bluuebunny/crossref_metadata_2025 huggingface dataset:
SHORT-TERM LYSIS BY ULTRAHIGH STREPTOKINASE TREATMENT IN CHRONIC ARTERIAL OCCLUSIONS AND ACUTE DEEP VENOUS THROMBOSIS
Authors: Martin M , Fiebach B J O
Published: August 2018

171 chronic arterial occlusions and 86 acute venous thromboses were treated by systemic ultrahigh streptokinase (UHSK) infusions. 38% of the patients were over 65, 27% over 70 years of age. The UHSK scheme consisted of a 1.5 million units SK per hour maintenance infusion over a period of 6 hours. 46% of the patients received one, 47% two, 6% three, and 1% four series (one series per day). 81% of the arterial patients had a history of less than 3 months. In 54% of the cases PTA followed UHSK treatment for dilation of a residual stenosis or removal of occlusion residues still persistent. In the venous patients the most proximal location was distributed as follows: calf veins 1%, femoral vein 57%, iliac vein 28%, subclavian vein 14%. The average thrombosis history was 8 days.

Clearance rates of chronic arterial occlusions

By setting up of sub-groups more favorable results were calculated. For exemple, a femoral occlusion group consisting of cases with a history shorter than 6 weeks and 2 or 3 calf arteries patent displayed a clearance rate of 77%, a figure much higher than the overall femoral result

Clearance rates of deep venous thrombosis

The thrombosis duration played a significant role for thrombosis dissolution. The average occlusion history was 6 days in the total clearance group compared with 12 days in the unsuccessful cohort.
FAMILY STUDIES OF PATIENTS WITH RECURRENT VENOUS THROMBOSES AND INHERITED DISORDERS OF BLOOD COAGULATION OR FIBRINOLYSIS
Authors: Hach-Wunderle V , Walter-Fincke R , Beck H K , Scharrer I
Published: August 2018

Several defects of the coagulation and/or fibrinolytic system have been found to be associated with venous thromboembolism. In young patients with recurrent thromboses or a positive family history, an inherited disorder should be excluded

535 young patients with venous thromboses, phlebitis and/or pulmonary embolism were investigated from 1980 until 1986. The first thrombotic event had occurred at an age of less than 45 years.An inborn disorder of the blood coagulation or fibrinolytic system was found in 18 families. Most of them (n=13/18) had a positive family history. In all families either thromboses had occurred in at least one member (n=12/18) and/or the defect could be detected in one of them (n=12/18)

Most often we found a deficiency of antithfombin III (n=6). A deficiency of protein C (type I) was detected in 3 and a deficiency of protein S in 5 families. In one patient a combined deficiency of anti thrombin III, protein C and protein S was found. Extensive family studies revealed a deficiency of antithrombin III in the grandmother of the patient, who suffered from arterial thrombosis. A deficiency of plasminogen and an abnormal plasminogen molecule were detected in 2 other families. Defective release of t-PA could be demonstrated in 3 members of one investigated family up to now

Seme family members with either defects of protein C, protein S or plasminogen as well as a defective release of t-PA lack thrombotic events. Furthermore thromboses of mesenteric veins occurred in 2 of 6 patients with anti thrombin III deficiency and in 1 of 5 patients with protein S deficiency. Superficial vein thromboses were mainly found in patients with protein C- or protein S-deficiency
PREVELANCE OF PRIMARY COAGULATION DEFICIENCIES IN PATIENTS WITH DEEP VENOUS THROMBOSIS
Authors: Grossman B , Duncan A
Published: August 2018

Hereditary causes of thrombosis are becoming more evident as assays (and antibodies) for antithrombin III, protein C, and protein S become more widely available. From March 1986 to January 1987, ninety-nine patients with venous thrombosis were referred to our laboratory for evaluation.This included 55 males and 42 females (age ranges:(1- 79 years). In 79 patients protein C antigens and activities were performed and 24 abnormally low values were obtained. Fourteen of these patients had multiple low values of other vitamin K dependent coagulation factors, reflecting warfarin therapy. Ten patients (12.7%) had isolated protein C deficiency with the other vitamin K dependent factors being within our normal ranges. Of 75 free protein S antigens performed there were 32 abnormally low values. Thirteen (17.3%) were isolated deficiencies. Of 62 antithrombin III antigens and activities measured, there were 8 (12.9%) abnormally low values. The prevelance of these hereditary deficiencies are higher in our referral population than previously reported. This may represent a true increase prevelance in our referral population or reflect a selection bias because of our careful screening of the patient́s history prior to performing the test, or an increased availability of the test to the clinicians. These test should be performed routinely in young patients with venous thrombosis and without predisposing risk factors. These results confirm that all patients with thrombosis should have a comprehensive evaluation done. Not only will the etiology be determined but given the cost of these evaluations, it is more efficient to profile rather than to order isolated request for one factor, as has often been the habit in the past
INCIDENCE OF DEFECTIVE T-PA RELEASE IN 158 UNRELATED YOUNG PATIENTS WITH VENOUS THROMBOSIS IN COMPARISON TO PC-, PS-, AT III-, FIBRINOGEN- AND PLASMINOGENDEFICIENCY
Authors: Scharrer I , Hach-Wunderle V , Heyland H , Kuhn C
Published: August 2018

The incidence of defective T-PA release in 158 young unrelated patients (<45 years old) with deep vein thrombosis was studied and compared to that of PC-, PS-, AT III-, fibrinogen- and plasminogen deficiency. Thrombotic episodes were documented using venography with contrast medium. Venous occlusion test (VO) over 20 min. was performed in all patients, 8-12 weeks after thrombosis. T-PA antigen (Biopool kit) , T-PA activity (on fibimplates) and PAI (T-PA-inhibitor, Biopool kit) were measured before and after VO in the fasting morning samples. Furthermore we investigated the functional and immunologic levels of PC,PS,AT III, fibrinogen and plasminogen. We detected 28 patients (15 females, 13 males)= 17.7% with abnormal T-PA release. In these patients the VO test was repeated three times in an interval of 6-8 weeks. Release of T-PA activity and T-PA-Ag was diminished in all these patients. PAI levels were enhanced in 12 of these 28 patients. The rate of recurrency of thrombosis was 52%. A family history of thrombosis was reported only in 20%

