Polycythemia Vera Study Group Criteria Research Articles

A data-mining approach to improving Polycythemia Vera diagnosis

This paper presents a data-mining approach to the extraction of new decision rules for Polycythemia Vera (PV) diagnosis, based on a reduced and optimized set of lab parameters. Ten laboratory and other clinical findings (eight parameters from the Polycythemia Vera Study Group (PVSG) criteria+sex and hematocrit (HCT)) on 431 PV patients from the original PVSG cohort, and records on 91 patients with other myeloproliferative disorders that can be easily misdiagnosed with PV, were included in this study. Significant differences were not found in the correctness of diagnostic classification of patients using either a trained artificial neural network (98.1%) or a support vector machine (95%) versus using PVSG diagnostic criteria, which are considered as a ‘gold-standard’ for the diagnosis of PV. Reducing the original parameters of our dataset to only four parameters: HCT, PLAT, SPLEEN and WBC, we still have obtained good classification results. New rules for improved differential diagnosis of PV are specified based on these four parameters. These rules may be used as a complement to the standard PVSG criteria, particularly in the differential diagnosis between PV and other myeloproliferative syndromes.

On the diagnosis of polycythaemia vera as assessed in the health and medical care in the Västra Götaland region, Sweden.

The aim was to assess how the diagnosis of polycythaemia vera (PV) was established and to study to which extent the classic Polycythemia Vera Study Group (PVSG) criteria and the revised criteria for the diagnosis of PV as proposed by Pearson and Messinezy in 1996 (PM criteria) were fulfilled when the diagnosis of PV was made. A questionnaire was sent to physicians in charge of haematological patients at the departments of medicine in 12 hospitals in the Health and Medical Care in the Västra Götaland Region (VGR), Sweden, with a population of 1.5 million inhabitants; they were asked to provide reports as regards all patients with an unequivocal diagnosis of PV during a 5-year period from January 1994 to December 1998. Full reports were obtained from six hospitals, which serve about 1.1 million inhabitants. The results from a total of 129 PV patients, 62 from two university hospitals (UHs) and 67 from four county hospitals (CHs), were the subject of the present analysis. Results. It was shown that measurement of the red cell mass (RCM) had been carried out in 61 of 62 (98%) patients in UHs compared with 24 of 67 (36%) patients at CHs (P < 0.01). By using ultrasound imaging and/or scintigraphy the spleen size had been determined in 55 of 62 (89%) patients at UHs and in 24 of 67 (36%) patients at CHs (P < 0.01). At the UHs, arterial oxygen saturation had been measured in 32 of 62 (52%) patients; the corresponding figure for the CH patients was 22 of 67 (33%). Plasma or serum erythropoietin (EPO) concentrations had been measured in 44 of 62 (71%) of PV patients at UHs and in 31 of 67 (46%) of patients at CHs; in all these cases the EPO concentrations were subnormal or not measurable. At the UHs only 37% of the PV patients fulfilled the PVSG criteria for the diagnosis of PV whereas the corresponding figure for CHs was 4% (P < 0.01). The adherence to PM criteria was, however, 71% at UHs compared with 16% at CHs (P < 0.01).

Diagnosis of Polycythemia Vera in an Anemic Patient

Criteria proposed by the Polycythemia Vera Study Group (PVSG) as well as several derived algorithms are currently used for the diagnosis of polycythemia vera. Although these guidelines have significantly enhanced diagnostic accuracy, they uniformly consider erythrocytosis as the requisite premise for instigating the subsequent workup. We describe the unusual presentation of a patient with microcytic anemia in whom the diagnosis of polycythemia vera was reached using the PVSG criteria and confirmed by in vitro culture assay of erythroid progenitor cells. This case highlights the usefulness of the PVSG criteria, including the red cell mass determination, for the diagnosis of polycythemia vera even in anemic patients. The roles of spleen red cell pooling and plasma volume expansion as major determinants of this unusual presentation are discussed.

Essential thrombocythemia in young adults: major thrombotic complications and complications during pregnancy--a follow-up study in 68 patients.

