[Clinical aspects of hemostatic balance].
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Blood Coagulation↗
Biomedical subjects
J Jespersen
Publications and source records attributed to J Jespersen.
The autodigestion of human plasmin follows a bimolecular mode of reaction subject to product inhibition.
Plasmin is a labile enzyme destroyed by a process termed autodigestion. Studied by a kinetic assay on the substrate Tos-Gly-Pro-Lys-pNA this process is shown to follow a bimolecular mode of reaction, which is retarded by plasmin degradation products. Plasmin is protected by fibrinogen, by epsilon-aminocaproic acid (6-aminohexanoic acid), by increasing ionic strength, and by glycerol. CNBr fragments of fibrinogen did not protect. Lack of substrate protection of plasmin may give rise to errors in a two-stage plasminogen activator assay, while the presence of substrate in a one-stage method prevents degradation of the generated plasmin.
Aminocaproic Acid↗
[Saint Hans: it is psychologically charged with identity-threatening working situation].
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Burnout, Professional↗
[Adult respiratory distress syndrome. Radiologic and clinical chemical findings].
Our present-day knowledge concerning the clinico-chemical and radiological findings in adult respiratory distress syndrome are described. Three typical case histories have been selected to illustrate this condition; they were due to multiple trauma or sepsis. It is stressed that radiology is in a key position for making the diagnosis and for observing the course of the illness.
Adolescent↗
Neurophysiological variables and fibrinolysis in insulin-dependent diabetes treated with an aldose reductase inhibitor or placebo. A double-blind randomized study.
In a double-blind study we randomized insulin-dependent diabetics (n = 19) into a group (n = 12) given daily 250 mg Sorbinil, a potent aldose reductase inhibitor reported to ameliorate diabetic neuropathy, and another group (n = 7) given placebo for 1 year. Objective, neurophysiological variables (biothesiometry, electromyography, nyctometri) were followed throughout the study and correlated with fibrinolytic variables in blood. We found that Sorbinil did not improve any of the selected neurophysiological variables. Neither did Sorbinil induce marked changes in the fibrinolytic activities of the extrinsic, tissue-type plasminogen activator (t-PA), or in the intrinsic factor XII-dependent or factor XII-independent (urokinase-like) plasminogen activator systems. We found no effect of Sorbinil on the activity of the fast-reacting inhibitor (PA-I) of plasminogen activator. Levels of PA-I in plasma influence the amounts of t-PA precipitated in euglobulins.
Aldehyde Reductase↗
A comparison of the determination of glucosylated haemoglobin by isoelectric focusing and cation-exchange chromatography on minicolumns.
The labile intermediate, pre A1c, formed in the glycosylation of haemoglobin A is a potential contaminant in the measurement of glycosylated haemoglobin when this is determined as the amount of HbA1c present in the sample. By isoelectric focusing on polyacrylamide gel plates this contamination could be avoided either by excision of the HbA1c leaving the neighbouring pre A1c behind on the slab, or by converting the pre A1c to HbA in glucose-free medium before electrophoresis. In cation-exchange chromatography on minicolumns (from Bio-Rad) the pre A1c was removed in the haemolysis process by borate-induced transformation to the non-interfering HbA. The chromatographic method nevertheless gave about 10% higher values than isoelectric focusing. The linearity between paired results of the electrophoretic and chromatographic methods was not perfect (p less than 0.05). Both methods measured decreasing concentrations of HbA1c equally well and with the same precision at both high and low levels (CV less than 5%). All HbF was simultaneously determined in the chromatographic method, while HbF did not interfere in the electrophoretic method. The HbA1c in whole blood samples was stable at 4 degrees C for up to 1 week. Carbon monoxide treatment made the HbA1c in haemolysates stable for at least 3 months at -70 degrees C making possible long-term control by both methods.
Chromatography, Ion Exchange↗
The mutual relationship between the two molecular forms of the major fibrinolysis inhibitor alpha-2-antiplasmin in blood.