The incidence of PC def. was 9.4%, of PS def. 6.3%, of AT III def 5%, of dysfibrinogenemia 0.6% and of plasminogen def. 1.2%. No combined defect of abnormal T-PA release with other known hereditary coagulation or fibrinolysis disorders could be detected.In 11 healthy volunteers we investigated 4 different time periods of VO, 5, 10, 15 and 20 min. in an interval of 10 days in order to find the suitable time for VO. It was striking that T-PA activity (on fibrin plates) did not decrease to the same extent as T-PA-Ag. The different behaviour is demonstrated on table 1. Decrease in % is compared to the values of 20 min. VO.
URINARY FIBRINOPEPTIDE A IN A HEALTHY POPULATION AND IN PATIENTS WITH PERIPHERAL VASCULAR DISEASE
Authors: Dawes J , Drummond D , Goodfield N
Published: August 2018

Urinary fibrinopeptide A (FpA) concentrations may be a useful clinical marker of the activation of coagulation. They are not susceptible to false positives resulting from ex vivo activation, and sampling is noninvasive.

Individual urine voidings were collected from cohorts of 30 healthy subjects in each age decade from birth to 70 years, and a further 24 between 70 and 100 years. Below the age of 70 the urinary FpA concentration was 1.72 ± 0.76 ng/ml, and there was no effect of age or sex. Within this population, 4% of samples contained FpA concentrations above the upper limit of normal (mean + 2.5 SD); intensive investigation of one case failed to reveal any renal or coagulative disorder, though the urinary FpA levels remained high (8.4 − 14.2 ng/ml). Above 70 years old, 29% of urinary FpA concentrations exceeded the upper limit of normal established on a younger population. Thus, urinary FpA does increase with advanced age, but this may well result from occult disease

Sampling of every urine voiding over 48h in 3 healthy individuals established that there is no diurnal pattern either in urinary FpA concentration or in rate of FpA excretion. Urinary FpA was unaffected by the phase of the menstrual cycle. Urine samples from patients with peripheral vascular disease were assayed, and 24% contained elevated concentrations of FpA. Urinary FpA is probably a valuable marker of low grade activation of coagulation, particularly in chronic conditions where the assay of plasma samples is frequently uninformative
BIOLOGICAL PRETHROMBOTIC MARKERS AND COAGULATION INHIBITORS IN NEPHROTIC SYNDROME
Authors: Picard P , Borg J Y , Vasse M , Boudhabhay D , Soria J , Fillastre J P , Soria C , Hannedouche T , Godin M , Monconduit M
Published: August 2018

Nephrotic syndrome (NS) has long been recognized as a clinical prethrombotic state, because of severe thrombo-embolic complications. But underlying mechanisms are still poorly defined. In 56 untreated nephrotic adult patients (most of them without renal failure), we investigate in vivo coagulation activation by measuring 0 plasmatic specific fibrin degradation products (FbDP) (immuno-enzymological assay using a monoclonal anti D-neo antibody) and (2) the ratio of factor VII coagulant activity (V11c) to factor VII:Anti gen (VII;Ag) tested by an ELISA method. We examined coagulation inhibitors in plasmas and urines (antithrombin III—AT III, heparin cofactor II-HC II by amidolytic and laurell methods; protein C-PC by an ELISA assay ;free and bound protein S—PS:Ag by laurell assays). In few patients we also determinecjfribronectin and t-PA inhibitor.

Results in plasma are submitted and expressed as mean ± DS and compared (t test) with controls (C) without nephropathy

Significantly elevated activated factor VII and FbDP levels show an “in vivo activation” of coagulation in NS. Plasmatic fibronectin, HC II, PC:frg, and tPA-I levels are alsp significantly elevated and roughly paralleled fibrinogen (6,25 ± 2,9 g/1) and other acute-phase proteins measurements. Significant amounts of AT 111:Ag were present in about half tested urines, but in a degraded form with low or absent heparin cofactor activity. Mean plasmatic AT III concentration was in normal range, but three of the 4 patients with a thrombotic disease had the lowest values of AT III and the highest fibrinogen levels.

We could demonstrate a biological prethrombotic state in NS and suggest the way of identifying patients with high risk of thrombosis.
COAGULATION AND FIBRINOLYSIS IN SICKLE CELL DISEASE
Authors: Dautzenberg M D , Monge F , Fischer A M , Girot R , Cornu P
Published: August 2018

Sickled erythocytes appear to be primarily responsible for occlusion of microvasculature in patients with homozygous sickle cell disease (SCD), but it is unknown whether the activation of the coagulation pathway is also contributory to these vaso-occlusive crisis and other complications as leg ulcers, aseptic necrosis of bone, strokes. Thus, we studied coagulation and fibrinolysis parameters in 12 patients (ages 2 to 26 years with SCD, in steady-state, far from thrombotic events which occurred in 3 of them) to determine if it would be possible to detect a high-risk group for thrombosis. We were surprised to observe that all the vitamin K dependent factors levels (II, VII+X, IX, protein C) were found next to the lowest values of the normal range.

