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Ten patients participated in this study which evaluated the effect of two heparin dose regimes, a high dose regime (mean dose 6750 IU) and a low dose regime (mean dose 3750 IU), on the thrombin activity, achieved during a 4-hour-dialysis. The thrombin activity was measured by use of the FPA assay. Heparin was administered as bolus dose followed by a constant rate infusion which was discontinued 1.5-2 hours prior to the end of the dialysis. Both dose regimes inhibited thrombin activity equally effectively as long as heparin was administered. In the high dose regime, the FPA levels remained unchanged until the end of the dialyses in all patients. In the low dose regime, six patients had the same FPA values at the end of the heparin infusion and at the end of the dialysis. In the remaining four patients much higher FPA levels were achieved at the end of the dialysis. No serious bleeding or clotting complications occurred, and all dialyses were uneventful.

We observed 70 male patients with a seriously proceeding Chronic myocardial ischemia. They were hospitalised because of frequent, permanent and serious attacks of stenocardia at rest and in stress situations. More than 2/3 of these patients had suffered from a myocardial infarct. In the course of two weeks an intensive therapy with all modern preparations for vasodilatation was made. This therapy proved to be unsuccessful. Nearly all patients were administered more than 10 tables of nitroglycerin per day and, in addition, they were injected analgetics as a compensation of attack. The ultraviolet own blood irradiation (UVB) had a positive therapeutic effect in all patients. There was a good success in 46 patients, in all patients satisfactory results could be registered. The effect of therapy was evident by the decrease of administration of nitroglycerin required, by an increase in the degree of stress capacity, and by an easier treatment of stenocardia attacks. The observation time for patients amounted to 2-8 months. The success of therapy remained in 38 patients. After this time the success of therapy could partially be regained by a repeated number of irradiation series. Then, it remained positive in 9 of 22 patients who had been followed-up for 10 months. The half decay period of eliminating 131I from an intradermal depot could be normalised under the influence of ultraviolet own blood irradiation. This ultraviolet own blood irradiation had no significant influence on the fibrinogen level, fibrinolytic activity, and erythrocyte aggregation (examined in 11 patients). A 2 1/2-fold diminution of monomer fibrin complexes in the blood could be observed. The titre of antistreptolysin-O was increased in all patients who had got over the infarct. It had completely normalised a week after finishing the ultraviolet own blood irradiation. Spectroscopic examinations of the blood and plasma made after ultraviolet own blood irradiation revealed that this irradiation will not only affect the properties of Hb, but will also cause a photochemical transformation accompanied by a destruction of some plasma proteins, of the membrane of formed blood elements, and a photosynthesis of biochemically active compounds. The mechanism of action of ultraviolet own blood irradiation is complicated and requires further exact investigations. Even today, however, this method can be recommended as a complex therapy in patients with severe myocardial ischemia.

To assess the nature of the hemostatic abnormalities associated with chronic liver disease, we have simultaneously evaluated the kinetic of radiolabeled platelets, fibrinogen, and plasminogen, together wit tests of platelet and fibrinogen function, and coagulation factors in 60 patients with documented, severe but stable cirrhosis of the liver. The mean platelet survival was substantially reduced (5.8 +/- 1.7 days compared with 9.5 +/- 0.6 days in normals, p less than 0.0001) and splenic sequestration of platelets was increased (mean recovery was 47% +/- 18 vs. 65% +/- 5 in normals, p less than 0.0001). Nevertheless the mean platelet count was nearly normal because platelet production was increased nearly twice normal values (mean turnover was 64,000 +/- 33,000 platelets/microliter/day; p less than 0.0001). The mean rate of fibrinogen removal was shortened (p less than 0.0001) and fibrinogen turnover increased about 20% (p = 0.008) while the mean fibrinogen concentration was not different from the results in normal control subjects (p = 0.212). Autologous and homologous fibrinogen disappeared from the circulation at equivalent rates (r = 0.751; p = 0.008), indicating that fibrinogen from cirrhotic patients was not kinetically different from normal fibrinogen. The mean plasminogen survival was significantly shortened (p less than 0.0001), but the mean plasminogen turnover was not increased (p = 0.388). Thus the plasminogen concentration was reduced (p less than 0.0001). For platelets, fibrinogen, and plasminogen, the production rate was the most important determinant of the concentration in the circulation. The administration of heparin to cirrhotic patients improved the survival of fibrinogen but not of platelets. LeVeen valve implantation generally resulted in parallel shortening of both the platelet and fibrinogen survivals and concentrations. Platelet function as assessed by template bleeding time, platelet retention by glass bead columns, and aggregation induced by ADP, epinephrine, and collagen was normal. Fibrinogen determinations by the Clauss and Jacobsson techniques were equivalent, indicating that the ability to polymerize fibrin monomer was not detectably altered. Sixty percent of patients had an abnormal prothrombin time and half that number had a prolonged partial thromboplastin time. Although most patients had a modest decrease in the prothrombin complex coagulation factors, fibrin degradation products were, in general, not elevated in the circulation. The wide range of values observed suggests that a number of different and complex processes may be ongoing in different patients. Overall, the kinetic data suggest that platelets are initially consumed, perhaps on incompletely endothelialized endovascular surfaces in the liver, and that fibrin subsequently forms secondary to local stasis. The absence of increased production of fibrinogen and plasminogen despite shortened survival times reflects the reduced capability of the cirrhotic liver to increase protein synthesis.

