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Excessive polycythemia of high altitude: role of ventilatory drive and lung disease.

Persons residing at high altitude who develop excessive polycythemia are more hypoxemic than normal high-altitude residents. We investigated the causes of hypoxemia in 20 patients with excessive polycythemia residing at an altitude of 3,100 m. Lung disease evidenced by abnormal spirometric features and results of a respiratory questionnaire was present in 10 of 20 patients and resulted in increased alveolar-arterial difference for PO2 [(A-a)PO2]. The excessive hypoxemia in the patients with normal lungs was not due to increased (A-a)PO2. We measured ventilatory responses to hypoxia and to hypercapnia to determine whether blunting of these responses was a cause of this excessive hypoxemia. We found, however, that chemical drives to breathe, although blunted, were the same in patients with polycythemia as in high-altitude control subjects. However, an abnormal breathing pattern was observed; the polycythemic patients had a smaller tidal volume and a greater ratio of dead space to tidal volume than did the normal subjects. In addition, the polycythemic patients had increased minute ventilation on breathing 100 percent O2, whereas the normal subjects did not. Thus, hypoxic depression of ventilation may have been present. Our findings suggested that blunted chemical drives are not causative in this disease, and that some other cause of hypoxemia must be present.

Altitude↗

Polycythemia vera--a case report and discussion on pathogenic mechanisms of increased thrombosis.

Polycythemia vera is a myeloproliferative disorder characterized by increased red cell mass and frequently complicated by venous and arterial thrombosis. The mechanism underlying the increased incidence of thrombotic events remains illusive. Presented in this report are a case of a 77-year-old man diagnosed with polycythemia vera and a review of the current literature on the mechanisms underlying the increased incidence of thrombotic events in polycythemia vera.

Aged↗

Subclavian steal phenomenon associated with stress polycythemia. A case report.

A case of stress polycythemia without symptoms of cerebral ischemia is presented. The patient demonstrated a blood flow reversal through the right vertebral artery that was caused by a complete obstruction of the right subclavian artery at its origin. This obstruction may have been due to thrombosis associated with stress polycythemia. This is a rare example of a case in which thrombotic complications of stress polycythemia occurred in a larger caliber vessel such as the subclavian artery.

Humans↗

Von Hippel-Lindau-dependent polycythemia is endemic on the island of Ischia: identification of a novel cluster.

Chuvash polycythemia (MIM 263400) is an autosomal recessive disorder characterized by a high hemoglobin level, relatively high serum erythropoietin, and early death. It results from a Von Hippel-Lindau (VHL) gene mutation (C598T) that causes increased HIF-1alpha activity and erythrocyte production in the face of normoxia. This polycythemia is endemic in Chuvashia, whereas its worldwide frequency is very low. We investigated the incidence of the Chuvash-type VHL mutation in Campania (South Italy) and identified 14 affected subjects (5 families). Twelve live on the island of Ischia (Bay of Naples). From analysis of the mutated allele, we found that the disease was more frequent on Ischia (0.070) than in Chuvashia (0.057). The haplotype of all patients matched that identified in the Chuvash cluster, thereby supporting the single-founder hypothesis. We also found that nonaffected heterozygotes had increased HIF-1alpha activity, which might confer a biochemical advantage for mutation maintenance. In conclusion, we have identified the first large cluster of Chuvash erythrocytosis outside Chuvashia, which suggests that this familial polycythemia might be endemic in other regions of the world.

Adult↗

Vascular and neoplastic risk in a large cohort of patients with polycythemia vera.