But in 3 out of 12 patients, protein C was significantly lower and 2 of them have had thrombotic events (stroke, leg ulcers). Factor V level was in the normal range except for 3 patients with low levels. As other authors, we observed normal fibrinogen, plasminogen and a 2 antiplasmin values and always very high factor VIII levels. Antithrombin III activity was normal or even high contrasting with the lower levels of the other factors synthesized in the liver. However all these abnormalities seem to balance since the thrombin generation test performed in the patients plasmas are in the normal range. As a marker of high-risk group for thrombosis, fibrin-D-Dimer levels (using a latex bead agglutination assay) were measured and found to be positive in 4 patients, 3 of them having suffered from thrombosis associated in two cases with a protein C deficiency. Thus, if the hemostatic modifications observed are involved in the mechanism of thrombosis, fibrin-D-Dimer and protein C seem to be the most significant parameters in this study.
ALTERATIONS OF THE HAEMOSTATIC SYSTEM IN SEVEN PATIENTS WITH HOMOCYSTINURIA
Authors: Stenzier W , Ostermann H , Ullrich K , van de loo J
Published: August 2018

Homocystinuria is an inborn error of methionine metabolism accompanied by an increased risk of thromboembolism. Seven patients (5 female and 2 male) aged 16 to 25 years were investigated. Some showed highly pathological homocystine serum levels during the last year despite treatment. One patient’s history revealed a thrombotic event. All patients were studied for changes in coagulation and the platelet and fibrinolytic systems (the latter before and after venous occlusion). Among the data obtained the following were pathological:

After venous occlusion normal values were obtained. These findings show a weak activation of both coagulation and the fibrinolytic system suggesting a prethrombotic state with consumption of protein C. It remains unclear whether the activation of the fibrinolytic system reflects endothelial cell damage associated with homocystinuria or a reaction to the activation of the coagulation system.
STUDY OF THE PROCOAGULANT ACTIVITY OF ASCITIC FLUID
Authors: Rodzynek J J , Van Rissenghem C , Leautaud P , Delcourt A
Published: August 2018

The aims of the study were to determine the nature of the procoagulant activity present in the ascitic fluid and the means to inhibit the thrombotic complications appearing after peritoneovenous shunting. In a prospective study, 10 ascitic fluids (5 exsudates, 5 transsudates) were studied. The procoagulant activity was defined as the capacity of ascitic fluid to shorten the recalcification time of a control plasma.

Our results showed :

1. All the ascitic fluids exhibited a procoagulant activity.

2. The procoagulant activity of the cellular fraction was related to the presence of platelet factor 3 (PF3) and polymorphonuclear elastase and may be inhibited by the combination of inhibitors of PF3 (phospholipase A inhibitor calbio-chem) and elastase antibody.

3. The procoagulant activity of the free cellular fraction was related to the presence of thrombin, factor Xa, PF3 and tissular thromboplastin, and may be inhibited by a combination of Antithrombin III, phospholipase A and Diisopropyl-fluorophosphate.

Conclusion :

1. The important procoagulant activity of ascitic fluid is present in both cellular and acellular fractions and is related to the presence of different coagulation activators (PF3, elastase, Xa, thrombin, tissular thromboplastin).

2. The administration of a combination of AT III and phospholipase A in the ascitic fluid before the contact with the whole blood allows to inhibit the procoagulant activity of ascitic fluid and could prevent the thrombotic complications appearing after peritoneovenous shunt.
FIBRINOLYSIS AND HAEMOSTASIS DURING ASCITES RECIRCULATION
Authors: Cooper P C , Triger D R , Kennedy H , Malia R G , Preston F E
Published: August 2018

The use of ascites recirculation in liver disease removes litres of incapacitating fluid and the patient is reinfused with the concentrated ascites, a rich source of albumin. Ascites is thought to contain plasminogen activator (PA) which may further affect deranged haemostasis in these patients. We have examined the effect that ascites recirculation has on levels of tPA, fibrinogen, FDP and platelet count on samples taken pre and approximately 4 hours into ascites recirculation. Using plasminogen rich fibrin plates we were able to demonstrate PA in unfractioned ascitic fluid (N=10, mean diameter lysis=10.2mm); this activity was quenched by addition of antibody to tPA (mean diameter lysis=0.2mm). Despite demonstrating tPA in unfractioned ascitic fluid, we were unable to demonstrate an increase in plasma tPA, mid recirculation, using a sensitive chromogenic assay (pre, geometric mean tPA = 0.061Iu/ml; mid, geometric mean tPA = 0.024Iu/ml). In addition we have also measured the effect that an intra-abdominal injection of the glucocorticoid, dexamethosone (dex), 24 hours prior to recirculation, has on PA content of the ascites, as well as the effect on coagulation screening tests. Fibrin plate lysis showed only a small, though significant reduction in mean lysis diameter in 9 of 10 patients receiving dex, (mean 11.6 to 10.2mm). Results of the coagulation tests showed marked changes during recirculation which were similar in both groups.

In conclusion, we have demonstrated free tPA in unfractionated ascites fluid of patients with liver disease, and shown a small reduction in tPA level 24 hours post injection of dex in ascites. Dexamethosone did not influence the changes in coagulation profile post recirculation. We suggest that the changes in coagulation are not due to primary fibrinolysis, but may be due to either dilution effect or DIG.
EVIDENCE AGAINST DIC IN LIVER CIRRHOSIS
Authors: Fiori G , Mombelli G , Haeberli A , Straub P W
Published: August 2018

To evaluate the hypothesis of disseminated intravascular coagulation (DIC) in liver cirrhosis (LC), we measured the plasma levels of fibrincpeptide A (FPA) and of fibrinogen-fibrin degradation fragment E (FgE) in 58 patients with LC, and compared the results with those measured in 32 healthy subjects as well as in 42 patients with ongoing fibrin formation and lysis related to acute thromboembolism (TE, n = 33) and overt DIC (n = 9).