Although essential thrombocythemia (ET) is usually primarily considered a disorder of middle age, it has been observed in children and young adults. However, the real risk for thrombosis in these patients has not been clearly established. Prospective analysis of consecutive patients younger than 40 at the time of the diagnosis of ET and followed in our department between 1980 and 1998. Sixty-eight patients (28 males and 40 females, median follow-up 99.14 months) affected by ET diagnosed in agreement with the Polycythemia Vera Study Group criteria. Asymptomatic ET patients were not treated. In contrast, patients with associated atherosclerotic risk factors, microvascular disturbances, or a previous major arterial thrombosis were given acetyl salicylic acid (ASA 100 mg/day). Only patients with major thrombotic complications and a platelet count > 1,000 x 10(9)/L received cytoreductive therapy. (1) to evaluate thrombotic complications in young patients with ET, (2) to relate thrombotic risk to the presence of general atherosclerotic risk factors, and (3) to adopt treatment, and (4) to report the outcome of the pregnancies monitored in our population. Fifteen patients had major thrombosis, 11 of which were the presenting features of ET. No rethrombosis has been observed. Only one patient with thrombotic complications was under efficient treatment. Atherosclerotic risk factors are more common in patients with major arterial thrombosis than in asymptomatic subjects. Thirteen normal babies were delivered out of 16 pregnancies, 6 of the pregnant women were on ASA therapy. Most thrombosis in young ET patients occurred at the time of the diagnosis, and venous thrombotic events represent one-third of total thrombosis. Cardiovascular risk factors seem to be concurrent stimuli for arterial thrombosis in ET. The thrombotic complication rate was 2.6/100 patients/year ASA reduces microvascular disturbances, thrombosis, and rethrombosis and possibly reduces obstetric complications in women with ET.

A Large Proportion of Patients With a Diagnosis of Essential Thrombocythemia Do Not Have a Clonal Disorder and May Be at Lower Risk of Thrombotic Complications

AbstractEssential thrombocythemia (ET) is traditionally considered to be a clonal disorder. No specific karyotypic abnormalities have been described, but the demonstration of clonality using X-chromosome inactivation patterns (XCIPs) has been used to differentiate ET from a non-clonal reactive thrombocytosis. However, these assays may be difficult to interpret, and contradictory results have been reported. We have studied 46 females with a diagnosis of ET according to the Polycythemia Vera Study Group (PVSG) criteria. XCIP results in 23 patients (50%) were uninterpretable due to either constitutive or possible acquired age-related skewing. Monoclonal myelopoiesis could be definitively shown in only 10 patients. Thirteen patients had polyclonal myelopoiesis, and in 8, it was possible to exclude clonal restriction to the megakaryocytic lineage. Furthermore, there was no evidence of clonal progenitors in purified CD34+CD33− and CD34+CD33+ subpopulations from bone marrow of 2 of these 13 patients. There was no difference between patients with monoclonal and polyclonal myelopoiesis with respect to age or platelet count at diagnosis, duration of follow-up, incidence of hepatosplenomegaly, or hemorrhagic complications. However, polyclonal patients were less likely to have experienced thrombotic events (P = .039). These results suggest that ET is a heterogeneous disorder, and the clinical significance of clonality status warrants investigation in a larger study.

Cerebral vascular accidents in young patients with essential thrombocythemia: relation with other known cardiovascular risk factors.

Since the advent of routine automated blood cell counts, an increased platelet count often is detected fortuitously in asymptomatic individuals. In the past, essential thrombocythemia (ET) was thought to be linked to an increase incidence of hemorrhagic complications, whereas thrombosis is now considered more frequently. Actually, the risk of thrombosis cannot be predicted in an asymptomatic patient with essential thrombocythemia. A total of 41 young patients (age range, 18 to 45 years) affected by ET and diagnosed in agreement with the Polycythemia Vera Study Group criteria are reported. Common risk factors, such as hypertension, smoke, obesity, dyslipidemia, and diabetes, have been registered. Particular attention has been given to cerebral vascular accidents (CVA) both of the arterial and venous systems. Platelet number, platelet serotonin content, and platelet aggregation under collagen, adenosine diphosphate (ADP), and adrenalin stimuli were evaluated. Nine out of the 41 patients affected by ET had CVAs, four of which occurred in the venous system. No difference in platelet function tests has been observed between patients with or without CVA. Six out of the 9 patients with ET and CVA had at least one atherosclerotic risk factor: four were heavy smokers, one had hypertension, and one had hypertension and obesity. Cerebral vascular accidents are confirmed to be frequent in patients with essential thrombocythemia, even at a young age. However, the presence of at least one atherosclerotic risk factor associated with increased platelet number seems to favor thrombotic complications. In particular, cigarette smoking seems to be related to arterial CVAs in essential thrombocythemia.

