Familial Polycythaemia Vera

The familial occurrence of polycythaemia vera (PV) is rare, with only 3 authentic reports in the world literature. This paper describes a family of 8 females, 3 of whom have PV and another has pernicious anaemia. Clinical and haematological data is presented to support the diagnosis of PV and exclude other causes of familial erythrocytosis. Cytogenetic studies were performed in 2 of the patients.     

Histamine Metabolism in Polycythaemia Vera

Histamine metabolism was studied in 35 patients with polycythaemia Vera (PV) at different stages of their disease and compared with controls and patients with secondary polycythaemia. In addition to blood and urinary histamine the main urinary metabolites of histamine, methylhistamine (MeHi) and 1-methyl-4-imidazole-acetic acid (MeImAA) were measured. In patients with active PV the excretion of MeHi and MeImAA was significantly higher than in controls and secondary polycythaemia, indicating an increased histamine formation. The MeImAA excretion was correlated to the blood histamine level, the degree of blood basophilia, the total white blood count and the spleen volume. The blood histamine level was significantly higher in PV patients compared with controls and secondary polycythaemia. No patients with secondary polycythaemia had an increased blood histamine level. With the bio-assay technique used in this study the urinary excretion of histamine in the PV patients was within the normal range. There was no correlation between the increased hstamine formation and ‘histamine-related symptoms’. Pruritus and duodenal ulcer occurred with a similar frequency in patients with and without increased MeImAA excretion. The similarity between the disturbance of the histamine metabolism in PV and that found by other authors in chronic myeloid leukaemia is pointed out.     

The Transcobalamins in Polycythaemia Vera

The unsaturated B₁₂ binding capacity (UBBC) of the serum and the binding capacity of each of the 3 vitamin B₁₂ binders - the transcobalamins (TC) I, II and III were determined in 21 patients with polycythaemia vera (PV) during the course of the disease and following treatment, using the recently described charged cellulose filter technique. High serum UBBC due to elevated serum TCIII was found in all patients. TCI was moderately elevated in patients who had leucocytosis with a shift to the left. The changes in serum TCIII and UBBC correlated with the activity of the disease. Chemotherapy resulted in a decrease in TCIII and UBBC. The decrease in TCIII and UBBC folowing chemotherapy may be observed before a decrease in the haema-tocrit and the leucocyte count occurs. Activation of the disease may be assessed by the elevation of TCIII and UBBC. The onset of acute myeloblastic crisis in 1 patient was associated with a decrease in TCIII and TCI levels and a rise in serum TCII. The determination of TCIII and UBBC may be helpful in differentiating true from secondary polycythaemia.     

Pernicious Anaemia and Polycythaemia Rubra Vera

Forty patients with pernicious anaemia and polycythaemia vera have been described. In order to determine whether this association was due to an autoimmune mechanism or to chance, the frequency of parietal cell antibodies was estimated in 51 patients with polycythaemia. The incidence of parietal cell antibodies in these patients was similar (8 per cent) to that in a matched control group (6 per cent).     

Erythropoietin Responsiveness in Polycythaemia Vera

A liquid bone marrow culture technique was used to study erythropoiesis in polycythaemia vera. Three patients with the diagnosis of polycythaemia vera treated only by phlebotomy were compared to three healthy volunteers. Erythropoiesis in vitro was assessed by counts of nucleated red cells and 3H-thymidine incorporation into erythroid precursors. Human urinary erythropoietin was found to stimulate erythropoiesis in cultures from the polycythaemia patients as well as normals. The erythropoietin effect was blocked by a rabbit anti-erythropoietin antibody. These results suggest that some erythroid precursor cells maintain an intact erythropoietin response mechanism in polycythaemia vera. They also support clinical studies of this disorder indicating that some regulation by erythropoietin may occur in vivo.     

Plasma Volume and Splenomegaly in Polycythaemia Vera

Blood volume studies in 23 patients with polycythaemia vera showed the mean plasma volume to be normal when compared with control subjects, and variation in plasma volume for the group as a whole was no greater than in normal subjects. However, the polycythaemic subjects proved to be heterogeneous with respect to plasma volume: in one subgroup, showing splenomegaly with demonstrable intrasplenic red cell pooling, there was a moderate increase in mean plasma volume. In addition, the effect of intrasplenic red cell pooling on the whole body haematocrit/venous haematocrit ratio was found to differ in this condition from the effect in non-polycythaemic subjects: the splenic pool failed to concentrate red cells significantly above the levels present in the extrasplenic circulation, and did not result in a rise in the H_b/H_v ratio.     

