bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Fibrinogen Degradation Products on in Vitro Lymphocyte Function
Authors: Harvey H.A. , Albright C. , Lipton A.
Published: May 2019

Fibrinogen Degradation Products (FDP) are increased in the sera of patients with advanced cancer and other immunosuppressive states. We studied the effect of micromolecular FDP on the function of normal human lymphocytes.

FDP were obtained by prolonged digestion of human fibrinogen with plasmin. Plasmin was prepared from plasminogen by activation with Streptokinase in 0.1M tris buffer, pH 8.0 at 37°C. After dialysis and lyophilization, terminal FDP were reconstituted in phosphate buffered saline, sterilized and added in varying concentration to a lymphocyte microculture system, sRBC and EAC rosette assays and a Lexy plate Migration Inhibition Factor assay (MIF).

FDP exhibited dose dependent inhibition of lymphocyte blastogenesis induced by the mitogens Phytohemagglutinin (PHA), Concanavillin A (Con A) and Pokeweed (PWM). FDP incubated with lymphocytes had no effect on MIF production or on T and B lymphocyte Rosette formation. FDP were further separated by gel electrophoresis on G–25 Sephadex column. Three peaks were obtained. Peaks 1 and 2 inhibited mitogenic response and Peak 3 enhanced PHA induced lymphocyte blastogenesis. Peaks obtained from the column were further characterized by isoelectric focusing.

Micromolecular FDP appear to play a role in the non-specific modulation of lymphocyte functions that depend on cell replication. Their role should be further investigated in clinical immunosuppressive states.
A Study on Coagulation Factors, Platelets and Inflammation in Burns
Authors: Boisseau M.R. , Hourdillé P. , Bernard P. , Pradet A. , Soria J. , Soria C.
Published: May 2019

A kinetic study on Burns was performed regarding both coagulation and platelet nucleotides on one hand and Prekallicreine levels on the other hand. These measurements were made as early as possible at the onset and over a long period of time. 1) At the initial phase, a Disseminated Intravascular Coagulation was detected (D.I.C.) hardly noticeable in the biological field. Fibrinogen and Fibrin degradation products were close to normal. The only way to make a diagnosis was by practising very sensitive research tests for soluble monomer complexes. 2) Platelet abnormalities were found : To begin with, a thrombopenia with a breaking down of the nucleotides showing an Acquired Storage Disease (A.S.D.), thena progressive rise until normal values for the nucleotides and higher values for platelet levels were reached, this last point connected with the inflammatory process. 3) Variations in Prekallicreine levels were observed in strict parallel directions with those of the platelet nucleotides.

The relationship between D.I.C., A.S.D. and inflammation was thus brought to light.
Platelet Glycocalicin
Authors: Jamieson G.A. , Okumura T.
Published: May 2019

Glycocalicin is a high molecular weight glycoprotein (Mr 150,000) present on the outer surface of platelets and obtained in soluble form following platelet homogenization. Glycocalicin has been purified and shown to bind to thrombin and to Factor VIII and to inhibit platelet aggregation caused-by these reagents. When solubilized from membranes, the thrombin-binding ability of glycoprotein I is identical with that of glycocalicin and the amount of thrombin bound is proportional to the amount of glycocalicin/glycoprotein I present on platelets. The thrombin-binding site has been located in the (nonglyco)peptide “tail” portion (Mr 40,000) of glycocalicin. These results suggest that glycocalicin plays a central role in platelet function.

This work was supported, in part, by PHS Grants HL 14697 and AI 09017.
Prophylaxis of Thromboembolic Complications in HIP Surgery - A Controlled Trial with low Dose Heparin and Dextran 70
Authors: Bergqvist D. , Efsing H.O. , Hallböök T. , Hedlund T.
Published: May 2019

The prophylactic effect of low dose heparin on postoperative thrombosis in general surgery is well established. Dextran 70 has been shown to reduce the frequency of fatal pulmonary embolism. The effect of these prophylactic methods in-hip surgery is debated. The aim of this study was to compare dextran 70, low dose heparin and no treatment in post-traumatic and elective hip surgery. The groups were separately randomized to either prophylaxis. In patients with hip fracture (75 patients) thrombosis was diagnosed with 125I-fibrinogen test. The same diagnostic method was used after elective hip arthroplasty according to Brunswik (96 patients). In the latter group screening for pulmonary embolism was made one week postoperatively with perfusion scintigraphy (Tc-labelled macroaggregated albumin) and x-ray; the diagnosis being based on the combination of a perfusion defect and normal x-ray. The frequency of thrombosis in patients with hip fracture was 67% in the control group, 67% in the low dose heparin group and 40% in the dextran 70 group. The corresponding frequencies for patients undergoing elective hip surgery were 50, 26 and 55%. Pulmonary embolism was seen in 38, 24 and 24% respectively (one fatal embolism in the control group). From this study it can be concluded that only dextran 70 lowers the frequency of thrombosis after hip fracture. Low dose heparin diminishes the frequency of thrombosis in elective hip surgery whereas the two prophylactic methods are equally effective in prophylaxis of pulmonary embolism.
A Link Between Aggregation of Red cells and Formation of Artificial Red–White Thrombi
Authors: Dintenfass L.
Published: May 2019

