In 1967, Dr. T. Kawasaki reported 50 cases of a previously undescribed infant disease. This was named acute febrile mucocutaneous lymph node syndrome, MCLS or MLNS, and was later called Kawasaki disease. The major symptoms of Kawasaki disease are summarized in Table 1. At the time of the first report by Kawasaki, this syndrome was thought to offer a good prognosis. However, since cases of sudden death from myocardial infarction were later reported, this syndrome is now considered to be sometimes serious. In this review, an outline of Kawasaki disease will first be given and then the prevention of thrombus formation in the disease will be discussed.
Incidence-Epidemiology: According to the investigations of a research group supported by the Ministry of Health of Japan, the patients have continously increased in number. The total numbers of cases with Kawasaki disease in Japan were 2, 798 in 1977 and 3, 489 in 1978 (Fig. 1). As regards the age distribution, there were peaks from 6 to 11 months old in males and from 12 to 17 months old in females respectively. Eighty percent of all cases were under 4 years old. The male: female ratio was 1.4-1.5: 1. The numbers of patients increased gradually from January to reach a peak in May or June, and then rapidly decreased in August or September.
Cases from Korea, Hawaii and Australia have also been described, as well as from Greece, West Germany and the mainland U. S. A. Replies submitted to a questionaire by Shibata, et al. in 1980 revealed that cases with Kawasaki disease had also been encountered in England, France, Denmark, Holland, Switzerland, Hungary, Kuwait and Canada.
Etiology: The precise etiology of Kawasaki disease remains unknown, although the possibility of infections such as by virus, Rickettia or Candida, or erythema exudativum multiforme induced by toxic effects of Streptococcus has been suspected. All investigations on pollutants such as compound cleansers, mercury, etc. have proved negative.
Pathology: The mortality rates of Kawasaki disease ranged from 1% to 1.7%. The morbid anatomy cases studied by Ohkawa, et al. consisted mostly of infants aged less than one year who died within 20 to 29 days after the onset of illness. Among them, cases with cardiac death amounted to 85%. The common findings in the morbid anatomy cases were arteritis, and thrombotic occlusions and aneurysma resulting from coronary arteritis.
Hamashima classified the course into four stages. At stage 1 (0-9 days), perivasculitis and vasculitis of capillaries, arterioles, venules and small arteries, associated with pericarditis, interstitial myocarditis and endocarditis, were seen. At stage II (12-25 days), panvasculitis and perivasculitis of larger arteries were prominent. Severe stenosis or obstruction of larger arteries due to th- or proliferative changes of the intima were also seen. Aneurysma appeared at this stage. At stage III (28-31 days), granulation of larger arteries was observed, but the vasculitis of the small arteries and arterioles disappeared. At stage IV (40 daysor more), severe stenosis or obstruction of larger arteries due to thickning of the intima was prominent. Scarring of larger arteries with calcification and recanalization was seen.
Although Kawasaki disease is clearly differentiated from classic periarteritis nodosa (Kussmaul-Maier type), it can be difficult to differentiate from some cases reported as infantile periarteritis nodosa (IPN). In this respect, it is possible that Kawasaki disease might represent IPN syndrome occurring through a certain, common etiology.
Laboratory findings, especially regarding coagulation: Leukocytosis, granulocytosis, str

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Factor XIII belongs to a group of calcium dependent glutamine-lysine endo-γ-glutamyl transferase. It circulates as a non-covalently associated tetrameric zymogen consisted of a subunit having enzymatic active center and b subunit regarded as carrier protein in a form of a₂b₂ in normal human plasma, while the platelet, uterus and placenta exhibit only a subunit as a zymogen and normal plasma shows an excess amount of b₂ being uncombined with a subunit. But the role of b subunit which is characteristic to exist only in plasma has not been clarified so much. To investigate the non-catalytic portion of plasma F. XIII, b subunit, a double antibody radioimmunoassay is newly developed for precise quantitation and slope analysis in antigen dilution curve with Rodbard's logit-log conversion method.
Sensitivity of this RIA for b subunit is 7ng/ml and the recovery of purified b subunit added to normal plasma and buffer control show over than 95%.Antigen expression of a₂b₂ and free b₂ concerning with b subunit are different on slope analysis of antigen dilution curve, while the 50% binding point, so called ED50, kept stayed at the same point. Reproducibility is good and CVs show less than 6% both on intraassay and interassay. Repeat of rapid freezing and thawing of normal plasma over three times shows 20% decrease of b subunit amount for original plasma. b subunit concentration in plasma of 37 normal adults show 11.98±2.35μg/ml and twelve cases of congenital F. XIII deficiencies show 5.77±1.34μg/ml, which is 48.2±11.5% to normal value.

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Tissue thromboplastin (TP) in gastric cancer tissue (Ca) from 9 patients were studied in comparison with that in normal mucous membrane (Ul) and muscular plus serous membrane (M) from the resected stomach of 8 patients with gastric ulcer. Azocaseinolytic activity and fibrinolytic activity (measured by standard fibrin plate method) were also studied.
Average TP activities measured by Nemerson's two stage method of the homogenates of Ca, Ul and M were 301±289 (SD), 123±76, and 34±19 units per mg protein, respectively. The activities of the former two were as strong as it of purified human brain TP. These homogenates also contained azocaseinolytic and fibrinolytic activities. These activities exist in granular fractions in differential centrifugation studies. Desoxycholate (DOC) extracts obtained by the method reported previously from Ca and Ul contained substance which showed partial identical antigenicity to purified human placenta TP (PTP) apoprotein by Ouchterlony analysis. DOC extracts regained TP activity when relipidated with phospholipid mixture (PL) from Ca. Similar result was obtained when PL from human brain was substituted for PL from Ca. In both cases, optimum ratio was obsereved in PL/protein and it was 1.3 for Ca and 0.16 to 0.33 for Ul. Relipidated TP activities of DOC extracts of three cases of Ca and a case of Ul seems to be dependent on Factors VII, X and V but not on Factors IX and VIII. Relipidated DOC extracts of a case of Ca and a case of Ul did not show azocaseinolytic and fibrinolytic activities. Anti-PTP γ-globulin fraction neutralized about 90% of the TP activities of the homogenates of Ca and Ul time dependently.
These results suggest that Ca and Ul tissues contain TP, which is lipoprotein, and has same properties to TPs from other tissues, and independent from fibrinolytic and protease activities.

