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At least 19 recordsLinked to original sources

PubMed1986

Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states.

Protein C is a natural vitamin K-dependent plasma anticoagulant, deficiencies of which have been found in patients with recurrent thrombosis and warfarin-induced skin necrosis. To appreciate more fully the role of protein C in disease states and during oral anticoagulation, a new functional assay for protein C involving adsorption of plasma protein C on a Ca+2-dependent monoclonal antibody, elution, quantitative activation, and assessment of plasma anticoagulant activity, has been developed. When oral anticoagulation is initiated, the anticoagulant activity of protein C decreases to a greater extent than either the amidolytic or immunologic levels. During stabilized warfarin treatment, there is no correlation between either amidolytic or antigenic levels and the functional protein C activity, suggesting that measurement of protein C anticoagulant activity may be necessary to reflect adequately the anticoagulant protection afforded by this protein. In contrast, there was a strong correlation between anticoagulant and amidolytic and immunologic levels in liver failure and disseminated intravascular coagulation. Two patients with thromboembolic disease have been identified who exhibit a marked decrease in anticoagulant activity, but who have normal immunologic and amidolytic levels. Thus, this assay permits assessment of protein C in individuals who have received anticoagulant treatment and identification of a new class of protein C-deficient individuals.

Adult↗

PubMed1991

Tissue anticoagulants in the human placenta: preliminary study with a heparin-like anticoagulant and review of the literature.

In this study a new heparin-like anticoagulant in the human placenta is described and an extensive review of the literature is given. An anticoagulant with a heparin-like activity was isolated from an extract of the human placenta. A two-stage purification procedure was applied: affinity chromatography on heparin-Sepharose and ion-exchange chromatography on DEAE-trisacryl. The isolated anticoagulant fraction was found to prolong both thrombin clotting time and activated partial thromboplastin time and to increase the activity of antithrombin III and heparin cofactor II. The placental-tissue anticoagulants described in the literature are divided by the author into five groups: (1) acidic peptides of low molecular weight; (2) thrombomodulin; (3) phospholipid-binding protein anticoagulants; (4) heparin-like anticoagulants, and (5) others. The anticoagulant described in the present study has been classified to the 4th group.

Annexins↗

PubMed1978

Incidence of emboli with cloth-covered Starr-Edwards valve without anticoagulation and with varying forms of anticoagulation. Analysis of 183 patients followed for 3 1/2 years.

One hundred eighty-three patients with cloth-covered valves were studied from 1 1/2 to 8 years after operation, with an average follow-up time of 3 1/2 years. Over the total period, patients taking Coumadin sustained a 4 percent embolic incidence (1.2 per 100 patient-years); those taking aspirin had a 7 percent incidence (2.6 per 100 patient-years); and those taking Persantine had a 43 percent incidence (10 per 100 patient-years). Patients on no regimen of anticoagulation had a 16 percent embolic rate (four per 100 patient-years), whereas another group of patients who stopped anticoagulants after a year incurred a 13 percent embolic incidence in the subsequent 2 years (6.4 per 100 patient-years). These data showed a significantly lowered embolic rate with anticoagulation and suggest that all patients with cloth-covered valves should be taking anticoagulants. That these valves become epithelialized and do not form thrombus after a year was not borne out by this study. Persantine alone is not a satisfactory anticoagulant. Coumadin appears to be the superior anticoagulant, but if careful monitoring of its use is in question or if serious bleeding complications ensue, aspirin may provide satisfactory protection.

Anticoagulants↗

PubMed1988

Anticoagulant therapy for prevention of spontaneous abortion in a patient with a lupus anticoagulant.

Lupus anticoagulants are associated with venous and arterial thrombosis and with recurrent spontaneous abortion resulting from placental infarction. Treatment with high-dose prednisone and aspirin has been reported to reduce the otherwise very high frequency of spontaneous abortion in affected women. We report the case of a young woman with an idiopathic lupus anticoagulant who had a history of arterial and venous thrombosis and of previous spontaneous abortion; anticoagulation throughout pregnancy was associated with normal fetal growth and with an absence of placental infarction. We conclude that anticoagulation without concurrent prednisone or aspirin may provide an alternative approach to prevention of habitual abortion in some women with lupus anticoagulants.

