The effect of an adrenaline infusion on the splenic blood flow and intrasplenic platelet kinetics

The effect of an adrenaline infusion on the venous platelet count, splenic blood flow and intrasplenic platelet kinetics was investigated in seven healthy male volunteers by using 111In-labelled platelets and dynamic gamma camera scintigraphy. The infusions were administered in two different doses, 0.2 microgram/kg/min and 0.1 microgram/kg/min, respectively. Regardless of the given dose, adrenaline was found to markedly decrease the splenic blood flow, decrease the exchangeable splenic platelet pool size and to prolong the intrasplenic platelet transit time. In response to the higher dose of adrenaline the splenic blood flow was 1.3 +/- 0.5 (SD) % of total blood volume per min and the intrasplenic platelet transit time 17.3 +/- 2.3 (SD) min. In contrast, after termination of infusion, the splenic blood flow was 7.0 +/- 2.1 (SD) % of total blood volume per min and the intrasplenic platelet transit time was 11.5 +/- 1.5 (SD) min. The present results firmly demonstrate that the splenic blood flow is the immediate variable governing the size of the exchangeable splenic platelet pool, and that the adrenaline-induced depletion of the splenic platelet pool is a consequence of the splenic blood flow reduction. Finally, the splenic perfusion appears to be a major determinant of the intrasplenic platelet transit time.     

The Peripheral Platelet Count in Response to Intravenous Infusion of Isoprenaline

5 healthy male volunteers received i.v. infusions of isoprenaline in doses of 0.03, 0.06 and 0.09 μg × kg^?1 × min^?1 over a period of 6 min. A statistically significant decrease in the peripheral platelet count was obtained, but no dose-response-curve for isoprenaline was observed. It is suggested that while an i.v. infusion of epinephrine causes a release of platelets from the exchangeable splenic platelet pool, isoprenaline might have the opposite effect on the spleen, thereby causing a decrease of platelets in the peripheral blood.     

In vitro and in vivo behavior of 111In-labelled platelets: An experimental study of healthy male volunteers

The aim of this study was to obtain a critical evaluation of a simple method for labelling platelets with ¹¹¹In-oxine. All experiments were carried out on healthy volunteers. 65 ± 7 (SD) % of the platelets in collected blood were labelled and reinjected. As compared to control experiments, only in response to a low final ADP concentration (1.0 μmol/l) did ¹¹¹In-labelled platelets show reduced in vitro aggregability. The mean platelet volume for ¹¹¹In-labelled platelets was slightly lower than the mean platelet volume in whole blood. The results for initial platelet recovery and platelet mean lifespan closely agreed with those of other studies in which considerably higher platelet extraction from whole blood was obtained. After injection, the splenic uptake and blood disappearance of ¹¹¹In-labelled platelets followed a monoexponential function with almost identical rate constants. By compartmental analysis of the equilibration of platelets between blood and spleen, the splenic blood flow was estimated to be 4.8 ± 1.9 (SD) % of the total blood volume/min; the intrasplenic platelet transit time was 9.7 ± 1.6 (SD) min, and the exchangeable splenic platelet pool 31 ± 8 (SD) %. Highly significant relationships were present between the splenic blood flow and the splenic platelet pool size, as well as between the splenic blood flow and the initial platelet recovery. It is concluded that the requirements for adequate interpretation of platelet kinetics are well met with the present method for harvesting and labelling of platelets.     

Splenic platelet kinetics in systemic lupus erythematosus (SLE)

The splenic blood flow, intrasplenic platelet kinetics and spleen size were determined in 8 females with systemic lupus erythematosus (SLE), all without signs of active disease, by using gamma-camera scintigraphy with 111In-labelled platelets and 99mTc-stannous colloid. The results for splenic blood flow, intrasplenic platelet transit time and splenic platelet pool size, obtained by compartmental analysis of the initial distribution of radiolabelled platelets between blood and spleen, did not differ from those of a control group. In all SLE patients the spleen size was within normal limits. There was a significant relationship between the spleen volume and the splenic platelet pool size (r = 0.75; p less than 0.05), and between the spleen volume and splenic blood flow (r = 0.76; p less than 0.05). A borderline, inverse correlation was present between an estimate of splenic perfusion and intrasplenic platelet transit time (r = 0.62; p = 0.1). It is concluded that the splenic function, measured as splenic blood flow and intrasplenic platelet kinetics, is not disturbed in SLE patients without active disease.     