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This paper deals with the antithrombin activities of synthetic acidic polysaccharides. These synthetic acidic polysaccharides have different viscosities and numbers of sulfates. Correlations between the anticoagulant activities and the viscocities and numbers of sulfates were investigated by means of the heparin cofactor method.
The following results were obtained:
1) The antithrombin activity of acidic polysaccharides alone showed a positive correlation between antithrombin activity and viscosity.
2) The cooperative actions of acidic polysaccharides which have high viscosities with AT III did not show any increase in the antithrombin activities of AT III. But the cooperative actions of acidic polysaccharides which have low viscosities showed an increase in the antithrombin activities of AT III.
3) There were no absolute correlations between the antithrombin activities of acidic polysaccharides alone and the numbers of sulfates.
4) Acidic polysaccharides with a 10% to 20% sulfate content were necessary to increase the antithrombin activities of AT III.

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α₂-Macroglobulin (α₂-M), one of the proteinase inhibitors in blood, binds to various proteinases such as plasmin, thrombin, trypsin kallikrein, and inhibits their activities. In this papers the respective reactions betweens α₂-M and plasmin, thrombin or trypsin were investigated with the use of α₂-M conjugated agarose.
α₂-M was purified from human plasma using lysin agarose, Sepharose 6B and the Ultrafiltration cell (M. W. 300, 000). Thrombin was purified using SP Sephadex and plasmin was made using lysin agarose.
It was found by the experiments using α₂-M agarose that plasmin was eluted with 1M NaCl in phosphate buffer (pH 7.5) but trypsin was not eluted with 1M NaCl in phosphate buffer (pH 7.5).
Thrombin was not eluted from α₂-M agarose even with 1M or 2M NaCl in phosphate buffer (pH 7.5) and it was strongly probable that the reaction between α₂-M and thrombin were irreversible. The reactions between α₂-M and thrombin was also examined by polyacrylamide disc gel electrophoresis. It was observed that three or four bands were found on the electrophoresis after the reaction, which indicated the changes in the low molecular structure changes of α₂-M due to reaction with thrombin. However, no quantitative change was found by immunological assay of the same specimen. It was made clear that α₂-M irreversibly changed in its properties by reacting with thrombin and lost its biological activity. On the basis of the fact that α₂-M in blood of a DIC patient loses its activities the following experiment in vitro was performed.
After the incubation of plasmin and α₂-M, different amount of thrombin was added and the fibrinolytic activity of this mixtures were examined on 0.2% plasminogen free fibrin plate.
It was noted that the lysis area was remarkably enlarged as the amount of thrombin was increased in the mixture. This implies that activity of α₂-M as a plasmin inhibitor was decreased and plasmin was released by the coexistence of thrombin.

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The agent capable of degrading fibrin was prepared from human spleen extract by chloroform treatment, ammonium sulfate precipitation and Sephadex gelfiltration. The agent degraded fibrinogen as well as fibrin at neutral pH. In kinetic studies, the fibrinogenolytic activity followed simple Michaelis-Menten kinetics, showing that the agent was a neutral proteinase. The activity was completely inhibited by DFP, but hardly by TLCK. These results suggest that the spleen proteinase has active serine, but no trypsin-type active histidine at its active center. The enzyme was not inhibited by trans-aminomethylcyclohexane carboxylic acid, a specific synthetic plasmin inhibitor, showing the different mode of action of the enzyme from that of plasmin.
In the studies using synthetic substrates, the spleen proteinase scarcely hydrolyzed the following synthetic esters and synthetic polypeptides: Ac-Gly-Lys-OMe, Ac-Phe-OEt, Ac-Try-OEt, Ac-Tyr-OEt, Ac-Lys-OMe, Tos-Lys-OMe, Tos-Arg-OMe and Ac-Arg-OMe; Suc-(Ala)₃-pNA, DNP-Pro-Leu-Gly-Ile-Ala-Gly-Arg-NH₂, H-D-Phe-Pip-Arg-pNA, H-D-Val-Leu-Lys-pNA, Bz-Phe-Val-Arg-pNA and <Glu-Gly-Arg-pNA. These results indicate different selectivity on synthetic substrates of the enzyme from those of trypsin, plasmin, chymotrypsin, collagenase and elastase. The enzyme did not lyse elastin at elastin-agar plates.

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A series of synthetic thrombin inhibitors, reported by us in 1975, exerted an extremely potent and highly selective inhibition on thrombin. In case of the compound No. 205 (dansyl-L-arginine-ethylpiperidine amide), I₅₀ for thrombin was 0.1μM; however, LD₅₀ was 80mg/kg i. p. in mice.
A compound No. 407, found by us in 1977, was characterized by its low toxicity (LD₅₀: 900mg/kg i. p. in mice); I₅₀ for thrombin was 0.3μM. Distribution volume of No. 407, calculated from its decreasing curve in plasma, was far smaller than that of No. 205, indicating the improved property for in vivo use.
Since then, approximately 400 new compounds were synthesized by us and several very active compounds (I₅₀:≤0.3μM) were obtained. It was noticed that all of the active compounds assumed the same basic structure; that is, they took tri-pod structure, one leg being L-arginine; another, aromatic; and the other, hydrophobic.
Results obtained also indicated that none of the homologues derived from D-arginine (such as dansyl-D-arginine-butylamide) exerted inhibition. CH₂ chain between α-carbon and guanidino groups of arginine could not be chemically changed without losing the inhibitory activity.
As to the hydrophobic and aromatic parts of our tri-pod inhibitors the possibility for successful chemical modification (without losing the inhibitory activity) was strictly limited.
Results accumulated from ca. 800 arginine derivatives indicated that “stereogeometry” of the active site of thrombin was so strictly defined that the enzyme could select the natural substrates with high accuracy.
Finally, No. 700 type inhibitors, in which α-NH₂ of arginine was protected by quinoline derivatives, should be added in present report because I₅₀ of No. 700 for thrombin was very small beyond expectation.