Results: Mean plasma FPA in LC was 2.4 ng/ml compared to 1.8 ng/ ml in normals (p < 0.05) and 12.2 ng/ml in patients with TE or DIC (p < 0.0001). Mean plasma FgE in LC was 108 ng/ml compared to 31.2 ng/ml in normals (p < 0.0001) and to 616 ng/ml in patients with TE or DIC (p < 0.0001). 15 patients with LC (26%) had hypo-fibrinogenemia (fibrinogen< 1.7 g/L). Among these patients, plasma FPA and FgE were 2.3 and 134 ng/ml, as compared to 22.1 and 1310 ng/ml in patients with hypofibrinogenemia related to DIC (p < 0.0001). Intravenous heparin (60 IU/kg) resulted in a prompt decrease of plasma FPA in 14 patients with TE or DIC from 11.8 to 4.3 ng/ml (p < 0.005), but did not significantly change the FPA level in 15 patients with LC as well as in the healthy subjects. Discussion: The present data indicate that thrombin mediated proteolysis of fibrinogen is only marginally increased in LC regardless of whether hypofibrinogenemia is present or not. The data are strongly against the hypothesis of DIC as a frequent and quantitatively important complication of LC and substantiate the conclusion that a “oonsunption coagulopathy” is not a major determinant of impaired hemostasis in liver cirrhosis.
INCREASED PRODUCTION OF PROCOAGULANT ACTIVITY BY PERIPHERAL BLOOD MONOCYTES IN HUMAN AND EXPERIMENTAL OBSTRUCTIVE JAUNDICE
Authors: Semeraro N , Montemurro P , Chetta G , Altomare D , Giordano D , Coluucci M
Published: August 2018

Fibrin formation and subsequent microvascular thrombosis are important pathogenetic factors in renal failure associated with severe obstructive jaundice (OJ) particularly after surgery, but the mechanism of blood clotting activation is poorly understood. We have studied the procoagulant activity (PCA) of peripheral blood monocytes (M) in 35 patients with severe OJ (serum bilirubin > 8 mg% ) and in 27 nonjaundiced control patients, using a one-stage clotting assay. Monocytes from jaundiced patients, tested immediately after isolation, expressed low levels of PCA (7.3 ± 2.0 u/ 105 M) which was, however, significantly higher than in cells from controls (2.5 ± 0.4 u; p<0.05). In addition, following incubation in short-term cultures with and without endotoxin, they generated significantly more PCA than did control cells (p< 0.005) No significant difference in PCA was found between patients with and without malignancy in either group. In rabbits made icteric by bile duct ligation (15 days), the endotoxin-induced monocyte PCA was markedly increased as compared to sham-operated animals ( p<0.05). In all instances PCA was identified as tissue factor. When related to the clinical outcome of the disease, PCA was about 3-fold higher in the jaundiced patients who died than in the survivors (p<0.01). All patients with a fatal evolution had more than 500 u of endotoxin-induced PCA/105 M; such high levels of PCA were found only in 26% of icteric, uncomplicated patients and in 4% of controls (all without complications). The increased capacity of mononuclear phagocytes to produce PCA might help explain activation of blood coagulation in severe 0J. The association between exceedingly high levels of PCA and lethal outcome suggests that PCA may have a prognostic significance.
USEFULNESS OF FOLLOW UP OF ANTIGENIC AND FUNCTIONAL LEVELS OF PROTEIN C AND FACTOR VII FOR EARLY DIAGNOSIS OF LIVER TOXICITY
Authors: Scrobohaci M L , Drouet L , Bertin L
Published: August 2018

Protein C (PC) and Factor VII (F VII) are both vitamino-K dependent factors with similar short half-life. Differential behaviour of both factors in their two expressions was assessed on :

- 16 resolutive liver toxicity due to reinforced chemotherapy,

- 7 specific liver toxicity of Asparaginase or Bisanthrene

- 6 veno-occlusive disease complicating an allogenic bone marrow transplantation

- 5 cirrhotic liver insufficiencies

- 10 patients submitted to stabilised treatment by oral anticoagulant

- 3 families of congenital deficiencies in F VII.

In case of congenital deficiency in F VII, both expressions of this factor were parallely decreased and PC was normal. During anti-vitamin K therapy, functional levels of PC and F VII were parallely decreased, more profondly than antigenic dosages. In case of severe liver insufficiencies both expressions of both factors were parallely decreased. Evoluated V0D behaved as severe liver insufficiency. Onset of therapy by asparaginase and bisanthrene, resolutive toxicity due to reinforced chemotherapy and early phase of the V0D were characterized by a decrease of the functional activities of these factors before molecular decrease and despite a systematic preventive treatment by injection of vitamin K. Often one of these factors was more affected than the other (in these cases : PC more often than F VII). The ratio activity/antigenicity of these factors proved to be an early and sensitive marker of liver involvement. Changes occured earlier than modifications in prealbumin or in liver enzymes. Considerations of these tests to follow liver functions and specially to assess early diagnosis of VOD must be considered.
PESTICIDE INDUCED CHANGES IN COAGULATION AND FIBRINOLYSIS IN EXPERIMENTAL ANIMALS
Authors: Grover Anjana , Pandey K C , Satija N K , Rai R M
Published: August 2018

A relationship between the quality of environment and incidence of human health has been recognized in recent years. While the diseases such as carcinogenesis, respiratory diseases, skin disorders are often correlated with exposure to environmental toxins, the possibility of a link between blood coagulation and chemical contaminants in food, water and air has rarely been suspected. Wide usage of DDT in public health and plant protection programmes have led to a considerably higher levels of the pesticide in the blood and body fat of Indian population. Therefore, in order to explore the possibilities of an alteration in blood coagulation and fibrinolysis in response to pesticide insult, a study was undertaken in experimental animals.

