Relative Polycythemia Research Articles

In vitro culture growth of erythroid progenitors and serum erythropoietin assay in the differential diagnosis of polycythaemia.

We assessed the in vitro culture growth of erythroid progenitors [burst forming unit-erythroid (BFU-E)] and serum erythropoietin (EPO) levels in different groups of polycythaemia to determine the discriminative power in differential diagnosis of polycythaemia. We used the methylcellulose culture technique to study the growth of endogenous erythroid colonies (EECs) and EPO-dependent BFU-E from bone marrow (BM) and/or peripheral blood (PB) cells from 40 patients with polycythaemia vera (PV), 13 with secondary polycythaemia (SP), 19 with pure erythrocytosis (PE), five with PE and PV evolution later (PE-PV), and 12 with relative polycythaemia (RP). The serum EPO levels were measured by radioimmunoassay before treatment in 47 patients, 23 SP patients, 19 PE patients, five PE-PV patients and 16 RP patients, as well as after treatment in 38 PV patients, five PE-PV patients and 12 PE patients. The results of the erythroid progenitor culture assay showed that the numbers of EPO-dependent BFU-E in BM did not differ significantly among groups. The PB BFU-E were significantly higher in PV than in SP or PE, and no statistical difference were found among patients with SP, PE and RP. There was a correlation between BM BFU-E and PB BFU-E in the individual PV and PE patients. EECs were present in all BM and PB cultures of untreated and phlebotomy-treated PV and PE-PV patients, but were absent in 6 of 17 PV patients who had received cytotoxic therapy. EECs were not found in SP, PE and RP. PB could substitute for BM in the EEC or the BFU-E assay. Both pretreatment and post-treatment serum EPO levels of PV and PE-PV were similar, which were significantly lower than SP, PE or RP. The serum EPO levels in treated PV or PE-PV patients who had normal haematocrit values were not significantly different from those in untreated patients. In contrast, the phlebotomy-treated PE patients had significantly higher serum EPO values than untreated PE patients. In the differentiation between PV and PE, the sensitivity, specificity, positive predictive value and negative predictive value of post-treatment serum EPO levels at a cut-off level of < or = 9 UL-1 were 74%, 92% and 52% respectively. The discriminative power of post-phlebotomy serum EPO levels was even higher with a positive predictive value of 80% and negative predictive value of 92% for the prediction of PV evolution in patients with pure erythrocytosis of unknown origin. The present study showed that apart from EEC assay, the post-phlebotomy serum EPO level was a sensitive and specific parameter in the differential diagnosis of polycythaemia, in particular for the identification of PV among patients with unclassifiable polycythaemia.

Coagulation factor XIII in pregnant smokers and non-smokers.

Human blood coagulation factor XIII is a transglutaminase zymogen. Two forms exist, an extracellular or plasma factor XIII and an intracellular form. Factor XIII occurs in platelets, blood, monocytes, megakaryocytes, the liver, the placenta, and the uterus. In obstetrics, factor XIII deficiency has been associated with fetal wastage. The interaction of smoking and the quantity of coagulation factor XIII during normal pregnancy was examined in 75 non-smoking and 118 smoking (> or = 20 cigarettes/day) women. A group of subjectively healthy, non-smoking, age-matched females served as a control group (n = 30). Smokers had a higher plasma concentration of factor XIII than non-smokers. Factor XIII declined during normal gestation. During the second half of gestation the plasma concentration of factor XIII was significantly higher in smokers than in non-smokers. In smokers the decline of factor XIII was less, possibly due to platelet activation and a relative polycythemia. The later decline of factor XIII in pregnant smokers remains unexplained. More extensive research with larger patient numbers is needed to address this matter.

A retrospective study of apparent and relative polycythaemia: associated factors and early outcome

Thirty four consecutive patients (31 male, 3 female) with raised PCV (males >0.51, females >0.47) and normal red cell mass (apparent polycythaemia) and with normal red cell mass but a low plasma volume (relative polycythaemia) were studied retrospectively. Male sex, smoking, hypertension and diuretic therapy were found to be associated factors while obesity and excessive alcohol consumption were less clearly linked. Only three patients (all males) were negative for all these factors. Approximately 15% of patients had arterial hypoxaemia. There was no difference in the incidence of these factors in the two sub-groups. Possible mechanisms relating these factors to the raised PCV are discussed. Preliminary follow-up data show that in approximately one third of the patients the PCV returns to normal and that this is most likely in those patients with a normal recumbent PCV (at the time of the blood volume study). In one third the PCV continues to be raised, and the remainder have only intermittently raised PCV. As a result of this study, prospective studies of the incidence of hypoxaemia in these patients and of the PCV outcome with and without correction of associated factors are planned.