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In order to elucidate the involvement of kallikrein-kinin system in the body, it is necessary to measure its components accurately. Plasma kallikrein once activated is readily inhibited by proteinase inhibitors in plasma, thus making it difficult to estimate its activity in biological fluids. Therefore, a residual activity of a proenzyme, prekallikrein, should be determined. In this report, we describe an assay method for prekallikrein in human plasma using peptidylfluorogenic substrate, Z-phe-arg-MCA. The method consists of two steps: 1) The first step involves activation of prekallikrein with acetone and kaolin. The procedure used was similar to Imanari's method. Normal human plasma, 50μl, was mixed with 850μl tris buffer-acetone mixture. Then, 100μl kaolin suspension (10mg/ml) was added and mixed vigorously. After incubation for 30 or 60min at room temperature, a 20μl aliquot of the mixture was taken and assayed for its amidolytic activity as follows: 2) Each aliquot was taken into Tube A or Tube B. Tube A contains soy bean trypsin inhibitor and 1ml of Z-phe-arg-MCA solution, and Tube B contains lima bean trypsin inhibitor and the substrate solution. Each tube was incubated at 37°C for 10min and the reaction was terminated by addition of 17% AcOH solution. The fluorescence generated was then read at 380 (excitation) and 460 (emission) nm. The difference in values between Tube A and B was calculated to give the prekallikrein activity.
The enzyme activity generated was stable upto 60min. Ten % of the normal level of Hageman factor and high molecular weight kininogen were required for the full activation of prekallikrein by this method. The results obtained suggest that this assay system can be applied to the measurement of prekallikrein in deficient plasmas and also to samples from pathological conditions provided that these samples are examined in the presence and absence of normal plasma.

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The activity of factor X in the plasma of 123 patients with various diseases was measured by the clotting method and by the amidolytic method. Measurement of clotting activity of factor X was carried out by assay of the prothrombin time with factor X deficient plasma. Measurement of the amydolytic activity of factor X was made by end-point assay with S-2222 as the substrate.
In 29 patients, a distinct discrepancy was observed between the clotting activity and amidolytic activity of factor X. This discrepancy was shown markedly in patients with chronic renal failure (CRF) and uncontrolled diabetes mellitus (DM). In the patients with CRF, the amidolytic activity was higher than the clotting activity of factor X. On the other hand, in the patients with DM, the clotting activity was higher than the amidolytic activity of factor X.
The changes in activities of factor X by addition of each fraction of plasma from patients with CRF or DM were observed. Fraction of the patient plasma was carried out by ultrafiltration with membrane filter PM 10 and gel filtration with Bio-Gel A-15m. On the experiment by the addition of low molecular weight fraction (MW<10⁴) and high molecular weight fraction (MW≈10⁶) from the plasma of patient with CRF, the amidolytic activity of factor X in the control plasma of factor X deficient plasma was increased by the addition of each fraction. The clotting activity of factor X in the control plasma was decreased by the addition of middle molecular weight fraction from the plasma of patients with DM.
Based on these results, it is suggested that an intensifying effect on the amidolytic activity of factor X in the plasma of patients with CRF existed in the low molecular weight fraction (MW<10⁴) and high molecular weight fraction (MW≈10⁶), and that the factor X in patients DM had a different charactor from that in plasma of normal subject.

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The coagulability of Urokinase (UK) has been assessed by recalcification time well known as “zero coagulant assay method” reported by Alkjaersig (1965). However it is quite difficult to obtain suitable substrate plasma as described by him. The platelet poor plasma routinely prepared by silicon technique does not seem to produce a good response with UK.
It has been shown that there are two modes in the coagulative action of UK preparation. One is based on a contaminant of a thromboplastin like substance (TLS) from urine, the other one can be initiated or stimulated by the fibrinolytic process as reported previously by Prentice (1969) and Fujimori (1978).
In this report, it was demonstrated that TLS possesses a potent supplementary effect for plasma deficient in Factors XI and XII, and also that a celite exhausted plasma (artificial deficient plasma of Factors XI and XII) which was prepared by Nossel's method, was more suitable for determining the coagulant activity of UK preparations by means of zero coagulant assay.
It was demonstrated that to eliminate the influences of coagulability stimulated by the fibrinolytic process, a plasminogen free plasma obtained by treatment with celite and lysine-Sepharose was very useful for detection of TLS in UK preparations.

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Plasma and serum FDP levels in various malignant diseasez wers measured by RIA using anti-FgDP (FgE)_neo antibody and following results were obtain.
Anti-FgDP_neo antibody, purified by affinity chromatography to remove antifibrinogen activity, did not show any cross-reactivity with fibrinogen, but showed apparent cross-reaction to early products revealed by inhibition curves of double antibody method (RIA).
The result indicated that FgDP_neo antigen is exposed at early stage of fibrinogen degradation process. This antibody reacted with fibrin degradation products as well as fibrinogen degradation products.
In most of patients with malignancy, high level of FDP was detected in both plasma and serum. Some of them had elevated levels of FDP in plasma with normal levels in serum. This discrepancy was assumed to be due to the increased early (clottable) products of fibrinogen or fibrin in plasma which was removed in serum.
Thus, it was considered that patients with malignancy generally have elevated levels of FDP in plasma regardless of serum levels, and this hyper-FDP levels in plasma may well be related to the latent fibrinolitic activity in blood.

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The change of fibrinogen level and the problem of its measurements were investigated on 16 patients suffered from peripheral vascular occlusive diseases (DVT, ASO, TAO, CAT, etc.).
Plasma fibrinogen level decreased to 60±55mg/dl 24 hours after the initial intravenous infusion of Batroxobin in doses of 30 to 60μl/kg. And it recovered to the pre-treatment level 6 to 8 days after the termination of Batroxobin administration.
Fibrinogen level measured by thrombin time method was lower than that measured by gravimetric method within 24 hours after the initial Batroxobin infusion. Fibrinogen levels measured by nephelometry (T-G meter) and immunological method (M-Partigen) were higher than that measured by gravimetry and thrombin time method. Prothrombin time was prolonged at a fibrinogen level of below 100μg/dl.
The dose of Batroxobin which decreases fibrinogen level below 60mg/dl 24 hours after the initial infusion of Batroxobin, correlated well with the pre-treated fibrinogen level (r=0.952, Y=21.2X-511.4).
It was suggested from these results as follows:
1) Fibrinogen level measured by thrombin time method might be lowered due to FDP which increased markedly within 24 hours after the initial Batroxobin infusion.
2) Fibrinogen levels measured by nephelometry and immunological method were inaccurate, because of being affected by fibrin monomer or des A fibrin.
3) It is possible to fix a dose of Batroxobin correctly that controls the fibrinogen level below 60mg/dl, with the use of the formula as
μl/kg=pre-treated fibrinogen level/20+25
4) The maintenance dose of Batroxobin might be approximately 25μl/kg, if the plasma fibrinogen level decreases to unmeasurable level just before the Batroxobin administration.