PURPOSE: The clinical course of polycythemia vera is often complicated by thrombosis as well as by the possible transition to myeloid metaplasia with myelofibrosis or acute myeloid leukemia. The aim of this study was to assess the rate of these complications in subjects receiving currently recommended treatments. PATIENTS AND METHODS: Overall, 1,638 patients from 12 countries were enrolled onto a large, prospective multicenter project aimed at describing the clinical history of polycythemia vera for the following outcomes: survival, the cumulative rate of cardiovascular death and thrombosis, the cumulative rate of leukemia, myelodysplasia, and myelofibrosis. The mean duration of the disease at entry and the duration of the follow-up were 4.9 and 2.7 years, respectively. RESULTS: The overall mortality rate of 3.7 deaths per 100 persons per year resulted from a moderate risk of cardiovascular death and a high risk of death from noncardiovascular causes (mainly hematologic transformations). Age older than 65 years and a positive history of thrombosis were the most important predictors of cardiovascular events. Antiplatelet therapy, but not cytoreductive treatment, was significantly associated with a lower risk of cardiovascular events. We found a consistent association between age and risk of leukemia, and between duration of the disease with risk of myelofibrosis. CONCLUSION: The European Collaboration on Low-Dose Aspirin in Polycythemia Vera study documents that large international collaborative studies are feasible in this field, in which few epidemiologic data are available. The persistently high mortality rate from hematologic malignancies characterizes the unmet therapeutic need of polycythemic patients and suggests a priority for future studies in this disease.

Aged↗

Diagnostic impact of bone marrow histopathology in polycythemia vera (PV).

The criteria of the Polycythemia Vera Study Group (PVSG), although acknowledged as the gold standard to establish the diagnosis of polycythemia vera (PV), do not regard bone marrow (BM) histopathology. Arguments include the existence of sufficient objective markers of disease and the lack of independently performed morphological studies or standardized criteria. The aim of this review is to evaluate morphological characteristics of erythrocytosis and to determine whether distinctive patterns of histopathology exist. A review of the pertinent literature and evaluation of 334 patients from our files with a borderline to marked increase in hemoglobin was performed. In extension to former descriptions of BM features by the PVSG, a tri-lineage myeloproliferation (panmyelosis) with a pleomorphous appearance of megakaryopoiesis revealed that, besides increase in size, there was a lack of gross cytological anomalies. Differentiation from secondary polycythemia (SP) was accomplished by regarding these features and the conspicuously expressed stromal changes (plasmacytosis, eosinophils, cell debris and iron deposits). In about 96% of this cohort a clear-cut separation from SP was achieved, even in the initial (latent) stages. When accompanied by an elevated platelet count, these precursor stages may clinically mimick essential thrombocythemia because they are not recognized by the conventional criteria. Advanced stages (spent phases) of PV were consistent with an increased left-shifted granulocytic proliferation, accompanied by reduction of erythroid precursors and progressive myelofibrosis (post-polycythemic myeloid metaplasia). Finally, an increase in dysplastic changes and immaturity signalled a transition into blastic crisis. In conclusion, PV is characterized by a distinctive pattern of histopathology that has been gained in an independent and blind fashion and therefore, dissolves arguments about failing specificity.

Animals↗

An unusual cause of hypercalcemia in polycythemia vera: parathyroid adenoma.

In this paper we describe a patient with polycythemia vera (PV), who presented with hypercalcemia due to a parathyroid adenoma. In November 1999, the patient was admitted to our hospital with meteorism and constipation. Her physical examination revealed plethora and hepatosplenomegaly. Laboratory data revealed hyperparathyroidism in addition to PV: Rbc 8 x 10(6)/mm3, Hct 63.7%, serum calcium 13.4 mg/dl, serum phosphorus 1.2 mg/dl, albumin 4.25 mg/dl, and alkaline phophatase activity 433 U/l. Intact Parathyroid Hormone level (iPTH) was 376 pg/ml (n.v.12-72 pg/ml). Twenty-four hour urinary calcium excretion was higher than normal (900 mg). A parathyroid adenoma was detected with Tc-99m sesta-MIBI scanning under the left lobe of the thyroid gland and an ultrasonographic examination of the neck also supported the diagnosis. The patient was recommended for surgery. The histopathological examination confirmed the diagnosis. Postoperatively, iPTH dropped to 53.4 pg/ml at the 15 th minute and to 33.5 pg/ml at the first hour. The calcium level was 7.5 mg/dl one hour after the operation. Five days later, Hct was 40.8%. This case represents a rare association between PV and primary hyperparathyroidism, and may provide evidence for a causal link between PTH and polycythemia vera in our patient. In conclusion, this case indicates that the differential diagnosis of hypercalcemia and polycythemia vera should also include the possibility of a parathyroid tumor in addition to malignancy.

