bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigations of the Hemostasis System in Different Stages of Coronary Heart Disease
Authors: Sulek K.
Published: May 2019

Fifty patients with stable coronary heart disease (CHD), 100 patients with unstable CHD, 74 patients on the first day of myocardial infarction (MI), 40 atherosclerotic patients, and 50 subjects without these diseases were investigated. The following tests were performed: activated partial thromboplastin time, thromboelastography (TEG), platelet number, platelet aggregation (PA), heparin-thrombin clotting time (HTCT), anti-thrombin level (AT), fibrinolytic activity (FA), plasminogen level (PLG), FDP, and paracoagulation tests. There were no significant changes in the hemostasis in the group of stable CHD. In unstable CHD we observed a decrease in AT and a shortening of HTCT. During the first day of MI similar changes were noted in addition to shortening of “r” TEG, increases in both PA and PLG. In atherosclerotic patients decreased FA and shortening of “k” TEG were observed. The correlation between CHD risk factors and some of the indices of hypercoagulability suggest that hypercoagulability may represent their functional manifestations. Development of CHD is associated with an increasing number of hypercoagulability indices. Changes in the hemostasis system have small diagnostic importance, but some of them suggest that this system can play a role in the pathogenesis of CHD and MI in some patients. Some indices can also have prognostic value. Selection of patients with hypercoagulability can facilitate more rational, effective methods of treatment of CHD.
Beta-Thromboglobulin in Peripheral Arterial Disease
Authors: Bevan D. , Yates C.J.P. , Dormandy J.A. , Flute P.T.
Published: May 2019

Plasma beta-thromboglobulin concentration has been measured by radioimmunoassay using the kit from the Radiochemical Centre, Amersham, England. Results for 19 healthy volunteers had a mean of 33 ng/ml (range 13-60) with coefficients of variation within assay of 7%, within sample 14%, and within subject of 23%. Results for 50 patients with arterial disease had significantly higher mean of 51 ng/ml (range 10-127). The highest values were found in those with prosthetic (DACRON) grafts and previous endarterectomy. The raised values may be of significance as markers for anti-platelet drug therapy.
Blood Products in the Treatment of Acute Bleeding Complications Following Open-Heart Surgery
Authors: Crow M. , Kaul T.K. , Rajah S.M.
Published: May 2019

We studied the bleeding patterns in 377 patients undergoing open-heart surgery in the last 18 months. The number of patients with excessive bleeding requiring a coagulation screen was 56 (14.84%), of which 30 (7.95%) had a normal profile, with moderate thrombocytopenia. In 22 of these 30 patients specific bleeding sites were found at re-operation and effective surgical haemostasis was achieved. No specific bleeding sites were found in the remaining 8 (2.12%) and the cause for excessive bleeding was not determined. Treatment with fresh frozen plasma (FFP) gradually controlled the bleeding. Twenty-six (6.89%) had abnormal coagulation findings. Severe thrombocytopenia occurred in 1 patient (0.25%) who was treated with platelet concentrates. Prolonged partial thromboplastin time was recorded in 14 (3.71%) cases and these patients were treated with cryoprecipitate, FFP or fresh blood (depending on the haematocrit and blood volume). The final 11 patients had low levels of all clotting factors, were thrombocytopenic and had significantly raised fibrinogen degradation products, indicating a limited form of intravascular coagulation. These patients were treated with cryoprecipitate, FFP and platelet concentrates. Sixty per cent of the patients with post-operative bleeding required specific blood component therapy besides other medication.
The Effect of Hirudin on the Generalized Shwartzman Reaction (GSR) in Rabbits
Authors: Ishikawa A. , Rafter R. , Seemüller U. , Graeff H.
Published: May 2019

The inhibitory effect by hirudin on the course of the GSR induced by two spaced injections of endotoxin (E.coli) 24 hours apart was investigated in two groups of six animals: I: endotoxin only. II. endotoxin with hirdin, which was infused (1000 ATU/kg/h) for a period of 6 hrs after the endotoxin injection (EI). Fibrinogen, soluble fibrin monomer complexes (SFHC), AT III, platelet- and leukocyte counts were determined and pathological studies performed. Fibrinogen in II remained significantly elevated over the whole experiment, while in I the fibrinogen decreased significantly after the 2.EI. SFMC was significantly increased in I from 3.2% before the 1. El to 10.7% before the 2. El, and to 16.7% 6 hrs aer the 2. EL SFNC of 11 increased from 3.0% before the 1. El to 10. 5% bef ore the 2.EI and stayed unaltered during hirudin infusion. The decrease of AT III and platelets was significantly smaller in 11 than in I. The decrease of leukocytes was similar in I and 11. The findings indicate,that the hematological consequences of GSR can be corrected by infusion of hirudin while the dysfunction of the kidneys can be improved only slightly.
Inhibition by Peptidic Fragments of Clq of Platelet - Collagen Interactions
Authors: wautier J.L. , Reid K.B.M. , Legrand Y. , Caen J.P.
Published: May 2019

Clq (first component of complement) has been shown to inhibit platelet aggregation induced by collagen. Platelet aggregation and adhesion to purified type I or type III collagen have been studied in the presence of various fragment of Clq.

The collagen like region was obtained by digestion of Clq by pepsin and by isolation of the fragments by chromatography on sephadex G 200. The globular region was prepared by digestion of Clq by collagenase, and filtration. The collagen like region is as effective as native Clq in inhibiting platelet aggregation or adhesion in the presence of type I or type III collagen, while the globular region was without effect.

Using peptides obtained from the collagen like region of Clq (reduction and alkylation, performic oxidation, CNBr treatment, extensive pepsin digestion) it could be shown that the fragment (FR II = 70 Amino Acid) was responsible for the inhibition of the platelet adhesion and aggregation induced by type I or type III collagen.