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By use of a newly developed automatic erythrocyte sedimentation curve recorder (sedimentimeter), ESR curves of normal subjects and several patients with augmented ESR were recorded, and the hemorheological characteristics of them were analyzed based on the semi-empirical model of Puccini.
The automatic sedimentimeter differs in principle from the existing ones in that 1) the optical image of the whole sedimentation tube is focussed on a small photoelectronic image sensor (Reticon^®) and (2) the output signals from this image sensor are electronically processed with the resulting curve of the time course of blood sedimentation. Performance of the apparatus was found excellent.
Characteristics of erythrocyte sedimentation process were estimated quantitatively in terms of two parameters of the Puccini's equation, i. e., t₅₀ and 1/b. The accuracy of the approximation was found over 0.96 of correlation coefficient, which seemed satisfactory for the practical purposes.
It was confirmed in normal subjects that t₅₀'s increased almost linearly with the values of hematocrit, while 1/b's were nearly constant. Blood samples obtained from the diseased group which contains one case of diabetes mellitus, rheumatoid arthritis, Hodgkin's disease, thromboangitis obliterans, malignant thymoma (post op.), aneurysm (chronic DIC) and atherosclerotic occlusive disease (post amputation) showed mostly augmented ESR. Parameters of t₅₀ and 1/b in these patients were found in the range of ±175% of normal values, which shows the possible use of these parameters as a diagnostic measure of clinical conditions in some of these diseases.

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Red cell deformability (RCD) is closely related with non-Newtonian flow property of blood as well as with red cell survival time in blood circulation. The abnormality of RCD has recently been observed in various diseases that are thought to cause disturbances of microcirculation, intravascular hemolysis and tissue hypoxia. In this paper the effect of Pentoxifylline on RCD was studied by using a new device of a polycarbonate membrane filter (Nuclepore) and a transducer of the differential pressure type. Differential pressure fluctuations due to the passage of red cell through the Nuclepore membrane could be recorded as a differential pressure curve of red cell filtration in this method.
RCD was measured with a diluted red cell suspension (10×10⁴/mm³) in Trisbuffer NaCl solution of normal osmolarity, 300mOsm/l as a suspending medium. Blood samples were taken from healthy subjects and patients with diabetes mellitus, liver disease and micellaneous diseases.
The effect of Pentoxifylline to modify red cell deformability was investegated under two concentrations of 20μg/ml and 40μg/ml in diluted red cell suspension which was incubated at 37.0°C for two hours. Changes of RCD was estimated from the gap between two pressure difference curves recorded in blood supension with or without Pentoxifylline. Addition of Pentoxifylline increased RCD in both the groups of blood suspension of healthy subjects and patients. Significant increase of RCD was observed in 40% of samples with addition of Pentoxifylline 20μg/ml and in 77% of those with 40μg/ml, respectively.

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Wound healing is very imortant in surgery.
In the process of wound healing, the development of granulation tissue is necessary, and here the enhancement of insoluble fibrin is essential.
As development of the insoluble fibrin clot plays an important role in the process of wound healing, we carried out studies to immobilize thrombin and Factor XIII on absorbable gelatin sponge and suture materials, which would hopefully enhance the local accumulation of fibrin.
A gelatin sponge sheet (5×2.5×0.5cm) was immersed into a solution containing thrombin and Factor XIII and then it was lyophilized. DEXON (polyglycolic acid gut) and Cat gut were also treated by the same methods. Nylon gut had been dehydrolized with 3N HCl and then thrombin and Factor XIII were immobilized on the surface.
Each material was incubated in normal human plasma to test the activities of the proteins immobilized.
Fibrinogen levels and FDP in the plasma were measured before and after the incubation. Fibrinogen levels were detected by the method of turbidimetric analysis and FDP, by Latex coagulation method. All materials were studied histologically. Non-treated materials were served as controls.
The fibrinogen levels in the plasma incubated with the immobilized materials decreased remarkably and the FDP levels varied.
The histology showed that a large amount of fibrin had accumulated on the treated materials, however, no fibrin formation was observed on the controls.
In vivo study is now underway.

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The Chandler's loop method has been widely used for producing thrombus in vitro and evaluating thrombolytic agents. In the present study, the Chandler's loop method was used for evaluation of thrombic and thrombolytic states in 50 normal subjects and 20 patients with cerebral thrombosis. In normal subjects, the experimental clot showed increase in weight with progression of age, while thrombolytic effect showed little correlation with the age. The clot weight from stroke patients immediately after the onset of accident varied from twice of, to less than, the weight from normal subjects, and thrombolysis in vitro by Urokinase tended to occur more easily in larger clots. Correlation between decrease in thrombus weight and increase in thrombolytic rate were observed in convalescent stage of the disease. Within 2 weeks after discontinuation of Urokinase treatment, an acute rebound rise in thrombus weight was frequently seen. Experimental thrombus formation and thrombolytic rate in the present study might be correlated to the homeostatic balance in the normal and the diseased and reveal some aspects of pathophysiological mechanisms in thrombosis.

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Close relation of an experimental gastric ulcer development to coagulative, fibrinolytic and kinin systems has been widely recognized. In the present study, the fluctuations of coagulative, fibrinolytic and kinin systems in passage of time were compared against the morphological alteration in the ulcer healing process. Male adult beagles were used as experimental animals, and an acute gastric ulcer (UL-II) was produced in each by contact freezing of the branches of gastric arteries on the serosal side in the lower corpus. The tissue plasminogen activator levels in the ulcer region, surrounding embankment and in distant normal regions continually lowered for 24 hours, after which they all recovered to the normal levels. The plasma plasmin inhibitor levels started to be elevated after the passage of 24 hours, but returned to their normal range in 2 weeks. The plasma plasminogen stayed relatively unchanged throughout the process. The coagulation factors V and VIII were low untill the end of the 2nd week, after which they returned to normal. The kinin like peptide activity was low throughout the first week, showed marked release in the 2nd week, and was restored to normal at the end of the 4th week. The histologic view and microangiogram revealed repair and a marked change in fine vessels consisting of variegated and dense hyperplasia in the 2nd week, while the coagulative, fibrinolytic and kinin systems also underwent changes of a similar pattern, which indicates that the former was correlated to the latter.

