Natural coagulation inhibitor proteins in young patients with cerebral ischemia.

Disturbances of coagulation and fibrinolytic pathways were studied in 53 young patients with cerebral ischemia. Upon admission 26 of 53 patients had abnormality in at least one of the antithrombin-III, protein C, protein S activities or in activated protein C (APC) ratios. Three months after the first examination the majority of the previously detected abnormalities returned to normal values and the most frequent alterations were decrease in protein S activity (3 patients) and APC resistance (3 patients). Conditions resulting in impaired fibrinolysis were frequently detected upon admission. Elevation of plasminogen activator inhibitor-1, lipoprotein (a), and alpha-2-antiplasmin was present in 23, 10, and 4 cases, respectively. It is concluded that abnormalities of coagulation as well as of the fibrinolytic systems are prevalent in the acute phase of cerebral ischemia, however, the results may be significantly influenced by the disease process or the acute phase effect.

[Analgesics-induced chronic renal failure in patients on dialysis therapy in Hungary]. / Analgetikum-nephropathia elófordulása krónikus veseelégtelenség miatt dializált betegekben Magyarországon.

In recent years elaboration of the diagnosis of analgesic-nephropathy (ANP) with the help of imaging techniques significantly increased the possibility of diagnosing the disease. Therefore, evaluating the prevalence of ANP has become more accurate in our country as well. The prevalence of ANP has been investigated in patients who have newly been taken into the dialysis program due to renal disease of unknown aetiology in 22 dialysis centers between December 1994-December 1997. The diagnosis of ANP has been based on revealing chronic drug abuse in the history and positive results of renal imaging (decrease in length of both kidneys combined with either bumpy contours and/or papillary calcification). Among 284 patients dialysed with unknown diagnosis 42 (14.8% of all cases) proved to have ANP. All patients except 2 took analgesic mixtures containing phenacetin/paracetamol, phenason derivatives, acetilsalysilic acid, caffeine and/or codeine. According to their investigations, ANP is a common disease resulting in end-stage renal failure in Hungary as well.

[Hemostatic abnormalities in ischemic stroke]. / Haemostasis eltérések ischaemiás stroke-ban.

The authors studied whether haemostatic abnormalities connected with the development of cerebral circulatory disturbances can be demonstrated in young stroke patients in whom Doppler and angiographic examination failed to reveal deviations indicative of stroke. They determined the in vivo activation of the coagulation system (TAT, F 1 + 2), the degree of secondary fibrinolysis (D-dimer), the plasma levels of the markers of fibrinolysis, with special regard to inhibitors: plasminogen activator inhibitor (PAI-1), alpha 2 antiplasmin (alpha 2 AP), alpha 2 macroglobulin (alpha 2 M), the frequency of pathologic serum lipoprotein (a)-Lp(a)-values and the association of PAI-1 and Lp(a) with the fibrinolytic system. They conclude that in the acute phase of the disease, the TAT and F 1 + 2 values were significantly elevated compared to the control, without change in the D-dimer value. The results suggest that in the tested period increased thrombin generation dominated and it significantly surpassed plasmin activity since the D-dimer values of that period did not indicate substantial increase in secondary fibrinolysis. The results of the study were separately analyzed in acute, chronic TIA and stroke groups. In the TIA and acute group the F 1 + 2 values, while in stroke the TAT values were more elevated. The in vitro fibrinolytic capacity of the patients significantly decreased compared to controls, showing significant correlation with the Lp(a) level, but not with the PAI value. Examination of the marker molecules renders possible to assess the degree of hypercoaguability and of endogenous lysis. Their knowledge is held important for judging the progression of the disease and the therapeutic consequences.

Monocytes express tissue factor in young patients with cerebral ischemia.

Activation of blood coagulation and fibrinolysis has previously been detected in stroke patients. It is unknown, however, what factors contribute to the acceleration of coagulation reactions, especially in cases where no obvious predisposing factors exist. We therefore postulated and tested the hypothesis that in such patients monocytes may trigger the pathway leading to thrombosis by expressing tissue factor (TF). TF antigen was determined in 48 patients and 40 controls by flow cytometry using an indirect immunofluorescent technique. TF antigen expression was significantly increased on monocytes in young stroke patients in both the acute (p < 0.01) and chronic (p < 0.05) phases of the disease. The TF antigen also possessed functional activity, quantitated by a one-stage clotting assay. TF expression on monocytes was not associated with an elevation in C-reactive protein values. In both acute and chronic phases, blood coagulation activation markers, e.g. the thrombin-antithrombin complex and F1 + 2 fragments, were significantly elevated. However, in the acute phase D-dimer levels were similar to those in controls and were only elevated in the chronic phase of the disease (p < 0.05). In conclusion, in cerebral ischemia TF expression on monocytes suggests enhanced activation of blood coagulation and subsequent fibrinolysis.