While aggregation of red cells appears to be related to coagulation, in particular to formation of red clots, it has not been proven whether this is the case in respect of arterial thrombi. To explore this point, a study of aggregation of red cells (estimated from erythrocyte sedimentation rates defined in Westergren tubes on EDTA blood, corrected for plasma viscosity and adjusted to haematocrit of 30%) and of apparent viscosity of artificial in vitro red/white thrombi (obtained in VFTV - variable frequency thrombo viscometer) has been carried out on 500 subjects. These comprised patients with diabetes, post-myocardial infarction states, melanoma, and normals. Only in normals a correlation of significance P < 0.001 has been found. In all disease groups no significant correlation was noted. However, a comparison of the slopes, elevations and residual variance of regressions showed highly significant differences between ‘aggregation of red cells - apparent viscosity of red/white thrombus’ functions for different disease groups (up to P < 0.005), and for different ABO blood groups within any single disease group (up to P < 0.001). It appears that a link between aggregation of red cells and the apparent viscosity of artificial red/white thrombus does not form a single general pattern: it is different in different groups and subdivisions.
Brinolase Dose Prediction with the Protease Resistance Test
Authors: Roschlau W.H.E. , Sutton D.M.C.
Published: May 2019

Systemic thrombolytic therapy with brinolase (fibrinolytic enzyme from Aspergillus oryzae) requires the determination of circulating inhibitors, a reliable method of predicting individual dosage to reduce inhibitors to predetermined targets, and post-treatment inhibitor determination to indicate adequacy of treatment. Several methods using chromogenic substrates were employed clinically with varying success, all allowing the calculation of approximate individual dosage.

The protease resistance test, a rapid method of total inhibitor determination in whole blood, is performed in a serial set of serological tubes containing fixed amounts of thrombin and increments of brinolase, to which 1 ml of the patient’s blood is added and incubated for 10 min at 37°C. The endpoint is determined visually as the tube in which lysis indicates a balance between the content of brinolase and the blood inhibitor titer, expressed as test-tube requirement (TTR) units. In 19 dose predictions in patients undergoing brinolase therapy the inhibitor reductions corresponded roughly to the amounts of enzyme infused, with greatest variability at higher doses; but the method provided a satisfactory guide to avoid overdosage in individual patients. The correlation (r=0.896) was better than that of other clinically applied methods, although patho-physiological conditions such as individual inhibitor composition, extra-vascular enzyme distribution and inhibitor binding may in part be responsible for the observed variability of results with all methods.
Monitoring Oral Anticoagulants in Heparinized Patients
Authors: Williams W.D.
Published: May 2019

The assessment of hypocoagulability induced by oral anticoagulants in patients who are heparinized is very often difficult. The determination of the prothrombin time in such samples has been shown possible by a procedure developed in our laboratory by the removal of heparin from citrated plasma samples. Five different patients on heparin therapy, all of whom were subsequently coumadinized during the period of heparinization, have been evaluated by this method. Heparin is selectively removed by chelation and the procedure has been shown by experimental methods not to alter the determination of either prothrombin or partial thromboplastin times. Prothrombin time determinations on all five patients, prior to initiation of Coumadin therapy and during the administration of heparin, were all found to be normal after the chelation of the plasma. Further, we were able to show a progressive prolongation of the prothrombin time as coumadinization took effect. The method is rapid, simple, inexpensive, and reproducible. It offers the clinician early knowledge of the effect of oral anticoagulants in the presence of heparin.
Changes in Euglobulin Lysis Following Intermittent Pneumatic Calf Compression
Authors: Stevenson Mabel M. , Rohr Paul R. , Davidson Ann G. , Byars Edward F. , Hopkins Gordon , Tarnay Thomas J.
Published: May 2019

Intermittent pneumatic compression of the calf has proven beneficial as prophylaxis for calf vein thrombosis. To define a possible role for the fibrinolytic system, two studies were performed.

Two groups of normal male volunteers aged 18-42 years were rested for one half hour; a control blood sample was drawn and one arm or both legs pumped for one half hour using a pneumatic boot inflated intermittently to 50mm Hg (90 sec. on, 90 sec. off; filling time 60 sec.). A second blood sample was obtained. In group one (arm pumped; antecubital vein sample, same side) the euglobulin lysis time decreased 23% (191 to 147 min., n=13, p=.05). In group two (both legs pumped; simultaneous sample from femoral and antecubital veins) there was a 25% reduction in euglobulin lysis (230 to 172 min., n=16, p=.01) in femoral vein blood and an 18% decrease in antecubital vein blood (229 to 188 min., n=16, p=.04). As expected the effect was most pronounced in the local venous effluent and less noticeable in the systemic circulation due to dilution.

The possibility that mechanical compression of the calf veins produces chemical changes that might exert a beneficial effect in preventing venous calf thrombosis is consistent with the data.
Fibrinolytic System and Fibrinolytic Inhibitors in Behcet’s Disease
Authors: Asbeck F. , Meyer-Boernecke D. , van de Loo J.
Published: May 2019

An increase of the inhibitory potential seems to be the generally accepted cause for the suppression of the fibrinolytic system in Behcet’s disease. To prove this theory, we investigated 5 male patients (31-46 yrs.) suffering from severe Behcet’s syndrome. Additionally, three of them were treated with Stanozolol (1o mg/d) and Phenformin (1oo mg/d) during a period of one year. The following parameters were investigated in detail: Fibrinogen; plasmin (different fibrin plate assays) ; plasminogen, fast reacting antiplasmin, plasmin-antiplasmin complex, alpha2-macroglobulin, C1-esterase inhibitor, alpha1-antitrypsin, antithrombin III (different immunological methods).