Adenoma↗

Secondary polycythemia associated with multiple myeloma.

A 58-year-old man with polycythemia of more than 8 years duration developed multiple myeloma. Extensive examination indicated his polycythemia to be of a secondary type, but failed to reveal an underlying disorder. To the best of our knowledge, this is the first reported association of multiple myeloma in a patient with definitely-diagnosed secondary polycythemia.

Humans↗

Spinal cord compression due to extramedullary hematopoiesis associated with polycythemia vera--case report.

A 69-year-old woman with a 14-year history of polycythemia vera suffered progressive paraparesis due to epidural involvement of hematopoietic tissue. Magnetic resonance (MR) imaging demonstrated extensive epidural masses. Decompressive surgery and radiotherapy were performed and she made an almost complete clinical recovery. Serial MR imaging showed no regrowth of the other epidural masses. Extramedullary hematopoiesis occurs in patients with various hematologic disorders involving a chronic increase in the production of red blood cells, and is often associated with thalassemia, but is less common with polycythemia vera. The most frequent sites are the spleen, liver, and kidney. Extramedullary hematopoietic tissue occurring within the spinal canal and causing cord compression is very rare. Total surgical excision is not usually feasible because of the diffuse nature of extramedullary hematopoietic tissue and the possibility of recurrence, but acute neurological deterioration does require emergency surgery. Extramedullary hematopoiesis is radiosensitive and displays a rapid response to low dosages, so radiation therapy is recommended for residual tumors. Considering the possibility of central nervous system extramedullary hematopoiesis in patients with polycythemia vera, an early diagnosis is necessary for a favorable prognosis.

Aged↗

Polycythemia: a review article and case report of erythrocytosis secondary to Wilms' tumor.

We describe a child with Wilms' tumor whose only finding at presentation was polycythemia. A review of the mechanism of erythropoiesis regulation as well as the differential diagnosis, work-up, and management of polycythemia in children is presented. Our report emphasizes the need for a thorough evaluation of children who present with polycythemia.

Child, Preschool↗

Twelve-year remission of polycythemia vera following Hodgkin's disease and chemotherapy.

Polycythemia vera is a condition characterized by the overproduction of red blood cells, and in many cases of leukocytes and platelets as well, in the absence of hypoxia or other known inciting factors. The association of polycythemia vera and acute leukemia is well known, but the author is unaware of prior reports of polycythemia vera and Hodgkin's disease concurrent in the same patient.

Cyclophosphamide↗

Alpha-1-antitrypsin deficiency resulting in a hitherto unseen presentation of hepatocellular carcinoma: polycythemia but with normal alpha fetoprotein.

Polycythemia is a known paraneoplastic manifestation of hepatoma, but only in the presence of alpha-fetopro (AFP). We present a case of polycythemia in the absence of AFP, and suggest concurrent alpha-1-antitrypsin deficiency as the cause for breaking this rule. We also suggest a reason for the apparent constant conjunction between polycythemia and AFP in hepatoma.

Aged↗

Diagnosing polycythemia vera: a paradigm shift.

The primary objective during the evaluation of erythrocytosis is to ascertain the presence or absence of polycythemia vera (PV). Because of prognostic and treatment differences, PV must be distinguished from relative polycythemia and secondary erythrocytosis. This distinction is currently accomplished through the laboratory measurement of red blood cell mass, plasma volume, and arterial oxygen saturation and determination of oxygen pressure at 50% hemoglobin saturation (P50). Furthermore, according to the Polycythemia Vera Study Group guidelines, the demonstration of an increased red blood cell mass is an absolute criterion for the diagnosis of PV. This article discusses the use of the serum erythropoietin level and endogenous erythroid colony assay as a potential alternative in the diagnosis of PV.

Decision Trees↗

Concurrent renal adenocarcinoma and polycythemia in a dog.