Adult male albino rats were administered technical grade DDT, 100 mg per kg body weight i.p. for 3 consecutive days for acute exposure study and fed food containing the pesticide at a concentration of 100 mg per kg diet for a duration of 90 days for chronic exposure. Coagulation and fibrinolytic status was assessed at the end of exposure period. Acute exposure to DDT significantly increased platelet count but decreased wall adherence of blood while chronic exposure to DDT elevated platelet counts by 21% and increased wall adherence of blood by 28%. Plasma clotting times were found to be shortened considerably both in acute and chronically exposed animals. DDT seemed to activate both extrinsic and intrinsic pathway of coagulation as evident by marked acceleration in prothrombin time and partial thromboplastin time. Plasma fibrinogen concentrations were found to be higher by 31.6% in rats given acute treatment but 40% lower in chronically exposed animals. A marked increase in fibrinolytic activity was observed in both acutely and chronically exposed animals. Thus, administration of chlorinated pesticides like DDT seemed to have a prothrombotic effect in experimental animals.
COAGULATION ABNORMALITIES IN LEAD EXPOSED RATS
Authors: Satija Narendra Kumar , Singh Har Bhajan , Grover Anjana , Rai Ram Mohan
Published: August 2018

The accelerated rate of development of modern technology has greatly expanded the range of health hazards. Lead, a widely used industrial material, is a significant environmental pollutant that contaminates food, water, soil and air. Although much progress has been made in elucidating its adverse effects on various systems of the body like hepatic, CNS, renal etc., its effect on coagulation remains to be established. In view of this an experimental study was carried out in animals to understand how lead influences hemostasis.

Male albino rats were exposed to lead either acutely by administering 20 mg lead acetate per kg body weight daily i.p. for 3 days or chronically by administering lead through drinking water containing 5 ppm lead for 150 days. Acute exposure to lead caused severe coagulopathy characterized by significant prolongation of plasma recalcification time, decrease in platelet count and decreased wall adherence of blood, decreased fibrinogen and euglobulin lysis time and significant increase in prothrombin time, thrombin time, and partial thromboplastin time. Similar observations were found in chronically exposed animals. It is concluded that exposure to heavy metals like lead may lead to a state of hypocoagulability.
EVALUATION OF PREOPERATIVE HEMOSTATIC SCREENING
Authors: Caprini J A , Mitchell A , Rao L , Vagher J P
Published: August 2018

The records of 705 surgical patients were reviewed to ccrrpare the value of history, bleeding risk factors, preoperative template bleeding time (BT) and activated partial thromboplastin time (APTT) in predicting excessive operative bleeding and/or the need for intra or postoperative transfusion. Bleeding was classified as normal or excessive by a panel of physicians evaluating operative blood loss, operative pathology including trauna, postoperative hematocrit, tube drainage, wound hematoma, etc. These assessments were compared with the incidence of intra/postoperative blood transfusions. 25% of the patients had excessive intra/postoperative bleeding and 35% of the population were transfused. A BT > 10 minutes and an APTT > 111% of pooled-normal-piasma were considered abnormal. 9.6% of patients had an abnormal BT and showed a statistically significant higher incidence of bleeding (42.6%) and transfusion (58.8%) compared with a 23.2% incidence of bleeding and 32.3% incidence of transfusion in those with a normal BT (p< 0.001). 18.7% of patients had an abnormal APTT and 31.8% bled compared to 23.6% of those with a normal APTT (p< 0.05). When both tests were abnormal, 54.5% bled compared to 22.4% when the tests were normal (p< 0.001). When both tests were abnormal 63.6% were transfused whereas only 32.1% with normal tests were transfused (p< 0.005). 72.5% of the 705 patients were considered high risk because of a history of bleeding, drug
ingestion, cancer, sepsis, trauma, clinical bleeding, diabetes, uremia, or cardiovascular surgery. 76.3% of the patients who bled at surgery came from this high risk group. Of the high risk patients, those with an abnormal BT bled more often (42.9%) (p< 0.005) and were transfused more (60.3%) (p< 0.001) than those high risk patients with a normal BT (24.2% bled and 36.4% were transfused). Although a greater percentage of high risk patients with an abnormal APTT bled and were transfused, the comparisons were not statistically significant. Patients with abnormal tests, regardless of history, whose surgery was delayed because of the test results bled less often (13.8%) than those whose surgery was not delayed despite abnormal tests (34.8%) (p< 0.05). 14.4% of patients without any history or risk factors (Low Risk) had abnormal tests and bled more often than those low risk patients with normal tests but the comparison was not statistically significant. These results suggest that a combination of history, high risk factors, BT and APTT can better identify surgical patients more likely to bleed excessively or require transfusions than any one parameter. No combination of parameters will identify all bleeders, but including these two tests increases predictive accuracy in certain groups. We feel the cost of these two tests ($40) is much less than the potential expense of unexpected bleeding, particularly if transfusions are required or transfusion related complications occur.
CONJUGATED ESTROGENS (CE) TO REDUCE BLEEDING IN UREMICS
Authors: Vigano G , Marchesi E , Remuzzi G , Mecca G
Published: August 2018

Bleeding is a major complication of uremia. Both cryoprecipitate and desmopressin favourably infuence clinical bleeding, but the former carries the risk of transmitting blood-borne infectious diseases and both have a short duration of action. We recently demonstrated in a controlled study that CE effectively shortened bleeding time (BT) (the best available marker of clinical bleeding) in uremics. The effect of CE on BT is long lasting. Thus CE might represent an alternative to cryoprecipitate or desmopressin when long-lasting hemostatic” competence is required. In the present study we followed for two years 6 uremic patients on chronic hemodialysis with severe bleeding tendence, often requiring blood transfusion. In the first year each hemorrhagic episode was treated only with a replacement therapy, while the subsequent year CE infusions (Emopremarin, 0.6 mg/Kg/die for 5 consecutive days) were given after each bleeding episode. The incidence of hemorrhagic episodes/year and the number of blood transfusions/year decreased from 39 to 8 and from 26 to 9 respectively. No side effects of CE have been noted. Results of this study indicate that CE are effective and safe in treating hemorrhages of uremics.
CAPILLARY PERMEABILITY IN CONNECTIVE TISSUE DISEASE: INFLUENCE OF FIRBOGAMINR-THERAPY
Authors: Piliger E J , Bertuch H , Ulreich A , Rainer F
Published: August 2018