The influence of qualitative and quantitative changes in plasma fibrinogen upon the amount of heparin precipitable fraction (HPF), obtained during the course of acute disease states, were examined. Whereas fibrinogen in plasma includes 3 species of different molecular weights (HMW, LMW, LMW'), fibrinogen in HPF, from normal as well as from "acute phase" plasma, consisted almost exclusively of HMW-fibrinogen (3% SDS-PAGE). Sub-unit chain electrophoresis (10% PAGE-SDS and two-dimensional electrophoresis) did not disclose any signs of abnormalities in the fibrinogen precipitated in HPF. Studies on patients revealed that the composition of plasma fibrinogen changed (increased HMW) during the course of acute myocardial infarction and following hip operations, and indicated that the amount of HPF was governed by the relative amount of HMW-fibrinogen as well total fibrinogen. This assumption was strengthened by quantitating the amount of HPF obtained after addition of highly purified HMW and LMW fibrinogen to normal and "acute phase" plasma. It is concluded that fibrinogen quality (per cent HMW or HMW/LMW ratio) is of major importance for the amount of HPF, thereby explaining some of the HPF-variations seen during the course of acute diseases.

Disseminated intravascular coagulation is often characterized by organ failure and bleeding. By use of light microscopy, previous studies have shown extensive fibrin deposition in vessels. However, quantification of fibrin deposition using ultrastructural methods has not been reported. In this study dogs were infused with thrombin, and disseminated intravascular coagulation developed. Using a blinded morphometric analysis method, we observed deposition of fibrin in nearly half of the microvascular vessels. Such deposition probably accounts at least for part of the organ dysfunction. Almost half the vessels also had altered endothelial structure including thinning of the endothelial membrane, formation of extremely thin spots, fenestrations, and even a few ruptured areas. These findings at least in part explain the extravasation of blood in disseminated intravascular coagulation.

The enhancement of canine arterial thrombolysis with native tissue type plasminogen activator (nt-PA) obtained from human-derived normal cells by pretreatment with heparin or the defibrinogenating agent, batroxobin, was evaluated with angioscopy. The nt-PA, 0.25 mg/kg, was infused intravenously to lyse 1-hour-old thrombus (eight thrombosed arteries without medication, seven with nt-PA alone, seven with nt-PA and heparin, and seven with nt-PA plus batroxobin). Angioscopy provided a cross-sectional view of the vessel lumen with clear visualization of the thrombus. Thirty minutes after nt-PA infusion, the percent luminal obstruction decreased from 74 to 61 in nt-PA alone (p less than .025), from 77 to 37 in nt-PA plus heparin (p less than .005), and from 79 to 25 in nt-PA plus batroxobin (p less than .005). Fifteen minutes after drug infusion, plasma fibrinogen levels decreased to 89% of preinfusion value in nt-PA alone, to 84% in nt-PA plus heparin, and to less than 5% in nt-PA plus batroxobin. Thus rapid infusion of nt-PA alone provided slight thrombolytic effects. However, heparin and batroxobin showed marked enhancement of thrombolytic effects of nt-PA.