[Low doses of acetylsalicylic acid effectively inhibits thrombocyte aggregation after ischemic stroke]. / Kis dózisú acetil-szalicilát hatásosan gátolja a thrombocytaaggregatiót ischaemiás stroke után.

Platelet aggregation was examined in 43 patients after ischemic stroke and in 16 healthy subjects using multiparametric aggregation index (MAI). The value of MAI was significantly higher in stroke patients (3.15 in patients and 0.92 l/mumol in controls, p < 0.0001). Patients who had increased MAI (n = 26) were treated with a daily dose of 100 mg acetilsalicylic acid (ASA). Platelet activity was measured before and on the 7th and 28th day of treatment measuring three parameters: MAI, spontaneous dysaggregation and collagen induced aggregation. All 3 methods showed a significant decrease in platelet aggregation on the 7th day of treatment, but further changes were not found on the 28th day. Serum levels of thromboxane-A2 (TXA2) and prostacycline (PGI2) metabolites (TXB2 and 6-keto-prostaglandin-F1 alpha) were determined before and on the 28th day of treatment. The effect of 100 mg ASA per day proved to be selective: comparing the serum levels before and after treatment, a significant decrease of TXB2 concentration was found without changes in the concentration of 6-keto-prostaglandin-F1 alpha. Evaluating MAI and the value of dysaggregation might reflect ineffectiveness of antiplatelet therapy in patients not responding to a daily dose of 100 mg of ASA. For these patients the increase of the daily dose of ASA, or changing to another antiplatelet drug might be recommended.

[Serum elastin peptide concentration and human leukocyte elastase/antiproteinase balance in peripheral obstructive atherosclerosis]. / A szérum elasztin peptid koncentrációjának és a human leukocyta elasztáz/antiproteáz egyensúlyának vizsgálata perifériás obstructiv atherosclerosisban.

In some pathological states such as therosclerosis tissue destruction may be accelerated due to uncontrolled protease release of polymorphonuclear leukocytes and other events such as decreased concentration and/or the inactivation of main protease inhibitor molecules in the serum. In this study, the authors measured the elastase release of polymorphonuclear leukocytes which increased in atherosclerosis independently of the patients aged compared to healthy young subjects. These findings were similar to the response of polymorphonuclear leukocytes separated from healthy elderly subjects. Simultaneously, the main plasma proteinase inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin in healthy and atherosclerotic subjects were determined. alpha-1-antitrypsin did not decrease significantly, whereas alpha-2-macroglobulin did in sera of atherosclerotic patients compared to age matched subjects (p < 0.05). In contrast, the activity of porcine pancreatic elastase was more effectively neutralized by the plasma obtained from healthy subjects suggesting diminished antiprotease activity of sera obtained from patients. The authors concluded that increased elastase release and decreased antiproteinase activity should be considered in atherosclerotic arterial wall damage. The similarity of the results in aged and therosclerotic subjects suggests that arteriosclerosis is an earlier aging process.

[Experience with echocardiographic examination of patients with left bundle branch block under intensive care]. / Echocardiographiával szerzett tapasztalataink az acut kardiológiai betegellátásban balszárblokk esetén.

In the 3 and a half year patient material of their Intensive Care Unit the authors studied the diagnostic value of the echocardiography in left bundle branch block. From the 925 patients treated this period they analysed retrospectively the clinical data of 51 patients with left bundle branch block. In 37 cases acute myocardial infarction was suspected (group A), 14 patients were hospitalized because of severe left ventricular dysfunction without chest pain (group B). The echocardiography was performed always within 48 hours after admission. In 18/37 respectively 8/14 cases the left bundle branch block had already been known from the previous examinations. In the group A the enzyme test verified acute myocardial infarction in 23 patients, in each of them segmental wall motion abnormality--either akinesis or dyskinesis--was detected by echocardiography. In group B 5 dilated cardiac diseases, 1 aortic and 2 mitral vitiums were verified by echocardiography. From the 6 patients of the group B the wall motion abnormalities were caused by acute myocardial infarction in 1 patient and by a previous myocardial infarction in 5 patients. At the Intensive Care Unit 8, and during the further observation in hospital 5 patients died. In each cases the section reinforced the findings of the echocardiography. According to the authors' experiences, echocardiography is proved to be a very useful help in the acute cardiac care of patients with left bundle branch block.