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The analysis of the blood coagulation and fibrinolysis system was performed to evaluate the effect of splenectomy for the patient of hepatic cirrhosis and the degree of recovery of hepatic function after surgical procedures.
Seventeen patients with known hepatic cirrhosis were selected for study. All patients were performed splenectomy, devascularization, and esophageal transection, and were investigated about blood examination, biochemical test, blood coagulation and fibrinolysis test.
1) Preoperative platelet count was 9.8×10⁴±1.0 (SE). After splenectomy it was increased to 22.5×10⁴±2.1 significantly. As platelet function, it showed high activity preoperatively but after operation normalized. On the other hand, there was a high statistical correlation between platelet count and weight of removed spleen. (r=-0.57, p<0.001).
2) The preoperative fibrinogen (Fbg.) level was lower than normal and this thend was not changed after operation. In the prothrombin time (PT) and the hepaplastin test (HPT), the vitamin K dependent factors were decreased in cirrhotic patients and it's values were not recovered by the operation. The Fbg. and PT level of preoperative cirrhotic patients were well correlated with their serum albumin level.
3) In cases of which the fibrinogen and fibrin degradation product (FDP) value showed more than 10μg/ml, the disappearance of FDP was not observed until about 4 weeks after the operation. There is a high statistical correlation between the Fbg. and FDP in cirrhotic patients (r=-0.67, p<0.001).
4) The patients having continous fever after splenectomy showed low platelet count and low level of Fbg. postoperatively.

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Previously, Lee & Walsh reported that the FDP was cleared by the RES. And we reported previously that the change of blood coagulation factor VIII are closely related to the activity of the RES.
Hepaplastintest (HPT), Thrombotest (TT), Prothrombin time (PT), blood coagulation factors I, V, VII, VIII, plasminogen, plasmin inhibitor plasminogen activator and FDP were measured in 5 patients with fulminant hepatitis and in mice with MHV-2 hepatitis.
The following results about FDP in blood were obtained.
1) In mice with MHV-2 hepatitis, the FDP in blood increased with the progression of hepatic necrosis. And furthermore, hepatic necrosis progressed, the FDP in blood decreased.
2) Increased FDP and increased factor VIII suggested primary fibrolysis.
3) Increased FDP and decreased factor VIII suggested secondary fibrinolysis.
4) Decreased FDP and increased factor VIII suggested hyperclearance of FDP by the RES.
5) Decreased FDP and normal factor VIII suggested slight hepatic necrosis.
6) Decreased FDP and factor VIII suggested final stage.
Therefore, FDP was determined by two important factors producing FDP by hepatic necrosis and clearing FDP by the RES.

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The function of coagulation and fibrinolysis was examined in various hepatic diseases. Coagulation and fibrinolytic test such as prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombotest (TT), plasminogen (plg), FDP, antithrombin III (AT-III), α₁-antitrypsin (α₁AT), α₂-macroglobulin (α₂M), inter-α-trypsin inhibitor (IαI), α₁-antichymotrypsin (α₁X) and immunoglobulin were measured in 75 cases with various hepatic diseases.
In acute hepatitis, PT prolonged, but fibrinogen and α₁AT slightly increased, α₁X slightly decreased, and FDP and TEG showed almost normal range.
In chronic hepatitis, PT prolonged, fibrinogen, α₁AT and α₂M increased, plg and IαI slightly decreased, TEG k prolonged, TEG r and TEG ma showed almost normal range.
In liver cirrhosis, PT significantly prolonged, but aPTT, TT, fibrinogen and FDP showed almost normal range. On the other hand plg, AT-III and IαI significantly decreased, and α₁AT and α₂M increased. Alpha₂M, AT-III and plg were remarkably decreased in a group which PT showed more than 14 seconds.
Relationship between PT and α₂M or AT-III or plg were negative. Positive correlation between PT and FDP was observed. Correlation between AT-III and α₂M or IαI were positive. And correlation between plg and α₂M or IαI were positive. TEG k prolonged. TEG ma decreased.
In primary hepatoma, PT prolonged, α₁AT, α₁X increased, and AT-III, IαI and plg decreased. TEG k shortened. TEG ma increased.
It was demonstrated that the identification of coagulation and fibrinolysis is an indispensable tool in the diagnosis as well as in the evaluation of the course and prognosis of diseases of the liver.

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We have studied experimentaly the influence of coagulofibrinolysis system and platelet on the metastases of cancer.
In this series especially, the hepatic metastasis was investigated on the effect of liver cirrhosis. Cirrhosis was produced by CCI₄ injection i. m., 2 times a week, for 6 months in rats.
Result; Hepatic metastasis in liver cirrhosis after the intraportal injection of AH130 and AH66F cells, increased remarkably as compared to controls without cirrhosis.
The laboratoly findings of blood and tissue was examined during cirrhosis production.
At the early phase, fibrinogen and antiplasmin increased, but at the time of completed cirrhosis, fibrinogen and antiplasmin decreased inversely. At the time of tumor cells injection, cirrhosis groupes has a hyperfibrinogenemia, high level of antiplasmin and more high level of tissue thromboplastin activity than normal liver groups. Addly, intrahepatic portal vein branch of cirrhosis showed narrowing and stenosis by microangiography. Also, the hepatic metastasis increased in normal liver by injection of tumor cells added ADP (Adenosine diphosphoric acid).
Discussion; The increased incidense of hepatic metastasis may be due to the disturbance of microcirculation and hypercoagulability of blood and tissue.
Our clinical studies indicated of 38 cases with hepatic metastasis of gastric and colo-vectal cancer. 9 cases were present liver cirrhosis.
Therefore, we suggested that the hematogenous metastasis were influenced by coagulo-fibrinolysis system and platelet in the liver as well as the lung, and the difference between clinical and experimental studies was made on the phase of liver cirrhosis.

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The platelet specific protein, β-thromboglobulin (β-TG) is released into the circulation when blood platelets undergo the release reation.
Plasma β-TG levels in several thrombotic diseases were measured by radio-immunoassay kit (Radiochemical Centre).
The results were as follows,
1) Normal β-TG levels was 33.6±22.6 (±SD) ng/ml (n=29).
2) In arterial and venous thrombosis, β-TG levels were significantly increased in comparision with normal levels.
3) In several thrombotic diseases, β-TG levels were usualy increased after U. K. therapy.
But, in effective case of U. K., β-TG levels were decreased to normal range.
4) In other thrombotic diseases, for example, diabetes mellitus and malignant diseases (carcinoma etc.), β-TG levels were significantly increased.
5) We could find the negative correlation between β-TG and platelet count in PRP.
Conclusion:
From the above results, it's concluded that plasma β-TG levels shows signicant increase and closely related to platelet count in thrombotic diseases.
We also found that the measurement of β-TG is a good indicator to evaluate the effectiveness of thrombolytic therapies.