The exchangeable splenic platelet pool in response to intravenous infusion of isoprenaline

8 healthy volunteers and 4 asplenic subjects, in whom autologous platelets had been labelled with radioactive sodium chromate, received i.v. infusions of isoprenaline in a dose of 0.03 microgram x kg-1 x min-1 over a period of 6 min. In the former group these infusions caused a significant decrease in the concentration of labelled as well as unlabelled platelets in the peripheral blood. Body surface countings showed that a significant increase in the count rate over the spleen occurred concomitantly with the decrease in the circulating platelet-bound radioactivity (PBR). In the group of asplenic subjects no change in PBR occurred. It is concluded that adrenergic beta-receptor stimulation causes a transitory trapping of platelets in the exchangeable splenic platelet pool.     

Kinetics, in vivo redistribution and sites of sequestration of indium-111-labelled platelets in giant platelet syndromes

Six patients with giant platelet syndrome were examined: four with Bernard-Soulier syndrome (two were asplenic); one with hereditary thrombopathic thrombocytopenia; and one with May-Hegglin anomaly. Autologous platelets were labelled with In-111-oxine and in vivo redistribution and sites of sequestration measured with quantitative imaging. In Bernard-Soulier syndrome platelet survival was normal or moderately shortened; platelet turnover was decreased only in the two patients with thrombocytopenia. In the patients with thrombopathia or May-Hegglin anomaly, platelet survival and turnover was moderately decreased. In those patients with normal-sized spleens, the mean splenic platelet pool consisted of 35.5% of the platelet mass, i.e. normal. The intrasplenic transmit time of the megathrombocytes was prolonged. Splenic blood flow was within normal limits. There was a marked accumulation of platelets in the liver at equilibrium: 15.5-58.8% of whole body radioactivity (normal 9.6 +/- 1.2%). This finding is unexplained. The final sites of sequestration of platelets were mainly in the liver and spleen, similar to that seen in normal subjects. We conclude that there is no inverse relationship between cell size and splenic platelet transit time. Platelet size therefore does not determine the size of the splenic platelet pool. The size of the platelets also does not seem to affect the sites of sequestration at the end of their life span.     

Blood cell kinetics in the spleen

The mean intrasplenic blood cell transit time (STT), splenic blood cell volume (SV) and the slow mixing splenic blood cell volume (SSV) have been measured in normal subjects and patients with congestive and infiltrative splenomegaly. The normal red cell SV was 0.47 +/- 0.14 (mean +/- SD) % of the circulating red cell volume (RCV). In patients with congestive and infiltrative splenomegaly, SV was 9.82 +/- 3.55% and 0.96 +/- 0.71% of RCV, respectively. The SSV was 69.1 +/- 8.4% of the SV in normal subjects, but in patients with splenomegaly, its value was lower than that of normal SSV. The STT was 0.43 +/- 0.11 min. in normal subjects. In the patients with splenomegaly, it prolonged. But, the STT/SV and STT/SSV were rapid in patients with congestive splenomegaly and low in infiltrative splenomegaly. It seemed that SST/SV and STT/SSV were useful to distinguish between congestive and infiltrative splenomegaly. In the intrasplenic granulocyte kinetics, SV was similar to that of red cell. The STT was longer than that of red cell, in normal subjects and patients with splenomegaly. In the intrasplenic platelet kinetics, the ratio of cellular splenic volume to general circulation was the largest in platelets. The STT of platelet was the slowest in blood cells.     