In all patients, the concentration of fibrinogen and alpha1-antitrypsin were elevated. There were normal concentrations of plasminogen, fast reacting antiplasmin, plasmin-antiplasmin complex, alpha2-macroglobulin, C1-esterase inhibitor, and antithrombin III. Using the venous occlusion technique, a marked reduction of the in-vivo activation of the fibrinolytic system could be demonstrated. - During therapy with Stanozolol and Phenformin, a high fibrinolytic response was induced by venous occlusion. The analysis of the different inhibitors, however, could not explain this phenomenon. An increased production or release of vessel activator(s), therefore, seems to be the mechanism of fibrinolysis induction by anabolic steroids and Phenformin.
Accelerated Hemostasis in Coronary Artery Disease
Authors: Wajima T. , Burkett L. L.
Published: May 2019

Reduced antithrombin III levels and positive paracoagulation tests occur in some cases of coronary artery disease. This could be related to the cause of atherosclerosis or it could be the result of the disease itself. Thirty-one patients who had arteriosclerotic heart disease, well documented coronary artery occulusions (1-2 vessels), and were subjected to coronary artery bypass surgery were studied for active hemostatic mechanisms of coagulation. Plasma fibrino-peptide A (FPA) levels, fibrinogen, paracoagulation tests, and antithrombin III assays were performed. In addition, PT, PTT, TT, ECLT, and EDP were examined. The blood samples were taken 2-3 days before surgery. Ten of 31 had elevated levels of FPA, and 21 had normal FPA. Eleven patients had positive paracoagulation tests. Six of 31 showed decreased antithrombin III. Seven had an increased fibrinogen level (over 500 mg%). Four of ten patients with elevated FPA had positive tests for paracoagulation, decreased antithrombin III and increased fibrinogen. PT, PTT, TT, Platelet counts, FDP, and ECLT were normal in all patients, except three who had shortened euglobulin clot lysis time. Evidence for activated fibrinolysis was not observed except in 3 cases with shortened englobulin clot lysis time. There was no difference between elevated FPA groups and normal groups in the postoperative period. The degree or extent of coronary artery occulsion was not correlated with the level of FPA or positive paracoagulation tests. Since there were no clinical and laboratory data suggesting disseminated intravascular coagulation, the increased FPA, positive paracoagulation and the reduced level of antithrombin III strongly favor an accelerated hemostatis, probably of localized nature.
Platelet Aggregation in Heart Disease
Authors: Oversohl K. , Theiss W. , So C.S. , Seidl K.F.
Published: May 2019

Increased platelet adhesion and aggregation has been reported in patients suffering from rheumatic valvular heart disease and from atherosclerotic heart disease. We therefore measured spontaneous aggregation “PAT III” (Breddin) and ADP-induced platelet aggregation (Born) in 141 patients who underwent cardiac catheterization. There were 50 patients with coronary heart disease, 41 with valvular heart disease, 18 with cardiomyopathy; 32 with normal findings at catheterization served as control group.

In comparison to controls, patients with coronary heart disease had significantly increased aggregation. Subdivision into 1, 2, or 3 vessel disease revealed no significant differences. Patients with valvular heart disease also had significantly increased aggregation. This appears to be particularly the case after valvular grafting. Cardiomyopathies were not associated with increased platelet aggregation.
Experimental Study of a platelet Antiaggregating Agent - Application to Ticlopidine
Authors: Stoltz J.F. , Verry M. , Farge B.
Published: May 2019

The authors consider the various methods suitable for in vivo study of the anti-aggregating properties of a new drug - Ticlopidine :

- study of photometric ADP-induced aggregation and screen filtration pressure in vivo in the rabbit treated per os for 5 days with doses of 25 and 50 mg/kg/d. This gave average inhibitions of 30% and 45% respectively.

- study of circulating platelet aggregates using the method of Wu and Hoak after continuous infusion of ADP or of thrombin. The principle of the method involves definition of an aggregation index : the ratio between the platelet counts in the two specimens (EDTA + formol 1 % + EDTA alone).

The average results showed : control group index 0.9 -after infusion of ADP 0.57- after infusion of ADP under the influence of Ticlopidine (50 and 100 mg/kg/d) 0.66 to 0.78.

- the mechanism of action of the drug was studied using crossed aggregation experiments and by the study of interference with ionised or ionisable groups of the platelet membrane (isotope method, electrophoresis in liquid phase).

In parallel with these experiments, studies in vivo in the rabbit and in patients (obliterative arterial disease, Raynaud’s syndrome) are in progress : interference with membrane groups, rheological properties (viscosity, rouleau formation, erythrocyte deformability) and biochemical properties (erythrocyte glycolysis enzymes).
Measurement of Amount of Invaginated Membrane in Mammalian Platelets by Osmotically-Induced Spherocyte Formation
Authors: Milton John G. , Frojmovic M.M.
Published: May 2019

Invaginated membrane of the surface-connected canalicular system (SCCS) of the resting platelet can be potentially externalized. We have estimated the SCCS surface area by carefully swelling platelets in hypotonic media. Platelets were osmotically stressed by either interfacing a drop of platelet-rich plasma (PRP) with distilled water on a siliconized glass slide or directly in a test tube by careful additions of 60-80% by volume water. Surface areas of the platelets were estimated from a cinematographic analysis of freely rotating platelets. Within five minutes of the addition of water, large smooth spheres (spherocytes) are formed. Soluble, cytoplasmic lactate dehydrogenase activity is not released and visible membrane damage as estimated from dark-field microscopy observations does not occur for at least one hour. The mean value of the spherocyte diameters was 3.9 ± 0.6 um (3 human donors) and did not change over 5 - 60 minutes. It is estimated that the volume of the spherocyte is ~550% greater than that of the original disc and that the surface area has increased by ~300%. Similar results were obtained for rabbit platelets.