In 13 patients with effusions of varying etiology, considerably higher fibrinopeptide A (FPA) immunoreactivity were found in the effusions than in the corresponding plasmas. After instillation of heparin into the effusion the FPA concentration diminished significantly but very slowly. The difference in concentration between plasma and effusion therefore represents a relative FPA accumulation in the effusion. In view of its extremely short half-life in plasma, the FPA produced in the effusions is thought not to contribute to the increased plasma FPA levels. In addition, injection of amounts of FPA into the effusion such as to produce an acute increase of the local FPA level did not lead to a significant change in the FPA level in plasma.

Incubation of plasma with granulocyte enzymes in the presence of kallikrein inhibitor resulted in a prolonged thrombin time of the plasma and in an increased level of fibrinogen fragments, indicating that fibrinogen was digested. In accordance with this, fibrinogen digestion products could be purified by affinity chromatography from plasma after incubation with granulocyte enzymes. The isolated products resembled early X-like fibrinogen fragments, which are produced by limited digestion of purified fibrinogen with elastase. On SDS gel electrophoresis both had no intact A alpha-chains, but apparently intact fibrinogen B beta- and gamma-chains. Also, both fragments isolated from plasma and the X-like fragments produced with purified elastase had a low anticoagulant activity. Although elastase, the main fibrinolytic enzyme of the granulocyte, was rapidly complexed with inhibitors, 10-20% of the elastase activity towards succinyl-trialanyl-paranitroanilide was detectable in plasma no matter if the mixture of granulocyte enzymes or purified elastase had been added. A possible role for the alpha 2-macroglobulin-granulocyte elastase complex in the production of the digestion products in plasma is discussed.

In the determination of plasma fibrinogen by electroimmunodiffusion, commercial sodium heparin, previously included in the agarose gel, by interacting with fibrinogen molecules, enhances their anodic mobility more strongly than after carbamylation with potassium cyanate. The proposed method provides an increase in sensitivity and specificity which practically eliminates the influence of fibrinogen degradation products.

This study reports an unusual subpopulation of rats bearing transplanted tumors approximately 50% of the total and apparently unrelated to the presence of metastases, that exhibited shortened bleeding times despite reduced platelet numbers and/or fibrinogen levels. The remaining rats exhibited the expected inverse relationships between bleeding time and platelet numbers and/or fibrinogen level. Tumors were hepatomas and squamous cell carcinomas initially induced in the Fischer strain of rats and carried by passage through tissue culture or syngenic recipient animals.

To try to define the significance of disseminated intravascular coagulation (DIC) in head-injured patients, we correlated clinical, laboratory, and pathological findings in 16 patients with head injury as their main problem who had DIC, who died within 4 days of injury, and who were examined postmortem. Patients were ranked according to the number of abnormal laboratory screening tests for DIC and the severity of these abnormalities. The most frequently abnormal laboratory tests were the fibrinogen degradation products and fibrinogen, followed in order by the activated partial thromboplastin time, prothrombin time, and thrombin time. The platelet count was the least abnormal value. The patients with the fewest abnormalities had the least abnormal computed tomographic scans. Autopsy reports revealed necrosis and bleeding in the brain and in a number of other organs, particularly the lungs. Microthrombi were not reported in the original autopsy reports. However, when these cases were reevaluated and their slides were stained with an immunoperoxidase technique using rabbit anti-human fibrinogen antiserum, microthrombi were seen frequently. Large microthrombi were more common in patients who had died within less than 24 hours, suggesting a relationship to death or to less time for lysis. In order of frequency, the brain/spinal cord, liver, lungs, kidneys, and pancreas were most commonly affected, and the liver, pituitary gland, pancreas, thymus, brain/spinal cord, large intestine, kidneys, and lungs had the greatest density of microthrombi. Pulmonary dysfunction had been a frequent problem in these patients, which may have been related to the high incidence of microthrombi and bleeding found in the lungs.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated the influence of an acute inflammatory reaction that triggers the synthesis of exportable proteins by hepatocytes on liver regeneration after partial hepatectomy, which induces the synthesis of proteins necessary for liver cell proliferation. In hepatectomized rats with a turpentine-induced acute inflammatory reaction, the first peaks of hepatic DNA synthesis and mitosis were significantly inhibited compared with pair-fed controls subjected to partial hepatectomy only, and the liver DNA concentration at various times after partial hepatectomy was significantly lower in the former than in the latter. Inhibition was not obtained when the acute inflammatory reaction was induced 12 h or more before partial hepatectomy, suggesting that the inhibitory effect of turpentine administration depended on early events in the acute inflammatory reaction. These data suggest that one possible mechanism responsible for inhibition of regeneration might be competition at the transcriptional or the translational level between liver syntheses of various proteins, and that, under certain conditions, liver-specific functions might take precedence over regenerative functions.

