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Giant uterine fibromyoma producing secondary polycythemia.

BACKGROUND: Although the association between large uterine fibromyomas and secondary polycythemia has been described previously, the mechanism has not been elucidated definitively. Investigators have measured erythropoietin levels in fibromyomas to determine whether these tumors are causing the polycythemia by erythropoietin overproduction; however, these studies were performed before the availability of recombinant erythropoietin assays. CASE: A 59-year-old woman presented with a 3-year history of polycythemia. Pelvic examination revealed a large lower abdominal mass. Laboratory evaluation revealed a hemoglobin of 20.8 g/dL, red blood cell mass of 3300 mL, oxygen pressure of 58 mmHg with an oxygen saturation of 89%, and erythropoietin level of 18 mU/mL. Cardiac echocardiogram showed no evidence of shunt. Computed tomography scan of the abdomen showed a large mass arising in the pelvis and compressing both ureters. The patient was treated surgically with a total abdominal hysterectomy. Pathology confirmed a uterine leiomyoma weighing 2320 g. Two months post-surgery, the patient was asymptomatic with a hemoglobin of 13.9 g/dL and erythropoietin level less than 4.0 mU/mL. CONCLUSION: This case provides evidence for three of the postulated mechanisms by which uterine fibromyomas may cause polycythemia. First, the patient was hypoxic, suggesting shunting within the tumor. Second, the leiomyoma was compressing the ureters, so the kidneys may have been inappropriately producing excess erythropoietin. Third, the tumor itself may have been producing the erythropoietin. In any case, the erythropoietin level in this patient was inappropriately high, providing useful evidence that her polycythemia was secondary to her fibromyoma.

Female↗

Two new EPO receptor mutations: truncated EPO receptors are most frequently associated with primary familial and congenital polycythemias.

Primary polycythemias are caused by an acquired or inborn mutation affecting hematopoietic/erythroid progenitors that results in an abnormal response to hematopoietic cytokines. Primary familial and congenital polycythemia (PFCP; also known as familial erythrocytosis) is characterized by elevated red blood cell mass, low serum erythropoietin (EPO) level, normal oxygen affinity of hemoglobin, and typically autosomal dominant inheritance. In this study we screened for mutations in the cytoplasmic domain of the EPO receptor (EPOR; exons 7 and 8 of the EPOR gene) in 27 unrelated subjects with primary or unidentified polycythemia. Two new EPOR mutations were found, which lead to truncation of the EPOR similarly to previously described mutations in PFCP subjects. The first is a 7-bp deletion (del5985-5991) found in a Caucasian family from Ohio. The second mutation (5967insT) was found in a Caucasian family from the Czech Republic. In both cases the EPO dose responses of the erythroid progenitors of the affected subjects were examined to confirm the diagnosis of PFCP. In one of these families, the in vitro behavior of erythroid progenitors in serum-containing cultures without the addition of EPO mimicked the behavior of polycythemia vera progenitors; however, we show that antibodies against either EPO or the EPOR distinguish the in vitro growth abnormality of polycythemia vera erythroid progenitors from that seen in this particular PFCP family. We conclude that PFCP is a disorder that appears to be associated in some families with EPOR mutations. So far, most of the described EPOR mutations (6 out of 8) associated with PFCP result in an absence of the C-terminal negative regulatory domain of the receptor.

Adult↗

Microcytic polycythemia. Frequency of nonthalassemic causes.

A high RBC count combined with a low mean volume generally is attributed to thalassemia minor, either alpha or beta, or to polycythemia vera with iron deficiency. Among 330 patients with a mean corpuscular volume (MCV) less than 70 cumu, 35 had increased RBC counts. Of these, 26 had thalassemia minor and four had polycythemia vera. Five had secondary polycythemia (four from hypoxia, one from hypernephroma) with incidental iron deficiency. In the four of these patients given iron, the RBC count remained above normal and the MCV rose to normal. The RBC size distribution curves reliably distinguished between thalassemia minor and polycythemia with iron deficiency.

Anemia, Hypochromic↗

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.

Adult↗

Relative and absolute polycythemia. How to tell them apart.

Relative and absolute polycythemia can be differentiated by measuring red cell mass and plasma volume. Often no treatment is recommended for patients with relative polycythemia unless directed toward vascular complications; phlebotomy is definitely contraindicated. For patients with polycythemia vera, however, phlebotomy is used routinely to decrease blood viscosity, while myelosuppression is reserved for patients who are not relieved by phlebotomy alone. Secondary polycythemia is controlled by correcting the cause or by circumspect use of phlebotomy if the cause cannot be remedied.