Since platelet swelling induced osmotically has been shown to yield large spheres with the disappearance of SCCS (J.G. White, personal communication), it is concluded that: 1) the SCCS of the resting platelet can be easily externalized, and 2) osmotic spherocyte formation allows a quantitative estimation of the SCCS surface area.
The Effect of Sulfinpyrazone and Aspirin on the IVY Template Bleeding Time
Authors: Stuart R. K. , Barnett H.J.M.
Published: May 2019

The Canadian Stroke Study has afforded us an opportunity to study the effect of sulfinpyrazone 800 mg daily, aspirin 1200 mg daily, both drugs together, and a placebo on the Ivy template bleeding time. Patients with transient cerebral ischemic attacks were randomized to one of the treatment groups and studied before and during treatment.

In 352 patients studied pre-drug, the mean bleeding time was 5.02 ± 2.38 (± 1 SD) minutes. Aspirin significantly prolonged the bleeding time (p=.001). Sulfinpyrazone alone had no effect on the bleeding time. In patients receiving both drugs, the effect was no greater than that of aspirin alone. 51Cr platelet survival studies have been completed in 47 patients during treatment. The mean of 8.4 days was similar to the mean in 17 normal controls(8.3 days). However, analysis by treatment groups remains to be done.
Relations of Serum α1-Antitrypsin and α1-Antichymotrypsin to Restoration of Movement Ability in Cerebrovascular Patients
Authors: Satoh K. , Takamatsu S. , Araya K. , Yamada Y. , Mizuno S.
Published: May 2019

Because fibrinolysis and blood clotting system is closely related to arteriosclerotic disorders, determination of serum α1-antitrypsin (α1 - AT), α1-antichymotrypsin (α1-ACT) must be reasonable to detect the pathophysiologic status in patients with sequelae of cerebrovascular accidents. α1-AT and ai-ACT were determined by means of single radial immunodiffusion method. The level of α1-ACT was demonstrated by area of precipitating ring formed on the agar plate. The mean values and standard deviations of α1-AT was 272158.1 mg/dl in 86 patients admitted in rehabilitation hospital, 312134.9 mg/dl in 32 patients residing in the geriatric nursing home and 229148.0 mg/dl in 135 healthy adults, being significantly higher in patients than healthy, and in nursing patients than in hospitalized patients, α1-AT level was significantly higher in the patients aged over 40 than in those under 39, higher in the patients poor marks in the test of activities of daily livings (ADL-T) than in those with good marks, higher in those.with impaired renal functions than in those with normal functions. α1-ACT level was 52110.0 mm2 in 86 hospitalized patient, 70115.1 mm2 in 32 nursing patients and 48±6.3 mg/dl in 135 healthy adults, being significantly higher in patients than in healthy, and in nursing patients than in hospitalized patients. These results suggest that the fibrinolytic factor and proteinase inhibitor are closely associated with restoration of patient’s movement ability. It is concluded that the study of this system contributes not only to the etiologic research but also to the progress of the rehabilitation medicine in the cerebrovascular diseases.
Calibrated Plasmas, Surveys and Standardization of Prothrombin Time: A Model Practised in the Federal Republic of Germany
Authors: Fischer J. , Beeser H.
Published: May 2019

In order to establish comparable results of prothrombin time (PT) between laboratories, a system of calibrated plasmas for accuracy control at different activity levels was developed. For each thromboplastin commonly used, assigned values are given as ratio and percent activity, which all refer to the mean result of standardized normal plasma pools and corresponding saline dilutions from selected reference laboratories. This system for complete internal quality control has been practised in Germany for three years in addition to external quality control, routinely carried out by quarterly proficiency testings with more than 250 laboratories. Proceeding in this way PT results and performances in Germany now prove to be increasingly reliable and comparable despite having twelve different thromboplastins on the market. Stimulated by this progress some further efforts to standardize PT measurements are being realized using lyophilized calibration plasmas and a deep frozen plasma pool preparation as a generally accepted reference point of ‘normal’. Nevertheless it is still desirable that various commercial thromboplastins with different composition and sensitivity be standardized.
Importance of Human Platelet Echinocytes for Procoagulant Activity
Authors: Toth E. , Frojmovic M.M.
Published: May 2019

Various agents can be used to transform platelets from the disc-form (discocytes) into spherical shapes from which many pseudopodia project (echinocytes). This shape change normally precedes platelet aggregation and release. The relative importance of these changes for platelet procoagulant activity was investigated. Recalcification times of platelet-rich plasma were used to monitor procoagulant activity, and echinocytes were maintained by the addition of either thrombin, serotonin, adenosine diphosphate (ADP) or water. The amounts of these agents added were insufficient to cause aggregation and release, and had no effect on the recalcification times of platelet-free plasma. Platelet shape and extent of aggregation were assessed from the stirring dependent changes in light transmission in an aggregometer, and by direct observation under a phase contrast microscope. When more than 60% of the platelets were echinocytes, recalcificat ion times were shortened by at least 50%. Aggregates preformed with serotonin and ADP did not further shorten the reca1cifi cat ion times. The importance of the echinocyte for procoagulant activity is further supported by the observations that:1)aggregates of discocytes formed with adrenaline caused only 20% shortening of recalcification times,2)both echinocytes (for discocyte preparations) and their aggregates appeared only during the last 10% of the total recalcification time, and3) inhibition of the ADP-induced discocyte-echinocyte transformation by AMP prolonged recalcification times by 300%. These results suggest that platelet discocyte-echinocyte transformation is an important rate limiting step for platelet procoagulant activity in blood clotting.
Potency Differences in F VIII Concentrates Associated with Blood Groups
Authors: Miller-Andersson M. , Kirkwood T. , Seghatchian M.J.
Published: May 2019