The Amino Acid sequence of this fragment was compared to the known sequence of the collagen peptides involved in platelet adhesion (see Fauvel et al).
Studies of the Activation of Human Factor X in Plasma.
Authors: Marlar Richard A. , Kleiss Alice J. , Griffin John H.
Published: May 2019

Purified human Factor X (FX) was used to develop a new assay and studies were made of the activation of FX initiated by tissue factor (TF) in normal and various deficient plasmas. FX was purified to > 95% homogeneity from commercial FIX concentrates using DEAE-Sephadex, heparin-agarose and preparative polyacrylamide gel electrophoresis. FX (59,000 MW), a glycoprotein, consists of two disulfide linked chains (42,000 and 17,000 MW). The carbohydrate of FX was labeled by a mild oxidation-reduction procedure using periodate and NaB(3H)4. The specific radioactivity was 1.58 μCi/unit FX with no loss of procoagulant activity . The amount of TCA-soluble 3H-activation peptide released by RVV activation was directly correlated with both FXa clotting and amidolytic (S-2222) activity. The assay background was much less than 1% of the total radioactivity and the maximum amount of 3H-peptide released by RVV was 78% of the total radioactivity. In studies of the activation of 3H-FX in normal and various deficient plasmas initiated by various dilutions of TF, there was a significant reduction of FX activation in FVII-, FIX-, and FVIII-deficient plasmas compared to normal or FXI-deficient plasmas. The potential influence of FIX and FVIII on the activation of FX in the presence of dilute TF emphasizes the need to revise current concepts of coagulation pathways and may be related to the abnormalities associated with Hemophilias A and B.
Structural and Functional Characteristics of Proteolytically Modified Bovine Factor X and Xa (Des Light Chain Residues 1-41)
Authors: Morita T. , Jackson C.M.
Published: May 2019

Incubation of bovine Factor X with α-chymotrypsin produces a peptide, residues 1-41 of the light chain and a modified Factor X designated “headless Factor X”. Clotting activity of “headless Factor X” is virtually zero by one stage assay. Composition, chromatographic elution characteristics and molecular weight estimates by SDS gel electrophoresis form the bases for the aforedesignated structure of “headless Factor X”. Activation of “headless Factor X” by the Russell’s viper venom activator requires Ca2+ as does normal Factor X, however, the rate is much slower. After full activation the specific activity of “headless Factor Xa” and normal Factor Xa differed by less than 20% using BOC-L-Val-L-Leu-Gly-L-Arg-pNA as substrate. However, clotting specific activity is less than 0.002% of normal Factor Xa in the one stage clotting assay. The activation peptides released from “headless Factor X” (residues 1-51 and 291-307) of the heavy chain were identical to those released from normal Factor X. Similar rapid, highly selective chymotryptic cleavage of Prothrombin Fragment 1, and the similarity in the amino acid sequences of the light chain of Factor X and Fragment 1 suggests that the region around the susceptible peptide bond must lie on the surface of both these molecules and perhaps exist in a “hinge” region connecting the Gla containing domain and the reamining structural domain of these portions of prothrombin and Factor X. (Supported by HL12820).
Plasma Inhibition of the Heparin Accelerated Neutralisation of Xa by Antithrombin
Authors: MacGregor I.R. , Lane D.A. , Kakkar V.V.
Published: May 2019

The ability of heparin fractions of different MW (mean MW 8500-30,000) to potentiate the action ot antithrombin III against the coagulation factors thrombin and Xa has been examined in purified reaction mixtures and in plasma. Residual thrombin and Xa have been determined by their peptidase activities against the synthetic peptide substrates H-D-Phe Pip-Arg-pNA and Bz-Ile-Glu-Gly-Arg-pNA. High MW heparin fractions were found to have higher anticoagulant activities than low MW heparin when studied with both thrombin and Xa incubation mixtures in purified mixtures. The inhibition of thrombin by heparin fractions and antithrombin III was unaffected by other plasma components. However, normal human plasma contained a component that inhibited the heparin and antithrombin III inhibition of Xa, particularly when the high MW heparin fraction was used. Experiments using a purified preparation of platelet factor 4 suggested that this platelet derived heparin neutralising protein was not responsible for the inhibition and that a hitherto undescribed inhibitor of heparin action is present in plasma. Preliminary studies have indicated that the inhibitor is concentrated in a fraction rich in lipoprotein and obtained by ultracentrifugation of plasma in high density salt.
Interaction of Thrombin with Antithrombin III and α2Macrogeobulin
Authors: Takada A. , Takada Y.
Published: May 2019

When one unit of thrombin was added to recalcified diluted plasma, more thrombin activity was shown in the presence of heparin than in its absence, but no difference was shown after two hour incubation. When one unit of thrombin was added to diluted plasma without the addition of Ca++, no difference in thrombin activities was shown in the presence and absence of heparin. When highly purified α2macroglobulin (α2M) and antithrombin III (ATIII) were used, thrombin activity was initially enhanced in the presence of either ATIII or ATIII, and quick inactivation of thrombin by ATIII regardless of the presence of heparin was observed. Electrophoresis shows that migrating patterns of ATIII depended upon amounts of heparin added to plasma, and ATIII migrated more to the anode with larger amounts of heparin. Thrombin-ATIII complex formed quickly in the undiluted recalcified plasma in the presence of heparin, but little complex formation was shown in the absence of heparin. When α2M was mixed with thrombin, and the mixture was added to TLMe at intervals, hydrolysis of TLMe was enhanced initially, then decreased quickly. α2M-thrombin complex seemed to be not as effective as free thrombin in the capacity to hydrolyze TLMe in contrast to α2M-trypsin or α2M-plasmin complex. α2M may be a primary inhibitor of thrombin in the plasma in the absence of heparin. In the presence of heparin, ATIII seems to be a primary inhibitor of thrombin.
Platelet Adhesion and Aggregation in Arteries of Rats, Rabbits and Guinea Pigs in-vivo Correlate Negatively with Their Prostacyclin (PG I2] Production
Authors: Tschopp Th.B. , Baumgartner H.R.
Published: May 2019