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In addition to the coagulation and fibrinolytic activities, changes in plasma C₃, C₄ and C₁INH levels were investigated in 52 patients with obstructive jaundice. Increase of fibrinogen levels and prolongation of euglobulin lysis time (ELT) were the common features in patients without cholangitis. Whereas, patients with cholangitis showed more prominent prolongation of activated partial thromboplastin time and ELT, and reduction of thrombotest values, hepaplastintest (HPT) values, antithrombin III levels and plasminogen levels than those without cholangitis. These abormalities improved favorably after the appropriate biliary drainage. A marked reduction of plasminogen levels associated with prolonged ELT was considered to be an unfavorable sign suggesting a significant risk of major complications especially acute gastrointestinal hemorrhage and shock after the biliary drainage. The postoperative rise of HPT values and plasminogen levels, which occurred generally in the control group, was not proved in the patients who had the postoperative complications especially gastrointestinal hemorrhage and liver failure.
Among the complement system, levels of C₃, C₄ and C₁INH showed a significant increase in obstructive jaundice. Increased levels of C₃ and C₁INH improvedd significantly after the biliary drainage. There was a significant correlation between the levels of C₁INH and ELT. This result suggested that the increase of plasma C₁INH levels should play a certain role in decrease of fibrinolytic activity in obstructive jaundice.

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Fibrinopeptide A (FPA) in both urine and plasma was measured using radioimmunoassy in order to confirm the presence of intrarenal coagulation in renal disease. Patients were divided into 2 groups according to the urinary FDP (mg)/urinary protein (g) ratio: Group A, patients with above 1.0 of the ratio. Group B, patients with less 0.5 of the ratio.
The results were as follows: (1) Urinary FPA did not correlate to plasma FPA. (2) Urinary FPA were significantly high in group A, but were normal in group B. (3) The renal functions of group A were all markedly deteriorated. But, the renal functions of group B showed widely spread values. (4) Heparin administration on group A patients reduced their urinary FPA with improvement of renal functions and azotemia.
These results indicate: (1) Above 1.0 of urinary FDP (mg)/urinary protein (g) ratio and high urinary FPA reflect the presence of extensive intrarenal coagulation. (2) Extensive intrarenal coagulation was occured only in the patients with markedly deteriorated renal functions. (3) These patients were only a few in renal disease patients. (4) It might be difficult to get good clinical improvement in chronic patients even when intrarenal coagulation is both accuratetly detected and completely eliminated by anticoagulants. (5) However, anticoagulant therapy has proved to be benificial in acute pacients with extensive intrarenal coagulation.

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小児急性糸球体腎炎 (AGN), ネフローゼ症候群 (NS), および紫斑病性腎炎 (PN) の腎糸球体光顕像とフィブリノゲン (Fg), 第VIII, XIII因子の血中濃度および糸球体内沈着度について比較検討した.
AGN急性期の光顕像が Diffuse mesangial proliferation を呈する患児の糸球体毛細管壁にはFg, 第VIII因子関連抗原 (VIII R: AG), 第XIII因子 Subunit A (XIII-A), Subunit S (XIII-S) の軽度の沈着が見られ, また同時期の血中Fg量は軽度高値を, 一方第XIII因子は逆に低下する傾向にあった. これに対し遷延期や恢復期の患児の糸球体内にはVIII R: AG, XIII-Aの沈着はなく, また, 血中Fg, 第XIII因子は正常域にあった.
NS増悪期の血中Fg, 第VIII, XIII因子は高値を, 寛解期では正常域に復していた. Minimal change を呈する患児の糸球体内には各凝固因子の沈着はなかったのに対し, Mesangial proliferation や Focal sclerosing を呈する患児では, Fgの沈着が強く, またVIII R: AG, XIII-A, XIII-Sの軽度の沈着が認められた.
PN急性期の血中Fg, 第VIII因子活性 (VIII: C), VIII R: AGは高値にあった. また光顕像で半月体形成を伴う患児では, 発症後の時期には関係なく, 血中XIII因子の低下がみられた. PN患児の大部分の糸球体内には, Fg, VIII R: AG, XIII-A, XIII-Sの沈着がみられまた強いFgの沈着が特徴的であった. Fgの沈着は, 半月体内にも観察されたのに対し, VIII R: AG, XIII-A, XIII-Sは半月体内には存在せず, 管腔内にみられた.

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The role of platelets on the progression of immune complex induced nephritis (BSA nephritis) was examined in the albino rabbits, and the effect of dipyridamole was tested.
All animals were sensitized with 3mg of BSA with adjuvant followed by 2 shots of BSA (250mg and 500mg) on the 3rd day and the 10th day after the initial BSA injection, respectively.
All animals were examined for urinary protein contents, platelet number, platelet volume, platelet aggregability induced by ADP and collagen, fibrinolytic activity and blood coagulation. Animals were killed for the histological examination of the kidney on the 16th day after the initial administration of BSA.
The control group (9 cases) developed lesions which revealed glomerular endothelial-mesangial cell proliferation, and animals which received low dose of dipyridamole (2.5mg/day, i. v., 9 cases) developed more severe glomerular endothelial-mesangial cell proliferation and interstitial cell infiltration than non-treated groug, however, the group which received moderate dose of dipyridamole (10mg/day, i. v., 5 cases) showed mild glomerular changes.
The level of proteinuria was 1.0-308mg/day (mean±SE; 56.0±27.5mg/day) in the control group; 51-340mg/day (268±115.6mg/day) in the low dose therapy group. The level in the moderate dose group is in study.
The platelet volume decreased in the control group, and the platelet number increased in the low dose therapy group. The disaggregation induced by ADP was prominent in the control and the low dose therapy group. These data suggest that the large size of platelets may be consumed by BSA injection in the control group.
All three groups revealed hyperfibrinogenemia, high level of serum fibrinogen/fibrin degradation products, and low plasminogen activator activity after BSA treatment, and there were no differences between these groups. These results indicate that the hypercoagulability and the comparative lower fibrinolytic activity occurred in non-treated and treated group, and these states seem to influence the progression of this nephritis. Judging from the results of histlogical study, adequate dose of dipyridamole may have beneficial effect, but low dose of dipyridamole may have adverse effect on this nephritis.