Transition of Myelofibrosis to Polycythaemia Vera

A case of typical myelofibrosis with a huge spleen is described in a 62-year-old man. During the subsequent 2-year follow-up, a clinical picture of polycythaemia vera with pancytosis and disappearance of the marrow fibrosis was observed. The pancytosis necessitated treatment with busulphan and frequent phlebotomies. The transformation was associated with prednisone treatment for a suspected haemolytic state. During this treatment, the spleen no longer became enlarged on clinical palpation, although it was still enlarged at post mortem examination, but much less than 2 years earlier.     

Dual Presentation of Polycythaemia Vera and Lymphatic Leukaemia

Summary: Dual presentation of polycythaemia Vera and lymphatic leukaemia. E. Januszewicz and F. C. Firkin, Aust. N.Z. J. Med ., 1980, 10, pp. 209–211.
A case is described in which polycythaemia Vera was found to co-exist with chronic lymphatic leukaemia at the time of presentation. This case can be added to five other reported cases of an association between polycythaemia Vera and well-differentiated lymphocytic neoplasia, and adds further emphasis to the tendency for dual presentation, which has now occurred in all but one of these cases. One explanation is that the association is due to chance, but the tendency for dual presentation raises the possibility that the overall picture reflects neoplastic involvement of stem cells with capacity to differentiate into the lymphoid as well as the erythroid, myeloid and megakaryocytic series     

Red Cell Fatty Acids in Polycythaemia Vera

S ummary Total lipids of red cells as well as plasma from polycythaemia Vera patients and normal subjects were fractionated and the fatty acid composition was analysed by gas-liquid chromatography. The following statistically significant differences were found in the percent fatty acid levels.
Red cell . Linoleic acid level of total lipids was decreased in polycythaemia whereas oleic acid level of phospholipid fractions was increased. Stearic acid level of cholesterol ester fraction was increased in polycythaemia whereas that of triglyceride fraction was decreased. Significantly low levels of arachidonic acid associated with cholesterol ester fraction were noted in polycythaemia patients.
Plasma . Palmitic acid associated with total lipids and oleic acid levels of phospholipid fractions were higher in polycythaemia. Stearic acid associated with phosphatidyl ethanolamine was found to be decreased in polycythaemia. Similarly arachidonic acid associated with total lipids as well as sphingomyelin was decreased in polycythaemia. A wide difference between the lipids of the red cell and the surrounding plasma was observed.     

Skin Window Studies in Polycythaemia Rubra Vera

S ummary . The inflammatory response was studied in patients with primary polycythaemia by means of a modified skin window technique. In untreated patients, the overall cellularity was a prominent feature and, as compared with the controls, the 48 h preparations showed a significantly greater percentage of granulocytes with a corresponding decreased percentage of macrophages. In the peripheral blood of these patients, both total white cells and granulocyte counts were significantly higher than in the control subjects. A highly significant relationship between the blood and skin window neutrophils was demonstrated. In polycythaemia patients in remission, the results were generally similar to the controls, except that there was still a highly significant increase in the percentage of skin window basophils.
The results provided no evidence of a defect in cell migration or in the phagocytic activity of macrophages in polycythaemia vera. Possible mechanisms of the cutaneous basophilia and its relevance to the manifestation of this disorder are discussed.     

Erythrocyte 2,3-Diphosphoglycerate and Adenosine Triphosphate in Polycythaemia Vera

Erythrocyte 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) were measured in 16 patients with polycythaemia vera and found to be normal. The determination of erythrocyte organic phosphate concentration can be helpful in the differential diagnosis of different types of polycythaemia due to the lack of 2,3-DPG rise in patients with polycythaemia vera, as compared to the 2,3-DPG increase usually observed in patients with secondary polycythaemia.     

Chromosome Abnormalities after Chlorambucil Therapy of Polycythaemia Vera

Bone marrow chromosomes were studied in 2 patients with polycythaemia vera (PV) at the time of diagnosis and several times subsequently during therapy with chlorambucil. Both patients were normal in the initial study, but later developed pathological diploid cell lines with structural chromosome abnormalities. Case 1 presented after 25 months of myelosuppressive therapy a deletion of chromosome no. 12, del (12) (p11), in 60% of the diploid cells. 10 months later all studied cells in the marrow contained this deletion. In addition, the deletion of chromosome no. 20, described as characteristic for PV, was found in 3 cells. Case 2 demonstrated after 40 months on chlorambucil the presence of a balanced translocation, t (1; 5) (p36; q31) in 90% of the cells. In none of the patients were any definite clinical, laboratory or morphological signs of an approaching leukaemic transformation of the polycythaemic disorder present.     