In this study computerized capillaroscopy was used to investigate permeability of nailfold capillaries in patients with scleroderma and mixed connective tissue disease (MCTD) after i.v.sodium fluorescein. Fluorescence light intensities (FLI) were measured around the capillary loop over a period of 2 min. FLI was defined by arbitrary units; the relative light intensities were calculated as percentage of the maximal intensity in each patient. A significant increase in capillary wall permeability and pericapillary diffusion of sodium fluorescein was observer in all patients. In a subsequent study Factor XIII (FibrogaminR Behring) (2 × 1250 IU i.v. per week) was given to 13 outpatients (9 progressive scleroderma, 4 MCTD) over a period of ten weeks. Capillary permeabilities was studied at the same capillary loop of the nailfold before and after treatment. In four cases the capillary studied before treatment could not be identified again and they were excluded from further study. In nine patients capillary wall permeability decreased significantly (p 0.001) after therapy. Seven patients reported a greater suppleness of the skin and an improved mobility of the finger joints. We conclude that Factor XIII treatment reduces capillary permeability and has a clinically beneficial effect in patients with scleroderma and MCTD. We speculate that these patients have a local Factor XIII deficiency in relation to elevated tissue levels of collagen and fibronectin. Administration of Factor XIII could then increase the meshing of endoendothelial fibrin lining leading to reduced capillary permeability and clinical improvement.
LOW MOLECULAR WEIGHT HEPARIN, STANDARD HEPARIN AND ANCR0D AS ANTICOAGULANT FOR EXTRAC0RP0REAL MEMBRANE LUNG CO2 REMOVAL IN DOGS
Authors: Reber G , de Moerloose Ph , Sinclair M , Schweizer A , Gardaz J P , Bouvier C A
Published: August 2018

A low molecular weight heparin (LMWH, Sandoz), a standard heparin (SH, LiqueminR) and ancrod (Arvin^)have been compared in an extracorporeal veno-venous bypass for CO2 removal using a membrane lung in dogs. Four animals received 150 anti-FXa U/kg in bolus followed 90 min later by 40 anti-FXa U/kg/h of LMWH and four other 300 IU/kg followed by 100 IU/kg/h of SH. Six dogs received 1 U/Kg of ancrod intravenously during 2 h before bypass started.

Mean FXa inhibition was 49% in LMWH group and 29% in SH group, mean FI la inhibition 31% and 49% respectively. No statistically significant differences were found between LMWH and SH groups for any of the parameters measured (fibrinogen, FV, antithrombin III, plasminogen, α 2-anti piasmin, platelet counts). At the end of bypass 5000 U protamine abolished both anti-FXa and anti-FIIa activities in SH group, but failed to neutralize more than half of anti-FXa in LMWH group. In ancrod group no clottable fibrinogen was detectable. A dramatic fall of α2-antiplasmin was observed after ancrod infusion and, during bypass, sharp decreases in FV and platelet counts without significant antithrombin III and plasminogen consumption were noted.

No bleeding occurred in any group throughout the seven hours of bypass. The main finding was fibrin deposition in the tubing in three out of four dogs receiving LMWH, whereas no fibrin deposition occurred either in SH or in ancrod group.

These results suggest that in this model which involves blood contact with artificial surfaces (1) SH and ancrod are efficient to prevent clotting, but not the LMWH used at the dosage reported (2) high anti-FIIa activities are required to prevent fibrin formation (3) ancrod defibrination does not protect against severe haemostatic disturbances and (4) the use of LMWH may raise problems when emergency neutralisation procedures are required.
THE THROMBOGENICITY OF PTFE ARTERIAL GRAFTS INCREASES IN THE WEEKS FOLLOWING IMPLANTATION
Authors: Chidlow A , Meek A C , Lane I F , Pate P , McCollum C N
Published: August 2018

Despite few failures in the initial weeks, polytetrafluoro-ethylene (PTFE) femoro-popliteal grafts, which have a non-thrombogenic flow surface, frequently occlude between 2 and 6 months following implantation [1]. Radiolabelled platelet uptake was studied during this risk period.

In 20 greyhounds, 6cm lengths of 6mm PTFE were implanted in the femoral artery and autologous 111In-platelet accumulation measured 1 and 8 weeks later. Radioactivity over the graft was compared to the contralateral thigh and the daily rise in this ratio expressed as the Thrombogenicity Index (TI). At 8 weeks the graft was excised, 111In-platelet content counted in a well crystal and pseudointimal hyperplasia measured by grid microscopy.

Mean (± sem) TI of 0.054±0.02 at 1 week almost doubled in the grafts that remained patent at 8 weeks to 0.10±0.02 (p<0.05). Radioactivity on the excised grafts was 0.012±0.0027 percent of injected activity and this correlated closely with TI at 8 weeks (r=0.83, p<0.001). Even in grafts remaining patent, this late accumulation of radiolabelled platelets correlated closely (r=0.63, p<0.02) with pseudointimal hyperplasia which narrowed the graft by a mean of 18±4.7 percent of luminal area.

PTFE grafts had a low initial thrombogenicity which increased by the second month. This rising thrombogenicity, which presumably follows luminal deposition of fibrin and platelets, is associated with pseudointimal hyperplasia which may explain why these grafts frequently occlude in the months following discharge from hospital.