This study investigates whether PG I2 produced locally by the vessel wall is important for the interaction of platelets with subendothelium (SE) in-vivo. Aortic endothelium in the three species was experimentally removed. Subsequent platelet deposition on SE was assessed by morphometry. After a 10 min exposure, surface-coverage with adherent platelets in rats, rabbits and guinea pigs amounted to 63±4, 82±3 and 97±1% (means ± EE, n>5) with adhesion-induced aggregates to 0±0, 6±2 and 15±41, respectively. Conversely, as measured by bicassay, excised aortic segments of rats, rabbits and guinea pigs produced 135±14, 34±3 and <<15 pmol PG I2/10 mg aorta/30 min incubation in buffer, respectively (n=4 In a second set of experiments, the aorta of an exsanguinated rat was cannulated with Silastic tubing, rinsed with buffer and denuded of endothelium. Blood from the aorta of a heparinized rabbit was then circulated (33±1 ml/min) through the abdominal aorta of the rat and back into the vena cava of the rabbit. Adhesion and aggregation of rabbit platelets on SE of untreated rats after 5 min exposure amounted to 16±7 and 7±4%, respectiliy (n=8). In contrast, on SE of rats pretreated with aspirin (50 mg/kg p.o.) which inhibits production of PG I2 by >80t, platelet adhesion and aggregation amounted to 43±9 and 24±7%, respectively (n=8, 2p <0.05). Conclusion. Platelet adhesion and aggregation on SE in-vivo correlate negatively with the production of PG I2. The data suggest that PG I2-production is an important determinant of blood vessel thrombogenicity.
Atherosclerosis in Homozygous and Heterozygous von Willebrand Pigs
Authors: Fuster V. , Bowie E.J.W. , Fass D.N.
Published: May 2019

We have reported that pigs with severe homozygous von Willebrand’s (vW) disease are resistant to spontaneous and high cholesterol diet-induced atherosclerosis. In this study we report the incidence and quantitation of aortic fibrous atherosclerotic plaques in three groups of pigs fed with a high (2%) cholesterol diet from age 3 to 9 months.

Normal pigs (normal factor VIII antigen - VIII R:AG and ristocetin co-factor - VIII:RWF). Of 11 pigs, 8 (73%) had significant plaques involving more than 3% (mean 7.6%) of the aortic surface. Homozygous vW pigs (undetected VIII R:AG and VIII:RWF). None of the 7 pigs had significant plaques involving more than 3% of the aortic surface (p<0.01, rank ≤ test). Heterozygous_vW pigs (approximately 40% VIII R:AG and VIII.RWF). Of the 5 pigs, 3 (60%) had significant plaques involving more than 3% (mean 7.7%) of the aortic surface, the results not being significantly different from those obtained in the normal pig.

This study suggests that resistance to atherosclerosis is not found in animals with moderate reduction of VIII R:AG and VIII:RWF. This might have implications in man since in human vW disease both factors are almost always present to some degree.
Prothrombin Activation in the Presence of Platelets
Authors: Dahlbäck B.U. , Stenflo J.
Published: May 2019

The role of fragment 1, the vitamin K-dependent part of prothrombin containing γ-carboxyglutamic acid residues, and of fragment 2, the factor V-binding part of prothrombin for rapid prothrombin activation was studied. Activation rates of bovine prothrombin, acarboxyprothrombin and prethrombin 1 by factor Xa in the presence of platelets on the one hand and by the prothrombinase complex (factor Xa, factor V, phospholipid and Ca2+) on the other were compared. The conversion products of prothrombin in the presence of factor Xa and platelets were found to be the same as those seen when prothrombin was activated by the prothrombinase complex. The complete prothrombinase complex was more efficient even for activation of acarboxyprothrombin and prethrombin 1, which do not bind to phospholipid, than an abortive complex lacking the phospholipid. This was probably due to more effectively bound factor X . For rapid prothrombin activation by factor Xa in the presence of platelets both fragment 1 and fragment were found to be required. Acarboxyprothrombin and prethrombin 1 were slowly activated to thrombin by factor Xa in the presence of platelets but only after the platelet release reaction. The apparent KH of 0.6 uM prothrombin was 6 times lower than that of acarboxyprothrombin and the coefficient for proteolytic efficiency was approximately 50 times higher. The platelet surface ex posed upon the release reaction gradually lost its catalytic property during the prothrombin activation, probably due to destruction of the platelet factor Xa receptor by thrombin.
Structure of Heparin and Related Glycosaminoglycans
Authors: Casu B.
Published: May 2019

The structure of heparin is largely accounted for by disaccharide sequences of α1,4-linked 2-0-sulphated L-iduroic acid and N,6-0-disulphated D-glucosamine. However, the insertion of other residues (especially D-glucuronic acid, nor-sulphated L-iduronic acid and N-acetylated D-glucosamine) leads to hybrid structures. Also the other iduromc acid-containing glycosaminoglycans are structurally heterogeneous. Heparan sulphates contain variable amounts of heparin-like blocks, ana dermatan sulphate contains also chondroitin -like segments.

