Megakaryocytes and Megakaryocyte Progenitors in Human Cord Blood

Olson, Thomas A.; Levine, Rachmiel; Mazur, Eric Michael; Wright, Daniel G.; Salvado, August J.

doi:10.1097/00043426-199208000-00011

Cited by 54 publications

(25 citation statements)

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“…Our finding of a low megakaryocyte size in neonates, compared to adults, is consistent with a large body of literature documenting the smaller size and ploidy of fetal (9,10,21) and cord blood-derived megakaryocytes (11,12). However, this is the first study to directly and objectively measure megakaryocytes in the bone marrow of living neonates.…”

Section: Discussionsupporting

confidence: 91%

Megakaryocyte Size and Concentration in the Bone Marrow of Thrombocytopenic and Nonthrombocytopenic Neonates

et al. 2007

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Thrombocytopenia is frequent among sick neonates, but little is known about its underlying mechanisms. It is known, however, that neonatal megakaryocytes are smaller and of lower ploidy than their adult counterparts and that smaller megakaryocytes produce fewer platelets than larger, more polyploid, megakaryocytes. We hypothesized that neonatal megakaryocytes would not increase their size in response to thrombocytopenia, thus limiting the ability of neonates to mount a response. To test this, we obtained marrow specimens from thrombocytopenic and nonthrombocytopenic neonates and adults. Megakaryocytes were immunohistochemically stained, quantified using an eyepiece reticle, and measured using an image analysis system with incorporated electronic micrometer. We found that, after adjusting for differences in cellularity, neonates and adults had similar megakaryocyte concentrations. When samples from the same sources were compared (tibial clot and vertebral body sections in neonates, iliac crest biopsies in adults), there were also no differences in megakaryocyte concentration between thrombocytopenic and nonthrombocytopenic subjects. The megakaryocyte diameter, however, was greater in adults than in neonates (19.4 Ϯ 3.0 versus 15.3 Ϯ 1.7 m, p Ͻ 0.0001). Thrombocytopenic adults also had a higher proportion of large megakaryocytes than nonthrombocytopenic adults (p Ͻ 0.001). This was not observed among thrombocytopenic neonates, suggesting a developmental limitation in their ability to increase megakaryocyte size. T hrombocytopenia is a common problem among sick neonates, affecting 20% to 35% of neonates admitted to neonatal intensive care units (NICUs) (1,2). In approximately 50% of cases, the thrombocytopenia is thought to be secondary to increased platelet consumption, mainly associated with sepsis, necrotizing enterocolitis (NEC), or alloantibodies. In the remainder of cases, the mechanism underlying the thrombocytopenia is frequently unclear, although a mounting body of evidence suggests that decreased platelet production causes or complicates many such cases (3-5).In adults with thrombocytopenia due to increased platelet consumption, the marrow attempts to compensate by increasing megakaryocyte number, size, and ploidy (6 -8). It is unknown whether thrombocytopenic neonates can compensate in a similar manner, particularly since megakaryocytes from normal fetuses and neonates are smaller and of lower ploidy than megakaryocytes from adults (9 -12). Indeed, the number and size of megakaryocytes in thrombocytopenic neonates have never been systematically evaluated, and it is not known whether neonates are capable of increasing their megakaryocyte size and number in response to platelet consumption.This study was designed to answer this question by quantifying the megakaryocyte number and size in bone marrow samples from thrombocytopenic and nonthrombocytopenic neonates. Because small megakaryocytes with low DNA content cannot be reliably differentiated from other cell types using hematoxylin and eosin-st...

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Section: Discussionsupporting

confidence: 91%

Megakaryocyte Size and Concentration in the Bone Marrow of Thrombocytopenic and Nonthrombocytopenic Neonates

et al. 2007

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“…Megakaryocytes cultured from cord blood have one tenth the c-Mpl compared with adult receptors . However, cord blood contains increased numbers of megakaryocytes and their progenitors (Olson et al, 1992). The number and af®nity of c-Mpl on neonatal platelets are unknown, in contrast to adult platelets (Broudy et al, 1997;Kuwaki et al, 1998).…”

