[Treatment of manifest thrombosis].
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Anticoagulants↗
Biomedical subjects
D L Heene
Publications and source records attributed to D L Heene.
Differences in the risk factor patterns for coronary heart disease in China, Japan, and Germany.
In Asia coronary heart disease mortality is almost 10 fold less frequent than in European countries. These findings attract interest to search for different risk factor patterns. From 1982 to 1985 epidemiologic surveys were carried out in China (n = 2047), Japan (n = 7580) and Germany (n = 6052). Healthy, male subjects, aged 30 to 59 years were enrolled. The prevalence rate of hypertension for the Germans was 20% versus 18% for the Japanese, and 11% for the Chinese. About 69% of Chinese, 55% of Japanese, and 37% of Germans were smokers. About 66% of the Germans were overweight (BMI greater than 25), 17% of the Japanese, and 11% of the Chinese. The highest risk group with cholesterol levels of greater than 300 mg/dl included no Chinese subject, 0.1% of the Japanese, but 5% of the Germans. The lipoprotein profiles among the Japanese and the Chinese collectives typically showed antiatherosclerotic characteristics, whereas most Germans exhibited profiles which support development of atherosclerosis. About 36% of the participants from Germany showed 3 or more risk factors accumulated per person (Japan and China 5%). Multifactorial risk factor reduction for Germany is recommended.
Adult↗
[Clinical aspects of hemorheology in the aged].
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Aged↗
Noninfectious thrombosis of the superior sagittal sinus in a patient with iron deficiency anemia.
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Anemia, Hypochromic↗
Cardiogenic shock associated with verapamil in a patient with liver cirrhosis.
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Half-Life↗
Randomized controlled study of heparin and low molecular weight heparin for prevention of deep-vein thrombosis in medical patients.
166 patients aged 40-80 years were included in a controlled, randomized, double-blind study to determine the efficacy and safety of a single daily injection of a low molecular weight (LMW) heparin for prevention of deep-vein thrombosis compared to low dose conventional heparin. Patients received 1 x 1.500 aPTT units of a LMW heparin fraction (plus 2 x placebo injection) or 3 x 5.000 IU of an unfractionated heparin. During 10 days of treatment, patients underwent repeated clinical investigation, serial impedance plethysmography, and Doppler sonography for detection of thrombosis of the lower limbs. Combined application of these methods revealed evidence of thrombosis in 4.5% of patients on unfractionated heparin and 3.6% of patients on LMW heparin. Subcutaneous hematomas were significantly smaller in diameter upon treatment with LMW heparin (p less than 0.001). Antithrombin III levels were significantly higher at the end of the observation period in the LMW heparin group (p less than 0.005). Thrombocyte count, transaminases, creatinine, and haemoglobin did not change in either group. The results indicate that LMW heparin administered by a single s.c. dose daily may be as effective as low dose heparin in prevention of deep venous thrombosis in medical inpatients.
Adult↗
Coagulopathy after snake bite by Bothrops neuwiedi: case report and results of in vitro experiments.
Coagulation studies were performed in a patient who had been bitten by a snake of the species Bothrops neuwiedi. The patient presented with hemorrhagic necrosis at the envenomization site and considerable bleeding from venous puncture sites. He developed a severe defibrination syndrome with a clottable fibrinogen level of approximately 0.1 g/l. Fibrinogen was not measurable by clotting time assay. Fibrin degradation products were greatly elevated. Treatment with antivenom caused an anaphylactic reaction within ten minutes and serum sickness after three days. In vitro experiments revealed that B. neuwiedi venom directly activates Factors II and X, but does not activate Factor XIII. In vivo consumption of Factor XIII after B. neuwiedi envenomization is ascribed to the action of Factor IIa. At low venom concentrations clotting is initiated by activation of prothrombin by the venom either directly or via Factor X activation. Treatment with heparin might be beneficial in coagulopathy secondary to snake bite by reducing circulating active thrombin. The venom contains thrombin-like proteases which cause slow clotting of fibrinogen, and plasmin-like components causing further proteolysis of fibrinogen and fibrin. Antivenom has no effect on the proteolytic action of the snake venom. The in vivo effects of antivenom are presumably caused by acceleration of the elimination of venom components from the circulation. Intravenous administration of antivenom caused normalization of blood coagulation parameters within 48 h.
Adult↗
[Comparative study of 2 dosage forms of liquid dimethicone for ultrasound premedication].