Differences in plasma obtained from different blood groups are well etablished. For many-years AHF Concentrate Kabi has been prepared from donations of single blood group. This fact allowed examination of the effect of blood groups on the F VIII yieldin concentrates. 211 batches of these concentrates were studied, 103 group 0, 83 group A and 25 group B. Each batch was assayed twice against a large frozen normal plasma pool (-150°C) using an automated F VIIIic assay system. Statistical analysis of the results show that there is no significant difference between A and B batches and that the A and B contain 21% on average more than the 0 batches. These results agree very well with the findings in some other studies. The implications of this are twofold: Firstly it can be seen that simply by selecting only A or B plasma for F VIII recovery a significant increase in F VIII in concentrates may be achieved. Secondly, the “normal plasma unit” and the use of normal plasma pools as reference standards heavily depend on the blood groups of the donors. This was clearly demonstrated by the chance use of a normal plasma pool containing 75 %. A group as compared to the usual use of 50 %. Quality control assays performed against this pool showed an alarming drop of 10-15% F VIII content of the production batches. Therefore F VIII potency estimation given in terms of normal plasma units are of limited value without detailed specification of the donor blood groups.
Effects of Lipid-Lowering Drugs Upon Fasting-Induced Platelet Aggregation
Authors: Gjesdal K.
Published: May 2019

During fasting, plasma free fatty acid (FFA) concentration increases, correlating with an increase in the percentage of venous reversible platelet aggregates (Gjesdal et al, Thromb. Haemostas. 36, 325, 1976). In the present study 20 healthy males, who had fasted for 72 hours, received either 1 g of sodium salicylate (SS) or 0.2 g of a nicotinic acid analogue (NAA) orally. Blood was collected before, and 1/2, 1 and 2 hours after drug intake. FFA was assayed by titration and platelet aggregates according to Wu and Hoak (Lancet 2, 924, 1974).

After SS, mean FFA concentration was reduced (p<0.01) from 1.87 to 1.34 (1/2h), 1.49 (lh) and 1.66 (2h) mmol/1, whereas NAA resulted in a reduction (p<0.01) from 1.43 to 0.94 (l/2h), 0.65 (lh) and 0.67 (2h) mmol/1. Concomitantly, platelet aggregate percentage decreased transiently (nat significantly) from mean values of 38% (SS group) and 32% (NAA group) to minimum levels of 21 and 23% respectively. During lipolysis inhibition, no significant correlation was found between FFA concentration and aggregate percentage, suggesting that other factors than FFA then had the greater influence upon reversible platelet aggregation.
Blood Coagulation in High Altitude Pulmonary Hypertension
Authors: Singh I. , Chohan I.S.
Published: May 2019

Blood coagulation studies were carried out in 38 Indian soldiers who were resident at altitudes between 3690 and 5540 m for 2 years. Compared with 16 sea-level controls, 6 of these 38 subjects who had developed pulmonary hypertension during their stay at high altitude showed a significant increase of plasma fibrinogen, fibrinolytic activity, platelet adhesiveness, platelet factor 3, factor V, and factor VIII. In the remaining 32 subjects who did not develop pulmonary hypertension there was a significant increase of plasma fibrinogen and fibrinolytic activity only.

The above differences between subjects who develop pulmonary hypertension at high altitude and those who do not develop pulmonary hypertension suggest that high altitude pulmonary hypertension is of occlusive origin and is dependent on changes in blood coagulation at high altitude.
Complex Formation of Fibrin Monomers Studied by Gel Filtration and Polyacrylamide Gel Electrophoresis
Authors: Hafter R. , Baumgärtner M. , v.Hugo R. , Graeff H.
Published: May 2019

Estimation and characterization of thrombin mediated products of fibrinogen (soluble fibrin monomer complexes=SFMC) can be achieved by gel filtration and PAA-gel electrophoresis. In order to gain further information about complex formation in vitro tests were performed. Fibrin monomers were prepared from fibrin dissolved in 3 M KBr after action of thrombin (des-AB-fibrin) and reptilase (des-A-fibrin) on fibrinogen and added to plasma. In a certain range of fibrin concentration (up to 3% for des-AB-fibrin and up to 15% for des-A-fibrin) soluble complexes are formed with fibrinogen in a 1:1 molar ratio. Further increase of fibrin percentage results in a partial precipitation of complexes. Additionally, a marked increase of SFMC (up to 60 %) is observed with des-A-fibrin. This latter reaction indicates complex formation with a higher ratio of fibrinogen involved. An influence of temperature on complex forming could be observed. Gel filtration at 37°C reveals a shift in the elu-tion profile, indicating dissociation of high molecular weight complexes (5 million daltons) to lower molecular structures. The dissociation behaviour of SFMC from plasma samples of patients with hypercoagulability is similar. However, crosslinked fibrinoligomers showed no temperature dependant dissociation behaviour. It is concluded that SFMC exist during the state of hypercoagulability in vivo predominantly as a dimeric fibrin-fibrinogen complex.
Variability of Platelet Function Response to Aspirin
Authors: Atik M.
Published: May 2019