[Ruptured myocardial infarcts]. / Untersuchungen an rupturierten Herzinfarkten.

Forty one cardiac rupture complicating acute myocardial infarction (AMI) were studied in a ten-year period. The anterior AMIs are most likely to be observed with ruptures. The interval from the onset of AMI to the clinical detection of rupture was short (acute period). Some factors such as physical work in the acute period and transmural infarctions strongly infiltrated with leukocytes cause a higher frequency of rupture. Diabetes and hypertension might be predisposing factors.

[Pathophysiological relations and clinical significance of serine protease inhibitors (serpins)]. / A szerin proteáz inhibitorok (szerpinek) kórélettani vonatkozásai és klinikai jelentösége.

Serine proteases, like all other proteases, are biologically active substances. Their effects are inhibited by serine proteases inhibitors. The disturbance of balance between protease and antiprotease leads to several diseases and to their progression. The authors give an overview on some important data on serpins (biochemical parameters, structural composition), and on the clinical considerations of some diseases that are arisen from the changes in inhibitor levels. The paper includes some own examinations, too. Finally the possibilities of prevention and therapy are discussed.

[Clinico-pathological observations in myocardial rupture]. / Szívizom-rupturával kapcsolatos klinikopatológiai megfigyeléseink.

In their material of 10 years authors describe 42 myocardial ruptures developed as complication of acute myocardial infarct. The rupture developed in the acute stage of infarct. Rupture of anterior wall infarct is the most frequent. The most decisive clinical factor in development of rupture is the loading in acute stage, from pathologic aspect the strongly infiltrated, transmural infarct is considered the most decisive pathologic factor. Diabetes mellitus and hypertonia can predispose to myocardial rupture.

Action of hormonal contraceptives on the coagulation system and some of its inhibitors.

Changes in the level of inhibitors of the coagulation system, primarily of thrombin neutralizing factors have been studied during the prolonged use of four products of contraceptive preparations containing various amounts of oestrogens and progestogens, two fixed dose pills (Bisecurin, Ovidon), a low dose combination pill (Rigevidon) and a biphasic preparation (Anteovin). Thrombelastographic values referred to hypercoagulability while the results of other examinations indicating activation of the coagulation system did not show definite changes in comparison with the control. The activity and quantity of antithrombin III decreased but never below 80%. Except Anteovin all contraceptives significantly enhanced alpha 1-antitrypsin while alpha 2-macroglobulin levels, remained nearly the same as the control values. Attention is called to that the increased alpha 1-antitrypsin level may be a biochemical risk factor. The results showed that the increased coagulability and disposition to thromboembolic disorders caused by hormonal contraceptives may be attributed not only to the decrease of thrombin inhibitors but also to increased alpha 1-antitrypsin levels which may cause increased inhibition of the fibrinolytic system.

PIP: Inhibitors of the coagulation system were measured in 71 women taking 4 oral contraceptives for 1-8 years, 2 combined pills, Bisecurin and Ovidon, a low-dose combined pill, Rigevidon, and a biphasic, Anteovin. The article begins with a review of the clinical significance and recent research on serine protease inhibitors. The pill formulations were: Bisecurin, 50 mcg, ethinyl estradiol and 1 mg ethinodiol diacetate; Ovidon, 50 mcg, ethinyl estradiol and 250 mcg, d-norgestrel; Rigevidon, 30 mcg ethinyl estradiol and 150 mcg, d-norgestrel; Antiovin 50 mcg, ethinyl estradiol and 50 mcg, d-norgestrel for 11 days and with 125 mcg d-norgestrel for 10 days. Thromboelastographic values r and I, indicating hypercoagulation, were significantly higher for pill users compared to 28 controls. No change was seen in prothrombin time (PT), and partial prothrombin time (PTT), fibrinogen values or ethanol gelation. Antithrombin III biological activity and quantity assayed immunologically decreased as much as 20%. The fixed dose pills significantly enhanced alpha 1-antitrypsin, a possible biochemical risk factor for thromboembolic disease. Alpha 2-macroglobulin levels did not change. The results showed that the increased coagulability and enhanced incidence of thromboembolic disorders associated with oral contraception may be caused by a decrease in thrombin inhibitors as well as increased alpha 1 antitrypsin, which inhibits the fibrinolytic system.