A double-blind study was carried out to compare the effects of a premedication with 4 x 500 mg dimethylpolysiloxane (DPS)/24 hours and with 2 x 500 mg/12 hours before abdominal ultrasonography. The investigations covered 13 abdominal regions in specified planes. The incidence of the unobscured presentation of the selected organs and organ sections per patient served as a basis for a sonography index. This index was 67%, without significant difference between the two groups. We believe that the optimal conditions for sonography are given when the patient is fasting and two 500 mg doses of DPS are administered, one in the evening before and one in the morning at the day of investigation.
Abdomen, Acute↗
Morphological quantification and differentiation of left ventricular hypertrophy in hypertrophic cardiomyopathy and hypertensive heart disease. A two dimensional echocardiographic study.
Differentiation between hypertrophic cardiomyopathy and hypertensive heart disease is a diagnostic challenge. M-mode echocardiography only permits assessment of hypertrophy in limited areas of the left ventricular wall. 2-D echocardiography allows visualization of most of the myocardium. To assess the reliability of conventional M-mode echocardiographic and 2-D echocardiographic criteria in patients with hypertrophic cardiomyopathy (HCM) and hypertensive heart disease (HY), 30 patients with hypertrophic cardiomyopathy and 30 patients with hypertension and severe cardiac hypertrophy were examined using M-mode and 2-D echocardiography. Although the M-mode echocardiographic features showed statistically significant differences between the mean values in the two groups, the degree of overlap made the differentiation of the individual patients difficult. The diagnostic sensitivity and specificity of classic echocardiographic features were assessed: ventricular septal thickness greater than or equal to 1.5 cm, 90% and 43% (sensitivity and specificity, respectively); ventricular septal thickness to posterior wall ratio greater than or equal to 1.5, 83% and 56%; cross-sectional area at papillary level greater than 21 cm2m-2, 80% and 73%; septal segment of the myocardial ring at papillary level greater than 6.5 cm2m-2, 80% and 87%; and the combined criteria of cross-sectional area at papillary level greater than 21 cm2m-2 and septal segment greater than 6.5 cm2m-2, 77% and 93%. Quantitative 2-D echocardiography is useful to differentiate patients with hypertrophic cardiomyopathy from those with secondary myocardial hypertrophy due to hypertension. Hypertrophic cardiomyopathy is characterized by a spectrum of different morphological patterns of hypertrophy. Patients with the predominant region of hypertrophy in the anterolateral free wall or the apical region of the left ventricle were not detected with our quantitative method. Patients with this type of hypertrophy are relatively rare in the western population.
Adult↗
Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis.
Fifty patients presenting with acute deep-vein thrombosis were randomized in a prospective, controlled study to determine the safety and efficacy of a treatment with low-molecular-weight (LMW) heparin compared with unfractionated heparin. LMW heparin (n = 24) was administered twice daily subcutaneously at a dose of 2 X 150 anti-Xa units/kg body weight, and unfractionated heparin (n = 26) was given intravenously by continuous infusion at a dose of 450 anti-Xa units/kg body weight daily for 10 days. Doses were adjusted to maintain peak anti-Xa levels between 0.5 and 1.0 anti-Xa units per milliliter. One patient in the unfractionated heparin group and 2 patients in the LMW heparin group suffered from bleeding complications. Two patients on LMW heparin and on unfractionated heparin had high evidence of pulmonary embolism based on defects on ventilation-perfusion scintigraphy. Control phlebography and duplex sonography demonstrated a significant improvement during both treatment regimens. Reperfusion of the deep-vein system was 70% with LMW heparin and 75% with unfractionated heparin. The anti-Xa levels were significantly higher in the LMW heparin group, and activated partial thromboplastin and thrombin clotting times were significantly higher in the group receiving unfractionated heparin. Thrombin-antithrombin III complexes and D-dimer concentration decreased during the treatment, but did not differ between the two regimens. At the end of the treatment period with LMW heparin, protein C and antithrombin III were significantly higher.
Acute Disease↗
Impaired fibrinolytic capacity and tissue plasminogen activator release in patients with restenosis after percutaneous transluminal coronary angioplasty (PTCA).
To assess the role of the fibrinolytic system in the pathogenesis of restenosis after percutaneous transluminal coronary angioplasty (PTCA), we determined the components of this system in a retrospective study, including 16 patients with restenosis (gr. A) and 19 patients with long-term success (gr. B). In both groups at baseline fibrinolytic activity (FA) is unchanged, whereas tissue plasminogen activator antigen (tPA-Ag) is significantly increased (gr. A: 147.0%; gr. B: 139.8%; p less than 0.01). Fibrinolytic capacity (FC) and tPA-Ag release are significantly reduced in the restenosis group (FC: 46.5%, p less than 0.05; tPA-Ag release: 48.3%, p less than 0.01) compared to normal controls as well as to gr. B (FC: 84.3%, p less than 0.05; tPA-Ag release: 79.0%, p less than 0.05). Relating to the contact activation system, F XII (79.5%, p less than 0.05) is significantly, and F XI (82.3%) is clearly reduced in gr. A. Protein C (PC) is significantly elevated in gr. B (117.5%, p less than 0.05). There is a negative correlation between plasminogen activator inhibitor (PAI 1) and HDL-cholesterol (r = 0.37, p less than 0.05). It appears, that there is a typical pattern of defective fibrinolysis in patients with restenosis after PTCA and that this might be a pathogenetic factor in the development of restenosis.
