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The clinical significance of measurement of platelet volume in disease
Suppl . VI,
1986
THROMBOSIS RESEARCH
125
247
EVALUATION OF HUMAN THROMBOPOIESIS BY EXAMINATION OF MARROW MEGAKARYOCYTES. R.F.Levine and P.Shoff, VA Med Center and George Washington University, Washington, D.C. Animal experiments have,shown distinct megakaryocyte (mega) responses to induced thrombocytopenia or thrombocytosis, thought to be mediated by increased or decreased thrombopoietin (tpo), respectively. To see if similar changes occur in human diseases affecting platelet production, we have begun to measure the sizes, DNA levels (ploidy), and maturation stages of Feulgen-stained megas on routine marrow aspirates (N=lOO-300 megas/patient). In adults with ITP the values of these three mega parameters were no different from normal, while in childhood ITP the mega volumes were 4X normal, the median ploidy was two doublings higher, and the median maturity level was shifted rightward. A similar pattern of t'stimulatedt' megas was found in patients with secondary thrombocytosis. In contrast, mega characteristics were all t'suppressedll in CML. Three related children with congenital thrombocytopenia had marked decreases in ploidy and size, interpreted as a developmental block but also consistent with lack of tpo effect. Thus, in different human diseases these three parameters are affected, in parallel, as in the animal models. As mega size is dependent on the ploidy level and maturational state, size may be a clinically useful, simple criterion by which to judge whether megas are stimulated or suppressed. 248
THE CLINICALSIGNIFICANCE OF MEASUREMENT OF PLATELETVOLUMEIN DISEASE. Department of Laboratory Medicine,Universityof Laurence Corash, California
School
of Medicine,
San Francisco
CA 94143 USA.
Measurement of platelet volume(PV) is readily available on current A number of studies over the past two automated laboratory instrumentation. decades have utilized measurement of PV to diagnose platelet and megakaryomajor controversy continues over cyte disorders. Inspite of these efforts, choice of volume paramemultiple aspects of PV: choice of anticoagulant, and the significance of abnormal PV. To date no measurement method, ter, studies have directly examined the sensitivity, specificity, or predictive Mean platelet commonly performed laboratory test. value of this volume(MPV) appears to be inversely correlated with the platelet level durAlteration in the platelet level may be associing normal hematopoiesis. ated with a change in PV which is indicative of a specific pathophysiologic the diagnostic specificity of the PV measurement is process ; however, The weight of current evidence supports the conindeterminant at present. cept that PV is largely determined by events during thrombopoiesis, although minor changes in PV may occur with in vivo aging. Whether alteration in PV precedes or follows changes in megakaryocyte ploidy(MP) remains unclear.Preliminary studies from this laboratory demonstrate that changes in PV and HP are dissociated in responseto experimentalacute thrombocytoin PV and megakaryocytopen ia. Further careful assessment of alterations poiesis will be required to firmly establish the value of PV measurement to diagnose platelet disorders.
1986
THROMBOSIS RESEARCH
125
247
EVALUATION OF HUMAN THROMBOPOIESIS BY EXAMINATION OF MARROW MEGAKARYOCYTES. R.F.Levine and P.Shoff, VA Med Center and George Washington University, Washington, D.C. Animal experiments have,shown distinct megakaryocyte (mega) responses to induced thrombocytopenia or thrombocytosis, thought to be mediated by increased or decreased thrombopoietin (tpo), respectively. To see if similar changes occur in human diseases affecting platelet production, we have begun to measure the sizes, DNA levels (ploidy), and maturation stages of Feulgen-stained megas on routine marrow aspirates (N=lOO-300 megas/patient). In adults with ITP the values of these three mega parameters were no different from normal, while in childhood ITP the mega volumes were 4X normal, the median ploidy was two doublings higher, and the median maturity level was shifted rightward. A similar pattern of t'stimulatedt' megas was found in patients with secondary thrombocytosis. In contrast, mega characteristics were all t'suppressedll in CML. Three related children with congenital thrombocytopenia had marked decreases in ploidy and size, interpreted as a developmental block but also consistent with lack of tpo effect. Thus, in different human diseases these three parameters are affected, in parallel, as in the animal models. As mega size is dependent on the ploidy level and maturational state, size may be a clinically useful, simple criterion by which to judge whether megas are stimulated or suppressed. 248
THE CLINICALSIGNIFICANCE OF MEASUREMENT OF PLATELETVOLUMEIN DISEASE. Department of Laboratory Medicine,Universityof Laurence Corash, California
School
of Medicine,
San Francisco
CA 94143 USA.
Measurement of platelet volume(PV) is readily available on current A number of studies over the past two automated laboratory instrumentation. decades have utilized measurement of PV to diagnose platelet and megakaryomajor controversy continues over cyte disorders. Inspite of these efforts, choice of volume paramemultiple aspects of PV: choice of anticoagulant, and the significance of abnormal PV. To date no measurement method, ter, studies have directly examined the sensitivity, specificity, or predictive Mean platelet commonly performed laboratory test. value of this volume(MPV) appears to be inversely correlated with the platelet level durAlteration in the platelet level may be associing normal hematopoiesis. ated with a change in PV which is indicative of a specific pathophysiologic the diagnostic specificity of the PV measurement is process ; however, The weight of current evidence supports the conindeterminant at present. cept that PV is largely determined by events during thrombopoiesis, although minor changes in PV may occur with in vivo aging. Whether alteration in PV precedes or follows changes in megakaryocyte ploidy(MP) remains unclear.Preliminary studies from this laboratory demonstrate that changes in PV and HP are dissociated in responseto experimentalacute thrombocytoin PV and megakaryocytopen ia. Further careful assessment of alterations poiesis will be required to firmly establish the value of PV measurement to diagnose platelet disorders.