The interpretation of platelet kinetic studies for the identification of sites of abnormal platelet destruction

The kinetics of platelets labelled with 111In have been studied in a series of 175 subjects including 18 normal volunteers, and 12 patients with idiopathic thrombocytopenic purpura (ITP), but excluding patients in whom there was scintigraphic evidence of intravascular platelet consumption. From analysis of the kinetics, the following parameters were calculated: splenic blood flow (SBF), intrasplenic platelet transit time (t-), splenic platelet pool capacity (expressed as a percentage of the total circulating platelet population), the fraction of the dose of labelled platelets ultimately destroyed in the spleen and the mean platelet life span (MPLS). SBF increased with increasing spleen size up to values of 25% total blood volume (TBV) per min. Some patients with immune complex related diseases were identified with elevated SBF (up to 24% TBV min-1) but without significant splenomegaly. Patients with cardiac decompensation had reduced SBF relative to spleen size. t- showed no relationship with spleen size. It tended to fall in patients who had high SBF relative to spleen size and to rise in those with low SBF relative to spleen size; i.e. it was inversely related to splenic perfusion (flow per unit tissue volume). The splenic platelet pool capacity is dependent on platelet input (SBF) and splenic platelet clearance (reciprocal of t-), and showed a close relationship with spleen size. When all subjects except those with ITP were considered, splenic platelet destruction showed a good correlation (r = 0.70, n = 42, P less than 0.001) with the splenic platelet pooling capacity. The ratio of the fraction of platelets destroyed in the spleen to the fraction pooling there, the D/P ratio, was approximately unity and did not appear to vary with MPLS, spleen size or the patient's condition, except in ITP where it varied between about 0.5 and 2. This variation in ITP was thought to be the result of an immune mediated re-direction of reticulo-endothelial platelet destruction. It is suggested that the D/P ratio, rather than the absolute quantity of 111In labelled platelets destroyed in the spleen, may be a more useful predictor of response to splenectomy since it takes into account the observed, appropriate, tendency for the spleen to destroy platelets in proportion to its platelet pooling capacity.     

The peripheral platelet count in response to adrenergic alpha-and beta-1-receptor stimulation.

The aim of the present work was to investigate the effect of adrenergic alpha- and beta-1-receptor stimulation on the peripheral platelet count. The experiments were carried out on 8 healthy male volunteers using radioisotopically labelled platelets. 3 subjects received i.v. infusions of adrenaline (0.09 microgram X kg-1 X min-1) before and after the ingestion of 40 mg propranolol. In response to the first infusion there was an instant increase in the venous platelet-bound radioactivity (PBR) which amounted to 12% over basal value. This effect of adrenaline seemed to be potentiated by propranolol pretreatment. 5 subjects received i.v. infusions of the highly selective beta-1-receptor agonist H 133/22 (prenalterol, H?ssle, Sweden). In response to a cumulative dose of 4.75 mg prenalterol a slight but significant (P less than 0.05) decrease in PBR occurred. It is concluded that alpha-receptor stimulation causes a depletion of platelets from the exchangeable splenic platelet pool resulting in a concomitant increase in the peripheral platelet count. Beta-receptor stimulation has an opposite effect on the spleen. The trapping of platelets by the spleen is mediated both via beta-1- and beta-2-receptors, but the effect of beta-2-receptor stimulation seems to predominate.     

The Peripheral Platelet Count in Response to Adrenergic Alpha- and Beta-1-Receptor Stimulation