Diagnosis, Differential↗

Endogenous erythroid colony formation by peripheral blood mononuclear cells from patients with myelofibrosis and polycythemia vera.

Peripheral blood mononuclear cells from patients with polycythemia vera or myelofibrosis with myeloid metaplasia were studied for their erythroid colony growth characteristics in plasma clot cultures. In both diseases, erythroid colonies formed early in culture in the absence of added erythropoietin (endogenous colonies). In no instance did early, endogenous colony formation occur with peripheral blood cells from normals or patients with secondary polycythemia. A normal response to erythropoietin was observed with both control and patients' peripheral blood cells. Spleen mononuclear cells obtained from one patient with myelofibrosis also produced endogenous colonies and showed a response to erythropoietin. This study suggests that culture of peripheral blood mononuclear cells might serve as a useful tool in discriminating polycythemia vera from secondary polycythemia.

Cells, Cultured↗

Discrimination of polycythemias and thrombocytoses by novel, simple, accurate clonality assays and comparison with PRV-1 expression and BFU-E response to erythropoietin.

Essential thrombocythemia (ET) and polycythemia vera (PV) are clonal myeloproliferative disorders that are often difficult to distinguish from other causes of elevated blood cell counts. Assays that could reliably detect clonal hematopoiesis would therefore be extremely valuable for diagnosis. We previously reported 3 X-chromosome transcription-based clonality assays (TCAs) involving the G6PD, IDS, and MPP1 genes, which together were informative in about 65% of female subjects. To increase our ability to detect clonality, we developed simple TCA for detecting the transcripts of 2 additional X-chromosome genes: Bruton tyrosine kinase (BTK) and 4-and-a-half LIM domain 1 (FHL1). The combination of TCA established the presence or absence of clonal hematopoiesis in about 90% of female subjects. We show that both genes are subject to X-chromosome inactivation and are polymorphic in all major US ethnic groups. The 5 TCAs were used to examine clonality in 46 female patients along with assays for erythropoietin-independent erythroid colonies (EECs) and granulocyte PRV-1 mRNA levels to discriminate polycythemias and thrombocytoses. Of these, all 19 patients with familial polycythemia or thrombocytosis had polyclonal hematopoiesis, whereas 22 of 26 patients with clinical evidence of myeloproliferative disorder and 1 patient with clinically obscure polycythemia were clonal. Interestingly, interferon alpha therapy in 2 patients with PV was associated with reversion of clonal to polyclonal hematopoiesis. EECs were observed in 14 of 14 patients with PV and 4 of 12 with ET, and increased granulocyte PRV-1 mRNA levels were found in 9 of 13 patients with PV and 2 of 12 with ET. Thus, these novel clonality assays are useful in the diagnosis and follow-up of polycythemic conditions and disorders with increased platelet levels.

Adolescent↗

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.

Aged↗

[New criteria for differential diagnosis of polycythemia vera and erythrocytosis].

"Laborskel-analyzer" (PSL-1) was used to estimate red blood cell volume for the differential diagnosis in 36 polycythemia vera, 20 erythrocytosis patients and 30 normal subjects. Erythrocyte count of polycythemia vera patients (I, IIA and IIB stages) showed a shift to the left (an increase of microcytic fractions), while erythrocyte count++ of 20 erythrocytosis patients (16 of them with a relative erythrocytosis and 4 with an absolute erythrocytosis) were close to erythrocyte count++ of normal subjects. The counting of the percent content of erythrocytic fractions of varying volumes has proved fraction 5 with the erythrocytic volume from 56 microns 3 to 62 microns 3 to have the highest information content. The percent content of this fraction in polycythemia vera fluctuated from 3.9 to 19.5%, and in erythrocytosis it was from 0.9 to 3.0%, that could serve as a criterion for the differential diagnosis of polycythemia vera and erythrocytosis.

Adult↗

Polycythemia vera and idiopathic erythrocytosis: comparison of clinical and laboratory parameters.