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.

Res Scintigraphy in Polycythemia Vera and Secondary or Relative Polycythemia

Scintigraphy of the reticuloendothelial system (RES) was performed in 19 patients with polycythemia vera (PCV) and in 18 with secondary or relative polycythemia (PS). Bone marrow extension was found in all patients with PCV and in 11 of 18 patients with PS. The patients with PCV had a higher degree of extension than those with PS. Increased pelvic bone marrow activity was found in 16 of 19 PCV patients, but in none with PS. Splenomegaly was found in 9 patients with PCV, and in none with PS. It is concluded that RES scintigraphy in the majority of patients may differentiate between PCV and PS using the parameters pelvic bone marrow activity, bone marrow extension and splenic size.

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.

Serum erythropoietin in the diagnosis of polycythaemia and after phlebotomy treatment

Serum erythropoietin (S-Epo) was measured with a radiommunoassay method in 36 patients with polycythaemia vera, 17 patients with secondary polycythaemia and 14 patients with relative polycythaemia. The diagnoses were made without the aid of the S-Epo values. It was found that S-Epo was below the reference range in 34/36 patients with polycythaemia vera (mean 2.1 +/- 1.0 U/l), elevated in all cases of secondary polycythaemia (mean 121.7 +/- 242 U/l) and normal in all but one of the cases with relative polycythaemia (mean 7.0 +/- 2.5 U/l). Previous studies of S-Epo levels in the differential diagnosis of polycythaemia have shown significant differences between the means of the groups but a considerable overlap. After phlebotomy treatment to normal haematocrit levels, the S-Epo levels remained subnormal in most of the polycythaemia vera patients even after 18 months at a haematocrit around 45%. Two patients who had been kept at normal haematocrit for 6 and 7 years both had subnormal S-Epo. We conclude that with an Epo assay method of high sensitivity and specificity it is possible to differentiate between different forms of polycythaemia with a high degree of certainty, even between patients with relative polycythaemia and polycythaemia vera patients. The reason why S-Epo remains low in spite of a normal haematocrit in treated polycythaemia vera patients is not known.

Vascular compromise in newborn infants.

With improved neonatal resuscitation techniques a number of infants are now surviving only to develop vascular problems secondary to intravascular catheterisation, repeated venepuncture, or arterial blood sampling. Spontaneous thromboses are also more common in early life than in later childhood.' 2 Guidelines for the prevention, diagnosis, and treatment of blocked vessels in adult patients are not automatically applicable to the newborn. The size of the delicate vessels, the immature haemostatic mechanism, and the background of relative polycythaemia pose special problems. Thromboembolic vessel obstruction may result in death or irreversible damage to an organ or limb. In addition to blockage of peripheral vessels,3 4thrombosis ofthe cerebral,5 pulmonary,6 7 coronary,8 9 renal,I0 and mesenteric arteries, is reported in the neonate. Peripheral artery occlusion usually presents with a cold, pulseless, mottled, and discoloured limb. Obstruction of the central veins or arteries may be more difficult to recognise. Renal vein thrombosis, for example, does not always present with haematuria and an enlarged kidney, and thrombosis of the aorta may not disclose itself with congestive cardiac failure and ischaemia of the lower limbs.' association with radial,'9 femoral,0 pulmonary, and temporal artery22 lines, as well as with catheters into the jugular7 23 or femoral24 veins. Thrombi are also found when catheters are not used. A review of consecutive necropsies revealed a 4-5% incidence of thrombosis in uncatheterised cases, and an 11% incidence when intravascular catheters were used.25 Even temporary catherisation can cause problems. In a prospective study of children undergoing cardiac catheterisation, 3-6% developed clinical symptoms of femoral artery thrombosis.26 An extensive literature review of 1045 cannulations of the radial artery in newborn infants showed that 6% of cases suffered transient ischaemia and 0-5% had permanent ischaemic damage.27 Even hand amputation after radial artery cannulation has been reported.28 The incidence of vessel occlusion without ischaemic changes, however, is as high as 63%,29 and in such cases, an adequate collateral circulation exists. Flow in the blocked vessel is often restored several days after catheter removal. The propensity to develop thrombosis is related to size of the infant. The risk of vessel obstruction after cardiac catheterisation is highest in infants of less than 10 kg.27 30 31