The aim of the present work was to investigate the effect of adrenergic alpha- and beta-1-receptor stimulation on the peripheral platelet count. The experiments were carried out on 8 healthy male volunteers using radioisotopically labelled platelets. 3 subjects received i.v. infusions of adrenaline (0.09 μg × kg^-1 × min^-1) before and after the ingestion of 40 mg propranolol. In response to the first infusion there was an instant increase in the venous platelet-bound radioactivity (PBR) which amounted to 12 % over basal value. This effect of adrenaline seemed to be potentiated by propranolol pretreatment. 5 subjects received i.v. infusions of the highly selective beta-1-receptor agonist H 133/22 (prenalterol, Hässle, Sweden). In response to a cumulative dose of 4.75 mg prenalterol a slight but significant (P <0.05) decrease in PBR occurred. It is concluded that alpha-receptor stimulation causes a depletion of platelets from the exchangeable splenic platelet pool resulting in a concomitant increase in the peripheral platelet count. Beta-receptor stimulation has an opposite effect on the spleen. The trapping of platelets by the spleen is mediated both via beta-1- and beta-2-receptors, but the effect of beta-2-receptor stimulation seems to predominate.     

Splenic Platelet Kinetics and Platelet Production after Major Reconstructive Vascular Surgery

ABSTRACT By using ¹¹¹In-labelled platelets and dynamic gamma camera scintigraphy, platelet production rate and intrasplenic platelet kinetics were determined in 13 patients at 1 and 4 months after aortic reconstructive vascular surgery with implantation of dacron prostheses. A significant decrease in platelet production rate and venous platelet count was recorded over time after surgery. Irrespective of whether the exchangeable splenic platelet pool was estimated from initial recovery of platelet-bound radioactivity or from compartmental analysis, the size of this pool was significantly lower at the first study; a change in intrasplenic platelet transit time accounted for the observed difference. Platelet mean life-span increased over time after surgery but the difference between the duplicate studies was not statistically significant. It can be concluded that there is a reduction of platelet production rate and venous platelet count over time after major reconstructive vascular surgery. The early postoperative elevation in the platelet count is mainly the result of an increased platelet production and to a lesser degree due to redistribution of platelets between the splenic platelet pool and general circulation.     

In vivo tracking of platelets: circulating degranulated platelets rapidly lose surface P-selectin but continue to circulate and function.

To examine the hypothesis that surface P-selectin-positive (degranulated) platelets are rapidly cleared from the circulation, we developed novel methods for tracking of platelets and measurement of platelet function in vivo. Washed platelets prepared from nonhuman primates (baboons) were labeled with PKH2 (a lipophilic fluorescent dye), thrombin-activated, washed, and reinfused into the same baboons. Three-color whole blood flow cytometry was used to simultaneously (i) identify platelets with a mAb directed against glycoprotein (GP)IIb-IIIa (integrin alpha 11b beta 3), (ii) distinguish infused platelets by their PKH2 fluorescence, and (iii) analyze platelet function with mAbs. Two hours after infusion of autologous thrombin-activated platelets (P-selectin-positive, PKH2-labeled), 95 +/- 1% (mean +/- SEM, n = 5) of the circulating PKH2-labeled platelets had become P-selectin-negative. Compared with platelets not activated with thrombin preinfusion, the recovery of these circulating PKH2-labeled, P-selectin-negative platelets was similar 24 h after infusion and only slightly less 48 h after infusion. The loss of platelet surface P-selectin was fully accounted for by a 67.1 +/- 16.7 ng/ml increase in the plasma concentration of soluble P-selectin. The circulating PKH2-labeled, P-selectin-negative platelets were still able to function in vivo, as determined by their (i) participation in platelet aggregates emerging from a bleeding time wound, (ii) binding to Dacron in an arteriovenous shunt, (iii) binding of mAb PAC1 (directed against the fibrinogen binding site on GPIIb-IIIa), and (iv) generation of procoagulant platelet-derived microparticles. In summary, (i) circulating degranulated platelets rapidly lose surface P-selectin to the plasma pool, but continue to circulate and function; and (ii) we have developed novel three-color whole blood flow cytometric methods for tracking of platelets and measurement of platelet function in vivo.     

Platelet splenic transit times in idiopathic thrombocytopenic purpura. Compartmental vs. non-compartmental model.