Polycythemia vera treated with pipobroman as single agent: low incidence of secondary leukemia in a cohort of patients observed during 20 years (1971-1991).

The 'gold standard' for the treatment of polycythemia vera (PV) is to date undefined. We performed a retrospective analysis to evaluate the outcome of a cohort of PV patients treated with pipobroman (PB) at a single institution during a period of 20 years (November 1971-October 1991). During this period, a total of 366 adult PV patients were diagnosed according to Polycythemia Vera Study Group (PVSG) criteria. Of these, only 199 (54%) were treated with PB: 92 were males and 107 females, median age was 63.0 years (range 25.2-87.3 years). Major clinical characteristics at onset were as follows: 34 (17%) patients had splenomegaly >3 cm below costal margin, 70 (35%) had platelets >600,000/mm3, 79 (40%) had white blood cells >12,000 mm3; 97 (49%) had hypertension, 83 (42%) had minor neurological symptoms (as vertigo, headache, paresthesias), 33 (17%) had pruritus and 27 (13%) had thrombotic features. All patients received PB at the dosage of 1 mg/kg/day until response was achieved (hematocrit value <50% in males and <45% in females). Thereafter treatment was given according to toxicity and maintenance of response. All patients were phlebotomized before starting treatment (mean number of phlebotomies performed: three, range 2-4) and 47 of them received PB when hematocrit value was already reduced at response levels: therefore, while all patients are evaluable for acute and long-term toxicity, only 152/199 (76.4%) patients are evaluable for response to PB. During a median time of 2 months, all these 152 patients achieved the response; as maintenance, 128/199 (64.3%) patients were managed with PB alone and 71/199 (35.7%) patients received phlebotomies occasionally. Sixty-one out of 199 (30.6%) patients developed disease-related complications (25 neurological symptoms, 21 thrombotic complications, 12 cardiovascular problems, three hepatic failures). Eleven (5.5%) patients developed acute myelogenous leukemia (AML) after a median time of treatment of 89 months (range 33-188 months), 11 (5.5%) patients developed myelofibrosis (median time from treatment 71 months, range 31-182 months) and in six (3%) patients cancer occurred (median time from treatment 85 months, range 13-118 months). The cumulative risk of leukemia in PV was 2% (95% CI: 0-4%) and 6% (95% CI: 1-11%) at 5 and 10 years respectively; the cumulative risk of myelofibrosis was 2% (95% CI: 1-5%) and 9% (95% CI: 3-15%) at 5 and 10 years, respectively. As of May 1996, 33 (16.6%) patients are lost to follow-up, 40 (20.1%) are dead and 126 (63.3%) are alive with a median overall survival of 191 months. In conclusion, this retrospective analysis confirms the efficacy and safety of PB in PV patients and its low leukemogenic role; prospective studies are needed to evaluate the real impact of PB in the treatment of PV.

Two Methods for Intraplatelet Serotonin Evaluation: Their Use in Thrombocytosis

The content of platelet dense bodies is considered to be decreased in thrombocytosis associated myeloproliferative disorders and normal in reactive thrombocytosis. Intraplatelet serotonin i.e., 5-hydroxytryptamine (5HT), content is usually considered a particularly good marker. We report our experience of platelet 5HT levels evaluated by radioimmunoassay (RIA) and fluorimetric assays in patients with high platelet counts due to essential thrombocythemia (48 patients) or reactive thrombocytosis (34 patients). The diagnosis of essential thrombocythemia was made according to Polycythemia Vera Study Group criteria. A significant statistical difference was observed in serotonin platelet content between essential thrombocythemia and secondary thrombocytosis patients both with fluorimetric and RIA assays. On the contrary, no difference was evident between reactive thrombocytosis patients and normal control subjects. However, a significant difference was observed between 5HT in serum and platelet pellets when evaluated by RIA. Statistical analysis with the X2 test showed that the sensitivity of the fluorimetric assay is slightly higher than that of the RIA assay; however, specificity is about the same with the two methods. It is possible that the two assays measure different molecules. At any rate, the fluorimetric assay seems to be better in evaluating the platelet content of 5HT at least in patients with high platelet counts. Key Words: Thrombocytosis—Serotonin.