Available evidence on the structure and conformation of the above glycosaminoglycans will be discussed in terms of the availability ot individual functional groups for interaction with plasma proteins.
Partial Agonists as Probes of Human Platelet Stimulus-Response Coupling in the Response to ADP and Adrenaline
Authors: Scrutton M.C. , Grant J.A. , Egan C.M.
Published: May 2019

Previous studies have identified 2', 3'-dialdehyde-ADF (oADP) and -dialcohol-ADP (or ABI as partial agonists at the ADP receptor, and Clonidine and methoxamine as partial agonists at the n-adrenoceptor.oADP and orADP cause shape change but not aggregation (Euxop, J, Biochem, 88, 543): Clonidine and methoxamine fail to cause aggregation but enhance the response to ADP and other agonists (Nature, in press). Preincubation of platelets with non-aggregating concentrations of the ionophore A-23187 induces a primai aggregation response to o ADP, and a primary aggregation + a secretion response to or ADH This response is specific to the partial agonists; is blocked by an ADP antagonist and by agents which raise cyclic AMP levels (e.g. PGE) or block intracellular Ca++ movemenl (e.g. tetracaine); and is not inhibited by specific chelation of extracellular Ca+. Under similar conditions A-23187 provokes a full aggregation response to Clonidine (which is blocked effectively by yohimbine but not by praiosin) and a primary aggrtion response to methoxamine. Preincubation of platelets with an adenylate cyclase inhibit; (SQ-22536) fails to provoke an aggregation response to oADP or orADP. These data suppt the concept that an increase in oytosolic [Ca2+], rather than a decrease in [cAMP], is key step in initiation of the response of human platelets to ADP and adrenaline.
2-Methylthio-Adenosine 5'-Diphospllate (2MeSADP), A High Affinity Probe for ADF Receptors on the Human Platelet
Authors: Macfarlane D.E. , Srivastava P.C. , Mills D.C.B.
Published: May 2019

2MeSADP [β-32P] (6 ci/m mole) was synthesized and purified by HPLC. 2MeSADP aggregated platelets and inhibited the stimulation of adenylate cyclase by PGE1 with activities relative to ADP of 4 and 300 respectively. This selectivity for the cyclase site confirms the conclusion from other evidence that this site differs from the site that mediates shape change and aggregation. [B-32P] 2MeSADP bound rapidly (<20 sec) to platelets in PRP with half saturation at 18 nM and 450-500 binding sites per Platelet Under the same conditions PCE1-stimulated adenylate cyclase activity was 50% inhibited at 7 nM with a Hill coefficient of unity. With platelets in Tyrodes solution the apparent affinity was 2-4 nM. Other nucleotides competed for binding to washed platelets with the following Ki (μM):ADP, 3; ATP, 7;IDP, 150; GDP, 350 and AMP, 790. Binding was abolished by 100 μM p-chloromercuribenzene sulfonate, which blocks the inhibition of adenylate cyclase without affecting shape change. Bound 2MeSADP was completely displaced by excess ADP, with first order rate constant 1.54 mIn. These results, taken together with binding data for dlhydroergocryptine (Newman, et al JC1, 61: 395, 1978) and for prostacyclin (Siegl, et al, JCI, in press), suggest that the human platelet hae ca. 200-500 adenylate cyclase units per cell, each coupled to several specific receptors.
A Case of Familial Antithrombin III Deficiency in an English Family
Authors: Haas de H.A. , Scully M.F. , Clark S.E. , Kakkar V.V.
Published: May 2019

In this case a mother and three of her four sons living in southern England are affected. The mother’s At III level measured as progressive At III (chromogenic substrate) was 51% heparin cofactor 61% and by immunological assay 53%. Three sons have At III levels of 48%, 55%. and 56%, (progressive), 43%, 54% and 51% (heparin eofarctor), and 53%, 57% and 51% (immunological) respectively. By a clotting assay the sons were found to have values of 60%, 56% and 63% Crossover immmunoelectrophoresis against At III antisera in the presence of heparin (Sas et al, 1975) showed no difference from normal, distinguishing this form of deficiency from Antithrombin Budapest. A sister of the mother and four other members of the family had normal At III levels. All members of the family had normal levels of α1 antitrypsin and α-2 macroglobulin as measured by the radial immunodiffusion technique.

Clinically all the At III deficient sons have had recurrent DVT and have grade IV post phlebitic legs. One son has also had in addition, an inferior vena cava thrombosis (at age of 8 years) and mesenteric thrombosis (at age of 30 years). The development of a thrombosis at age 8 may illustrate that symptoms of At III deficiency may not be confined only 8 adulthood. Affected members of the family are at present: on a regimen of self administered low-dose subcutaneous heparin.
Pharmacological Studies on the Antithrombotic Action of Synthetic low Molecular Weight Inhibitors of Clotting Enzymes
Authors: Markwardt F.
Published: May 2019

Biochemical investigations allowed the identification of benzamidine derivatives as highly effective competitive inhibitors of clotting enzymes. Their anticoagulant effect is not only based on the inhibition of the thrombin-fibnn reaction, but also on that of thrombin-induced platelet reactions and activation of clotting factors. The inhibitory effect on factor Xa potentiates the anticoagulant action. However, the inhibitors interfere with the antithrombin III reaction.

Selected benzamidine derivatives are critically observed from the aspect of their use as antithrombotics. The pharmacokinetic behaviour was studied using radiolabelled compounds. Due to the relatively rapid elimination from the blood repeated administration is required in order to maintain an adequate concentration in blood. Experimental, venous, arterial, and microthromboses in rats could be prevented by infusion of the inhibitors. Their protective effect was dependent on the affinity for the clotting enzymes (Ki-values) and on the blood levels. Synthetic low molecular weight inhibitors of serine proteinases are considered therapeutically relevant compounds.
The Prostaglandin-3 Family and the Prevention of Thrombosis
Authors: Dyerberg J. , Bang H.O.
Published: May 2019

In the search for the cause of the rare occurrence of ischemic heart disease in Eskimos the interest is focused on cis 5,8,11,14,17 eicosapentaenoic acid (C20:5). C20:5 is not a precursor for proaggregatory prostaglandins whereas vascular tissue can convert it to a potent antiaggregatory substance. Greenlanders in whom C20:5 occurs in high concentrations in the plasma lipids in stead of C20:4 should have a balance between platelet aggregatory and antiaggregatory ability dislocated towards the latter. In a expedition to North-West Greenland during the autumn of 1978 this hypothesis was veryfied.