1. Veith FJ, Gupta S, Daly V. Management of early and late thrombosis of expanded PTFE femoro-popliteal bypass grafts. Surgery 1980; 87: 531-587.
PLATELET DEPOSITION AND PSEUDO-INTIMAL HYPERPLASIA IN PROSTHETIC VASCULAR GRAFTS
Authors: Harper R A , Lane I F , Backhouse C M , McCollum C N , Meek A C
Published: August 2018

Platelet and fibrin accumulation in arterial grafts may cause pseudo-intimal hyperplasia and graft occlusion. The relationship between the rate of post-operative platelet accumulation and subsequent pseudo-intimal hyperplasia has been studied in prosthetic grafts implanted in greyhounds.

The femoral artery in 30 greyhounds was replaced by a 6cm length of 6mm PTFE. Autologous 111In-platelet deposition over the graft was measured by probe and ratemeter for 7 days and radioactivity compared to the contralateral thigh. The daily increase in this ratio graft over reference was calculated as the Thrombogenicity Index (TI). Grafts were removed at 8 weeks and sectioned at 5, 30 and 55mm for measurement of pseudo-intimal thickening by grid microscopy.

The animals subsequently developing occlusion or pseudo-intimal harrowing of greater than 50% of the lumen had a markedly greater TI of 0.22±0.027 compared to 0.03±0.019 in the 23 grafts maintaining wide patency (p<0.05). TI was highest in the 4 grafts which occluded at 0.3110.09 compared to 0.04±0.02 in the 26 that remained patent (p<0.01). There was a highly significant correlation (r=0.69) between post-operative TI and subsequent pseudo-intimal hyperplasia (p<0.001).

Platelet deposition in the early post-operative period appears to promote the development of progressive pseudo-intimal thickening and ultimate occlusion
COAGULATION CONTROL MADE IN FIFTEEN RECIPIENTS OF JARVIK 7 ARTIFICIAL HEART. AN STATISTICAL STUDY
Authors: Bellon J L , Szefner J D , Castellanos C , Cabral C , Gandjbakhch I , Pavie A , Cabrol A , Leger Ph
Published: August 2018

From April to December of 1986 fifteen Jarvik-7 artifi cial heart were temporally implanted until definitive-heart transplantation in 12 men and 3 women of 18 to 55 years old.Jarvik's stay ranged between 48 hours to 20 days, The coagulation control applied was:PT,APTT, reptilase,fibrinogen,platelet aggregation by turbidi-metry to ADP,epinephrine,collagen and arachidonic acid thromboelastography in whole blood,plasma and serum antithrombin III and activated factor X by specific substrates,haematocrit, platelet count,platelet factor 4 and B-thromboglobulin by enzymeimmunoassays,fibrin/ fibrinogen degradation products,alfa-2-antiplasmin, fibrinopeptide A and Raby’s transference test.Number of controls for each patient were 1 to 3 daily.Measure ments were done in preoperative,immediate postoperative and maxim bleeding period.The most significant data were compiled in tables as number of cases, x ± S.E. and S.D.x.Statistical methods were correlation coeffic ient, Pares “t”and Newman-Keuls for p <0.05. It is concluded that the most critical period was the immediate postoperative and because of the treatments applied in the maxim bleeding period, it was possible to reach the patient’s healtn recuperation whenever either a se vere organic failure or sepsis did not appear.Treatments mainly applied were heparin,dipyridamol,aproti-nin and antithrombin III concentrates, dose being adag ted to the results obtained in controls.Jarvik’s status observations when explanted will be presented in a paper aside.No patient suffered any cerebral,vascular or thromboembolic event.
PLATELET FIBRONECTIN LEVELS AS A MARKER FOR THE PROGRESSION OF DIABETIC RETINOPATHY
Authors: Custodi P , Montecchio G P , Bendotti C , Vandelli G , Tenconi M T , Piovella F
Published: August 2018

Aim of the study was to correlate fibronectin (Fn) and von Villebrand factor (vWf) levels measured in plasma and in platelets with the progression of diabetic retinopathy. Patients were classified in five groups reflecting the progression of this microvascular complication, on the basis of fluorangiographic findings (0 = no microangiopathy; 1= simple microangiopathy; 2= oedematous retinopathy; 3= ischaemic retinopathy; 4= ischaemic proliferative retinopathy). 43 patients were studied, 22 suffering from type I diabetes and 21 from type II diabetes, according to the classification of National Diabetes Data Group. Fn and vWf were measured in plasma and in platelet samples using an original double-sandwich microELISA method and expressed as micrograms/ml or as micrograms/10* platelets. Platelets were counted and solubilized with 0.5% Triton × 100. Bleeding time and platelet adhesion to glass beads were also evaluated on every patient. Intraplatelet Fn levels were reduced in retinopathies and correlate with the severity of the microvascular alteration, being the difference significant between the two extreme groups (p<0.05). vWf intraplatelet levels were also significantly lower in patients with severe microvascular complications (p<0.05). No significant differences were detected for plasma Fn and vWf levels in the 5 groups. Intraplatelet Fn and vWf levels may therefore be considered as markers of the severity of diabetic retinopathy. The leakage of Fn and vWf from activated platelet and the incorporation of these glycoproteins in the subendothelial matrix may be responsible for the worsening of this microvascular complication.
EFFECT OF DIPYRIDAMOLE + ASA ON THE RETINE VASCULAR PATTERN OF ESTREPTOZOTOCIN-DIABETIC RATS
Authors: Moreno A , de la Cruz J P , Garcia Campos J , Sanchez de la Cuesta F
Published: August 2018

INTRODUCTION

We have used an experimental model which allows the evaluation of the qualitative differences in the retinal vascular pattern by means of the labeling of the retine vascular tree with radish peroxidase (HRP) in estreptozotocin-diabetic rats. The aim of the study was to evaluate the effect of ASA and DIP + ASA on the vessels platelet behaviour of said retine pattern in a group of rats in t-hich the diabetes had 3 months of evolution.