Polycythaemia Vera and Myelosclerosis: A Bone Marrow Study

Trephine bone biopsies have been performed on patients suffering from polycythaemia vera and other myeloproliferative disorders. These were assessed histologically with particular reference to cellularity and reticulin. It was found that marrow cellularity, when measured using Curtis's modification of a Chalkley array of points, is raised in polycythaemia vera and may become normal following radioactive phosphorus therapy.
Marrow cellularity was also shown to be proportional to spleen size and a linear relationship between marrow cellularity and packed cell volume was demonstrated, providing major degrees of splenomegaly were excluded.
Studies of the reticulin fibres in bone marrow showed that they increase in density with an increase in marrow cellularity, and that an increase is neither characteristic of any specific myeloproliferative disorder nor is it related to radioactive phosphorus therapy.
It was concluded that the histological diagnosis of myelosclerosis should be confined to those bone marrows showing evidence of fibroblastic proliferation and disruption of marrow architecture by a process of fibrosis, and should not be made on the basis of reticulin density.     

Glutamic Pyruvate Transaminase Phenotypes in Polycythaemia Rubra Vera

. Glutamate pyruvate transaminase (GPT) has been studied in the red cells of 46 patients with a confirmed diagnosis of polycythaemia rubra vera (PRV). The red cells of many of the patients showed low levels of enzyme activity. This activity could be restored by in vitro incubation with pyridoxal phosphate suggesting that the effect was due to low levels of B6 rather than to a primary abnormality of the GPT. Patients with the lowest levels of GPT activity were likely to have clonal chromosomal abnormalities in the bone marrow cells, particularly 20q —. Among 43 patients in whom the GPT phenotypes could be determined by an electrophoretic method there was a marked deficiency of heterozygotes. This disturbance in phenotypic expression may be related to the clonal nature of the disease in PRV, the clone showing lack of response to homeostatic controls and irregularities of gene expression.     

Quantitative Studies of Splenic Erythropoiesis in Polycythaemia Vera and Myelofibrosis

S ummary . A quantitative scanning method employing cyclotron-produced ⁵²Fe has been developed to assess splenic erythropoiesis in patients with myeloproliferative disorders. In 12 patients with myelofibrosis splenic uptake of ⁵²Fe was from 5.0% to 48% of the injected dose. Although a single patient with classical polycythaemia vera had a minor uptake of 2.8% six other patients with this diagnosis showed no concentration of isotope in the splenic area. The fraction of ⁵²Fe in the spleen of four patients with 'transitional'myeloproliferative disorders characterized by a high red cell mass, hypercellular bone marrow and a leucoerythroblastic blood film varied from 5% to 41%. No clear relationship was noted between the degree of splenic erythropoiesis as defined by this technique and the level of haemoglobin, the degree of splenomegaly, the effectiveness of erythropoiesis or traditional ⁵⁹Fe surface counting. If splenectomy is considered in patients with myelofibrosis splenic ⁵²Fe quantitation will provide more precise data on the contribution of splenic erythropoiesis than ⁵⁹Fe surface counting alone.     

Inhibitors of Fibrinolysis in Platelets in Polycythaemia Vera and Thrombocytosis

S ummary . The role of platelets in fibrinolysis was studied in relation to their content of fibrinolytic inhibitors. An antiplasmin was present in platelets when studied by the caseinolytic method, but this antiplasmin was weak when the fibrin plate method was used. Thus the fibrin plate method could be used for the study of the inhibitory action of platelets against three different types of plasminogen activator: urokinase, human heart tissue activator and human plasma plasminogen activator. It was found that normal human platelets contained inhibitors against all three plasminogen activators with the highest inhibitory activity against urokinase. Platelets from patients with thrombocytosis due to polycythaemia vera or secondary to bronchogenic carcinoma also showed similar inhibitory activity. The platelets from one patient with polycythaemia vera had an unusually high degree of inhibitory activity. The significance of these findings is discussed with respect to the relative resistance of a platelet thrombus to lysis and to its role in haemostasis.     

Two Additional Cases of Coexisting Polycythaemia Vera and Chronic Lymphocytic Leukaemia

2 patients with coexistent polycythaemia vera and chronic lymphocytic leukaemia are described. A 61-year-old man presented with an increased packed cell volume (PCV) and a leucoerythroblastic blood picture, which was reversible upon treatment, neutrophil leucocytosis, bone marrow lymphocyte infiltration and splenomegaly, and subsequently developed lymphomas, blood lymphocytosis and thrombocytosis. The second case was a 58-year-old female presenting with increased PCV and leucocyte alkaline phosphatase score. She later had neutrophil leucocytosis, thrombocytosis, lymphocytosis, lymphomas and splenomegaly. These cases, together with 6 cases published by others, suggest that an association exists between the two diseases.