Thrombocytopenic purpura complicating radioactive phosphorus treatment in a patient with polycythemia vera

A patient who had polycythemia vera was given radioactive phosphorus and developed severe thrombocytopenic purpura associated with prominent changes in the appearance of the megakaryocytes.     

Systemic mastocytosis in a patient with polycythemia vera treated with radioactive phosphorus.

Systemic mastocytosis occurred as a fatal event in a patient with long-standing polycythemia vera. The patient had been treated over the course of 21 yr with radioactive phosphorus. Possible relationships between mastocytosis and polycythemia vera, and also between mastocytosis and treatment with ionizing radiation, are discussed. Histopathologic and electron microscopic findings are illustrated. Difficulties in establishing the diagnosis of mast cell disease in this setting are also described.     

How I treat patients with polycythemia vera

The clinical course of polycythemia vera (PV) is marked by a high incidence of thrombotic complications; fibrotic and leukemic disease transformations are additional causes of morbidity and mortality. Major predictors of vascular events are increasing age and previous thrombosis; leukocytosis and high JAK2 V617F allele burden are currently being investigated for additional prognostic value in this regard. Myelosuppressive drugs can reduce the rate of thrombosis, but there is concern that their use raises the risk of transformation into acute leukemia. To tackle this dilemma, a risk-oriented management strategy is recommended. Low-risk patients should be treated with phlebotomy and low-dose aspirin. Cytotoxic therapy is indicated in high-risk patients, and the drug of choice is hydroxyurea because of its efficacy in preventing thrombosis and low leukemogenicity. Interferon-alpha should be reserved for selected categories of patients due to high cost and toxicity. The demonstration of JAK2 V617F mutation in the vast majority of PV patients opens the avenue for the development of promising new molecularly targeted drugs.     

Burst-stimulating activity in sera of patients with polycythemia vera

Summary Sera from patients with polycythemia vera without prior cytostatic therapy stimulate the growth of bursts during in vitro methylcellulose cultures of peripheral mononuclear cells from normal donors. Sera from patients with polycythemia vera in remission after treatment with ³²P or cyclophosphamid, did not significantly stimulate the growth of bursts during incubation with normal peripheral mononuclear cells. The stimulating factor was demonstrable again in patients during relapse.Supported by grants of Landesamt für Forschung NW     

Increased prevalence of polycythemia vera in parents of patients on polycythemia vera study group protocols

An investigation of relatives of 652 patients entered on studies of the Polycythemia Vera Study Group yielded five documented cases of the disease among the parents of patients. When compared with expected values based on the Connecticut Tumor Registry and other population studies a significant increase was found in the lifetime incidence of polycythemia vera in parents of these patients.     

Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera

OBJECTIVE: Circulating polymorphonuclear leukocyte (PMN) activation occurs in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We want to define whether this phenomenon plays a role in the formation of circulating PMN-platelet aggregates in these conditions. METHODS: In 80 patients (46 ET and 34 PV) and 50 control subjects, we conducted a flow cytometric analysis to evaluate the levels of PMN-platelet aggregates (defined as the percentage of CD11b-positive PMN coexpressing a platelet-specific marker, i.e., CD42b or CD62P) and the levels of activated PMN and activated platelets. In addition, the in vitro PMN-platelet aggregate formation in response to N-formyl-methionyl-leucyl-phenylalanine (f-MLP)-induced activation of PMN was studied. RESULTS: Significantly high PMN-platelet aggregates in ET and PV patients were found and were associated with increased PMN surface CD11b and surface platelet CD62P expression. In vitro f-MLP stimulation upregulated PMN-CD11b expression and simultaneously increased CD11b/CD42b and CD11b/CD62P aggregates, without affecting platelet surface antigens. In ET patients receiving aspirin, the increments in f-MLP-induced PMN-CD11b and in PMN-platelet aggregates were significantly lower versus ET subjects not treated with aspirin. CONCLUSION: Our data show that in ET and PV patients PMN activation plays an important role in increasing circulating PMN-platelet aggregates and suggest that aspirin treatment may decrease their formation.     

A prospective comparison between treatment with phlebotomy alone and with interferon-alpha in patients with polycythemia vera

Summary Interferon alpha (-IFN) is increasingly used for the treatment of patients affected by polycythemia vera (PV). As prior studies are difficult to interpret in view of the lack of appropriate controls, we undertook a randomized comparison of lymphoblastoid -IFN ( n–1 IFN) treatment against venesection treatment alone. In a crossover trial, we treated 22 PV patients alternatively for 5 months each with 3 MU/day sc of n–1 IFN and phlebotomy alone. During IFN treatment, red blood cell count and hematocrit level were well controlled in both trial groups, reducing or eliminating the need for phlebotomy in all patients; furthermore, platelet number and white blood cell count declined during -IFN therapy. In addition, the number of symptomatic patients was greatly reduced, and in six patients a reduction in splenic size was observed. Finally, the only patient with chromosomal abnormalities showed a complete cytogenetic conversion after 5 months of -IFN therapy. Thus, for the first time, our results provide the unequivocal demonstration that -IFN is superior to phlebotomy in controlling the pathologic expansion of erythroid elements and all the clinical aspects of this disease.     

Acquired von Willebrand disease in patients with polycythemia rubra vera

Platelet function and factor VIII complex were evaluated in ten patients with polycythemia rubra vera. Seven patients showed abnormal epinephrine-induced aggregation. The intracellular concentrations of adenosine diphosphate (ADP) were below normal, and the ratio of adenosine triphosphate (ATP)/ADP was greater than normal. In four of eight cases, there was a decrease in ristocetin cofactor activity and a reduction in the slowly migrating forms of vWF:Ag on crossed immunoelectrophoresis. Defect of large multimers of vWF:Ag was also observed. The ratio of vWF:Ag to ristocetin cofactor was elevated in these patients. Plasma from the patients had no effect on normal plasma except in one case, in which isolated IgG appeared to cause inactivation of ristocetin cofactor. Treatment with 1-deamino-8-arginine vasopressin caused correction of the vWF abnormalities with rapid return of ristocetin cofactor to baseline in some patients. The present study shows that the alterations of multimeric structure of vWF occur in more than 50% of patients with polycythemia rubra vera and are in some part due to the inhibitor specific for vWF.     

Treatment outcome in a cohort of young patients with polycythemia vera

The treatment of polycythemia vera in young adults is challenging, requiring one to run a balance between the increased risk of vascular complications, if left untreated, versus the potential of promoting secondary leukemia/myelodysplasia or cancer, if actively managed with chemotherapy. We report the results of a 20-year retrospective analysis in a cohort of 30 young adults with PV (median age 37 years, range 19–45) treated exclusively with phlebotomy, aspirin and hydroxyurea only in case of vascular complications occurring in the presence of thrombocytosis (platelet count > 600 × 10⁹/L). With this approach, vascular complications were no higher than in other published series, and secondary leukemia/myelodisplasia or cancer was not observed during a follow-up of 14 years.