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This study elucidates the relationship among hypercoagulability, microviscosity of platelet and lymphocyte, and lipids in serum and platelet of hyperlipidemic patients, especially of diabetes mellitus. The effect of pantethine on these parameters is also studied.
The microviscosity was measured with the microviscosimeter (The Elscint Co. Ltd. Israel) using DPH labeling at 25°C for 60min. Aggregation of the platelet induced by ADP was obtained with the Sienco dual sample aggregation meter (The Sienco, Inc. USA). Pantethine (The Daiichi-Seiyaku KK, Japan) was injected intravenously 10mg/kg or 100mg/kg and the venous blood added heparin or sodium citrate was taken before and 15min after injection. In vitro effect of pantethine on the microviscosity of platelets and lymphocytes was also studied successively at 15, 60, and 180min after incubation.
The microviscosity of healthy lymphocytes was 2.88±0.140 (M±SD) at 25°C, and 2.86±0.275 in diabetic lymphocytes with greater variation than healthy lymphocytes. Serum phospholipid was well correlated negatively with lymphocyte microviscosity (r=-0.34, p<0.05), but not with cholesterol, triglyceride and free fatty acid. Higher microviscosity was observed in platelets than lymphocytes, and in healthy platelets than diabetic platelets. Pretreatment (extra vivo) of healthy and diabetic platelets with pantethine at 10mg/ml concentration increased their microviscosities. Intravenously injected pantethine (10mg/kg) decreased ADP aggregation in 33.3% of cases, and increased in 26.7% at 15min after injection. Phospholipid in cases of decreased ADP aggregation reduced after injection of pantethine in both serum and platelets, in spite of few changes in cholesterol of serum and platelets, and in triglyceride and free fatty acid of serum. Fifteen min after injection of 100mg/kg of pantethine, the microviscosity increased slightly in platelets and lymphocytes in 2 diabetic patients out of three.
Incubation of platelets and lymphocytes in vitro with 1, 10, 100mg/ml of pantethine, the microviscosity increased at 60min in platelet and at 15min in lymphocyte.
As conclusion, the microviscosity of platelets was higher than lymphocytes. Healthy platelets had higher poise than diabetic platelets. Pantethine increased microviscosity of platelets and lymphocytes in vivo as well as in vitro. These changes of microviscosities were correlated with phospholipid level in serum and platelet negatively and molar ratio of cholesterol/phospholipid, positively.

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The cases of pregnant patients with the congenital coagulation factors deficiency, or its reduction, who underwent successful deliveries are very uncommon, so the management of hemorrhage during pregnancy and labor has not been established. As we experienced 6 cases (10 pregnancies) of the congenital coagulation disorders, we analysed the change of coagulation factors during pregnancy and clarified the change of hemostatic mechanism during pregnancy and the management of labor.
The activity of factor VIII in plasma increased during pregnancy, namely 108±10.2% in non-pregnant women, 150±53% in pregnant women at 3rd month, 173±47% at 5th month, 250±76% at 8th month. Also in plasma of factor VIII deficiency patients, such as von Willebrand's disease, mild case of hemophilia A carrier, its activity increased during pregnancy and exceeded 100% at 10th month, so they underwent successful deliveries without any replacement therapy. But in one case of severe hemophilia A carrier, factor VIII activity in plasma didn't increase over 20% of normal, so she, who underwent Cesarean section because of CPD, was treated with AHF replacement therapy. In this case hemorrhage from uterine cavity was normal, but hemorrhage from the operative wound couldn't be ceased easily.
We concluded as follows:
1. Even in patients of the congenital coagulation factors deficiency decreased activity of coagulation factors increases during pregnancy.
2. Even in these patients hemorrhage from uterine cavity can be ceased by the biological ligation of uterine muscle and by the extrinsic coagulation mechanism of tissue thromboplastin in placenta and decidua.
3. Hemorrhage from the wound of laceration or incision can't be ceased without replacement therapy.
4. Therofore careful, intentional and vaginal delivery is the absolute principle. Cesarean section should be elected for obstetric reasons only.
5. The heredity to newborn infant should be considered.

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The influence of various acid glycosaminoglycans on the platelet spreadability (PSA) was studied, along with the platelet aggregation test (PAT) and ADP aggregation test.
Acid glycosaminoglycans; chondroitin-6-sulfate (chondroitin A) dermatan sulfate (chondroitin B) and chondroitin-4-sulfate (chondroitin C) present in vascular endothelirium and heparin, amyropectin sulfate, amylose sulfate, glycogen sulfate and glycogen were added to PRP at the concentration of 0.0025mg/ml after 15 minutes, the number of platelets adhering to the plastic plate was counted to ovserve the spreading of platelet. PAT was conducted by Breddin I method and ADP aggregation induced by 10^-5M. ADP was measured in the same sample.
Addition of chondroitin C resulted in a marked decrease of the plastic plate adhesion on the plastic plate with disturbance of platelet spreading, indicating a definite inhibition of PSA. PAT was mildly inhibited. Chondroitin A and B mildly inhibited PSA but the responses of PAT were variable. Heparin definitely augmented both PAT and PSA with an increase of platelet adhesion on plastic plate. Amylose sulfate and amylopectin sulfate failed to influence the spreading definitly. While glycogen sulfate augmented PAT and PSA, glycogen exerted no such action. No difinite change occurred in aggregation in response to any of these substances tested.
Three of the acid glycosaminoglycans present in the vascular endothelium inhibited platelet spreading and interfered with the platelet adhesion to the plastic plate. Especially chondroitin C most abundantly found with in the endothelium showed a marked inhibitly effect. Heparin, on the contrary, interestingly augmented platelet adhesion at 0.0025mg/ml. Other acid glycosaminoglycans showed no inhibitory action on platelet adhesion. These observation provably suggest the relationship between acid glycosaminoglycans in the vascular endotherium and platelets.