The platelet aggregation after ADP and collagen stimulation and the bleeding time in Eskimos differed significantly from those of age and sex matched Danish controls. Investigations of haemostatic characteristics ruled out other explanations of the prolonged bleeding time and decreased platelet aggregability in Greenlanders.

The observations might have great inplications in the prevention of thrombosis, pointing at the possible role of the prostaglandin-3 family.
Prevention or Fatal Postoperative Pulmonary Embolism by Dextran 70 or Low Doses of Heparin, an International Multicentre Trial
Authors: Brokop T. , Eklőf B. , Eriksson I. , Goldie I. , Gran L. , Gruber U.F. , Hohl M. , Jonsson T. , Kristersson S. , Ljungstrőm K.G. , Lund T. , Maartman Moe H. , Saldeen T. , Svensjő E. , Thomson D. , Torhorst J. , Trippestad A. , Ulstein M.
Published: May 2019

The efficacy of dextran 70 or low dose heparin in preventing fatal postoperative pulmonary embolism was investigated in a multicentre randomized trial. 4352 patients over the age of 40 years undergoing elective major general, orthopaedic, urological or gynaecological surgery were included in the trial. The two groups were well matched for age, sex, weight and diagnosis. 75 patients died within 30 days after operation, 38 in the dextran and 37 in the heparin group. Autopsy frequency was 87 and 86% respectively. 5 patients in the dextran and 3 in the heparin group had pulmonary emboli as the only cause of death and 1 patient in the dextran and 3 in the heparin group had emboli which had contributed to death. The two methods of prevention thus seem to be equally effective in reduction of lethal pulmonary emboli. 2 cases with incidental pulmonary emboli were found in thex-tran and 4 in the heparin group. Wound haematoma and incomplete prophylaxie was more common in the heparin than in the dextran group. In 6 patients in the dextran and 94 in the heparin group prophylaxis was stopped due to bleeding. Side-effects occurred in 22 patients after dextran and in J patients aiter heparin. Most patients had mild reactions (skin erythema etc.) but in 5 dextran cases reactions were classified as severe.
Efficiency and Risk of Thromboembolism Prophylaxis in Surgery. Clinico-Expertmental Results in 1434 General Surgery Patients
Authors: Koppenhagen K. , Häring R. , Zühlke H.-V. , Wiechmann A. , Weing H.G.
Published: May 2019

Between 1975 and 1978, the frequency of both postoperative thromboses and pulmonary embolisms and of side effects (hemorrhages,hematomas) was examined in 1434 general surgery patients with varying prophylaxis by the radiofibrinogen test and pulmonary perfusion scintigraphy (double nuclide tests). Patients were selected at random and divided into 5 groups 150 patients without prophylaxis; low-dose heparin: 212 patients 3 x and 491 patients 2 x 5000 IU daily; combination prophylaxis of heparin and hemostasis-influencing dihydroergotamine=DHE (2 x daily):2500 IU heparin + 0.5 mg DHE were given to 351 patients, 5000 IU heparin + 0.5 mg DHE to 330 patients. The results of the prospective study show that the lowest thromboembolism rate occurs when heparin application is combined simultaneously with the hemostasis-influencing effect of DHE. The radiofibrinogen test indicated the most effective prophylaxis in petients receiving the combination of heparin and DHE (5000 IU heparin + 0.5 mg DHE, 2 x daily). The postoperative thrombosis rate decreased from 16.1% to 7.7% compared to the group treated only with heparin. The embolism-induced perfusion disorders amounted to 2.6% under the combination compared to 4.7% with 3 x 5000 IU heparin. Side effects of the prophylaxis are dependent on the amount of heparin both in the singledrug, low-dose treatment and the combination therapy. The combination of 2500 IU heparin + 0.5 mg DHE (2 x daily) yielded both the lowest rate of side effects and the thromboembolism prophylaxis of the standard law-dose heparin . The total result documents the efficiency of the combined thromboembolism prophylaxis with hepar in and DHE.
Effect of Low-Dose heparin and dihydroercotamine prophylaxis on incidence of postoperative deep-vein thrombosis in patients undergoing hip surgery
Authors: Lahnborg G. , Beerman B.
Published: May 2019

The favourable effect of low-dose heparin prophylaxis in preventing postoperative deep-vain thrombosis (DVT) in patients undergoing surgical treume has bean shown in several investigations. However, there are still some patients sustaining DVT in spite of heparin prophylaxis. In an attempt to improve the prophylaxis, dihydroergotamine (DHE) has been added to the heparin.

In a prospective trial the effect of low-dose heparin and DHE prophylaxis was studied in 190 patients undergoing nailing of fractured femoral neck. The patients were divided into 3 groups and were randomly given heparin or a combination of heparin and DHE and the third group was given only saline.

The frequency of DVT, detected by the 125-I-fibrinogen method was 167. in the group given heparin and DHE, 20%, in the heparin group and 39% in the control group.

