3–66.9% and 17–20.8 gr/dl) respectively. Patients not on ACEIs had a median peak Hct/HgB of 56.6% and 18.95 gr/dl (Mean peak values 56.54% and 19.2 gr/dl; range 53.0–61.1% and 17.4–21.8 grs/dl). EPO levels were available in 12/44 patients at the time of initial diagnosis with mean values 13.47 MIU/ml (range 5.9–22.3 MIU/ml) without any difference between two groups. Higher percentage of patients achieved decrease in Hct levels (>/=2.5%) from baseline after starting ACEI compared to placebo p=0.017.Discussion: Our results suggest that the use of ACEI decrease Hct levels from baseline in patients with hypoxemia induced SP. It is unclear if this decline is beneficial therapeutically in patients with chronic pulmonary disease. Further studies are warranted to determine if ACEI can decrease frequency of phlebotomies in SP due to hypoxemia.

ACUTE TOXICITY OF PIERISIN-1, A CYTOTOXIC PROTEIN FROM PIERIS RAPAE, IN MOUSE AND RAT

To investigate the toxicity of pierisin-1, a cytotoxic protein present in the cabbage butterfly, Pieris rapae, pierisin-1 was administered via intraperitoneally in mice and rats and the effects examined. Common findings in these experiments were hypoactivity with a gradual decrease in body weight due to decreased food intake, relative polycythemia with low serum albumin concentration and atrophy of the thymus, spleen, seminal vesicles and adipose tissue. Characteristic findings were diarrhea, fusion and atrophy of the villi and dilatation of the crypts in the small intestine at 6-100 microg/kg in BALB/c mice as well as elevation of LDH activity and creatinine value, hemolysis and renal and hepatic injuries at 1,000 and 10,000 microg/kg in BALB/c mice. In the case of ICR mice, severer renal injury was observed. On the other hand, in Fischer 344/Du rats, sudden stop of food intake, elevation of both AST and ALT activities, interlobar adhesion of the right hepatic lobe, capsular thickening, septal fibrosis and single cell necroses of subcapsular hepatocytes in the liver and basophilic tubules in the kidneys were observed. Oral administration of pierisin-1 at a dose of 10,000 microg/kg in BALB/c mice did not exert any obvious effects. Thus, existence of species and strain differences in toxicity of pierisin-1 to animals was demonstrated.

Primary Pulmonary Hypertension with Severe Systemic Hypertension, Raynaud's Phenomenon and Relative Polycythemia.

A 32-year-old Japanese man was hospitalized for evaluation of unconsciousness. He was diagnosed as having primary pulmonary hypertension (PPH) with severe systemic hypertension, Raynaud's phenomenon and relative polycythemia. Hemostatic studies revealed increased coagulation and decreased fibrinolysis, similar to findings of chronic disseminated intravascular coagulation (DIC). Although activation of coagulation and systemic hypertension were improved after treatment with phlebotomy and administration of nifedipine, enerapril and warfarin, pulmonary hypertension was unchanged, suggesting that irreversible change had already occurred in the pulmonary arteries. Those complications could modify the process of pulmonary hypertension by inducing a hyperviscosity state.

Erythropoietin receptor and hematological disease.

This review will discuss evidence for the role of the erythropoietin (Epo) receptor in the development of erythrocytosis and other hematological disorders. The possible causative role of mutations of other genes in the pathogenesis of idiopathic erythrocytosis will be considered. Polycythemia vera (PV) is a myeloproliferative disorder that is caused by an undefined stem cell abnormality, characterized by a significant erythrocytosis, leukocytosis, and thrombocytosis. However, erythrocytosis may arise from apparent (or relative) polycythemia in which the hematocrit is raised due to a low plasma volume. In such cases the red cell mass is normal. A group of disorders with increased red cell mass caused by stimulation of erythrocyte production is known as secondary polycythemia. Investigation of such patients may reveal a congenital abnormality such as high affinity hemoglobin or an acquired abnormality caused, for example, by smoking, renal vascular impairment, or an Epo-producing tumor. Even after thorough examination there remains a cohort of patients for whom no definite cause for the erythrocytosis can be established. A careful clinical history may reveal whether this idiopathic erythrocytosis is likely to be congenital and/or familial, in which case the term "primary familial and congenital polycythemia" is sometimes applied. Access to a range of laboratory investigations may define the molecular pathophysiology. We will now discuss how this process can be investigated.