OBJECTIVE: To evaluate the various clinical and laboratory parameters of Polycythemia vera and idiopathic erythrocytosis in order to differentiate between two entities at the Aga Khan University Hospital. METHODS: Twenty six patients of polycythemia vera and 34 patients of idiopathic erythrocytosis were analyzed with respect to clinical features and laboratory findings. RESULTS: Patients with idiopathic erythrocytosis were males with a mean age of 41 years and no splenomegaly. Patients with polycythemia were older males and females with splenomegaly, red cell count of mor than 6.5 million/cmm, haematocrit 55%, leucocytosis, thrombocytosis and low erythropoietin level. CONCLUSION: Based on the above-mentioned findings, we suggest that polycythemia vera and idiopathic erythrocytosis are separate entities and the diagnosis of these can be made on the basis of clinical and laboratory parameters.

Adult↗

[Polycythemia vera and 2,3-diphosphoglycerate deficiency. Apropos of 2 cases].

Two cases of mistaken diagnosis of polycythemia vera leading to useless or dangerous treatments exemplify the old saying "primum non nocere". Absolute polycythemia which lacks both the specific characteristics of polycythemia vera and lacks both the specific characteristics of polycythemia vera and any tumoral etiology (particularly renal) but is accompanied with normal arterial oxygen saturation should suggest the possibility of an anomalous hemoglobin with increased affinity for oxygen. Two alternative mechanisms may be present: anomalous hemoglobins due to the substitution of an amino acid or, as in the two reported cases, a deficit in intraerythrocytic 2,3 diphosphoglyceride. In both cases, polycyhthemia is compensative and does not warrant therapy.

2,3-Diphosphoglycerate↗

Red cell mass and plasma volume measurements in polycythemia: evaluation of performance and practical utility.

BACKGROUND: Despite the absence of any systematic evidence for diagnostic utility, red cell mass (RCM) measurement has been endorsed as a major diagnostic criterion for polycythemia vera (PV) based on a set of eligibility criteria for a clinical trial formulated by an International PV Study Group in 1967. METHODS: A retrospective analysis was performed on a consecutive series of 105 patients who underwent blood volume measurements for evaluation of polycythemia. In a previous study, the authors had systematically compared RCM measurement by 51Cr-labeled erythrocytes and 125I-labeled human serum albumin and demonstrated equivalence between the two methods. In the current study, they used the latter method and applied the International Committee for Standardization in Haematology recommendations for result interpretation in order to evaluate test performance and practical utility. RESULTS: RCM exceeded the 98-99% limits of the reference range in 76%, 20%, 22%, and 57% of patients with PV (n = 25), secondary polycythemia (n = 35), spurious or apparent polycythemia (n = 38), and essential thrombocythemia (n = 7), respectively. Decreased plasma volume was rarely seen in any of the disease categories. In all instances of PV, the diagnosis was readily apparent, based on alternative clinical and laboratory tests, and did not require the additional information from blood volume measurement. Furthermore, alternative methods of PV diagnosis, based on disease-specific biological markers as well as bone marrow histology, are now available. CONCLUSIONS: The continued use of RCM and plasma volume measurements for the diagnosis of PV is no longer warranted.

Adult↗

Coronary vasculopathy in polycythemia vera.

Thrombosis is a common complication in polycythemia often causing death. In coronary artery occlusion, thrombosis due to hyperviscosity and thrombocytosis is mostly discussed as the origin of the infarction. We discuss the case of a 30-year-old male patient, with polycythemia, who died of myocardial infarction. On autopsy the vessels showed neither ateriosclerotic changes nor thrombotic occlusions. Instead, a marked intima proliferation was found leading to multiple occlusions whereas media and adventitia were unchanged. This pattern of a coronary vasculopathy has not been described before, and can be interpreted as an alternative mechanism for vascular occlusion in polycythemia. Similar histopathological changes have already been found in skin lesions in erythromelalgia, a common symptom in polycythemia.

Adult↗

Secondary polycythemia as a paraneoplastic syndrome of testicular seminoma.

A 45-year-old man was referred to our hospital because of polycythemia. A physical examination revealed a large tumor in his scrotum enlarged to the size of 13 x 10 cm. A laboratory examination revealed severe erythrocytosis with a red blood cell count of 6,820 x 10(9)/L, a hemoglobin concentration of 21.2 g/dL, and a hematocrit of 59.8%. The total red cell volume was increased. A right radical orchidectomy was done with minimum bleeding, and he was diagnosed as having pure seminoma. After the operation, polycythemia improved spontaneously. Polycythemia is a rare complication of seminoma and only two cases have been reported previously. The precise mechanism of polycythemia in our patient could not be clearly evaluated, but clinical course did indicate a close relationship between two distinct disorders.