A multicenter randomized trial of anisoylated plasminogen streptokinase activator complex (APSAC) versus heparin in patients with acute myocardial infarction of less than 4 hours' duration was undertaken in 19 hospitals. Of the 313 patients, 151 received heparin and 162 APSAC (30 U as intravenous injection). Within 28 days of hospital stay, 19 deaths (12.6%) occurred in the heparin group and 9 deaths (5.6%) in the APSAC group (p = 0.032). After 24 hours, patients in the APSAC group had a significantly lower incidence of cardiogenic shock (3.2 vs 9.5%, p = 0.031), asystole (3.8 vs 10.8%, p = 0.015) and need for resuscitation (5.1 vs 11.5%, p = 0.039). There was no difference in global and infarct-related ejection fraction between the 2 groups. Thus, APSAC favorably influences prognosis and clinical course in hospital.

The fibrinolytic response to trauma was investigated in 23 patients. Patients were triaged upon arrival in the emergency center into three groups; group I-patients with significant trauma who maintained normal vital signs, had a good prognosis, and tolerated the trauma well (mean injury severity score 8, range 4 to 12); group II--patients with significant trauma and transient episodes of hypotension, hypoxia, or acidosis who recovered (mean injury severity score 22, range 9 to 38); and group III--patients with profound or continued hypoxia and hypotension who eventually died of the trauma (mean injury severity score 41, range 30 to 50). Serial measurements of prothrombin time, activated partial thromboplastin time, and platelet count; concentrations of fibrinogen, plasminogen, and fibrin degradation products; and assays of euglobulin fraction fibrinolytic activity on plasminogen-free and plasminogen-rich fibrin plates were obtained on all patients. Coagulation studies documented a trauma-related coagulopathy that correlated with the degree of trauma. Plasminogen concentrations were initially depressed in all three groups; however by 24 hours group III patients were noted to have significantly elevated plasminogen concentrations while group I and group II patients had normal plasminogen concentrations. Fibrinolytic activity measured on plasminogen-free and plasminogen-rich fibrin plates was initially increased in all three groups with group III patients demonstrating the greatest increase. Over the succeeding 14 hours fibrinolytic activity returned to baseline values in group I and group II patients while group III patients demonstrated no detectable fibrinolytic activity for the remainder of the study period. This absence of fibrinolytic activity and increase in plasminogen concentrations in group III patients is thought to be caused by depletion of the intravascular plasminogen activator with the subsequent development of a hypofibrinolytic state.

An acute phase reaction was elicited in four horses to which Freund's adjuvant was administered intramuscularly. The localised inflammation was accompanied by changes in the plasma concentrations of copper, iron and zinc. The plasma copper concentration, the plasma ceruloplasmin copper concentration and the ceruloplasmin oxidase activity in the plasma steadily increased to a maximum 24 days after the administration of the adjuvant. At this time, the plasma copper concentration was 2.2 micrograms/ml, a 90 per cent increase over the baseline concentration. The ratio of the concentration of plasma ceruloplasmin copper to plasma copper remained constant, indicating that the non-ceruloplasmin bound copper component of the plasma is also an acute phase reactant in the horse. The plasma zinc and iron concentrations decreased to 59 per cent and 30 per cent of their respective baseline concentrations and the severity of the inflammation appeared to influence the plasma concentrations of each metal. Weak correlations between the plasma fibrinogen concentration and the plasma copper and zinc concentrations of 25 horses with plasma fibrinogen concentrations of 5 g/litre or greater indicated that a single measurement of plasma copper concentration is not useful in the diagnosis of non-specific inflammatory disorders of the horse. However, the results suggest that the plasma copper concentrations in serial samples may be used to monitor the resolution of inflammatory disorders in the horse.