Platelet splenic transit times following injection of autologous or homologous 111In-labeled platelets were studied in 42 patients with idiopathic thrombocytopenic purpura. The transit times were determined by two methods from the splenic time-activity curves recorded with a gamma camera: closed two-compartmental model and non-compartmental model (deconvolution analysis). By compartmental analysis the mean splenic transit time for platelets was 6.3 +/- 0.3 min (mean +/- S.E.) and by non-compartmental analysis 7.6 +/- 0.4 min for all cases studied. The mean splenic transit time for autologous platelets was significantly (p less than 0.001) shorter (5.1 +/- 0.3 min) in patients with platelet-associated IgG (measured by platelet suspension immunofluorescence test) than in those with no autoantibodies (7.1 +/- 0.4 min), when the compartmental model was employed. There was no significant difference between mean transit times for autologous platelets in antibody positive and negative patients when deconvolution analysis was applied, but the residue of the splenic transfer function was lower for antibody positive than negative patients (7.2 +/- 1.0% vs. 11.7 +/- 1.6%, p less than 0.05). It is concluded that in idiopathic thrombocytopenic purpura the presence of platelet-associated autoantibodies expands the splenic platelet pool and reduces recirculation of platelets.     

Reversal of endothelin-1-induced vasoconstriction by nifedipine in human resistance vessels in vivo in healthy subjects.

The influence of blockade of voltage-operated calcium channels by nifedipine on endothelin-1-induced vasoconstriction was investigated in 10 healthy volunteers. Brachial artery infusions of nifedipine (0.25, 0.5, 1 and 3 micrograms/min/100 ml forearm tissue) resulted in dose-dependent increases (mean +/- SD) in forearm blood flow (103 +/- 63% to 833 +/- 426%). Intraarterial infusions of endothelin-1 (50 ng/min/100 ml) resulted in transient increases in forearm blood flow (2.6 +/- 0.9 vs 3.9 +/- 2.0 ml/min/100 ml, p less than 0.01) in the first minute of infusion and subsequent decreases (to 1.0 +/- .5 ml/min/100 ml, p less than 0.01) in the third minute of infusion. Endothelin-1-induced vasoconstriction was reversed by the lowest dose of nifedipine, whereas the higher dosages of nifedipine further increased forearm blood flow to 12.5 +/- 6.4 ml/min/100 ml. The percent increase of forearm blood flow during co-infusion of endothelin-1 and the highest dosage of nifedipine was significantly greater compared with nifedipine alone (1,204 +/- 531% vs 833 +/- 426%, p less than 0.05). The results demonstrate a dual action of luminally applied endothelin-1 in human resistance vessels in vivo (e.g., transient initial vasodilation followed by pronounced vasoconstriction) and suggest that blockade of voltage-operated calcium channels can effectively counteract the vasoconstrictor effects of endothelin-1.     

No difference in the lipolytic response to beta-adrenoceptor stimulation in situ but a delayed increase in adipose tissue blood flow in moderately obese compared with lean men in the postexercise period

This study was undertaken to determine the effect of previous exercise on adipose tissue responsiveness to beta-adrenoceptor stimulation and on adipose tissue blood flow (ATBF). Eight lean and 8 obese men (body mass index [BMI], 23.6 +/- 2.1 [SD] v 29.0 +/- 1.9 kg x m(-2)) were investigated with abdominal subcutaneous microdialysis and 133Xe clearance. A stepwise isoprenaline infusion (10(-8), 10(-7), and 10(-6) mol x L(-1)) was administered in situ in the microdialysis catheter before and 2 hours after a submaximal exercise bout (90 minutes of cycling at 55% of maximal O2 uptake). No differences in the response (increase in interstitial glycerol v preinfusion level) to isoprenaline infusions were found between the 2 groups. In both groups, there was no difference in the response to postexercise versus preexercise infusion. When the vasodilating agent hydralazine (0.125 g x L(-1)) was infused into the microdialysis catheter to control for the vascular effects of isoprenaline, an interaction effect between exercise and isoprenaline dose was found. Analyses showed an attenuated response to the high isoprenaline dose after exercise (lean, 251 +/- 42 [SE] micromol x L(-1); obese, 288 +/- 77 micromol x L(-1)) versus before exercise (lean, 352 +/- 62 micromol x L(-1), P = .045 v after; obese, 380 +/- 94 micromol x L(-1), P = .021 v after), indicating a desensitization of lipolysis to beta-adrenoceptor stimulation. ATBF and arterial plasma glycerol increased after exercise in both groups, but the increase was delayed in obese subjects. Arterial plasma insulin was higher in the obese versus lean subjects at all times, and decreased during recovery in both groups. In conclusion, abdominal subcutaneous adipose tissue responsiveness to beta-stimulation is not enhanced postexercise in lean and obese men, whereas previous exercise increases ATBF. Furthermore, the data suggest slower lipid mobilization postexercise and resistance to the antilipolytic effect of insulin in the obese.     

