H Fujita, S Kurosawa, S Nishimura, J Tomiyama, T Hamaki, A Ohwada
erythrocytosis, iron deficiency, jak2 v167f mutation, phlebotomy, polycythemia vera
H Fujita, S Kurosawa, S Nishimura, J Tomiyama, T Hamaki, A Ohwada. Significance Of Microcytosis In The Clinical Course Of Erythrocytosis. The Internet Journal of Geriatrics and Gerontology. 2009 Volume 6 Number 1.
Aim: Polycythemia vera (PV) usually occurs in people aged 60–79 years. It is difficult to diagnose PV among patients with erythrocyosis, because the test of
Polycythemia vera (PV) occurs in all age groups, although the incidence increases with age. Berlin NI reported the median age at diagnosis to be 60 years1), while Anía B et al found that the highest incidence was in people aged 70–79 years2).
Phlebotomy is used as an initial treatment for PV9). This procedure was performed for unclassified polycythemia before the development of tests for the
Methods and Subjects
Tokyo Metropolitan Bokutoh Hospital is a 729-bed acute-care hospital located in eastern Tokyo. We retrospectively reviewed the medical data of 19 patients with erythrocytosis (Hb: males, >18.5 g/dL; females, >16.5 g/dL) collected between August 2005 and December 2009. The patients were divided into 2 groups according to the presence or absence of the
The patients' charts were reviewed for age, gender, gastrointestinal bleeding events, laboratory test results (i.e., hematology, serum ferritin level, and the
We compared differences between groups using Wilcoxon analysis. The data represent the mean ± standard error (SE). The transient incidence of microcytosis in the clinical course between the groups was determined by Chi squared analysis (log rank). All statistical tests were conducted using JMP version 8.0 (SAS Institute, Inc., Cary, NC, USA). The level of statistical significance was set at
Clinical features of PV or
Among the 19 patients with erythrocytosis, 10 were positive for the
In the laboratory tests performed at initial presentation, the leukocyte, erythrocyte, and platelet counts were significantly higher in the PV than in the
Clinical course of microcytosis in PV and
Among the 19 patients with erythrocytosis, only 2 with PV (2/10, 20%) exhibited microcytosis at the initial presentation, whereas none among the mutation-negative erythrocytosis did (0/9, 0%). Moreover, MCV was significantly lower in the PV than in the mutation-negative erythrocytosis (Table 1). The level of serum ferritin at the initial presentation was significantly lower in the
Within the 2 year period, 8 patients with normocytic PV at the initial presentation exhibited transient microcytosis (8/8; 100%) throughout the initial presentation to days ~23–492 (Figure 1); However, only 1 mutation-negative patient exhibited this (1/9, 11%) at day 265.
Regarding the hematology of the microcytosis patients, erythrocyte count, hemoglobin concentration, and hematocrit (RBC: 6780 ± 190 × 109/L, Hb: 16.7 ± 0.6 g/dL, Hct: 52 ± 2%) were significantly lower than those measured at the initial presentation. However, the leukocyte (13.2 ± 0.2 × 109/L) and platelet (500 ± 100 × 109/L) counts were not significantly different from those at the initial presentation. Serum ferritin levels significantly decreased in the 8 patients with microcytosis (17.0 ± 2.9 g/L).
Phlebotomies were similarly required in both the PV (10/10, 7 ± 2 times) and mutation-negative erythrocytosis (9/9, 6 ± 2 times) during the 2-year period.
Hydroxycarbamide administration was required by 5 out of the 10 patients with PV (50%). After hydroxycarbamide therapy, 4 of 5 patients (80%) exhibited normocytosis ranging from days 73–221. Serum ferritin levels increased in the 5 patients with normocytosis (50.0 ± 8.7 g/L). Two of the four patients who exhibited normocytosis again exhibited microcytosis at the initial presentation. Six of 10 patients with PV still had microcytosis during the 2-year period. On other hand, 1 out of the 9 patients with
Microcytosis among the patients with erythrocytosis at the initial presentation was not associated with the presence of the
Two patients with polycythemia vera (2/10, 20%) exhibited microcytosis upon initial presentation. Eight patients with normocytic polycythemia vera upon initial presentation exhibited temporal microcytosis (8/8; 100%) throughout the initial presentation to days ~23–492. On other hand, 1 of 9 patients with
Clinical features of PV
Among the patients of the PV group that exhibited microcytic characteristics (2 and 8 cases during the initial presentation and clinical course respectively), red blood cell, leukocyte, and platelet counts were greater in comparison with those in the
Significance of microcytosis in PV
Several studies show that iron deficiency accompanies PV and secondary polycythemia8, 17). Rector et al. report that after 15 years, venesection caused iron deficiency in 6 patients with PV10). There are also reports on an increase in serum-soluble transferrin receptors, which are markers of iron deficiency17) after autologous blood donation, blood donation by healthy volunteers, and phlebotomy18, 19). Flesland et al. report that the number of soluble transferrin receptors increases with the number of blood donations in frequent blood donors18). We subsequently speculate that bloodletting contributed to part of the iron deficiency observed in our study. However, phlebotomies were similarly required in both PV and mutation-negative erythrocytosis groups during the 2-year period. Therefore, this suggests that the main cause of microcytosis in PV in our study is not iron deficiency due to phlebotomy. On the other hand, hydroxycarbamide therapy changed the hematological data of the PV patients, including MCV. Therefore, we speculate that if there are no events of gastrointestinal bleeding, microcytosis in PV may be a result of iron deficiency and excessive erythropoiesis due to the
A case report suggests that microcytic polycythemia is a combination of PV and thalassemia minor18). Two patients with PV with microcytosis at the initial presentation became normocytic after hydroxycarbamide therapy; the other 8 patients who were originally normocytic became microcytic during the clinical course. Therefore, this suggests that there is no possibility of thalassemia in our study.
Microcytosis is not a characteristic of
The test for the
In order to definitively diagnose this blood disorder by using low MCV, general physicians should refer patients to hematologists in specialized hospitals where the test for the
Microcytosis in the clinical course of PV may be a result of iron deficiency and excessive erythropoiesis due to the