To evaluate the effect of aspirin on platelet function, three groups of subjects were studied. Platelet adhesiveness (pl. adh.) was determined by the Hellem glass bead retention method, and platelet aggregation (pi. agg.) by the Born turbidimetric method using standardized collagen of various dilution. In eight healthy volunteers, the mean pl. adh. decreased insignificantly from 45% ± 13 to 41% ± 13 after 5-7 days of 600 mg/day of aspirin. They showed slight to moderate impairment of platelet aggregation. In 16 patients with massive gastrointestinal bleeding, following ingestion of aspirin, the mean pl. adh. was 22% ± 5 which is significantly lower (P<0.01) than for the normal individuals. These patients showed poor to no platelet aggregation. By contrast in 14 patients with rheumatoid arthritis, despite being on large doses of aspirin, the mean pl. adh. was 61% ± 15 which is significantly higher (P<0.05) than for the non-arthritics. In six.: of these patients pl. agg. was also measured. They showed no or slight impairment. These observations provide a plausible explanation for the conflicting reports regarding efficacy and complications of aspirin and emphasize the need to differentiate between its anti-inflammatory and antithrombogenic effects by actual determination of platelet function in patients treated with aspirin.
A Low Molecular Weight Fibrinolytic Enzyme from Polymorphonuclear Leukocytes (PMN)
Authors: Moroz L.A.
Published: May 2019

Despite evidence implicating PMN in fibrinolysis, the enzymes involved are incompletely characterized.PMN were prepared from normal blood by dextran sedimentation and fibrinolytic activity assayed by l25I-fibrin solid phase assay (Blood 46:543, 1975). More than 80% of activity was associated with intact PMN, was stimulated by Na salicylate (+65%, 20 mg/100 ml) and inhibited by α1-anti-trypsin (α1AT, -48%, 2 × 10-6 M). Similar activity was found in a PMN membrane fraction prepared by homogenization, differential centrifugation and Sepharose 4B gel filtration, from which fraction it was released by freeze-thawing and/or IM KCl treatment. Soluble enzyme activity was inhibited by of α1AT (-80%, 10-6 M), PMSF (-98%, 10-3 M), FeCl3 and ZnCl3 (-100%, 10-2 M), vitamin E(-38%, 10-4 M) and trypan blue (-40%, 10-3 M), but not by EACA (10-2 M), tranexamic acid (10-2 M), TLCK (10-3 M) or TPCK (10-3 M). This activity had an alkaline proteinase pH-activity profile, was localized to a single cationic protein band on acid Polyacrylamide disc gel electrophoresis, with pl of 8.6-8.7 by isoelectric focussing, and eluted between lysozyme and myoglobin on Bio-Gel P-10. On Bio-Gel A 0.5m and P-10, 125I-fibrin degradation products eluted after myoglobin. These findings indicate the presence in PMN of a low molecular weight, membrane-associated fibrinolytic enzyme of alkaline proteinase and serine active site type.
Factor VIII Concentrates - Forces of Supply and Demand
Authors: Britten Anthony F. H.
Published: May 2019

Some surprisingly simple artificial factors influence the availability of factor VIII for hemophilia treatment. Demand is affected by choice of product, and choice of treatment style (episodic vs. prophylactic), and also by availability funds.

Autobiographic data suggest the feasibility of long-term low dosage prophylaxis (6u/KgA8 hrs.). This tentative conclusion is based on 2½yrs. of unprecedented near-total freedom from hemorrhage. The significance is the potential saving of 60% of factor VIII concentrate, compared with the more orthodox dose (15u/KgA8 hrs.) which has been shown to increase factor VIII usage by 2.5–3 times compared with episodic therapy.

The American Red Cross produced 293,332 units of cryoprecipitate from 4,690,217 whole blood donations in 1975-6 (6.25% of blood collected). Production could readily be increased if the demand existed. The following artificial factors have an influence on cryoprecipitate production: health insurance policies; price structure; the international market for factor VIII.

It is concluded that there is no shortage of available factor VIII, that more could readily be made available, that prophylaxis may be possible without increasing demand for factor VIM, that financial considerations are seriously distorting hemophi1ia treatment, that hemophilia treatment in the United States is being subsidised by other countries, and that understanding of these factors can help to overcome them.
Preliminary Report of the Cooperative Study of Spontaneously Occuring Factor VIII Inhibitors in Patients with Hemophilia
Authors: Shapiro S.S.
Published: May 2019

A cooperative study was started in July 1975, sponsored by the Division of Blood Diseases, National Heart, Lung and Blood Institute, National Institutes of Health. The study includes 11 cooperating Centers throughout the United States as well as a computer center. All patients with Factor VIII coagulant levels below 0.10 u/ml (or even higher, if transfused often) are eligible for entry. Currently more than 1200 patients have been entered, including more than 200 with Factor VIII inhibitors. General information concerning the natural history of hemophilia is being collected, including a comparison of severity assessed clinically and in the laboratory, the incidence and degree of liver dysfunction, HBsAg positivity, and hypertension. More than 200 patients with Factor VIII inhibitors have been identified, falling clearly into categories of “strong” and “weak” antibody producers. More than 200 treatment episodes have been documented in inhibitor patients, over 100 treated with Factor VIII and an equal number treated with Factor IX concentrates. Among the latter, some 20% have resulted in secondary rises in Factor VIII antibody titer. A controlled, blinded study of the efficacy of several Factor IX concentrates will begin shortly, and should be completed within a year.
Electroimmunoassay of Factor IX in the Detection of Haemophilia B Carriers
Authors: Panicucci F. , Baicchi U. , Sagripanti A. , Pinori E.
Published: May 2019