Preliminary results. Completed evaluation will be presented during the congress.
Thromboembolism - Prophylaxis Using a Mechanical Device to Dorsiflex the Feet
Authors: Scurr J.H. , Robbe I. , Ellis H.
Published: May 2019

Heparin has been used successfully to reduce the incidence of thromboembolism, but there is increasing evidence that altering coagulation results in a complication rate that does not justify its use for the routine protection of all surgical patients. This has prompted us to look at a mechanical method for dorsiflexine; feet (Pedi Pulsor) to reduce the incidence of deep vein thrombosis. We have studied 66 patients using the I125 fibrinogen uptake test undergoing major abdominal surgery, many with additional risk factors predisposing to a DVT. The group was randomly divided into two separate well matched groups. The incidence of DVT was reduced from 45% in the control group to 18% in the study group (P = 0.05). There was no significant difference in the operation time or the active dorsiflexion time in those patients who developed a DVT and in those who did not. we were unable to show a specific effect in patients with malignant disease. There was no late rise in the incidence of DVT’s. We conclude that this device reduces the incidence of DVT, and it may have a place in the total programme of prophylaxis.
DFP (Dilsopropylfluorophosphate) Studies on Molecular Mechanisms of Surface-Dependent Activation of Prekallikrein(PK) and Factor XII(Hageman Factor, HF)
Authors: Griffin J.H. , Beretta G.
Published: May 2019

Previous 3H-DFP studies showed that HF binding to kaolin does not result in formation of new active sites. New studies show that single chain zymogen HF, in solution or surface bound, reacts slowly with DFP causing loss of coagulant activity and uptake of 1 mol DIP/mol HF with a 2nd order rate constant, k2=0.4 M-1 min-1. High MW kininogen (HMWK) did not affect the rate constant for this reaction. PK reacts with DFP causing loss of coagulant activity with k2=0.6 M-1min-1. These values are ~103lower than for the activated enzymes (160 and 500 M-1 min-1 for HFa and kallikrein respectively) and are similar to values for trypsinogen that exhibits weak enzymatic activity. HF, PK, HMWK, and kaolin were separately preincubated with 40mM DFP for 5 min to inhibit traces of active enzymes. Then, mixing of these reagents in the presence of 40mM DFP caused a burst of cleavage of 131I-HF and 125I-PK, the extent of which depended on the amount of HMWK. To avoid reciprocal proteolysis of HF and PK, “killed” zymogens (DIP-HF or DIP-PK formed by 48 hr incubation with 40mM DFP) were used in place of HF or PK. Controls showed that PK and DIP-PK were similarly cleaved by purified HFa. If DIP-131I-HF or DIP-125I-PK was substituted for HF or PK in mixtures of HF, PK, HMWK, and kaolin, no detectable cleavage occurred. These data allow that inherent activity of single chain forms of HF or PK may trigger-surface dependent reactions, but the vast majority of molecules are activated by reciprocal proteolysis between HF and PK with HMWK as a cofactor.
Correlation Between Serum IgG, Platelet Membrane IgG, and Platelet Function in Hypergammaglobulinemic States
Authors: McGrath K.M. , Stuart J. J. , Richards F.
Published: May 2019

Platelet membrane IgG levels were measured by the complement lysis inhibition test, and were correlated with serum IgG levels in twenty-nine patients with elevated immunoglobulins due to multiple myeloma, benign monoclonal gammopathy, systemic lupus erythematous, rheumatoid arthritis, benign hypergammaglobulinemic purpura and systemic infection. Platelet membrane IgG was increased in proportion to the elevation of serum IgG with a highly significant correlation coefficient (0.5615, P .01), irrespective of the underlying disease state. Further washing of the platelets did not significantly alter the amount of membrane bound IgG. Qualitative platelet defects were present in nine of the ten myeloma patients in whom platelet aggregation, platelet factor 3 availability, platelet adhesion to glass beads and bleeding times were studied. The most severe abnormalities occurred in those patients having the highest levels of platelet membrane IgG. These findings suggest that elevation of platelet bound IgG is not necessarily indicative of platelet autoantibodies in patients with elevated serum IgG. They also support the concept that the qualitative platelet abnormalities seen in multiple myeloma result from platelet coating by abnormal immunoglobulins.
The Clinical Use of Anti-Thrombin III
Authors: Kakkar V.V.
Published: May 2019

Thrombosis caused by inherited deficiency of anti-thrombin III (At III) was first described in a Norwegian family by Egeberg (1965). There are numerous reports on reduced At III concentrations in disease states, including acute venous thrombosis, disseminated intravascular coagulation, in postoperative patients and women taking oral contraceptives, as well as those receiving heparin therapy. To what extent these findings reflect a causal relationship between At III deficiency remains unclear. However, the possibilities now exist of administering purified At III to patients who are deficient in it, although no clear guide-lines yet exist on the clinical usefulness of replacement therapy with At III. Patients who undergo a major operation with low At III activity should probably be considered at very high risk of developing postoperative DVT. Four such patients, who had At III levels of less than 50% before surgery received an infusion of either 1500 or 1000 units of purified At III concentration; kinetic studies in these indicated that a single infusion will produce an effect which would last up to 36 hours. 50 patients undergoing total hip replacement were randomly allocated to receive either At III or identical placebo infusion in addition to low dose heparin prophylaxis. At III has also been administered to patients who failed to respond to full doses of hep rin therapy, those suffering from chronic thromboembolic hypertension or congenital deficiency of At III. The results of these studies will be presented and their clinical implications discussed.
Serologic Markers of Hepatitis Viruses in Hemophiliacs
Authors: Gerety R.J. , Tabor E. , Eyster M.E. , Drunker J.A.
Published: May 2019