Alpha-2-antiplasmin, a major inhibitor of fibrinolysis, is synthesized in the liver and occurs in blood in two molecular forms: a very active plasminogen-binding (PB) form and a less active nonplasminogen-binding (NPB) form. This study investigates the origin and mutual relationship of these two forms in vivo and in vitro. Despite wide variation in plasma concentration of the inhibitor (16% to 138%), the ratio between the two forms in vivo was found to be, in the main, constant among healthy volunteers, heterozygotes for a congenital deficiency of alpha-2-antiplasmin, and patients with a stable liver cirrhosis: PB/NPB = 2.41 +/- 0.34 (SD). Resynthesis after depletion or increased synthesis in the acute-phase reaction showed a specific increase of the PB form of the molecule in blood after discontinuation of L-asparaginase or streptokinase therapy and after myocardial infarction. In vitro studies demonstrated that only the PB form was present after one day in the culture medium of the human cell line Hep G2, while the NPB form appeared after 11 days. Clearance after inhibition of synthesis by L-asparaginase therapy revealed a more rapid decrease in the PB form relative to the NPB form in blood, demonstrated by a change in the PB-NPB ratio from 2.86 +/- 0.55 to 1.74 +/- 0.24 (mean of 6, SD). An apparently spontaneous first order conversion from the PB to NPB form, with an apparent half-life of about eight days, was demonstrated at 37 degrees C in plasma and serum in vitro. The conversion was found to be temperature dependent and uninfluenced by the fibrinolytic components fibrinogen, fibrin, and plasminogen. Additions of a variety of enzymes or inhibitors did not interfere with the process. These results demonstrate that the PB form of alpha-2-antiplasmin is produced by the liver and that the NPB form is formed in the circulation.
Asparaginase↗
Distinction by radioisotope technique of a subgroup with increased thrombophilic potential among patients submitted to major abdominal surgery.
Deep vein thrombosis (DVT) detectable by the 99mTechnetium-labeled plasmin test developed in 13 (37%) of 35 sequentially studied patients, all above 40 years, undergoing elective major abdominal surgery. Ten of the 13 patients with DVT had an abnormal pulmonary perfusion scintigram, suggesting pulmonary embolism (PE), but only three had clinical evidence of thrombotic disease.
Abdomen↗
Chronic interstitial cystitis and subcutaneous heparin.
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Chronic Disease↗
Increased euglobulin fibrinolytic potential in women on oral contraceptives low in oestrogen--levels of extrinsic and intrinsic plasminogen activators, prekallikrein, factor XII, and C1-inactivator.
Components of the fibrinolytic system were studied in samples of plasma from 15 normal, young women and from 11 women taking oral contraceptives containing 30 micrograms ethinyl oestradiol and 150 micrograms levo-norgestrel. Fibrinolytic activity of euglobulins precipitated at pH 5.9 was higher than normal in the hormone group, with significant fluctuations related to the cycle. Normal women showed only minor fluctuations. The concentration of C1-inactivator was lower in euglobulins of the hormone group. However, the difference in fibrinolytic activity was retained, when C1-inactivator was inactivated with sodium flufenamate. Fluctuations of the extrinsic (tissue-type) plasminogen activator (t-PA) activity parallelled those of the euglobulin activity. The intrinsic plasminogen activator activity (dextran sulphate precipitated euglobulin) was significantly increased in the hormone group and the cyclic pattern differed from that of the normal group. The increased activity was factor XII-dependent. Plasma prekallikrein did not differ. The factor XII level was increased in the hormone group but this could not explain the increased intrinsic fibrinolytic activity, suggesting an increase in the quantity of an additional factor XII-dependent proactivator.
Adult↗
On the significance of antithrombin-III, alpha 2-macroglobulin, alpha 2-antiplasmin, histidine-rich glycoprotein, and protein C in patients with acute myocardial infarction and deep vein thrombosis.
In a longitudinal study the plasma levels of antithrombin-III, alpha 2-macroglobulin, alpha 2-antiplasmin, histidine-rich glycoprotein, and protein C were followed in two groups of patients with acute myocardial infarction (AMI), one with and one without deep vein thrombosis (DVT). None of the sequentially studied periods revealed significant differences between the two groups of patients. However, small but consistently higher levels of histidine-rich glycoprotein in patients with DVT suggested the existence among patients submitted for myocardial infarction of a subgroup with increased thrombophilic potential. It was concluded that the inhibitors studied are of little value as possible indicators of the presence of DVT at early stages of the disease when clinical signs are absent and when antithrombotic prophylaxis should preferably be initiated.
Aged↗
Plasma histidine-rich glycoprotein and plasminogen in patients with liver disease.