[Effect of hormonal contraceptives on the coagulation system with special reference to its inhibitors]. / A hormonális fogamzásgátlók hatása az alvadás-rendszerre, különös tekintettel annak néhány inhibitorára.

PIP: A controlled study of the antithrombin III (AT III), alpha2-macroglobulin (alpha2M), alphal-antitrypsin values of 71 long-term users of local oral contraceptives (OC) indicated that OCs are the most reliable contemporary anticontraceptive drugs, although thromboembolic side effects can be expected. The subjects were 16-35 years old and used Bisecurin, Ovidon, Rigevedon or Anteovin for 1-8 years. Thrombelastography (TEG) was performed to study the global coagulation process, and the 3 TEG parameters, reaction time (r), coagulation time (c), and maximum amplitude (A max) were calculated, yielding a hypercoagulation index. Prothrombin time (PT) and partial thromboplastin time (PTT) were also measured. Results showed a significant shortening of r values and slight decrease of c values in the OC users, as compared to the control (a 28-year old nonuser). The value of A max did not change much. Hypercoagulation was evident in all 3 groups, especially in Ovidon users. PT, PTT, and fibrinogen values did not change significantly. AT III:HC (heparin cofactor) values decreased 83% for Anteovin users, 91-96% for other OC users, but they did not drop to the critical 80% level. The alpha2M values became slightly elevated and alphalAT levels increased significantly in all except Anteovin users. These inhibitors of coagulation play an important role in hemostasis, and it is more likely that hypercoagulation is caused by the decreased level of inhibitors rather than the increase of coagulation factors. The significantly increased level of alpha1AT can pose a biochemical risk factor for thrombosis of veins, as it inhibits the fibrinolytic activity of granulocytes i.e., the formation of cellular fibrinolysis. Therefore, it is important to investigate the alpha1AT levels whenever AT III is normal in thrombosis.^ieng

Antithrombin III determination by rate (kinetic) nephelometry.

Rate nephelometry immunological antithrombin III determination was elaborated with Beckman Immunochemistry System. The measuring can be carried out within 60 sec from 20 microliters plasma. The results show a close correlation with those of gained by the radial immunodiffusion method (r = 0.91( and by Coatest (Kabi-Ortho) (r = 0.77). Both laser-nephelometric and usual non-nephelometric anti-antithrombin III serum (Behring) may be applied.

Haemostasis in diabetics.

Haemostasis was studied in 34 diabetic patients with and without detectable vascular complications (micro- and macroangiopathy). Information on platelet functions was obtained by beta-thromboglobulin determination, and of heparin-thrombin coagulation time, platelet aggregation in vivo, and on the condition of the vessel walls by estimation of factor VIII-protein (VIIIR:Ag). The results were suggestive of an increased platelet activity, the most marked abnormalities having been found in cases of angiopathy. Attention is drawn to the therapeutic possibilities offered by studies of the pathogenetic role of the abnormalities of haemostasis in diabetes.

Antithrombin III levels in term and preterm infants measured by rate nephelometry.

The plasma antithrombin III level was measured in term and premature newborns within the first 24 h of life; in addition to the authors', own immunological method utilizing rate nephelometry the assays of Laurell and Kabi Coatest were used. Antithrombin III concentration showed a linear correlation with the degree of maturity, in accordance with previous data. The lowest values were found in premature babies affected by idiopathic respiratory distress syndrome who later developed pulmonary haemorrhage. At all gestational ages the antithrombin III functional index was lower than 1.0, indicating antithrombin III consumption. Since both concentration and activity of antithrombin III are low in prematures, they are at an increased risk for coagulopathies, hence substitution therapy is indicated. Measurement of antithrombin III by rate nephelometry can also be used for following changes in inhibitor concentration.