Platelet heterogeneity.
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Blood Platelets↗
Biomedical subjects
E A Trowbridge
Publications and source records attributed to E A Trowbridge.
The biological significance of platelet volume: its relationship to bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration.
Bleeding time, platelet thromboxane B2 production and megakaryocyte nuclear DNA concentration were measured in rabbits recovering from thrombocytopenia caused by a single injection of anti-platelet serum. Similar measurements were made on rabbits in a steady state of normal platelet production. The effects of a sustained state of thrombocytopenia on megakaryocyte DNA concentration were investigated by repeated daily injections of anti-platelet serum. It is shown that bleeding time depends on both platelet count and mean platelet volume. Furthermore changes in mean platelet volume appear to play a more important role in haemostasis than changes in platelet count. The mean megakaryocyte nuclear DNA concentration is significantly increased after 24 hours of thrombocytopenia and continues to increase as thrombocytopenia is sustained. Thromboxane B2 production/unit volume of platelet is increased in platelets produced after 24 hours of thrombocytopenia compared with platelets produced in normal steady state function. As a consequence platelets produced in response to thrombocytopenia not only have a larger mean platelet volume but are also more reactive. Mean platelet volume, as well as platelet count, should be considered as an index of haemostasis and its dysfunction, thrombosis.
Animals↗
Platelet production: a computer based biological interpretation.
The platelet volume distribution was measured in rat and rabbit in normal steady state platelet production. The animals were then sacrificed and the planimetric megakaryocyte and nuclear areas in each animal were measured using histological techniques. These areas were used to obtain an estimate of the megakaryocyte, megakaryocyte cytoplasm and nuclear volume distributions. The production, by physical fragmentation, of the platelet population from the measured megakaryocyte cytoplasm volume distribution was simulated on a computer. The platelet volume distribution predicted by physical fragmentation was then compared with the measured circulating platelet volume distribution from each animal. The physical fragmentation theory gave an accurate quantitative prediction of the observed platelet volume distribution over the whole volume range. Furthermore fragmentation theory predicted the mean platelet volume, the mode, the maximum frequency of the platelet volume distribution and the range of this distribution. Autopsy studies of megakaryocytes volume distributions in healthy man were fragmented to obtain predicted normal platelet volume distributions from the computer simulation. These distributions were compared with measured circulating platelet volume distributions from apparently healthy men who had a similar mean platelet volume. The platelet volume distribution predicted by physical fragmentation was again in quantitative agreement with the measured distribution over the whole volume range. This study provides further evidence that platelet production from megakaryocyte cytoplasm is by physical fragmentation. Furthermore the computer simulation suggests that the mode of production has a specific form. It also explains why different mammals have different mean platelet volumes.
Animals↗
The megakaryocyte in thrombocytopenia: a microscopic study which supports the theory that platelets are produced in the pulmonary circulation.
Thrombocytopenia can increase platelet production and thereby facilitate investigations into the mechanism. Megakaryocytes in the bone marrow, lung, spleen and liver have been studied by light and transmission electron microscopy after 6 days of experimentally induced thrombocytopenia in the rabbit. The findings support the theory that platelets are produced in the pulmonary circulation by the physical fragmentation of megakaryocyte cytoplasm.
Animals↗
Abnormal intrapulmonary platelet production: a possible cause of vascular and lung disease.
It is postulated that platelets are not produced by megakaryocyte budding within the bone marrow but by physical fragmentation in the pulmonary circulation. Alterations in the nature of the production site (the pulmonary vessels and their concomitant biochemical environment) or changes in the antecedent megakaryocyte cytoplasmic volumes with a concomitant alteration in protein structure can produce platelets with a mean volume larger than normal. If such platelets are more reactive then they may be involved in atherogenesis and arterial thrombosis. Furthermore several pulmonary pathological states may arise from dysfunction during pulmonary platelet production.
Blood Platelets↗
A biological approach to the platelet survival curve with criticism of previous interpretations.
The biological mechanisms of platelet destruction must be correctly identified before platelet survival curves can be interpreted. This report develops a theory of platelet destruction which is compared with experiments performed on platelets labelled with the radioactive isotope 51Cr. Platelet destruction rate is a complicated function of platelet number and the thrombokinetic destruction state of the body. A linear approximation of this function shows that destruction is dominated by constant and random consumption. A second order non-linear approximation shows the effect of 'platelet crowding'. This theoretical study explains the difference between predicting the complete platelet survival curve from only two experimental points (in the linear approximation) and the methods of curve fitting currently recommended by the International Committee for Standardization in Haematology. It indicates that the curve fitting of known functional forms to experimental data usually results in an under interpretation of the observations and dilutes the diagnostic potential of the platelet survival curve.