A longitudinal study of coagulation parameters was carried out on 100 Singaporean acceptors using Norplant-2 rods for contraceptive purposes. At the end of 2 years of use, results from this study show a return of platelet count to preinsertion level while platelet aggregation remained significantly enhanced. Thus the net effect of these two changes on an increased tendency for thrombosis needs further evaluation. The PT and APTT continued to remain persistently shortened during the period of use. There was also a general fall in fibrinogen and most other coagulation factors during the two years of use. Thus, again, the net effect of these two changes on the exposed potential for hypercoagulation at the end of the first year needs further evaluation throughout the five years of Norplant-2 use.

Fibrinolysis is a physiological process which aims at dissolving intravascular thrombi and is mediated by activation of plasminogen to plasmin. Streptokinase (SK) and urokinase (UK) are non-specific plasminogen activators. They have proved effective as thrombolytic agents, but their use is limited by the risk of haemorrhages due to systemic fibrinogenolysis. More fibrin-specific drugs have recently been developed. One is a tissue plasminogen activator (t-PA), the other is a urokinase precursor (pro-UK), also called single chain urokinase plasminogen activator (scu-PA). Genetic engineering techniques have resulted in the large-scale production of a "recombinant t-PA" (rt-PA) and a "recombinant scu-PA" (r scu-PA) for therapeutic use, notably in acute myocardial infarction. In vitro, these two drugs exhibit a thrombolytic activity that is equal to, or greater than that of SK or UK. In vivo, their fibrinogenolytic effect is less pronounced, and their thrombolytic effect greater than those of SK or UK. "Acyl-enzymes" have more recently emerged. These are inactive acylated SK-plasminogen complexes which progressively become effective in plasma after deacylation. So far, the most extensively studied of these complexes is BRL 26921 (anisoylated plasminogen streptokinase activator complex, or APSAC) which is administered by bolus intravenous injection. It is more thrombolytic than SK but produces systemic fibrinogenolysis to an equivalent degree. Injected intravenously (by infusion or bolus) during the first hours of a coronary infarction these three new thrombolytic agents have proved effective in promoting coronary reperfusion, with an early coronary patency rate of 70-75%.(ABSTRACT TRUNCATED AT 250 WORDS)

Both clinical and laboratory findings suggest that pregnancy constitutes a hypercoagulable condition; yet none of the observed laboratory changes are specific for thrombosis. An essential step involves thrombin-mediated fibrin generation. In the process, fibrinopeptide A (FPA) is cleaved from fibrinogen. Using a radioimmune assay, FPA was determined prospectively in a longitudinal and cross-sectional fashion. Fibrinopeptide A increased significantly over control by the end of the first trimester, from 1.3 ng/ml to 2.8 ng/ml. It continued to increase until 30 to 32 weeks' gestation and then plateaued at 4.3 to 4.7 ng/ml. In the immediate postpartum period, FPA remains elevated. In conclusion, thrombin generation as reflected in FPA production is increased throughout pregnancy, thus confirming a hypercoagulable milieu.

Blood filtration, hematocrit and fibrinogenemia have been evaluated in 80 patients with cerebrovascular ischemic disease and in 60 control subjects. We compared the results between patients and controls and between patients with and without risk factors. The filtration time of all patients and that of patients without risk factors resulted significantly higher than that of controls. The possible pathogenetic implications of our results are discussed.

Collagen induces a saturable 125I-fibrinogen binding to normal human platelets. A role for secreted ADP in this process is supported by studies on 2 patients with the Chédiak-Higashi syndrome. Both collagen-induced nucleotide release and 125I-fibrinogen binding were strongly reduced while ADP-induced fibrinogen binding was normal. Platelets from 2 patients with the gray platelet syndrome bound normal amounts of 125I-fibrinogen in the presence of ADP or collagen despite the severe reduction of secretable alpha-granule proteins. Binding did not occur to collagen-stimulated type I thrombasthenic platelets which lacked GPIIb-IIIa complexes but was detected in amounts which correlated with the residual concentrations of GPIIb-IIIa in the platelets of a patient with type II disease. Our results allow us to propose that collagen-induced fibrinogen binding to normal platelets requires the presence of GPIIb-IIIa complexes and secreted ADP but proceeds independently of alpha-granule release.