Angioplasty, Balloon, Coronary↗
Biological activity and safety of the subcutaneous administration of high doses of low molecular weight heparin for 8 days in human volunteers.
This study reports on the biological activity and safety of high dose low molecular weight (LMW) heparin therapy administered by two subcutaneous (s.c.) injections daily for 8 days in healthy human volunteers. Group 1 received 2 x 30 aPTT units LMW heparin/kg bodyweight, and group 2 received 2 x 50 aPTT units/kg per day. In group 1, activated partial thromboplastin time (aPTT) and thrombin clotting time (TCT) were uniformly prolonged by 3-5 sec 4 hrs after s.c. administration of heparin. Heptest coagulation time values were prolonged consistently as well by 57 sec on day 1 to 68 sec on day 8. Factor Xa inhibition measured by the S 2222 chromogenic substrate method continuously increased from 0.16 units/ml on day 1 to 0.28 units/ml on day 8. In group 2 prolongation of a aPTT and TCT values increased from 6 sec on day 1 to 15 sec on day 8 and of Heptest time from 70 sec on day 1 to 110 sec on day 8. S 2222 method showed factor Xa inhibitory activity which increased from 0.5 units/ml on day 1 to 0.75 units/ml on day 8. The clinical tolerance of the treatment was good. No changes in clinical chemistry parameters were detected, except for a reversible increase of serum transaminases. The coagulation studies demonstrate accumulation of LMW heparin when high doses are given twice daily. The half life of LMW heparin of factor Xa inhibition increases with increasing doses. Heptest coagulation values were prolonged to 4-6 times the normal values during administration of heparin.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The pharmacological profile of the low molecular weight heparin 21-23 in man: anticoagulant, lipolytic and protamine reversible effects.
The anticoagulant, lipolytic and protamine reversible effects of high doses of low molecular weight (LMW) heparin 21-23 and unfractionated heparin were compared in man. 7,500 units of each heparin were applied, which corresponds to 90 mg LMW heparin and 48 mg unfractionated heparin. The anticoagulant properties of the LMW heparin are characterized by a doubled half life of factor Xa activity, smaller influence on aPTT and thrombin after intravenous (i.v.) and subcutaneous (s.c.) injection, and higher bioavailability of factor Xa activity after s.c. administration (90% versus 15%). Protamine chloride completely neutralizes the effect on aPTT and thrombin and reduces the anti factor Xa activity by 60%. The bleeding time is prolonged by both normal and LMW heparin by 20%. This effect is normalized by protamine chloride, too. Thrombelastography with recalcified whole blood demonstrates that protamine chloride shortens but not completely normalizes the coagulation time in presence of either unfractionated or LMW heparin. The half life of lipoprotein lipase (LPL) activity is 60 min after i.v. administration of unfractionated heparin and 120 min with LMW heparin. Although the release of lipases (LPL and HTGL) is higher after i.v. and s.c. administration of the LMW heparin they do not induce higher releases of free fatty acids. This indicates that the lipolytic activity of this LMW heparin and unfractionated heparin is similar. The results show an improved anticoagulant pharmacological profile of this LMW heparin as compared to unfractionated heparin. Protamine normalizes the anticoagulant effects of LMW heparin with exception of a residual anti factor Xa activity and normalizes the changes of bleeding time and thrombelastography.
Adult↗
Long term anticoagulation with low molecular weight heparin in outpatients with side effects on oral anticoagulants.
A total of 70 outpatients with previous severe haemorrhages and other side effects on conventional oral anticoagulants given for prophylaxis of tromboembolism, were treated with low molecular weight (LMW) heparin fraction Kabi 2165. Anticoagulation was necessary in all patients because of recurrent venous thromboembolism (n = 39), artificial heart valve replacement (n = 12), atrial fibrillation with peripheral embolism (n = 10), and cardiomyopathy (n = 9). LMW heparin was injected sc at doses ranging from 2,500 to 15,000 antifactor Xa (aXa) units once daily by the patients themselves. The dose was adjusted on the basis of body weight, of bleeding risk, and risk of developing thromboembolism. Five of 70 patients with poor compliance, 3 experienced non fatal embolism during the treatment period. Two of 65 patients with good compliance experienced repeat embolism. No fatal embolism occurred. One major episode of gastrointestinal bleeding occurred in a patient with an undetected colon carcinoma. Nine minor hemorrhages were observed in all patients. The present experience suggests that LMW heparin may be used safely and effectively as an alternative anticoagulant in patients who have experienced bleeding and other complications with oral anticoagulants or conventional heparin.