Animals↗
The physics of arteriole blood flow. I. General theory.
A continuum physics theory of arteriole blood flow is presented based on the observed behaviour of blood using high-speed photography. The theory highlights the importance of time scales as well as length scales in constructing a physical theory of blood flow. Arteriole flow viewed at 8000 frames s-1 reveals a highly complicated cellular motion; however the same flow viewed at the same spatial magnification by the human sensor, the eye, reveals only a pinkish column of fluid. The eye 'smoothes out' the microscopic cellular behaviour. This principle is used in the continuum theory, where averages are taken over space and time, to explain how the observed collisions of the erythrocytes with themselves, plasma molecules and the arteriole wall determine blood, mass-averaged velocity profiles and mass flow rates. A new dimensionless similarity parameter arises from the continuum mixture. Its magnitude provides a measure of the relative importance of the viscous drag of a constituent and the frictional force experienced by one constituent due to the presence of another constituent in the mixture during arteriole blood flow. (The second paper in a series.)
Arteries↗
The physics of arteriole blood flow II. Comparison with experiment.
The results of paper I, General theory, are used to explain, using a continuum physics approximation, some of the experimentally observed phenomena which appear in the literature. The magnitude of the new dimensionless similarity parameter which arises from the mixture theory indicates that the internal frictional force acting on the plasma due to the presence of the erythrocytes (with an equal and opposite force acting on the erythrocytes due to the plasma) dominates the internal plasma viscous force. It is this feature that produces the observed slower flow rate of blood compared with water for a given pressure gradient. Quantitative predictions, which agree with experiment, of the cell-free layer, feed, dynamic and discharge haematocrits for cylindrical pipe flow are obtained. The observed decrease in apparent blood viscosity with decrease in cylinder diameter is also predicted. Finally an explanation is presented for the experimental observation of an off-centre peak in the tube radial viscosity profile.
Arteries↗
The relationship between platelet and megakaryocyte volumes.
Planimetric megakaryocyte and nuclear areas were measured by histological techniques in rabbits subjected to 6 days of thrombocytopenia and in normal steady state function. A theoretical correction factor enables an estimate to be obtained of the actual megakaryocyte, megakaryocyte cytoplasm and nuclear volumes in these two states. The corresponding platelet volumes after 6 days of thrombocytopenia and in normal function were also measured. This enables the number of platelets produced by a single megakaryocyte (on average) to be computed directly in the two states of platelet production. The experiments showed that the volume of megakaryocyte cytoplasm increased significantly in stimulated platelet production. The number of platelets produced per megakaryocyte doubled and the mean platelet volume also increased during stimulated production. An explanation is given for the observed behaviour of platelet and megakaryocyte volumes.
Animals↗
Evidence for a theory of physical fragmentation of megakaryocytes, implying that all platelets are produced in the pulmonary circulation.
The mathematical description of a fragmentation mechanism which leads to log normal volume distribution is applied to platelet production from megakaryocyte cytoplasm. Large cytoplasmic fragments and whole megakaryocytes are released from the bone marrow into the circulation. Physical fragmentation of the cytoplasm occurs in the pulmonary circulation producing the observed heterogeneity of platelet volume. Experimental evidence is used to provide quantitative verification that physical fragmentation is the process which produces all platelets. With this theory the currently accepted concept of the predesignation of the platelet population by the demarcation membrane system in megakaryocyte cytoplasm becomes redundant.
Animals↗
Theoretical requirements for the density separation of platelets with comparison of continuous and discontinuous gradients.
In continuous density gradients platelets will approach their equilibrium position with exponential deceleration. The time taken to reach an acceptable approximation to equilibrium will depend upon platelet radius, density and medium viscosity. If centrifugation is stopped before equilibrium has been achieved then platelet "subpopulations" produced will not be density dependent. Discontinuous gradients take longer to reach equilibrium. Separation of platelets by density must conform to theoretical physical criteria.
Blood Platelets↗
The fluid mechanics of blood: equilibrium and sedimentation.
