Leucocytosis, thrombocytosis, and plasma osmolality during rest and exercise: an hypothesis.

The mechanism for inducing leucocytosis (increase in white blood cells) and thrombocytosis (increase in platelets) during exercise is unclear. Because plasma osmolality (Osm) may influence T-cell proliferation, Osm and the number of leucocytes (WBC) and platelets in blood were measured periodically during a 90 min rest period, and were compared with those during upright sitting ergometer exercise in six untrained, healthy men who cycled for 70 min at 71% of their maximal oxygen uptake (VO2max). There were 6 experiments in which the subjects drank different fluid formulations (10 ml x kg(-1) of various ionic and osmotic concentrations intermittently during 60 min of the rest period and during the exercise period. Osmolality, and WBC and platelet counts increased significantly (p < 0.05) within the first 10 min of exercise, but the additional 60 min of exercise did not significantly change the leucocytosis or thrombocytosis. There were low but significant correlations between individual values of total WBC and total Osm during exercise (r0.001(2),284 = 0.39) and during rest plus exercise (r0.001(2),499 = 0.43). With combined data from the six experiments, mean Osm correlated highly and significantly with both mean WBC (r0.001(2),6 = 0.95, p < 0.001) and mean platelets (r0.001(2),6 = 0.94, p < 0.01) during the exercise phase. These data indicate that increases in leucocytes, thrombocytes, and osmolality occur primarily within the first 10 min of high-intensity exercise, but neither hypovolemia nor hyperthermia during exercise contributed to the leucocytosis, thrombocytosis, or hyperosmolality. The high correlations between plasma Osm and WBC or platelet counts suggest changes in osmolality may contribute to the mechanism of leucocytosis and thrombocytosis induced by exercise.

Increased thromboxane biosynthesis in essential thrombocythemia.

In order to investigate the in vivo thromboxane (TX) biosynthesis in essential thrombocythemia (ET), we measured the urinary excretion of the major enzymatic metabolites of TXB2, 11-dehydro-TXB2 and 2,3-dinor-TXB2 in 40 ET patients as well as in 26 gender- and age-matched controls. Urinary 11-dehydro-TXB2 was significantly higher (p < 0.001) in thrombocythemic patients (4,063 +/- 3,408 pg/mg creatinine; mean +/- SD) than in controls (504 +/- 267 pg/mg creatinine), with 34 patients (85%) having 11-dehydro-TXB2 > 2 SD above the control mean. Patients with platelet number < 1,000 x 10 (9)/1 (n = 25) had significantly higher (p < 0.05) 11-dehydro-TXB2 excretion than patients with higher platelet count (4,765 +/- 3,870 pg/mg creatinine, n = 25, versus 2,279 +/- 1,874 pg/mg creatinine, n = 15). Average excretion values of patients aging > 55 was significantly higher than in the younger group (4,784 +/- 3,948 pg/mg creatinine, n = 24, versus 2,405 +/- 1,885 pg/mg creatinine, n = 16, p < 0.05). Low-dose aspirin (50 mg/d for 7 days) largely suppressed 11-dehydro-TXB2 excretion in 7 thrombocythemic patients, thus suggesting that platelets were the main source of enhanced TXA2 biosynthesis. The platelet count-corrected 11-dehydro-TXB2 excretion was positively correlated with age (r = 0.325, n = 40, p < 0.05) and inversely correlated with platelet count (r = -0.381, n = 40, p < 0.05). In addition 11 out of 13 (85%) patients having increased count-corrected 11-dehydro-TXB2 excretion, belonged to the subgroup with age > 55 and platelet count < 1,000 x 10(9)/1. We conclude that in essential thrombocythemia: 1) enhanced 11-dehydro-TXB2 excretion largely reflects platelet activation in vivo; 2) age as well as platelet count appear to influence the determinants of platelet activation in this setting, and can help in assessing the thrombotic risk and therapeutic strategy in individual patients.

Platelet factor-4 excretion in myeloproliferative disease: implications for the aetiology of myelofibrosis.

Experimental evidence suggests that the fibroblastic proliferation often associated with the myeloproliferative disorders is not part of the neoplastic process, but is secondary to an unknown stimulus. This stimulus may be a factor derived from platelets which promotes the proliferation of fibroblasts in vitro (PDGF). Platelet-derived growth factor is localized to platelet alpha-granules together with PF4 and beta-TG. As an indicator of alpha-granule release, we have measured PF4 levels in plasma, platelets and urine in 46 normal subjects and 49 patients with myeloproliferative disorders, secondary thrombocytosis and miscellaneous malignancies. All 11 patients with elevated urinary PF4 excretion exhibited myelofibrosis, whereas 11 of 22 patients with documented myelofibrosis had urinary PF4 excretion in the normal range. No correlation was seen between marrow fibrosis and plasma levels or the platelet content of PF4. The data are consistent with the possibility that release of mitogen(s) from platelet or megakaryocyte alpha-granules in some patients with myeloproliferative disorders is pathogenetically related to the development of marrow fibrosis.