Section: Figmentioning

confidence: 99%

Age‐related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels

et al. 1999

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Summary. We studied thrombopoietin (TPO, Mpl ligand) values using a sensitive ELISA in 254 serum samples obtained from disease-free children and adult volunteers. TPO was detected in all samples, and its values ranged widely from 0´25 to 9´18 fmol/ml. When analysed by dividing the subjects into 11 age groups, the mean TPO levels from birth to 1 month of age were increased (3´73±5´92 fmol/ml). The highest values were found 2 d after birth; TPO levels then gradually decreased to adult levels (0´83 fmol/ml). The relationship between TPO values and platelet counts was not signi®cant in all subjects (r 0´27) or in children alone (r 0´12). In children > 1 month of age a 95% reference interval for serum TPO values was determined from 0´58 to 3´27 fmol/ml. A signi®cant correlation was found between TPO values in serum and plasma; serum TPO values À0´257 4´039´plasma TPO values (r 0´951, P < 0´001, n 22). This study is the ®rst to report agedependent changes in blood TPO levels throughout child development. Serum TPO values were signi®cantly high up to 1 month of age and were correlated with plasma TPO levels.Keywords: thrombopoietin, children, cord blood, serum, plasma.Thrombopoietin (TPO, c-Mpl-ligand) is a glycoprotein that primarily regulates megakaryocyte development and platelet production (Kaushansky, 1998). The binding to c-Mpl on megakaryocytes/platelets regulates the blood levels of TPO (Kuter & Rosenberg, 1995), and the synthesis of TPO mRNA is constitutive in the liver and kidney (Kaushansky, 1998). Elevation of endogenous TPO values has been observed in disorders with reduced platelet/megakaryocyte mass, including aplastic anaemia (Emmons et al, 1996;Kojima et al, 1997;Marsh et al, 1996) and chemotherapy-induced thrombocytopenia (Chang et al, 1996;Meng et al, 1996;Nichol et al, 1995). Increased TPO levels precede thrombocytosis in an in¯ammatory disorder, Kawasaki disease (Ishiguro et al, 1998), and are caused by decreased expression of c-Mpl in essential thrombocythaemia (Horikawa et al, 1997) and idiopathic myelo®brosis (Moliterno et al, 1998).These effects of TPO in thrombopoiesis are similar to the key roles played by erythropoietin in erythropoiesis and by granulocyte colony-stimulating factor (G-CSF) in granulopoiesis (Kaushansky, 1998). In contrast to extensive studies on endogenous levels of erythropoietin and G-CSF (Ishiguro et al, 1996;Krafte-Jacobs et al, 1995;Ruth et al, 1990), the changes in blood TPO levels throughout child development remain unknown. The absence of age-adjusted reference values in children has hindered the interpretation of TPO values in sick children. To expand therapeutic trials from adults (Kaushansky, 1998) to children, basic data on TPO in disease-free populations are necessary. The recent development of a highly-sensitive ELISA has enabled detection of blood TPO in healthy individuals (Tahara et al, 1996;Tamura et al, 1998). We measured blood TPO levels from birth through adulthood. Our results revealed that changes in serum TPO values are age-dependent and are correlate...

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“…Megakaryocytes are present in near normal amounts in fetal bone marrow in the last months ofpregnancy [90], though in mid-pregnancy they have been noted to be somewhat smaller (14-15 p diameter) than in the adult (18-21 p diameter) [91]. In the newborn, also, venous cord blood contains MKs which are significantly smaller than MKs of adults [92], though this could be due to stripping of cytoplasm during passage of blood through the placenta (see below). The newborn platelet count is about the same as in adult man; and fetal platelets appear normal on electron micoscopy [93].…”

Section: Objections To the Megakaryocyte/platelet Clump Hypothesismentioning

confidence: 99%

The aetiology of clubbing and hypertrophic osteoarthropathy

Dickinson

1993

Eur J Clin Investigation

133

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Abstract. The evidence is reviewed for the hypothesis that clubbing and hypertrophic osteoarthropathy are due to the peripheral impaction of megakaryocytes and platelet clumps in the fingers and toes, to which this particulate matter has passed in an axial stream. The normal pulmonary vascular bed retains these large particles, which fragment before entering the systemic circulation. A right-to-left shunt allows them to bypass the pulmonary vascular bed. A preliminary histological report of platelet clumps seen at necropsy in nail bed capillaries of clubbed fingers supports the hypothesis. Platelets contain and release platelet-derived growth factor, whose known effects could explain all the pathological changes in clubbing. In addition to explaining why clubbing should occur in cyanotic congenital heart disease, clubbing in sub-acute bacterial endocarditis and distal to infected arterial grafts and aneurysms can be understood in terms of platelet clumps breaking off valves or arterial walls, and passing distally. Clubbing in liver disease is associated with multiple small pulmonary arteriovenous anastomoses which allow large particles through. Hypertrophic osteoarthropathy probably shares the same mechanism, and is mainly attributable to PDGF release; but there may also be altered platelet function and an additional growth factor derived from the lungs.

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Megakaryocytes and Megakaryocyte Progenitors in Human Cord Blood

Cited by 54 publications

References 0 publications

Megakaryocyte Size and Concentration in the Bone Marrow of Thrombocytopenic and Nonthrombocytopenic Neonates

Megakaryocyte Size and Concentration in the Bone Marrow of Thrombocytopenic and Nonthrombocytopenic Neonates

Age‐related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels

The aetiology of clubbing and hypertrophic osteoarthropathy

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