A study on blood clotting has been carried out in a number of obese individuals and compared to a group of non-obese persons, in order to assess if the former can be considered to be in "high risk" regarding the onset of a thromboembolic process. The technique of thromboelastography was chosen. The results point out that in obese people a series of alterations take place, both in the time of clot formation, which is enlarged, as in the organization of its nets, which appear strongly structured, favoured by the hyperfibrinogenemia and thrombocytosis detected in these subjects. Likewise, the effect of a hypocaloric diet on clotting in obese persons has been evaluated and compared with the former groups. Clotting in treated obese individuals is modified in the same way as in the untreated group when compared to the non-obese population; nevertheless, when both groups of obese people are compared, no significant difference is observed in the different parameters studied, even though constants determined in citrated whole blood are closer to normality in the subjects undergoing caloric restriction.

When compared to age-matched control subjects factor VIII-related antigen was found to be significantly increased in patients with peripheral arterial diseases, while there were no significant differences concerning its plasma level between patients with thrombangitis obliterans and those with atherosclerosis of the lower limbs or between the various stages of the disease. Acute phase reactants such as plasma fibrinogen and alpha 1 antitrypsin were changed to a much lesser extent in the initial stages of peripheral arterial disease, and the afore mentioned antiprotease increased significantly only in stage IV. It is considered that the increased plasma level of factor VIII-related antigen occurring already in the initial stages of arterial disease, should be interpreted as an expression of widespread endothelial lesions and not as the mere result of an acute phase reaction. The relevance of changes affecting factor VIII-related antigen for the development of thrombotic complications could be assessed only in the context of other abnormalities of the hemostatic variables.

The correlation between the extent of intrarenal fibrin deposition induced by 15, 20 and 30-min bilateral occlusion of the renal arteries and the reduction of glomerular filtration rate (GFR) has been studied. The tissue level of fibrin was estimated by 125I-labelled human fibrinogen. There was a significant negative correlation between cortical and medullary fibrin content and GFR. In rats pretreatment with the defibrinating agent Arwin failed to prevent postischaemic coagulation in the kidney and the reduction of GFR.

Spontaneous resolution of hypofibrinogenemia after intrauterine death of one twin occurred and suggests that prophylactic heparin therapy in such cases is unnecessary.

Sera and plasmas from 50 patients with IgA nephropathy (IgA-NP) have been investigated for the presence of cryoglobulin (CG) and cryofibrinogen (CF), respectively, 2-5 cryoprotein determinations being made for each patient. CG was transiently found in 20 of 50 patients (40%), but in none of 20 healthy blood donors, whereas CF was found in 37 of 50 patients (74%) and in 4 of 20 healthy blood donors. The cryoprecipitates were of single and mixed component types. All but 2 of the patients with CF had haematuria. Nearly all of them had histories of long exposure to the cold as manual workers at the onset or recognition of their disease. There was no clinical remission during a 2-to-5-year follow-up if cryoproteinaemia persisted. A certain correlation was detected between the composition of the CP and the renal immunohistological findings. It is suggested that renal deposition of circulating CF or local formation of CF might be responsible for the tubulo-interstitial fibrocellular changes, which are of prognostic importance.

The two-component tissue adhesive system where the one component is a concentrated human fibrinogen solution and the other component is a thrombin solution containing Ca2+ is becoming increasingly important in surgery. In the commercially available tissue adhesive, the fibrinogen is separated from pooled plasma. The risk of transmitting foreign immunogens and viruses, always present when foreign biological materials are used, will be eliminated if the fibrinogen is separated from the patient's own blood. A method using ethanol precipitation is described for preparing a concentrated fibrinogen solution from plasma separated from small amounts of blood. The method is fast, the final product can be obtained within 30-60 min after collection of the blood. The recovery is compared with the recovery obtained by separating the fibrinogen with ammonium sulfate precipitation and with cryoprecipitation. The method using ethanol is by far the most profitable, and the product is evaluated by experimental liver surgery in pigs.

Ca2+ ions were transported into the cell by incubation of the erythrocyte suspension with ionophore A23187, a lipophil electric neutral ion complexing substance. Erythrocyte aggregation could be increased twice, when doubling the intracellular Ca2+-ion concentration. Our measurements lead to the suggestion that an increase of the cytoplasmatic Ca2+ ion changes the physical and/or biochemical properties of the aggregation receptors on the membrane surface, i.e., cell-protein interactions are regulated by alteration of the intracellular Ca2+-ion concentration.