Apparent polycythaemia

Patients with apparent polycythaemia are characterised by a raised packed cell volume (PCV; males above 0.51, females above 0.48) but normal red cell mass (RCM; less than 25% greater than predicted). Prediction and interpretation of RCM and PV should be based on height and weight, since the use of body weight alone is misleading. Patients with PCV values up to 0.60 may have apparent polycythaemia but only 18% have a reduced PV (relative polycythaemia). Therefore, the most common cause of the raised PCV is a change in RCM and/or PV within their normal ranges. The clinical associations and possible causes for the RCM/PV changes include male sex, obesity, dehydration, diuretics, smoking, hypertension, alcohol, arterial oxygen desaturation, renal disease and increased catecholamine levels. Retrospective studies of patients with apparent polycythaemia and information from other groups of polycythaemic patients suggest an increased risk of vascular occlusion, although other factors, such as hypertension and smoking, are also involved. Proposed management includes modification of possible underlying causes and examination for risk factors for vascular occlusion. In patients with PCV levels chronically above 0.54 venesection should be used, but patients with PCV values below this level should only be venesected if they are considered to be at risk of vascular occlusion. The suggested target value for PCV for venesected patients is 0.45 or below.

A Case of Chronic Mountain Sickness Diagnosed by Routine Pulmonary Function Tests

In summary, this is a patient who presented with respiratory acidosis and cor pulmonale. The major diagnostic challenge was in differentiating primary cardiopulmonary disease from a central abnormality of ventilatory drive. The arterial blood gases showed a normal A-a gradient suggesting hypoventilation as the etiology of his hypoxemia. Pulmonary function testing showed air trapping, but a relatively normal FEV1/FVC and airways resistance. The literature suggests that most altitude natives have depressed hypoxemic and hypercapnic drives with a distinct subset demonstrating a profoundly depressed drive to ventilation. This latter group has been labeled as having chronic mountain sickness or Monge's disease. As one might expect, ventilatory control during sleep is also abnormal in these patients with CMS. Our patient indeed showed typical frequent severe desaturations with hypopnea. The diagnosis of CMS in our patient was made with routine arterial blood gases and standard pulmonary function tests. Additional tests of ventilatory responsiveness to oxygen and carbon dioxide could have been performed, but are not necessary to make the diagnosis.

‘Polycythaemia of stress’ in subjects with type A and type B behaviour patterns

To determine the importance of emotional stress for relative polycythaemia, we studied 11 subjects with the Type A and 11 subjects with the Type B behaviour patterns during short-term mental stress. All subjects were healthy, normotensive non-smoking young males aged 20–34 yr, without any medication. During rest there were no significant differences in heart rate, blood pressure, or plasma catecholamines between the two groups, but the A-group had significantly higher haemoglobin concentration (147 vs 140 g/l; p < 0.005) and haematocrit (43.8 vs 42.1%; p = 0.05) than the B-group. In the whole group, there was a positive correlation between resting diastolic blood pressure and haemoglobin concentration ( r = 0.53; p < 0.05). In response to 10 min of mental arithmetic, haematocrit, haemoglobin and erythrocyte count rose approximately 2% ( p < 0.001 throughout). The stress-induced changes were not significantly different between the A- and B-groups. It is concluded that mild relative polycythaemia could be induced by acute emotional stress. In subjects with the Type A behavior pattern a slight haemoconcentration is present already at rest, which further increases during stress.

A retrospective study of apparent and relative polycythaemia: associated factors and early outcome

Thirty four consecutive patients (31 male, 3 female) with raised PCV (males greater than 0.51, females greater than 0.47) and normal red cell mass (apparent polycythaemia) and with normal red cell mass but a low plasma volume (relative polycythaemia) were studied retrospectively. Male sex, smoking, hypertension and diuretic therapy were found to be associated factors while obesity and excessive alcohol consumption were less clearly linked. Only three patients (all males) were negative for all these factors. Approximately 15% of patients had arterial hypoxaemia. There was no difference in the incidence of these factors in the two sub-groups. Possible mechanisms relating these factors to the raised PCV are discussed. Preliminary follow-up data show that in approximately one third of the patients the PCV returns to normal and that this is most likely in those patients with a normal recumbent PCV (at the time of the blood volume study). In one third the PCV continues to be raised, and the remainder have only intermittently raised PCV. As a result of this study, prospective studies of the incidence of hypoxaemia in these patients and of the PCV outcome with and without correction of associated factors are planned.

Polycythemia: Evaluation and management

The approach to diagnosis and classification of patients with polycythemia is reviewed with presentation of general and specific guidelines for the management of patients with polycythemia vera, secondary polycythemia and relative polycythemia.