Inapparent Polycythemia Vera: An Unrecognized Diagnosis

PURPOSE: The Polycythemia Vera Study Group (PVSG) has established useful criteria for the diagnosis of polycythemia vera. In some circumstances, an increase of plasma volume (PV) masks that of red cell mass (RCM), with hemoglobin (Hb) and hematocrit (Ht) remaining normal. This defines the concept of inapparent polycythemia.PATIENTS AND METHODS: One hundred and three patients seen in the hematology unit with the diagnosis of polycythemia vera were studied. There were 55 males and 48 females with a median age of 59 years. Ninety-five patients fulfilled the PVSG criteria. Spontaneous erythroid colonies and low serum erythropoietin level confirmed the diagnosis in the 8 other cases. Patients were classified according to Hb and Ht level.RESULTS: Group A consisted of 85 patients with increased Hb and Ht defined, respectively, by Hb >18 g/dL, Ht >0.52 in males and Hb >16 g/dL, Ht >0.47 in females. Group B included 18 patients (17%) with inapparent polycythemia vera (IPV) defined by a normal Hb and Ht value at diagnosis. In this group, the reasons to perform RCM were as follows: splenomegaly associated with increased platelets and/or leucocytes counts (n = 8), portal vein thrombosis (n = 5), increased platelets or leucocytes counts without splenomegaly (n = 3), and isolated splenomegaly (n = 2). The two groups were balanced in terms of age, sex, leucocyte, serum iron, and platelet level. Hemoglobin and Ht levels were significantly different between the two groups. The difference between the PV was indeed highly significant. The mean PV increase was + 9.5% (nL <+20%) in group A versus + 36.3% in group B (P <0.00005). Red cell mass was not different between the two groups.CONCLUSIONS: Increased Hb or Ht should not constitute the sole criteria for RCM determination. In the context of portal vein thrombosis, isolated hyperleucocytosis, thrombocytosis, or splenomegaly, a RCM should be performed. The frequency of IPV remains to be specified but the diagnosis of polycythemia vera is probably underestimated.

Essential thrombocythemia and pregnancy: a report of six normal pregnancies in five untreated patients.

To report our experience with essential thrombocythemia complicating pregnancy. Over a 5-year period, we studied 21 women of reproductive age affected by essential thrombocythemia. Diagnoses were based on previously published Polycythemia Vera Study Group criteria. Five of our 21 patients became pregnant (total six pregnancies). All pregnancies were carried to term, with uncomplicated deliveries of normally formed infants. No thrombotic or hemorrhagic complications were encountered. Normal pregnancy and delivery is readily possible in patients with essential thrombocythemia.

Deletion of the long arm of chromosome 5 in essential thrombocythemia

A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q−, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q− syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q− was the only clonal abnormality seen at diagnosis.

Spontaneous erythroid colony formation in erythrocytosis.

Erythroid colony formation from the bone marrow and blood of 30 patients with erythrocytosis has been studied. Seventeen patients formed spontaneous erythroid colonies. They included patients with polycythaemia vera (PV) and 4 patients who did not quite fulfil the Polycythemia Vera Study Group criteria for PV, but had suggestive evidence of a myeloproliferative disorder. Thirteen patients did not form spontaneous colonies. They included patients with secondary polycythaemia, patients with normal total red cell volume and patients with absolute pure erythrocytosis of unknown origin. All patients with PV, and none with secondary polycythaemias, had spontaneous erythroid colony formation. Three of 4 untreated and 2 of 9 treated PV patients had increased number of CFU-E colonies in bone marrow. From these results it can be concluded that erythroid progenitor cell culture is a useful differential diagnostic method in erythrocytosis patients who cannot be classified clinically under PV or secondary polycythaemias.