Parallel determinations of factor IX activity and factor IX antigen were carried out on 28 haemophilia B carriers and on 20 normal women. Factor IX activity was measured by a one stage method. Factor IX antigen was quantified by electroimmuno assay in agarose gel containing heterologous monospecific antiserum against human factor IX.

The activity was observed to be at the same level as the antigen in normal women. Discrepancy was not found between the antigen and the activity in almost all of carriers: only in the mothers of haemophiliacs Bor B+ or BM the factor IX antigen resulted greater than that activity. Our results show that electroimmuno-assay may be used to study carriers of haemophilia B genetic variants and confirm that in the majority of cases they can probably be diagnosed on the basis of factor IX activity alone.
Mental Health Collaboration in a Comprehensive Care Team
Authors: Jonas D.L. , Wincott E.
Published: May 2019

Effective multidisciplInary mental health participation in a comprehensive care center is discussed. Routinely, areas of input include Initial evaluation, periodic clinic follow-up, home care screening, and pre-surgical evaluation. Methods evolved by a psychiatrist and a social worker working separately and together will be reviewed, as well as techniques of communication and decision making among the whole team to develop effective treatment plans. Specific areas of activity in clinics, in-patient hospital, and office will be reviewed using case examples. The role of the mental health worker in educating health care professionals and community groups is discussed, as well as responsibilities to the National Hemophilia Foundation and its local chapters.
A National Reference Curve for Assaying Factor VIII Inhibitors
Authors: Mariani G. , Serbanescu F. , Ruggeri Z.M. , Mannucoi P.M.
Published: May 2019

The results of FVIII inhibitor assays obtained in different laboratories are of difficult comparison, and the dose—response curve from which the inhibitor potency is read in units appears to be one of the main variables. Differences in inhibitor kinetic behaviour make difficult to adopt as a reference the curve of a single patient. On the other hand, the use of individual curves for each patient is laborious and time consuming. We have evaluated whether the adoption of a single reference curve obtained from the mathematical elaboration of the individual experimental points of the curves of 33 inhibitors was statically acceptable and could be proposed as a national reference curve for factor VIII inhibitor assay. The experimental data have been used to make statistical series from which theoretical points were calculated by the least square method resulting in a second degree equation curve. Observed experimental values corresponded to the theoretical points of the calculated curve within a variation of ± 50%, resulting in a variation of the calculated inhibitor potency of ± 20% compared with those read on each individual inhibitor curve. A national trial to confirm the applicability of such reference curve is presently in progress.
Degradation of Factor VIII-Related Protein in Factor VIII Concentrates
Authors: Jakab T. , Pflugshaupt R. , Furlan M. , Beck E.A.
Published: May 2019

Lipolytic and/or proteolytic treatment of highly purified human factor VIII results in a progressive disappearance of high-molecular weight protein as shown by electrophoresis on 3% Polyacrylamide gels in the presence of sodium dodecyl sulphate. Partial degradation of factor VIII is typically accompanied by a relative increase of factor VIII-related antigen (VIII R:AG)whereas coagulant activity (VIII:C) or von Willebrand activity (VIII R:WF) may still appear intact. VIII R:AG was measured by crossed Immunoelectrophoresis against specific heterologous antibody in agarose gels. VIII R:WF was expressed as ristocetin cofactor activity in comparison with a normal plasma pool. Assuming a VIII R:AG/ VIII R:WF ratio of 1.0 in our normal plasma, we found a similar ratio using intact purified factor VIII. This ratio increased regularly following proteolytic degradation of factor VIII concentrate by contaminating proteases or plasmin. Our findings suggest that a high VIII R:AG/VIII R:WF ratio could indicate undesirable alterations of VIII-related protein(s) during plasma fractionation.
Improved Factor VIII Yield by Instrumented Cryo-Precipitate Harvesting Technique
Authors: Jewett Warren R. , Woods William
Published: May 2019

The present cryo-precipitate manufacturing process has been modified to utilize mechanical and electro-mechanical aids. Up to four bags of plasma are placed in a a rack of special design in which they are frozen and then thawed in a vertical position. Thawing takes place in a 4° C water bath where vibration transmitted through the water causes an increase in precipitate density at the bottom of the bag. Supernatant plasma is then transferred to the satellite bag using an expressor upon which is mounted a photo detector operated shut-off mechanism. In this device a photo cell monitors plasma color as it enters the transfer tube activating a solenoid clamp on the tubing when cryo-precipitate reaches the transfer point at the top of the bag. The signal from this detector may also be used to automatically trigger a dielectric heat sealer. An increase in Factor VIII yield has been achieved averaging 14%.
The Large Scale Preparation of Clottable Fibrinogen-Free, High Purity, High Potency Factor VIII Concentrate
Authors: Fekete L.F. , Wilson W.L. , Bick R.L.
Published: May 2019