Abortion, Spontaneous↗

PubMed1977

Management of anticoagulation in outpatients: experience with an anticoagulation service in a municipal hospital setting.

In 66 months, a general hospital's outpatient Anticoagulation Service (ACS) monitored 263 patients who received 280 courses of warfarin sodium totalling 254 patient treatment years. Major hemorrhagic morbidity was 4% of courses and there was no mortality attributable to warfarin therapy. Major hemorrhage occurred in patients with increased anatomic risk of bleeding (diverticulosis, hemorrhoids, cystitis), and was not a function of patient age, sex, anticoagulation control, or medications administered concurrently with warfarin. Control of anticoagulation was not correlated with age or other medications, but was worsened significantly by the presence of congestive heart failure. We attribute a favorable experience with outpatient ACS to careful patient selection, patient education and monitoring, attention to duration of anticoagulation, and continuing communication with primary physicians who retained responsibility for medical care. An ACS offers safety, consistency, efficiency, and a unified approach to outpatient anticoagulation in the general hospital setting.

Aged↗

PubMed1979

Structural basis for the anticoagulant activity of heparin. 2. Relationship of anticoagulant activity to the thermodynamics and fluorescence fading kinetics of acridine orange-heparin complexes.

Complexing heparin or dermatan sulfate with the fluorescent probe acridine orange provides a means of studying electrostatic as well as static and dynamic conformational aspects of these glycosaminoglycans via the thermodynamic and photochemical (fluorescence fading) properties of these complexes. The cooperative binding constants (Kq), fluorescence fading rate parameters (r''), and anticoagulant activities of heparins fractionated according to anionic density all showed qualitatively the same dependence upon anionic density. When Kq and r'' were plotted against anticoagulant activity, empirical relationships were observed. Interestingly, the corresponding values for unfractionated dermatan sulfate fell on the lines defined by the heparin fractions. Temperature-dependence, studies demonstrated that differences in fading rate observed for heparins of different anionic densities are entropic in origin and reflect differences in the ability to assume a special configuration. Differences in activation entropy for fluorescence fading can be empirically correlated with anticoagulant activity. The latter correlation suggests a physical similarity in the roles played by anionic density in both fluorescence fading and anticoagulant activity.

Acridine Orange↗

PubMed1989

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↗

PubMed1988

Anticoagulation clinics and the monitoring of anticoagulant therapy.

Patients attending an anticoagulation clinic were studied to delineate predisposing risk factors for bleeding and thromboembolic episodes. Seventy-three patients were observed for a total of 921.8 patient-treatment months. The mean duration of treatment was 12.6 months (range 3-36 months). No major bleed occurred (a bleed which caused discontinuation of therapy, hospitalization or death). Thirty-two patients had minor bleeding episodes (0.42 bleeds per patient-year of treatment). The average prothrombin time ratio during the third to the sixth month of therapy was predictive of the bleeding risk. There was no association between bleeding and age, sex, indication for anticoagulation therapy or associated illnesses. Four thromboembolic episodes occurred (0.05 per patient-year of treatment), 3 arterial and 1 venous. At the time of the one venous thromboembolic event the prothrombin time ratio was subtherapeutic. In all 3 patients with arterial thromboembolism the mean 3- to 6-month prothrombin time ratio was less than or equal to the lower limit of the recommended range of 1.6-2.5. In our study prothrombin time ratios of 1.3-1.5 for venous thromboembolic disease and 1.6-2.5 for arterial thromboembolic disease were not associated with thromboembolism or major bleeding. Anticoagulation clinics facilitate the close monitoring of patients on oral anticoagulant therapy.