Properties of the exchangeable splenic platelets released into the circulation during exercise-induced thrombocytosis

The human spleen normally retains about one-third of the body's platelets in an exchangeable pool which can be released into the circulation by alpha-adrenergic stimulation. Some previous investigators concluded that the splenic platelet population was enriched in a subpopulation of large, young, dense platelets (megathrombocytes) but more recent research suggests that platelet size, age, and density are largely independent variables. In this investigation the properties of the splenic platelets were studied after their release into the circulation by acute strenuous exercise in 11 normal subjects. The exercise caused a rise in mean platelet count from 245 +/- 49 to 328 +/- 71 x 10(9)/L--a net increase of 24 +/- 6% after correction for haemoconcentration. The mean platelet volume (MPV) of citrated platelets increased from 6.38 +/- 0.78 to 6.59 +/- 0.68 fL after exercise (P less than 0.01)--a rise of 3.7 +/- 4.1% suggesting that the MPV of the splenic platelet population was about 20% greater than that of the normal circulating population. The age distribution of the platelets was studied by measuring the platelet monoamine oxidase (MAO) activity several days after irreversible inhibition by tranylcypromine, when the young platelets had normal MAO activity but the older platelets had only 20% of normal activity. The mean platelet MAO activity did not change after exercise, indicating that the age distributions of the circulating and splenic populations were very similar. The platelet contents of several putative markers of platelet age (sialic acid, serotonin, beta-thromboglobulin, beta-N-acetylglucosaminidase) were also unchanged after exercise. Modal platelet density decreased slightly but not significantly after exercise. The splenic platelet population has a larger MPV but appears to have similar age and density distributions to the basal circulating population.     

Antithrombotic efficacy of recombinant tick anticoagulant peptide. A potent inhibitor of coagulation factor Xa in a primate model of arterial thrombosis

BACKGROUND. Tick anticoagulant peptide is a specific, potent inhibitor of blood coagulation factor Xa. The effects of recombinant tick anticoagulant peptide (rTAP) and standard heparin (SH) were compared in an anesthetized baboon model of arterial thrombosis where platelet deposition onto a Dacron vascular graft segment of an arteriovenous (AV) shunt was studied. METHODS AND RESULTS. Animals were randomized to receive systemic administration of SH (10 or 100 U/kg i.v. bolus followed by 0.4 or 1.0 U/kg/min i.v. infusion, respectively) or rTAP (6.25, 12.5, or 25.0 micrograms/kg/min i.v. infusion). rTAP, but not SH, caused a significant (p less than 0.05), dose-dependent reduction of indium-111 labeled platelet and iodine-125 labeled fibrin (ogen) deposition onto the graft. Deposition was not significantly increased from baseline values during infusion of 12.5 or 25.0 micrograms/kg/min of rTAP. Blood flow was maintained at 64 +/- 9, 95 +/- 2, or 97 +/- 2% of baseline following infusion of 6.25, 12.5, or 25.0 micrograms/kg/min of rTAP, respectively. Both SH and rTAP significantly (p less than 0.05) decreased the systemic fibrinopeptide A (FPA) elevation during exposure to the Dacron graft. rTAP was fully antithrombotic at APTT values of 42.6 +/- 2.4 seconds (less than twofold basal value), while SH had no antithrombotic efficacy despite APTT values greater than 150 seconds (greater than fivefold basal value). CONCLUSIONS. The demonstrated antithrombotic effect of rTAP in the absence of alterations in primary hemostasis suggests that controlling thrombin generation through inhibition of factor Xa may be a novel and effective pharmacological approach in the prevention of high-shear arterial thrombosis.     