A study was made of the erythrocyte sedimentation rate (ESR) in 258 normal nonhospitalized elderly subjects (189 women and 69 men). Their ages ranged from 70 to 89 years. Those who had been followed for at least one year showed a mean ESR of 13 mm/hr, with a range of 3-65 mm. A subgroup of 55 (47 women and 6 men) who had been followed for periods of 3 to 11 years showed a mean ESR of 14 mm/hr, with a range of 3-69 mm. The findings indicate that an ESR above the accepted normal range may be consistent with continued good health in the elderly. Thus the ESR determination may be of very limited diagnostic value in this age group.

Small modifications of the commercially available software of the I.L. Multistat Centrifugal Analyzer (MCA) enabled us to evaluate clot based prothrombin times (PT), activated partial thromboplastin times (APTT) and thrombin times (TT) simultaneously within one run. This imparted a great deal of flexibility to this procedure in that batches and/or panels of clot based and other types of turbidimetric tests can be performed concurrently in any combination. The PT and TT by this turbidimetric procedure correlated very well with those of the Fibrometer in normal specimens as well as in a wide variety of coagulation defects. The turbidimetric APTT procedure, however, often produced clotting times longer than those achieved with the Fibrometer. The discrepancy between the Fibrometer and turbidimetric APTT procedures was shown to be the consequence of greater sensitivity of the latter to detect low concentrations of heparin, elevated fibrinogen split products and mild factor deficiencies. The available clot based procedures are suitable for use in detecting specific factor deficiencies and the presence of coagulation inhibitors.

The increased risk of thrombosis seen in patients with malignancy also was recently confirmed in breast cancer patients undergoing hormonal or chemotherapeutic treatment. Besides changes within the coagulation system, alterations of hemorheologic variables have been implicated in the genesis of thrombosis. We evaluated plasma viscosity, erythrocyte aggregation, fibrinogen level, sedimentation rate, hematocrit concentration, and protein concentration in patients with breast cancer at the time of primary diagnosis and during follow-up with or without treatment. We then compared the results to a control group without malignant or infectious disease. Plasma viscosity and erythrocyte aggregation were significantly higher in patients with malignant disease, with a further increase at the time of dissemination. Plasma fibrinogen level was significantly higher only at the time of dissemination. The influence of therapy on hemorheologic variables was minor. Tumor volume was the most important factor. As individual values vary considerably and form a continuous spectrum, no cutoff line between normal and pathologic values can be defined. However, high values should induce further measures to diagnose metastatic disease. Second, these factors could explain the relative inefficiency of thrombosis prophylaxis in this patient group and suggest the addition of rheologically active drugs to the treatment regimen.

Plasma fibrinopeptide A (FPA), a dynamic measure of intravascular coagulation, was determined in 70 healthy Chinese women during normal pregnancy, labour, delivery and the early puerperium and compared to a group of healthy non-pregnant adult controls. In the normal controls the plasma FPA level (mean +/- SD) was 1.43 +/- 0.46 ng/ml. During pregnancy and labour, the FPA levels were 3.05 +/- 0.98 ng/ml and 11.47 +/- 4.43 ng/ml, respectively, and it reached a peak of 32.95 +/- 11.66 ng/ml at parturition, then falling to 6.15 +/- 2.52 ng/ml in the early puerperium. All these levels were significantly higher (p less than 0.001) compared to controls. Fifteen of the 21 mothers with blood sampling during parturition also had umbilical cord blood taken for determination of FPA level. There was no significant difference between the maternal (34.07 +/- 10.12 ng/ml) and cord (31.06 +/- 12.67 ng/ml) plasma FPA levels. It is concluded that the hypercoagulable state in women during pregnancy and the puerperium is associated with increased intravascular coagulation activity, and that increased intravascular coagulation activity also occurs in the fetus during parturition. This observation may account for the increased risk of thrombotic disorders observed in pregnant and parturient women as well as in the newborn.

Plasma levels of FPA and FPB beta 15-42 in patients with Behçet's disease were examined. In the patients, the mean levels of FPA and FPB beta 15-42 were significantly higher than controls (p less than 0.001). Fibrinolysis subsequent to coagulation may be activated in the patients. The levels of both FPA and FPB beta 15-42 were higher during attack than in remission. The caution should be taken these levels to understand the disease activity.