Histidine-rich glycoprotein (HRG) has been reported to be a fibrinolysis regulating protein due to its capacity to bind to the high affinity lysine binding sites of plasminogen. Using immunological methods we have measured the concentrations in plasma of HRG and total plasminogen and calculated the amounts of plasminogen not bound to HRG (free plasminogen) in 28 patients with moderate to severe liver disease. All three parametres showed wide individual variations, but with decreasing functional capacity of the liver the individual levels of plasminogen were reduced earlier than those of HRG leading to decreased amounts of free plasminogen. Simultaneous determinations of HRG and total plasminogen combined with a calculation of free plasminogen might yield valuable information when evaluating patients for the availability of plasminogen.
Adult↗
A functional plasminogen assay utilizing the potentiating effect of fibrinogen to correct for the overestimation of plasminogen in pathological plasma samples.
An overestimation of the plasminogen concentration occurs in patients with elevated levels of fibrin degradation products (fdp) and/or fibrinogen, when using assays based on the activation of plasminogen by streptokinase (Sk) followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be overcome by addition of fibrinogen in excess to the plasminogen assay thereby obtaining maximum stimulation of the Sk-plasminogen complex. The late degradation products of fibrinogen and fibrin, Dcate and Ddimer, respectively, had no potentiating effect on the Sk-plasminogen complex. The modified assay was designed as a manual method or for a centrifugal analyzer. The excellent reproducibility is illustrated by the coefficient of variation (CV) within series being 1.3% (n = 24) and from day to day being 1.9% (n = 20).
Autoanalysis↗
[Diagnostic and clinical aspects in patients with acquired circulating coagulation inhibitors].
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Blood Coagulation Disorders↗
Protection against venous thrombosis in an antithrombin-III deficient patient suffering from episodes of arterial thrombosis requiring major surgery. Effects of oral stanozolol in combination with subcutaneous heparin and intravenous AT-III.
In an antithrombin-III (AT-III) deficient patient suffering from recurrent episodes of venous and arterial thrombosis requiring major surgery an attempt was made to institute antithrombotic protection by long-term stanozolol treatment supplemented during periods of thrombogenic exposure with subcutaneous heparin and, when needed, infusion of AT-III as plasma or concentrate. Stanozolol raised the plasma levels of AT-III, demonstrating a sparing effect on the AT-III needed. Despite the repeated exposures to major surgery, protection against venous thrombosis was complete, but the arterial disease progressed and led to the demise of the patient.
Administration, Oral↗
The postoperative fibrinolytic shutdown: a rapidly reverting acute phase pattern for the fast-acting inhibitor of tissue-type plasminogen activator after trauma.
The plasma activity level of the recently discovered fast-acting inhibitor of tissue-type plasminogen activator (t-PA) was found to be temporarily increased after surgery, myocardial infarction and severe trauma. Detailed analysis of the postoperative period revealed simultaneously increased t-PA antigen and inhibition and decreased t-PA activity only on the first postoperative day. These changes were more rapid than those in fibrinogen and C-reactive protein. It is concluded that t-PA inhibition shows the most rapidly changing pattern observed so far in response to trauma. The postoperative fibrinolytic shutdown in blood fibrinolytic activity can be ascribed to a primary increase in t-PA inhibitor levels.
Antigens↗
Subcutaneous heparin in the treatment of interstitial cystitis.
Chronic interstitial cystitis (IC) is an inflammatory condition of the bladder of unknown aetiology. Clinically, IC is difficult to handle. Previously, we reported that administration of subcutaneous heparin has an immediate, ameliorating effect. We have now followed eight of the patients for one year or more, during which period they received subcutaneous heparin in doses varying from 5000 IU per day to 5000 IU 2-3 times a week. This treatment was found to have a long-term beneficial effect. No side effects were observed.
Adult↗
Improved assay of antithrombin-III. Effects of certain additives on thrombin and on chromogenic peptide substrates.
When manual assays of antithrombin-III with use of different synthetic chromogenic peptide substrates are modified for a centrifugal analyzer, the downward deflection of the reference curve at the zero point raises a serious problem, because the position of the zero value is included in the calculation of the reference curve. Complete linearity was obtained by addition of polyethylene glycol 6000 to the thrombin solution and Tween 80 to the substrate solution in final concentrations of 1 g/L and 100 mg/L, respectively. The additives increased the concentration of active thrombin in the solutions by preventing its adsorption and aggregation, and the solubility of the substrates in aqueous media is increased. The precision of the optimized method, tested in routine assays during three months, yielded an estimated day-to-day CV of 3.4%.
Animals↗