Smoking--a major cause of polycythaemia.

The importance of smoking in the aetiology of polycythaemia has been assessed in a group of patients referred to a general haematology clinic. All patients with true and relative polycythaemia (excluding those with polycythaemia rubra vera) were studied. Of the 21 such patients evaluated, 14 were smokers and had raised carboxyhaemoglobin levels and had no other demonstrable cause for their polycythaemia. The commonest physiological abnormality in these patients was a raised red cell mass combined with a low plasma volume. Six of the 14 patients were able to reduce their smoking with subsequent improvement in their haematocrits. These results suggest that smoking is a major cause of polycythaemia in an unselected series of referrals to a general haematology clinic. The early identification of these patients may be useful in planning therapy.

Use of Clinical Pathology in Evaluation of Horses with Colic

Clinical pathology is a valuable adjunct to physical examination of cases of colic. The present review considers evaluation of cases of colic for three main purposes: (1) making a prognosis, (2) deciding whether to operate, and (3) making a diagnosis. Blood tests noted to be useful for prognostication were hematocrit, lactate and urea nitrogen concentrations, pH, anion gap, fibrin/fibrinogen degradation products, antithrombin III activity, prothrombin time, and thrombin time. Horses with a poor prognosis often have relative polycythemia, marked lactic acidosis, high anion gap, azotemia, and coagulation abnormalities evidenced by increased fibrin/fibrinogen degradation products, decreased antithrombin III activity, and prolonged prothrombin and thrombin times. The decision to operate is usually a clinical one, supported by relative polycythemia, hyperglycemia, and, possibly, abnormal peritoneal fluid analysis. Diagnosis of the primary problem (causing the colicky signs) is also often based largely on physical examination. However, peritoneal fluid analysis provides worthwhile data, especially in cases of peritonitis or intestinal ischemia and infarction.

3 The contracted plasma volume syndromes (relative polycythaemias) and their haemorheological significance

Relative polycythaemia is a general term which includes patients with a normal red cell mass but a contraction of the plasma volume as the cause for the polycythaemia. The relative polycythaemias can broadly be divided into two groups. Firstly, relative polycythaemia may be due to a primary loss of plasma volume due to dehydration, capillary leak or hypo-oncotic pressure. Secondly, relative polycythaemia may be due to a primary contraction of the vascular compartment (i.e. reduced venous compliance). It is this second group which is the least understood and is analysed in detail in this review. In general, this group of polycythaemias is secondary to exogenous or endogenous stress and is mediated via the sympathetic nervous system. Hypoxia, smoking, neurological disorders, myocardial infarction and acute psychological stress have all been demonstrated as possible factors. In many cases of chronic stress polycythaemias aetiological factors may be identified, whereas in others the term idiopathic is probably appropriate. There appears to be a relationship between the idiopathic stress polycythaemias, hypertension and psychological stress. Other patients may have primarily a disorder of blood volume control involving the autonomic nervous system and its receptors. The haemorheological significance of relative polycythaemia and its management are discussed. Treatment is generally dictated by the underlying cause. In stress polycythaemias the stimulus should be removed as far as possible. However, in some patients with chronic idiopathic stress polycythaemia, regular venesection may be required to maintain the venous haematocrit at an appropriate level.

Cyanosis in the newborn.

RECOGNITION OF CYANOSIS IN THE NEWBORN Clinical cyanosis is chiefly dependent on the absolute concentration of reduced hemoglobin in the blood rather than on the oxygen saturation. Thus, when there is more than 3 g of reduced hemoglobin per deciliter of arterial blood, central cyanosis should be recognizable. The O2 saturation when clinical central cyanosis becomes apparent varies from about 62% when the hemoglobin is only 8 g/dL to about 88% saturation in the polycythemic infant with a hemoglobin of 24 g/dL. The normal relative polycythemia of newborn infants (hemoglobin 14 to 20 g/dL), therefore, facilitates recognition of cyanosis. Recognition of cyanosis in the newborn is rendered more difficult by the presence of fetal hemoglobin (Fig 1). The ratio of fetal to adult hemoglobin varies from infant to infant, and the proportions of each hemoglobin affect the oxygen saturation resulting at any give Pao2. Thus, if a baby with a pH of 7.4 and a temperature of 37°C has mostly adult hemoglobin, central cyanosis (arterial saturation 75% to 85%) will be observed at a Pao2 of 42 to 53 mm Hg, whereas if the baby has mostly fetal hemoglobin, central cyanosis will be observed at a Pao2 of 32 to 42 mm Hg. Thus, the newborn with a high proportion of fetal hemogolobin may have a serious reduction in oxygen tension before central cyanosis is clinically apparent.