Heterogeneity of Rabbit Platelets

Rabbits were either splenectomized or subjected to splenic blockade with phenylhydrazine in order to determine the splenic platelet and megathrombocyte (large-platelet) pools. The average splenic platelet pool calculated from both methods was 35% of total platelets. The average splenic megathrombocyte pool was 54% of total megathrombocytes. Adrenaline injection into rabbits or dogs revealed a rapid increase in both platelet count and megathrombocyte number which peaked at 2-6 min and returned toward normal in 5-10 min. The platelet volume distribution curve was shifted to the right, indicating the release of large platelets (megathrombocytes) into the circulation. The peak rise in megathrombocyte number was significantly greater than the peak rise in platelet count. Rabbits subjected to splenic massage shifted their platelet volume distribution curve to the right in the absence of a rise in platelet count. It is concluded that the spleen preferentially sequesters megathrombocytes.     

Value of portal hemodynamics and hypersplenism in cirrhosis staging

AIM: To determine the correlation between portal hemodynamics and spleen function among different grades of cirrhosis and verify its significance in cirrhosis staging. METHODS: The portal and splenic vein hemodynamics and spleen size were investigated by ultrasonography in consecutive 38 cirrhotic patients with cirrhosis (Child's grades A to C) and 20 normal controls. The differences were compared in portal vein diameter and flow velocity between patients with and without ascites and between patients with mild and severe esophageal varices. The correlation between peripheral blood cell counts and Child's grades was also determined. RESULTS: The portal flow velocity and volume were significantly lower in patients with Child's C (12.25±1.67 cm/s vs 788.59±234 mm/min, respectively) cirrhosis compared to controls (19.55±3.28 cm/s vs 1254.03±410 mm/min, respectively) and those with Child's A (18.5±3.02 cm/s vs 1358.48±384 mm/min, respectively) and Child's B (16.0±3.89 cm/s vs 1142.23±390 mm/min, respectively) cirrhosis. Patients with ascites had much lower portal flow velocity and volume (13.0±1.72 cm/s vs1078±533 mm/min) than those without ascites (18.6±2.60 cm/s vs1394±354 mm/min). There was no statistical difference between patients with mild and severe esophageal varices. The portal vein diameter was not significantly different among the above groups. There were significant differences in splenic vein diameter, flow velocity and white blood cell count, but not in spleen size, red blood cell and platelet counts among the various grades of cirrhosis. The spleen size was negatively correlated with red blood cell and platelet counts (r= -0.620 and r= -0.8.34, respectively). CONCLUSION: An optimal system that includes parameters representing the portal hemodynamics and spleen function should be proposed for cirrhosis staging.     

Use of lllIndium-labelled Platelets to Measure Spleen Function

The distribution of ¹¹¹In-labelled platelets following intravenous bolus injection has been studied using a gamma camera and computer system. Liver uptake, which accounted for about 10% of the dose, was completed between 6 and 10 min after injection. Blood pool and splenic ¹¹¹In, which accounted for the remainder of the dose, reached constant levels simultaneously about 20 min after injection. The kinetics of splenic uptake are consistent with a two compartmental model in which circulating and splenic platelets are in dynamic equilibrium with each other. From analysis of the kinetics, splenic blood flow and the mean transit time of platelets through the spleen have been calculated in normal subjects and in patients with haematological disorders. Blood flow, which was about 200 ml per min in normals, tended to increase with increasing spleen size. Transit time was not dependent on spleen size; it was about 10 min in all but one of the subjects.