Crude Factor VIII was initially extracted from plasma as cryoprecipitate. This crude concentrate was treated with high molecular weight polymer F-48 to remove the bulk of fibrinogen. The yield of Factor VIII at this point was 6356 theoretical and 42% actual (the starting plasma contained,66 units/ml VIII), Total protein in the cryoprecipitate was 2,2 gm# and 0.93 gn# after removal of fibrinogen bulk. The next step was addition of a thrombin-like enzyme, at a concentration of 0.5 units, with the resultant removal of remaining fibrinogen. After clotting out residual fibrinogen, resultant fibrin strands were removed by high speed centrifugation. The final product gave a theoretical yield of 65% and an actual yield of 28%; thus, 65% of the initial Factor VIII was recovered in the final product. Prior to lyophilization, the final product was stabilized with albumin. After lyophilization, no loss of activity occurred and solubility was excellent. Protein electrophoretic analysis revealed 70% in the albumin region, 7% in the alpha & beta globulin region, and 20% in the gamma region. Tests for hemolysins were negative and isoagglutin-in titers were 1:6. Plasminogen and plasmin were undetectable and fibrin(ogen) degradation products were 80 ug/ml. The large scale preparation of this fibrinogen-free Factor VIII concentrate may prove highly useful in sparing the hemophilic patient fibrin(ogen) deposits in the kidneys and other organs, a complication of existing concentrates. In addition, much higher potency in much less volume may be achieved with this material. The cost for large scale preparation of this material should be the same as for existing concentrates.
Synovectomy Revisited
Authors: Pietrogrande V. , Mannucci P.M. , Torri G. , Ruggeri Z.M.
Published: May 2019

15 operations of knee synovectomy carried out from 1969 to 1971 in severe hemophiliacs were revaluated after a follow-up period ranging from 5 to 7 years. In the majority of the patients (53%) there was non recurrence of hemarthrosis: in others, this was only reduced (40%) or unchanged (7%) and joint scintigrams carried out with 99m TC showed a significant uptake of the tracer. Joint motion was markedly impaired in a number of patients (53%) despite prolonged and intensive physiotherapy. Nevertheless the majority of patients expressed satisfaction with the operation, which allowed them to lead a more active life through the reduction of frequency and severity of joint bleeding. It is suggested that the possibilities offered by conservative treatment presently available should be more extensively explored before establishing an indication for sinovectomy.
Leukemia in Families with Isolated Cases of Severe Hemophilia A.
Authors: Egeberg O.
Published: May 2019

In 80 Norwegian families with severe hemophilia A (f.VIII ≤1%) 119 living cases are under study. In 40 of these families only one hemophiliac is known, and in 2 families only 2 hemophilic brothers; investigations showed that of 38 of the mothers 30 were carriers, 8 not carriers or uncertain. In 7 of the 42 families, 9 cases of leukemia, most of them myeloid type, were recorded, and one case of myelomatosis. In 6 of these families low blood f.XII, about half of normal average activity, was demonstrated in the hemophiliac and/or in his mother and/or in one of her parents. Informations from Norwegian families with non-isolated severe hemophilia A, have given no records of leukemia. The high incidence of leukemia in families with isolated cases of severe hemophilia A indicates a common predisposing cause to leukemia and to mutations to hemophilia A.
Treatment of Joint-Bleedings in Hemophiliacs with Antibodies to Factor VIII with High doses of Fraction Feiba.
Authors: Schimpf Kl. , Zimmermann K. , Zeltsch P.
Published: May 2019

Observations in 3 patients demonstrated, that joint-bleedings can be controlled with high doses of fraction FEIBA alone or in combination with factor (f) VIII on out-patient basis. First patient, inhibitor 5-10 units (u) per ml, suffered from 24 joint-bleedings within 392 days. 2o of them could be stopped by a single injection of 150-200 u of fraction FEIBA per kg bodyweight (bw). A combination of 90 u of FEIBA and 36 u of f VIII per kg bw had the same effect. But after 5 injections of this combination within 6 weeks, the inhibitor level had risen from 10 to 240 u per ml. During further treatment with 180 u of fraction FEIBA without addition of f VIII, the inhibitor fell down with a half life time of 50 days. The clinical effect of fraction FEIBA was not influenced by the elevated antibody level. Two further patients, inhibitors 2-4 and 32 u respectively, obtained combined injections of 50-100 u of FEIBA plus 36-42 u of f VIII. One patient was on a prophylaxis of 3 injections weekly for 193 days. After 57 injections the inhibitor had fallen from 2-4 u to unmeasurable values. The third patient obtained the above mentioned dosis twice a day for treatment of a knee joint effusion. After 1 week the inhibitor was diminished from 32 to 13 u.
The Role of the Dental Hygienist in a Community Hospital Hemophilia Program
Authors: Cea J. , Sachs S. , Lipton R. , Schachter M.
Published: May 2019

In order to improve the quality of dental care provided to the hemophilic patients at Long Island Jewish-Hillside Medical Center, a part time dental hygienist has recently joined the staff. In this new position, the hygienist is able to evaluate the dental needs of hemophilia team patients, monitor the ongoing care of these patients, and provide liaison between hospital based care and the services provided in the private sector. In addition, preventative care, including examination, radiographic survey, dental prophylaxis, placement of fissure sealants and dietary counseling are provided on a regular direct care basis. This addition to the Comprehensive Hemophilia Diagnostic and Treatment Center has clearly enhanced its ability to provide meaningful, personal dental health care.