Concurrent renal adenocarcinoma and polycythemia were diagnosed in a 19-month-old, female Rhodesian ridgeback. An unusually early presentation for this neoplasm, it is the second reported case of renal adenocarcinoma in a dog less than two years of age. Concurrent renal adenocarcinoma and polycythemia have been reported previously in four older dogs. In the dog of this report, clinical signs included brick-red mucous membranes, lethargy, a periodic systolic heart murmur, and engorged retinal vessels. A large retroperitoneal mass and pulmonary metastatic nodules were present at the time of diagnosis. Red blood cell count, packed cell volume, and hemoglobin concentration were greatly increased (12,940,000 red blood cells/microliter; 73.2%; and 26.6 g/dl, respectively). Histopathological diagnosis was renal adenocarcinoma. Polycythemia was the result of excessive erythropoietin production by the neoplasm.

Animals↗

Hairy cell leukemia variant developing in a background of polycythemia vera.

We report a case of hairy cell leukemia variant developing in a background of polycythemia vera in a 77-year-old man who presented with lymphocytosis and splenomegaly. Classic hairy cell leukemia in a patient with polycythemia vera has been reported previously, but hairy cell leukemia variant arising in a patient with polycythemia vera has never been described to the best of our knowledge. Initial testing of the peripheral blood showed circulating medium to large leukemic cells with large, centrally placed nuclei, each containing a prominent nucleolus, and some cells showed cytoplasmic projections. A bone marrow biopsy had marked myeloid and erythroid hyperplasia and interstitially distributed cells with a fried-egg appearance. We verified a monoclonal B-cell population by flow cytometric analysis, which revealed expression of bright CD11c, CD22, and CD103 expression, and a lack of CD25 expression. The patient received a 5-day course of cladribine and subsequently had a complete remission. Approximately 2 months later, he had a relapse and was treated with pentostatin; however, he had no clinical response and died.

Aged↗

Long-term successful coronary artery angioplasty in polycythemia vera.

In a 65-year-old man with Polycythemia Vera, invalidating angina pectoris was associated with severe narrowing of the right coronary artery. After percutaneous coronary angioplasty (PTCA) the patient became symptom free and remained so for 12 months, while receiving an antiplatelet agent, a calcium antagonist and nitrate. Coronary angiography repeated after a year, because of reappearance of angina, documented good patency of the treated artery and some progression of a narrowing involving another coronary vessel. This is the first reported case of long-term success of PTCA in Polycythemia Vera, a disease exposed to a high risk of thrombosis and, possibly, of restenosis. It is undefined whether medical treatment contributed to the anatomical and clinical results. As far as a single case can say, Polycythemia Vera might not represent a prohibitive background for coronary PTCA.

Aged↗

Hydroxyurea for treatment of polycythemia secondary to right-to-left shunting patent ductus arteriosus in 4 dogs.

Four adult dogs with polycythemia secondary to reversed patent ductus arteriosus (rPDA) were treated with hydroxyurea, a myelosuppressive agent, for 6-22 months. Regardless of initial hematocrit, clinical signs attributed to the presence of polycythemia improved with hydroxyurea treatment. Chronic hydroxyurea therapy (40-50 mg/kg PO q48h) was well tolerated in this group of animals; mild, clinically silent thrombocytopenia and leukopenia were detected in some animals but resolved with decreased dosage or dose frequency. Chronic hydroxyurea therapy may provide an alternative to repeated phlebotomy for therapy of polycythemia secondary to rPDA.

Animals↗

[The feature of T cell clonality with polycythemia vera].

OBJECTIVE: To investigate the expression and clonality of TCR V beta subfamily genes in the T cells in polycythemia vera. METHODS: The 24 genes of the TCR V beta subfamily were amplified with peripheral blood mononuclear cells from 3 cases of polycythemia vera(PV) by RT-PCR, then the PCR products were further analyzed by genescan technique to evaluating the clonality of the detectable TCR V beta T cells. RESULTS: Only 4-14 of the 24 V beta subfamily T cells were found in the 3 PV cases, the commonly expressed V beta subfamily genes were V beta 2, V beta 3, V beta 16, V beta 21 and V beta 23. Two clonal T cells of V beta 3 and V beta 23 were identified in 2 cases. CONCLUSIONS: The skew distribution and clonal expansion of TCR V beta subfamily T cells in patients with polycythemia vera might be a feature of the immune response for malignant cells.

Cloning, Molecular↗