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The effect of a novel compound, cilostamide [OPC-3689 N-cyclohexyl-N-methyl-4-(1, 2-dihydro-2-oxo-6-quinolyloxy) butyramide] on cyclic nucleotide metabolism and in vitro aggregation of platelets was investigated. The concentrations of cilostamide producing 50% inhibition of rabbit platelet aggregation induced by 7.5μM ADP, 20μg/ml of collagen and 40μg/ml of arachidonic acid were 17, 1.3 and 1.6μM, respectively. Single addition of cilostamide did not affect significantly adenosine 3′:5′-monophosphate (cyclic AMP) content but increased the cyclic AMP level of platelets in the presence of prostaglandin E₁ in a dosedependent fashion at concentrations ranging from 0.1 to 10μM, suggesting that this drug inhibits cyclic AMP degradation (phosphodiesterase) rather than stimulates its biosynthesis (adenylate cyclase). In fact, cilostamide inhibited specifically platelet cyclic AMP phosphodiesterase which was separated from guanosine 3′:5′-monophosphate (cyclic GMP) phosphodiesterase by DEAE-cellulose column. The Ki value of the drug for cyclic AMP phosphodiesterase was 0.005μM and the Ki value for cyclic GMP phosphodiesterase was 5.5μM. Cilostamide was approximately 1, 000 times more potent as an inhibitor of human platelet cyclic AMP phosphodiesterase than of cyclic GMP phosphodiesterase. The Ki value of cilostamide is the lowest among reported Ki values of the phosphodiesterase inhibitors.

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It is well recognized that increased platelet stickness and aggregation are the major causes of thrombosis at the sclerotic intima of the arteries. The purpose of this study is to evaluate the platelet consumption in patients with the ischemic heart disease, especially with myocardial infarction, by measuring the plasma Beta-thromboglobulin (Beta-TG).
MATERIALS AND METHOD: Control group, 29 healthy young adults (19 males, mean 25.1yrs and 10 females, mean 21.2yrs) and 11 middle aged men (mean 36.8yrs) are volunteers who have no atherosclerotic change. Patient group consists of myocardial infarction (23 males, mean 59.3yrs and 3 females, mean 60.3yrs) and angina pectoris (8 males, mean 51.6yrs and 3 females, mean 64.7yrs). The plasma Beta-TG were measured with the RIA kit^® (Radiochemical Centre, Amersham, England). In cases with myocardial infarction, the Beta-TG measurements were performed during the three periods. Coronary angiography (CAG) was performed in the 21 patients (11 myocardial infarction and 10 angina pectoris). Twenty one cases were divided into 4 groups according to the severity of stenosis.
RESULTS: The Beta-TG levels in each group were as follows, a) Control: 29.6±18.7ng/ml. b) myocardial infarction: 74.4±43.0ng/ml (during 0-2 days), 34.4±21.0ng/ml (during 3-30 days) and 51.0±26.5ng/ml (after 30 days), respectively. The mean levels during the acute phase (0-2 days) and the chronic phase (after 30 days) were significantly higher than the control (P<0.01) (Fig. 1 and 2).
The Beta-TG level in angina pectoris group (without recent attack) was 30.6±12.4ng/ml which was not significantly different from the control. The 17 patients without aspirin administration were classified in 4 groups depending on the number of the stenosed coronary arteries. Their Beta-TG levels were as follows: P. C. 28.5±8.9ng/ml, S. V. D. 48.8±19.8ng/ml, D. V. D. 58.2±14.8ng/ml and T. V. D. 53.7±22.4ng/ml. Four cases with stenosis had been administered aspirin. The Beta-TG levels of these 4 cases were 22.9±5.4ng/ml which was not significantly different from the control.

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Coagulation-fibrinolitic system and platelet in hepatitis, liver cirrhosis, and liver cirrhosis with hepatoma were investigated.
Results:
1) The shortening of ¹³¹I-fibrinogen turnover rate were recognized.
2) In hepatitis, plasminogen and antithrombin III showed the decrease.
3) As regards to the platelet function, the decrease in platelet count and the increase in platelet volume were recognized, but platelet factor 3 availability showed the elevation in several cases.
4) The appearance of endotoxin were recognized.
5) In comparison between Reptilase Time (R. T.) and Thrombin Time (T. T.), the discrepancy of both value, and the prolongation of RT were recognized.
6) Fibrin polymerisation were prolonged in hepatitis, but in several cases of liver cirrhosis and liver cirrhosis with hepatoma fibrin polymerisation were shortened.
Conclusion: From the above results, it was suggested that in hepatitis, thrombotic tendency under hypo-coagulable state were shown, and we considered the possibility of progress to DIC in hepatitis with fibrinogen abnormality due to hepatocelluler damage.

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Native platelets are generally discoid in shape and easily transformed into spheres with pseudopods by various stimuli. Therefore, platelet shape may reflect the state of activation in vivo as well as the state of thrombopoiesis.
This report deals with the platelet shape in disseminated intravascular coagulation (DIC) and hemolytic anemia examined by our method in which glutaraldehyde-fixed platelets are classified into discs (D), hemispheres (HS), spheres (S), bipolar forms (B), others (O), and ones with pseudopods (Ps). The index of platelet shape is calculated from percentage of each form of platelets as follows: Index=D-S/D+HS+S
DIC included acute promyelocytic leukemia (APL; 3 cases), metastatic cancer (5 cases) and obstetrical diseases (2 cases), while hemolytic anemia included hereditary spherocytosis (2 cases), paroxysmal nocturnal hemoglobinuria (PNH; 4 cases) and post valvular replacement (PVR; 5 cases).
In DIC, decrease in D (46.5±23.1%, M±ISD) and increase in S (17.0±19.3%) and HS (29.6±15.6%) were significant as compared with each value of normal subjects (P<0.01, P<0.01 and P<0.05, respectively) and the index (0.325±0.42) was lowered (Fig. 1). Ps did not so much increase as that induced by various platelet aggregating agents including thrombin in the in vitro experiment. The index did not corelate with any tests of blood coagulation and fibrinolysis in these patients. In two cases, however, platelet shape changes were noted at the earlier stage of DIC when only FDP and act-PTT showed a slight change, suggesting a usefullness of this examination for the diagnosis of DIC at an early stage.
In hemolytic anemia, decrease in D (74.1±5.0%) and increase in 0 (11.5±5.0%) and Ps (30.1±6.3%) were significant (P<0.01, respectively). Hereditary spherocytosis, however, showed a normal platelet shape distribution, while PNH and PVR showed a considerable change, suggesting that intravascular hemolysis caused platelet shape changes due to coincident release of ADP from erythrocytes. Platelet shape changes may also reflect dysthrombopoiesis in PNH and blood coagulation in PVR.
In conclusion, the platelet shape in DIC and intravascular hemolytic anemia, apart from the causes, is a sensitive index for a platelet activation in vivo and its examination may be a help for the early diagnosis of these pathological states.

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