Adult↗
Monitoring of heparin and low molecular weight heparin with capillary and venous whole blood.
A method for determination of antifactor Xa-like activity in capillary whole blood obtained from the fingertip is described, which employs the Heptest coagulation assay. Values obtained with capillary whole blood are compared to values of corresponding plasma and venous whole blood samples. Normal values in plasma, venous whole blood, and capillary blood from the fingertip were 17.1 +/- 2.1, 10.0 +/- 1.3 and 10.4 +/- 1.3 sec, respectively. The intraindividual coefficients of variations range from 0.4 to 1.8% in all assays. The day to day coefficient of variation of normal values ranged between 0.8 and 2.0% for all assays. The within assay coefficients of variation ranged from 3.0 to 7.7% for whole blood samples and from 1.5 to 2.2% for plasma samples after addition of no, 0.2 or 1.0 units of normal or LMW heparin to the samples. After administration of heparin or LMW heparin in healthy persons the coagulation values of the different coagulation assay systems displayed coefficients of correlation between r = 0.87 and r = 0.95. Correlation coefficients between the coagulation tests and the S 2222 chromogenic substrate method ranged from r = 0.77 to r = 0.92. In patients, who received LMW heparin for prophylaxis of thromboembolism the coagulation assay correlated between r = 0.78 and 0.92. The coagulation assays and the S 2222 method displayed coefficients of correlation between r = 0.74 and r = 0.83. The data indicate that Heptest sensitively measures antifactor Xa-like activity in capillary whole blood as well as venous whole blood samples containing low quantities of heparin or LMW heparin.
Adult↗
[Conjunctival oxygen pressure in patients with acute cerebral infarct].
Conjunctival oxygen tension and arterial blood gases were measured in 20 patients with acute ischaemic stroke and compared to values obtained in a reference group. The conjunctival capillary bed is perfused by the ophthalmic artery and, thus, reflects the oxygen delivery to the areas supplied by the internal carotid artery. Patients with acute ischaemic stroke showed especially on the ipsilateral side, i.e. the side of the infarction, and to a lesser extent on the other side a lowered conjunctival oxygen tension and a reduced ratio of conjunctival to arterial oxygen tension. These findings indicate disturbances of the blood fluidity, of the cerebrovascular autoregulation and of brain microperfusion. Monitoring of conjunctival oxygen tension is simple and safe. This method allows the assessment of oxygen tension in a tissue bed vascularized by the internal carotid artery. It appears to yield an objective criterion of the effectiveness of therapeutic procedures aiming at an improvement of cerebral perfusion and oxygen supply in patients with acute ischaemic stroke.
Aged↗
Pharmacology and special clinical applications of low-molecular-weight heparins.
In this overview, the rationale of the development of low-molecular-weight (LMW) heparins and their toxicological, anticoagulant, fibrinolytic, lipolytic, and protamine interactions are summarized. Clinical experiences are reviewed on the benefit of LMW heparin for anticoagulation in patients with bleeding and other complications on conventional anticoagulants and during pregnancy. It is concluded that animal experiments have demonstrated the safety of LMW heparins, that the pharmacologic profile is improved compared with normal heparin, and that the simple and safe applicability of LMW heparins gives rise to new indications for the long-term prophylaxis of thromboembolism.
Animals↗
A model for the comparison of pharmacologic agents influencing gallbladder contraction.
Investigations on pharmacologic effects on gallbladder contraction must take into consideration the spontaneous motility of the gallbladder. In 20 healthy subjects, we measured the area of the gallbladder sonographically over 10 h at hourly intervals. The spontaneous motility expressed as a coefficient of variation varied between 1.6 and 13% (mean value, 6.3%). Afterwards, we checked the cholecystokinetic action of ceruletide and fatty meal in eight subjects. Here, an alteration of the area by four times the previously found coefficient of variation was defined as significant. A significant contraction occurred earlier after ceruletide administration than after a fatty meal (10 min as compared to 20 min). This lasted longer (40 min. vs. 25 min) and led to a very much more marked reduction in area (69% as compared to 53%). These differences were significant on a 5% level. The end of the contraction did not differ (50 min as compared to 45 min). We conclude that drugs which affect gallbladder contraction can be compared with consideration of spontaneous motility.
Adult↗