Hematologic Tests↗

Pheochromocytoma, polycythemia, and venous thrombosis.

Polycythemia is rarely associated with pheochromocytoma. A patient with a 22-year history of malignant pheochromocytoma is presented in whom major complications developed as a result of long-standing polycythemia, apparently due to secretion of erythropoietin by the tumors. Despite attempts to reduce tumor burden by surgery, chemotherapy, and large doses of I-131-metaiodobenzylguanidine, polycythemia persisted. Extensive venous thrombosis developed requiring hospitalization and anticoagulation. Thus, polycythemia itself may be a cause of major morbidity in patients with pheochromocytoma, and prophylactic measures may be warranted. Review of the 130 patients with benign and malignant pheochromocytoma studied since the introduction of I-131-metaiodobenzylguanidine in 1980 revealed another six patients with hematocrits over 50 but only one had a hematocrit greater than 55 and required regular phlebotomy. In contrast, anemia (hematocrit less than 35) due to variety of causes was present in 18 cases.

Abdominal Neoplasms↗

Secondary polycythemia does not increase the risk of perioperative hemorrhagic or thrombotic complications.

STUDY OBJECTIVE: To determine the effects of secondary polycythemia on perioperative hemorrhagic and thrombotic complications. DESIGN: Retrospective chart review. SETTING: Surgical patients at a university-affiliated Veterans Administration Hospital. PATIENTS: One hundred patients with a diagnosis of chronic obstructive pulmonary disease and a preoperative hemoglobin concentration (Hb) greater than 16 g/dl and 100 age-, sex-, operation-, and ASA physical status-matched control patients without secondary polycythemia having operations during January to June 1988. MEASUREMENTS AND MAIN RESULTS: Anesthetic and perioperative records were retrospectively analyzed for excessive bleeding and transfusion requirements. Charts also were retrospectively analyzed for the presence of hemorrhagic and thrombotic complications for 30 days following surgery. The secondary polycythemic patients were compared with the matched control group and did not have a higher frequency of these complications. Red blood cell transfusion requirements for patients with secondary polycythemia were less than that for the matched controls (p less than 0.005). There was no statistical difference for transfusions of other types of blood products such as platelets and fresh frozen plasma (FFP). CONCLUSION: Secondary polycythemia does not impart any added perioperative risk.

Hemorrhage↗

Idiopathic erythrocytosis and other non-clonal polycythemias.

Idiopathic erythrocytosis (IE) is characterized by an increase of red blood cell mass without an identified cause. Its diagnosis is based on the exclusion of polycythemia vera (PV), secondary acquired polycythemias and various congenital primary and secondary polycythemias. The frequency of IE has been estimated to be 1.1 per 1000 subjects, which is higher than that observed in PV. Heterogeneous mechanisms underlying IE have been suggested, including 'early' PV and unrecognized secondary or congenital polycythemia. However, the transition of a patient initially classified as IE into PV is a rare occurrence, when more sophisticated diagnostic techniques are employed. IE is a stable disease with a low thrombotic risk and a low, if any, tendency to spontaneous progression to acute leukemia or myelofibrosis. Phlebotomy in patients with IE is controversial. Myelosuppressive drugs should be avoided since their use is associated with evolution into acute leukemia in about 10% of patients.

Humans↗

Effects of neonatal polycythemia and hemodilution on capillary perfusion.

The effects of neonatal polycythemia on nutritive capillary perfusion were investigated by a television microscopy technique. The capillary blood flow velocity in skin was measured in 12 neonates with polycythemia before and after treatment with hemodilution, and in 13 healthy control infants. The capillary blood flow velocity in the patients was 0.11 (0.02 to 0.34) mm/sec and in the healthy control infants 0.30 (0.17 to 0.44) mm/sec (p less than 0.01, median and range values). In relation to the absolute hematocrit change after treatment range, -20% to 0%), the capillary blood flow velocity increased nonlinearly (range, +733% to -14%; r = -0.98; p less than 0.001). The postnatal age was found to contribute significantly to the variation in results--the neonates with polycythemia studied during the first day of life had a very slow skin capillary circulation and responded to treatment with a more pronounced increase in capillary blood flow velocity than did the older patients. This in vivo model for capillary perfusion indicates that an insufficient microcirculation may be involved in the pathophysiology responsible for the morbidity associated with neonatal polycythemia.

Age Factors↗