Cyanosis in the Newborn

RECOGNITION OF CYANOSIS IN THE NEWBORN Clinical cyanosis is chiefly dependent on the absolute concentration of reduced hemoglobin in the blood rather than on the oxygen saturation. Thus, when there is more than 3 g of reduced hemoglobin per deciliter of arterial blood, central cyanosis should be recognizable. The O2 saturation when clinical central cyanosis becomes apparent varies from about 62% when the hemoglobin is only 8 g/dL to about 88% saturation in the polycythemic infant with a hemoglobin of 24 g/dL. The normal relative polycythemia of newborn infants (hemoglobin 14 to 20 g/dL), therefore, facilitates recognition of cyanosis. Recognition of cyanosis in the newborn is rendered more difficult by the presence of fetal hemoglobin (Fig 1). The ratio of fetal to adult hemoglobin varies from infant to infant, and the proportions of each hemoglobin affect the oxygen saturation resulting at any give Pao2. Thus, if a baby with a pH of 7.4 and a temperature of 37°C has mostly adult hemoglobin, central cyanosis (arterial saturation 75% to 85%) will be observed at a Pao2 of 42 to 53 mm Hg, whereas if the baby has mostly fetal hemoglobin, central cyanosis will be observed at a Pao2 of 32 to 42 mm Hg. Thus, the newborn with a high proportion of fetal hemogolobin may have a serious reduction in oxygen tension before central cyanosis is clinically apparent.

4 Polycythaemia and thrombocythaemia in the elderly

The investigation of elderly patients presenting with raised PCV values has been described. Suitable clinical and laboratory investigation enables the separation of those with a raised red cell mass (RCM) into three groups: primary proliferative polycythaemia (PPP), secondary polycythaemia and idiopathic erythrocytosis. Those patients with a raised PCV but normal RCM either have apparent polycythaemia (normal plasma volume) or relative polycythaemia (low plasma volume). PPP is a clonal disorder with a peak incidence in the elderly. It commonly presents with vascular occlusive symptoms/signs involving larger vessels, both arterial and venous. The microvasculature may also be involved, particularly when there is associated thrombocythaemia. Effective treatment is required to minimize the future vascular occlusive incidence and diminish the complication rate of surgery if it is ever required. Both the PCV and the platelet count, if elevated, should be adequately controlled. 32P is probably the simplest treatment and is very effective, but venesection and intermittent low-dose busulphan is equally satisfactory in the co-operative patient with good peripheral veins. Secondary polycythaemia may arise from a variety of causes, particularly from arterial hypoxaemia and renal lesions. Occasionally, more than one pathology is identified in the elderly patient. Lung disease is the most common cause of hypoxaemia. Venesection may be indicated in those patients with excessively raised PCV values. The term idiopathic erythrocytosis should only be used for patients who have been adequately investigated. These patients most commonly present with ischaemic or vascular occlusive symptoms/signs. Relative polycythaemia may be caused by fluid loss, but generally the origin of the low plasma volume is not established. Apparent polycythaemia may represent a physiological variant or a stage before the development of a definitely raised RCM. The management of idiopathic erythrocytosis, and relative and apparent polycythaemia, should initially involved removal of known risk factors if present (e.g. hypertension) with the addition of venesection in selected patients. Reactive thrombocytosis in the elderly is most commonly due to malignant disease of chronic infection. The high platelet count is usually asymptomatic, and antiplatelet therapy is rarely required. Primary thrombocythaemia (PT) is a clonal myeloproliferative disorder similar to PPP. The finding of splenomegaly, abnormal platelet morphology or function helps to separate PT from reactive thrombosis. PT most commonly presents with digital or transient cerebral ischaemia or haemorrhage.(ABSTRACT TRUNCATED AT 400 WORDS)

Dose-effect relationship between smoking and blood rheology.

Five groups of male blood donors were investigated. The first group had never smoked, the second were ex-smokers, the third smoked between 10 and 20 cigarettes per day, the fourth between 21 and 40, and the fifth more than that. Haematocrit, white cell count, plasma and native blood viscosity, blood cell filterability and aggregation, plasma colloid oncotic pressure as well as fibrinogen were measured. Results show that smoking is associated with a progressive significant deterioration of the above haemorheologic variables. These changes are interpreted as an absolute and a relative polycythaemia possibly in conjunction with a chronic inflammatory process. It is concluded that smoking induces a dose-related increase in viscosity of blood among young men which is reversible by abstention.