PROCEDURE

22 Wistar male rats were divided into A groups; 1) control group, 2) diabetic rats without antiaggregant, 3) dietetic rats treated with 6 mg/day ASA p.o., 4) diabetic rats treated with 6 mg/day ASA +12 mg/day DIP p.o. For inducing diabetes 30 mg/Kg of i.v. estreptozotocine were administered. The animals were considered “diabetic” when glucemia was over 200 mg/100 ml. After 3 months of treatment with 4IU insuline and ASA, or ASA + DIP, the animals were sacrified. Samples of blood and rings of descending aorta were extracted. Platelet aggregation in IJB in front of 1 μg/ml of collagen and the prostacycline-like activity of the aorta ring were evaluated. The configuration of the retine vascular tree labeled with HRP was observed.

RESULTS AND CONCLUSIONS

Maximal aggregation intensity: 11.1 Ω in the control group,10.9Ω in the diabetic non-treated group, 4.8Ω in rats receiving ASA and 4.6Ω in rats treated with DIP + ASA. The incUbation during 10 min. of aorta rings in blood samples produced 38.7% inhibition in the control group, 12.8% in the non treated-diabetic group 0% in the ASA group and 49.3% in the group treated with DIP + ASA.

The qualitative changes in the diabetic rats retinal vascular network non treated with antiaggregants showed a scarce visibility of capillars as well as large zones of tortuous vessels. The rats treated with ASA showed a continuous vascular bed and less tortuous vessels than the ones in the non treated group but the vascular diameters were smaller than the ones observed in non-diabetic rats; the rats treated with DIP + ASA showed a continuous vascular bed, scarce tortuous vessels and vascular diameters similar to the ones found in non-diabetic rats. Mortality rates: 0% in the control group, 50% in the non-treated diabetic group, 16% in the ASA group and 0% in the DIP + ASA group. The administration of DIP + ASA normalized the prostacycline-like activity and the retinal vascular pattern in estreptozotocin-diabetic rats.
HYPOGLYCEMIC EFFECT OF INDOBUFEN,AN ANTIAGGREGATING AGENT,IN ELDERLY DIABETIC PATIENTS
Authors: Barzizza F , Belloni G , Trespi E , Venturini A , Richichi I
Published: August 2018

Inibition of platelet aggregation is of value in therapy for Transient Ischemic Attacks(TIA).We observed 2 consecutive elderly patients with type 2 diabetes mellitus(DM)and TIA,in whom chronic treatment with Indobufen(I) provoked a reduction of blood glucose levels; for this reason we started a cross-over study to assess the possible hypoglycemic effect of I in elderly patients with DM.Ten patients(5 males,mean age 75±5 years)with DM and TIA have been included in our study. After 1 month of diet treatment(1)all patients took either placebo tablets 2)or I 200mg every 12 hours for 4 weeks in a random cross-over fashion.After each period a daily blood glucose profile has been obteined. Results are the following:

Indobufen in the dose of 200 mg every 12 hours has an hypoglycemic effect. This side effect can be dangerous in patients already treated with hypoglycemic agents, but can be usefull as a single drug therapy for aged patients with type 2 diabetes mellitus and atherosclerotic vascular disease.
ADHESION OF BLOOD PLATELETS FROM PATIENTS WITH DIABETES MELLITUS TYPE I, TO THE ENDOTHELIAL CELL MATRIX OF HUMAN VASCULAR ENDOTHELIAL CELLS, UNDER FLOW CONDITIONS
Authors: Nievelstein P F E M , Banga J D , Ottenhof-Rovers M , Zwaginga J J , de Groot P G , Sixma J J
Published: August 2018

Platelet activation in diabetes mellitus may precede vasculopathy. We have studied platelet adhesion and thrombus formation in flowing blood of diabetic patients without macro-and microvascular complications. Platelet function and release, bleeding time, fibrinogen, FVIII:RAg, Ri:Co, Triglycerides, Cholesterol and HDL Cholesterol levels, Apo A, Apo B and TK values were in the normal range. Glucose levels and HBA1 were increased. The matrix of cultured human umbilical vein endothelial cells (ECM) was used for adhesion studies.

In an adhesion model with citrated blood (3.1%) and an untreated ECM, three male and three female diabetics (mean age 29.6 y., range 20-32 y., average duration of diabetes 10.6 y., range 2-23 y.) were compared with six age and sex-matched corf-trols. No differences in platelet coverage (en face) was obtained at low (300 s™1 ) and high (1300 s™1 ) wall shear rates, and the time dependence (1-20 min) was the same.

We also used a thrombosis model, consisting of the matrix of PMA-treated endothelial cells which induces tissue factor production, perfused with blood anticoagulated with low molecular weight heparin, which does not inhibit local thrombus formation. Four male and two female patients (mean age 25.4 y., range 22-40 y., average duration of diabetes 10 y., range 2-28 y.) were compared with six age and sex matched controls. Cross sections showed equal total adhesion at 300 s™1 and 1300 s™1 after 1, 3, 5 or 10 minutes perfusion. In the diabetics, spread platelets were significantly decreased at 300 s™1 after 1 and 3 min, and at 1300 s™1 after 5 min; small aggregates (< 5μM) were increased after 1 min at 300 s™1 . At 300 s™1 some patients (2 of 6) showed a faster and more extensive fibrin formation.

We conclude that _ in this group of diabetics there is no difference in primary adhesion but that there is an enhanced tendency in thrombus formation and fibrin deposition.