To determine and compare the risks of exposure to hepatitis A and B viruses in patients with hemophilia A receiving intravenous replacement therapy, sera from 138 patients, ages 9 months to 67 years, were studied. Sera from all 138, exposed to either cryoprecipitate (Cryo) or antihemophilic factor (AHF) concentrates for periods ranging from a few months to 15 years were tested for hepatitis B surface antigen and antibody by radioimmunoassay, for antibody to the hepatitis B core antigen by complement fixation and radioimmunoassay, and for antibody to hepatitis A virus by immune adherence hemagglutination. Serologic evidence of past or present hepatitis B was detected in 88.4 percent, while 29.7 percent had evidence of past infection by the hepatitis A virus. The former prevalence is consistent with the known high frequency of exposure to hepatitis B in hemophiliacs as a result of replacement therapy. The latter prevalence, similar to prevalences of antibody to hepatitis A virus seen in populations lacking parenteral exposure to blood products or plasma derivatives, was unrelated to the degree of exposure to Cryo or AHF concentrate. These findings confirm that hepatitis A unlike hepatitis B, is infrequently transmitted by Cryo or AHF concentrate.
Induced Coronary and Aortic Atherosclerosis in Swine with Von Willebrand’s Disease
Authors: Griggs T.R. , Sultzer D. L. , Reddick R.L. , Brinkhous K.M.
Published: May 2019

Swine with von willebrand’s disease were used to study effects of balloon denudation of coronary endothelium and cholesterol feeding on coronary and aortic atherogenesis. Thirty-two pigs were prepared. Eight were phenotypic normals, 10 were carriers and 9 were bleeders. Coronary narrowing by atherosclerosis (induced by balloon denudation and diet) developed to some degree In all of the pigs. Greater than 50% luminal narrowing of one vessel was present in 6 normals, 8 carriers and in 6 bleeders. Myocardial infarction occurred in 2 normals and 4 carriers. No infarctions occurred in bleeder animals.

Aortic lesions (diet-induced) of 3 types were produced: 1) a flat, fatty lesion, 2) a raised, fatty lesion, and 3) a raised, fibrous cap lesion. Every test animal developed lesions of each type. The extent of total raised lesion as per cent of total aortic luminal surface averaged 8.5% in normals, 6.0% in carriers and 5.5% in bleeders.

In summary:1) Ballooned coronary vessels developed narrowing of a similar degree la normal, carrier and bleeder pigs. 2) Bleeder pigs developed no myocardial infarction in spite of the presence of coronary disease of the same degree as in careers and normals. 3) Bleeder pigs developed less aortic atherosclerosis in response to cholesterol feeding than did normals and carriers; but no pig was free of lesions.
Identification of D-Dimer-E Complex in Disseminated Intravascular Coagulation (DIC)
Authors: Whitaker A.N. , Rowe E.A. , Masci P.P. , Gaffney P.J.
Published: May 2019

D-dimer (D2), a product of the plasmin lysis of cross-linked (XL) fibrin, but not of non-XL fibrin or fibrinogen, has been identified in the plasma of patients with DIC due to amniotic fluid embolism. In vitro, D is involved with fragment E as a stable complex (D2-E) but D2 -E has not been identified in vivo before. Fibrin degradation products (FDP) were studied in a patient having fulminant postsplenectomy pneumococcal sepsis and DIC, by immunoprecipitation with anti-fibrinogen (f) and anti-fragment E and characterization by SDS polyacrylamide gel electrophoresis (PAGE). With both antisera soluble HMW fibrin complexes, D2 and E but no X, Y or D were obtained from serum. D2 and E were identified in the supernatant after removing partially XL HMW complexes and fibrinogen from plasma with 2.5 M β-alanine. The presence D antigen in the D2-E complex precipitated by monospecific anti-E was confirmed by crossed Ag-Ab electrophoresis. Crossed Ag-Ab electrophoresis of serum in agarose gave E peaks of slow mobility and no fast-moving free E was found. Thus, D2-E complex exists in vivo and its easy identification, proving the lysis of XL fibrin, would be of value in studying thrombosis. D2-E complex has been identified in other patients with sepsis but at lower concentrations than described above.
Antiplasmin Levels After Surgery: The Failure of α2 Antiplasmin Rise in Patients With Venous Thrombosis
Authors: Taberner D.A. , Poller L.
Published: May 2019

Levels of antiproteases have been determined before and after surgery in twenty-five gynaecological patients by rocket immunoelectrophoresis using specific antisera. The patients who developed deep vein thrombosis during the first post - operative week were identified by screening all patients with the 125I fibrinogen scan. α2 antiplasmin rose post-operatively in all fifteen patients who did not develop thrombosis. This rise was not modified patients receiving low-dose heparin. In the patients who developed positive fibrinogen scans no rise in α2 antiplasmin occurred and on the second post-operative day levels in these patients were significantly lower than in the fifteen patients whose scans remained negative in contrast, α2 macroglobulin tended to fall post-operatively but this change was only significant in the thrombotic group. α1 antitrypsin levels rose significantly in both thrombotic and non-thrombotic groups after operation. Plasmin-α2 antiplasmin complexes were not found in the thrombotic patients so that consumption of α2 antiplasmin does not explain tne lower levels observed.
Effectiveness of Coumadin for Secondary Prophylaxis in Patients with Established Venous Thrombosis(DVT)
Authors: Hull R. , Genton E. , Hirsh J. , Delmore T. , Gent M. , Sackett D.
Published: May 2019

