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Biomedical subjects

G A Shah

Publications and source records attributed to G A Shah.

14 recordsLinked to original sources

Comparison of fibrin networks in plasma and fibrinogen solution.

Mass-Length ratio of fibrin fibres (microT and microP) derived independently from turbidity and permeability respectively, in networks made in fibrinogen solution and plasma, have been compared under similar conditions of clotting. Amount of fibrinogen conversion to fibrin was similar in both systems when high thrombin concentrations were used. But networks in plasma had significantly thicker fibres (higher microT and microP) than those in fibrinogen solution. This difference arises from differing kinetics of fibrin assembly in the two systems. When lower thrombin concentration is used, fibrin fibre thickness (as indicated by microP and microT) is increased in fibrinogen solution but the fibrin content of the network remains unaltered. In plasma, on the other hand, the fibrin content of the network is decreased, microT remains relatively unchanged while microP increases. The thrombin concentration dependence of the fibrin content of the network in plasma and the bimodal distribution of fibrin fibre thickness explain the breakdown in correlation between microP and microT.

Blood Coagulation

Effect of temperature, pH and ionic strength and composition on fibrin network structure and its development.

Networks were developed in fibrinogen solution under pathophysiological conditions of clotting. Mass-length ratio (a measure of fibre thickness) was derived independently from the turbidity (microT) and from the permeability (microP) of the network. Kinetics of network growth were investigated turbidimetrically. Physiological concentrations of Ca++and Mg++increased microT while those of K+, Na+, Cl-, HCO-3, H2PO-4 and SO--4 had no effect. As pH and ionic strength were increased stepwise within the pathophysiological range, network development was delayed. Under these conditions the turbidity curves did not cross and both microT and microP were progressively decreased. When temperature was lowered, although network growth was delayed, the turbidy curves crossed: the equilibrium turbidity was higher at lower temperatures. It appears that while pH and ionic strength affect network structure by influencing fibrin assembly, lowering the temperature influences both the rate of fibrin monomer generation and fibrin assembly.

Fibrin

Physiological studies on fibrin network structure.

Networks were developed in fibrinogen solution under pathophysiological conditions of clotting and their permeability and turbidity were measured. Mass-Length ratio of fibrin fibres (a measure of fibre thickness) was derived from two independent methods based on turbidity (mu T) and permeability (mu P). Both mu T and mu P increased as thrombin concentration was decreased. Data are in agreement with the concept that the fibrin network develops initially as a mesh of protofibrils. Fibrin monomer generated subsequently is incorporated into the existing network making individual fibres thicker. Consequently, slow fibrin monomer generation promotes thicker fibres. When the concentration of thrombin or fibrinogen was altered systematically, mu T and mup were found to mirror each other except when the fibrinogen concentration was increased at low thrombin concentrations. This breakdown between the two derivations of mass-length ratio is discussed in terms of the two network model.

Blood Coagulation

Fibrin network structure: modification by platelets.

Platelets play a fundamental role in haemostasis and thrombosis. They are known to undergo characteristic changes including release of subcellular material during clotting. The effect of subcellular platelet material on fibrin network structure, however, has not previously been investigated. Using opacity ratio, syneresis, permeation and electron microscopy it was found that subcellular platelet material extracted into NaCl is able to influence fibrin network structure of clots made from purified fibrinogen as well as platelet-poor plasma. Such clots had higher opacity ratio, reduced syneresis and lower permeability than control clots. Further, the responsible platelet material is heat labile and is released from the platelets during their aggregation with several common aggregating agents. Morphometric analysis of transmission electron micrographs has shown that fibrin fibres in plasma clots made in the presence of platelet subcellular material are thinner than those in control clots. In addition, plasma clots made in the presence of platelet extract had a higher resistance to fibrinolytic digestion than control clots. Thus, platelets play a hitherto undescribed role in regulating fibrin network structure.

Blood Coagulation

Preoperative blood tests in prediction of postoperative deep vein thrombosis.

Fifty six patients undergoing elective abdominal surgery were investigated preoperatively with tests of coagulation, platelet function and fibrinolysis. Ten patients developed postoperative deep vein thrombosis, detected by the labelled fibrinogen uptake test and confirmed by ascending phlebography. None of the tests showed a statistically significant difference between the group mean of patients who developed DVT and of those who did not. Potential discriminators were used to derive a prognostic index for prediction of patients who would develop postoperative DVT. An index based on two preoperative blood tests i.e. three hour fibrin digestion and APTT had a successful prediction rate of 59 percent.

Blood Coagulation Tests

An evaluation of the British Pharmacopoeial assay of heparin: a comparison with other methods.

The potencies of six commercially manufactured heparins have been measured by the British Pharmacopoeial (BP) assay and activated partial thromboplastin time (APTT), protamine sulphate, and anti-Xa assays. The APTT/BP potency ratios were found to vary with the preparation but this was not dependent on the tissue source of heparin. For mucosal heparins, the anti-Xa/BP potency ratios were close to unity, but for heparin of lung origin the anti-Xa potency was approximately one-quarter of the BP potency. Four heparin fractions prepared by column gel chromatography of a commercial heparin were similarly examined by all four assays, and there was a wide divergence between the BP potency estimates and those obtained with the other methods. The degree of divergence was found to depend on the molecular size of the fraction.

Biopharmaceutics

Extension of platelet concentrate storage by addition of sodium bicarbonate.

Viability of platelet concentrate (PC) stored in polyvinylchloride bags in an elliptical rotator at 22 degrees C (standard PC) was assessed by in vitro tests, and an alternate approach to extending the shelf-life of PC by the addition of hypertonic sodium bicarbonate (test PC) was investigated. The fall in the pH which occurred during storage in standard PC was arrested in test PC. Furthermore, platelets stored under these test conditions maintained their morphology better than in standard PC as judged by their mean platelet volume and platelet distribution width. Recovery of stored platelets from hypotonic shock at 37 degrees C following resuspension in fresh plasma was better for test platelets. Results indicated that platelets in standard PC were viable up to day 3 but were not viable at day 7. Platelets store better in PC to which sodium bicarbonate has been added and behave as viable platelets up to 7 days.

Bicarbonates