A continuum physics theory of blood in equilibrium and sedimentation is presented, based on the observed behaviour of blood using high-speed photography. Present interpretation of the rheological behaviour of blood is based on particulate suspension theory. When the observed cellular behaviour of blood (by high-speed photography) is considered carefully it is found that none of the initial assumptions made in that theory are realistic. Thus although such a theory provides sophisticated mathematics it really gives no insight into the true fluid mechanics of blood. The theory developed in this paper highlights the importance of time scales as well as length scales in understanding the physics of blood. It emphasises that blood should be considered (for macroscopic rheological purposes) as a mixture of two continuous fluids. The average behaviour of plasma molecules gives a continuous plasma fluid while the average behaviour of the erythrocytes gives a continuous erythrocyte fluid. Blood is simply a mixture of these two fluids. The fluid mechanics of blood in equilibrium and during sedimentation is developed using these concepts. Confirmation of the theoretical predictions is provided by simple laboratory experiments.
Blood Physiological Phenomena↗
A mathematical model of the ultra-filtration process in a single glomerular capillary.
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Capillaries↗
Flow of a newtonian fluid through a permeable tube: the application to the proximal renal tubule.
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Animals↗
Platelet and megakaryocyte changes in cholesterol-induced experimental atherosclerosis.
Rabbits were fed either 2 g cholesterol in 10 ml olive oil daily with normal diet (n = 5) or normal diet alone (n = 5). After 12 weeks, the cholesterol-fed animals had developed fatty plaques involving 24% +/- 4% of the surface area of the aorta; the control animals had none. Mean platelet volume was significantly smaller (p less than 0.04) in the cholesterol-fed animals (4.1 +/- 0.3 fl) compared with the controls (4.8 +/- 0.4 fl). The heterogeneity of the average volume distributions of the two groups, characterized by the statistical parameters of the coefficient of variation, skewness, and kurtosis, was also significantly different. Platelet count was significantly higher (p less than 0.001) in the cholesterol-fed group (7.48 +/- 1.06 x 10(11) platelets/liter blood) compared to the control group (4.86 +/- 0.60 x 10(11) platelets/liter blood). Mean megakaryocyte cytoplasmic volume was significantly larger (p less than 0.001) in the cholesterol-fed rabbits (12,262 +/- 1485 fl) compared with controls (6,814 +/- 761 fl). The range of cytoplasmic volumes was also significantly increased in the cholesterol-fed rabbits. A significant (p less than 0.01) increase in mean megakaryocyte nuclear volume in the cholesterol-fed animals was accompanied by a nonsignificant increase in mean nuclear DNA content: 30.2 +/- 3.7 N compared with a control value of 23.6 +/- 4.0 N. This evidence indicates that a high cholesterol diet in rabbits is associated with changes in platelet production from megakaryocytes as well with as the development of atherosclerosis.
Animals↗
An examination of one-piece metacarpophalangeal joint implants using finite element analysis.
Reconstruction of the rheumatoid metacarpophalangeal (MCP) joint is generally achieved by means of implantation of a hinged silastic prosthesis. These implants reduce the pain in joint and restore some degree of mobility. However, they are prone to failure after a relatively short life-span. In this study, two popular designs of MCP implant, the Swanson and the Sutter, were compared by means of three-dimensional finite element analysis. The aim was to examine how the differing geometry effected their relative stiffness as replacement joints, and whether they were inherently prone to high stress concentrations during flexion. Although the Swanson design implant exhibited relatively greater resistance to flexion, both designs showed regions of high stress concentration and it was noted that neither was without its limitations. The use of the finite element technique was found to be an excellent way to provide preliminary design evaluation information, allowing further evolution before clinical trials.
Arthritis, Rheumatoid↗
Modelling dual isotope parathyroid scans: objective decision making for tumour detection.
Parathyroid subtraction imaging using the radioisotopes thallium-201 and technetium-99m was first described in 1983. Since then it has become a routine method for the pre-operative localization of parathyroid tumours. Despite its widespread use, the interpretation of the subtraction images remains very subjective. This paper describes and evaluates an automatic objective method for the analysis of parathyroid scans. The method is based on the calculation of a likelihood ratio (the probability of obtaining a count in a given pixel if a tumour is present divided by the probability of obtaining that same count if a tumour is not present). The likelihood ratio is calculated for each pixel in a subtraction image. The calculated value is compared with a threshold. Pixels with likelihood ratios greater than the threshold are classified as belonging to tumour sites. Pixels with likelihood ratios less than, or equal to, the threshold are classified as belonging to 'no tumour' sites. The probability density functions required were obtained from computer simulated images. The likelihood ratio technique has a similar sensitivity and specificity to that of experienced human observers analysing computer simulated images. Furthermore, it is a completely automatic method which can provide the basis of a decision support system.
Computer Simulation↗
Mathematical concepts of blood flow and blood rheology.
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Blood Flow Velocity↗