The evidence to support the use of oral anticoagulants to prevent recurrent venous thrombosis is not conclusive because it is based on one single non-randomized study. We have performed a study in 68 patients with acute DVT confirmed by venography. All patients were treated with full doses of heparin For 14 days and then randomized into either adjusted dose Coumadin therapy (prothrombin time 1½-twice control) or fixed dose subcutaneous heparin, 5,000 units 12 hrly for 12 weeks. The patients were followed in a special clinic and routinely screened with leg scanning and impedance plethysmography at 3 weekly intervals and were seen on an emergency basis if they developed recurrent symptoms. Eight of 35 patients on subcutaneous heparin (23%) developed a new episode of DVT confirmed by venography and one patient developed recurrent pulmonary embolism confirmed by ventilation perfusion lung scan. There were no detectable episodes of venous thrombosis or pulmonary embolism in the 33 patients treated with Coumadin (p<0.001). Seven of 33 patients treated with Coumadin developed bleeding complications, 4 of which were major, compared with no patients receiving subcutaneous heparin (p<0.002). Thus, adjusted dose Coumadin therapy is more effective than fixed low dose subcutaneous heparin in preventing recurrent venous thromboembolism but at a significant risk of bleeding in this patient group.
Prophylaxis Against Postoperative Thromboembolic Complications. A Comparison Between Dextran 70, Dihydroergotamin Heparin and a Sulphated Polysaccarid
Authors: Bergqvist D. , Hallböök T. , Lindblad B.
Published: May 2019

Dextran 70, a fixed combination of dihydroergotamine and low dose heparin (DHEH) and a sulphated polysaccarid (PZ68B) have been compared for prevention of postoperative thromboembolism. The trial has been prospective with separate randomization of patients undergoing elective general surgery, elective hip surgery and hip frecture surgery. Deep vein thrombosis has teen diagnosed with the 125 I-fibrinogen test. In patients undergoing elective hip surgery pulmonary x-ray and perfusion scintigraphy have been made preoperatively and on postoperative day 7, The patients have been followed for 30 days to detect late fatal pulmonary emboli. 253 patients have been studied -(34 exclusions), the main results being as follows:

In conclusion there is a good and equal prophylactic effect against postoperative thrombosis of DHEH and PZ68E in elective surgery, and the two methods are as effective as dextran 70 in hip fracture patients.
Activaed Platelets and Platelet Function in Traumatic, Septic and Hemorrhagic Pre-Shock Conditions
Authors: Ziemen M. , Friedrich I. , Breddin H.K.
Published: May 2019

Subcutaneous and other tissues contain a lipoprotein which induces instant morphologic platelet changes (sphering and pseudopode formation), which can be evaluated using phase contrast microscopy. Such material might get into circulation in different forms of shock and in pre-shock conditions. Besides measuring the extent of morphologic platelet changes with time after blood sampling the following parameters were investigated at 12-24 h intervals in 13 patients with different forms of shock: platelet-count and -spreading, beta-thromboglobulin, PTT, fibrinogen, thrombin-, reptilase-, and thrombincoagulase-time, fibrinogen degradation products, antithrombin III, heparin cofactor and plasminogen.

In patients with septicaemia and septic shock activated platelets were found increased in each case. In other forms of shock and pre-shock the findings were not as uniform. Beta-thromboglobulin was increased during the first phase of traumatic shock with decreasing levels during the following days. Generally the platelet number was reduced and spreading was inhibited. The increased activity of platelets in septic and other shock conditions may be caused by tissue lipoproteins in the circulation.
F VIII R:Ag/F VIII:C Ratio and Beta-Thromboglobulin Levels in Haemolytic-Uremic Syndrome in Children
Authors: Rossi E. , Cossu M.M. , Margstakler E. , Mondonico P. , Tantalo V. , Edefonti A.
Published: May 2019

Four infants with Haemolytic-Uremic Syndrome (HUS) were investigated sequentially for F VIII R: Ag/F VIII: C ratio, F VIII: C (one-stage method)/ F VIII: C (two-stage method) ratio and beta-thromboglobulin levels. There is a close relationship between the patterns of FVIII R: Ag/F VIII: C ratio and beta-thromboglobulin, as well as between these parameters and the course of the disease. High values of F VIII R: Ag/F VIII: C ratio and beta-thromboglobulin levels were found in the acute phase of the disease and normal values during remission (after treatment with plasma and anti-aggregating agents). Moreover, normal values of F VIII: C (one-stage method)/F VIII: C (two-stage method) ratio (indicating enhanced thrombin production) were always found.

These data confirm the prominent role of endothelial damage and subsequent platelets aggregation in the pathogenesis of HUS in children.
The Effects of Dietary Fats in Rabbits on Platelet Survival, Platelet Turnover, Platelet Density, PGI2 Production and Thrombus Formation in Response to an Aortic Indwelling Cannula
Authors: Winocour P.D. , Groves H.M. , Dejana E. , Kinlough-Rathbone R.L. , Mustard J.F.
Published: May 2019

Diets enriched with saturated fat and/or cholesterol enhance experimental thrombosis and shorten platelet survival. We compared the effect of saturated and unsaturated fat on platelet survival, platelet turnover, platelet density, PGI2 formation and experimental thrombosis. Forty-eight rabbits were given stock laboratory chow (ST) or semi-synthetic diets rich in milk fat (MF), safflower oil (SO) or corn oil (CO) for 33 wks. Detached endothelium from the SO group produced significantly less PGI2 (bioassay) than endothelium from the other groups (SO 2.05, CO 6.72, MF 5.07 ST 7.27 ng/100 mm2). Mean platelet turnover in the MF group (7,800/mm3/hr) was similar to that in the ST group (7,100/mm3/hr) but was significantly greater than in the SO (4,600/mm3/hr) and CO (4,800/mm3/hr) groups (p < 0.01) . Short aortic cannulae had no demonstrable effect on platelet survival or thrombus formation at one wk in any of the groups (thrombus weight SO 26.6 ± 8.8, CO 44.4 ± 13.1, MF 39.8 ± 20.9 mg) but platelet turnover was increased in the SO (7,100/mm3/hr) and CO (5,100/mm3/hr) groups. The diets did not change platelet density (stractandensity gradient centrifugation). The data from these experiments show that MF diets increased platelet turnover and SO diets decreased endothelial PGI2 formation. None of
these changes was associated with enhanced thrombosis.