Aged↗

PubMed1985

The mechanism of action of oral anticoagulants and its consequences for the practice of oral anticoagulation.

A short review on the discovery of the relation between vitamin K and the synthesis of clotting factors and on the development of anticoagulant therapy is given. The procoagulant activity induced by vitamin K resides in the postribosomal modification of N-terminal glutamic acids in gamma-COOH glutamic acids. The mode of action of oral anticoagulants is explained. The concentration-effect relations and the choice of an oral anticoagulant is discussed.

Administration, Oral↗

PubMed1976

[The anticoagulant property of a lipoid anticoagulant and the mechanism of its influence on hemocoagulation].

A lipoid anticoagulant (LA) from human brain tissue was shown to possess a higher anticoagulant activity than previously obtained preparations. It has been established that out of four phospholipids present in LA, only phosphatidyl serine inhibits the coagulant activity of plasma. In isolated hemocoagulating systems LA and phosphatidyl serine were shown to inhibit prothrombin conversion catalyzed by thrombokinase and to exert the antithrombic action in the system thrombin--fibrinogen. Kinetic study of phosphatidyl serine- and LA-induced inhibition of thrombine formation and the thrombine--fibrinogen reaction by conjugated inhibition. Similar kinetic behaviour, observed upon inhibition of both processes by phosphatidyl serine and LA suggest that phosphatidyl serine is a main anticoagulant agent of LA.

Anticoagulants↗

PubMed1991

Novel anticoagulant peptides from the functional site of human placental anticoagulant protein.

Histidine-containing peptides SHLRKV and DHTLIR, corresponding to placental anticoagulant protein-I (PAP-I) residues 204-209 and 266-271, respectively, are included in the functional site of PAP-I and exhibit anticoagulant activity, but the peptides in which alanine is substituted for histidine do not. However, the peptide KHALKG, corresponding to the region from Lys-97 to Gly-102, did not exhibit an anticoagulant activity, showing that it is not included in the functional site. These findings thus suggest that His-205 and His-267 are involved in the Ca(2+)- or the phospholipid-binding site of PAP-I but that His-98 is not.

Amino Acid Sequence↗

PubMed1989

[The effects of various anticoagulants on blood coagulation: with special reference to false positive lupus anticoagulants].

We studied the effects of heparin, dextran sulphate (MDS), gabexate mesilate (FOY), nafamostat mesilate (FUT-175) and argipidine (MD-805) on APTT, PT, thrombin time (TT) and kaolin-activated PTT (KPTT) with various concentrations of phospholipid for screening of lupus anticoagulants (LA). Heparin, MDS and FUT-175 had a greater effect on APTT than PT. On the contrary, MD-805 had a similar effect on both APTT and PT, which suggests that MD-805 inhibits thrombin generation equally on intrinsic and extrinsic coagulation pathways. Heparin and MD-805 were more effective on TT than MDS, FUT-175 and FOY at high concentrations significantly prolonged TT. But, at even higher concentrations of FUT-175, prolongation of TT was reduced contrary to our expectation. With FOY TT became less prolonged with a passage of time, suggesting time-dependent reduction of its anticoagulant activity. Heparin (0.1-0.2 U/ml) and MDS (0.1-0.3 mg/ml) did not have any effect on KPTT with high concentration of phospholipid, but did FUT-175. It suggests that phospholipid inhibits anticoagulant activity of heparin and MDS. Anti-phospholipid activity of heparin and MDS is similar to that of LA. We concluded that the differentiation of LA from heparin-like inhibitors is needed.

Anticoagulants↗

PubMed1987

Oral anticoagulant therapy control: evidence that INR expression improves the inter-laboratory comparability of results--the Bologna oral anticoagulant control exercise.

The aims of the present study were: 1) interlaboratory normalization of prothrombin time (PT) testing for anticoagulant therapy control through calibration of customary thromboplastins against international reference materials, and 2) "on field" validation of the advantages offered by expression of results as International Normalized Ratio (INR) as opposed to percentage activity. PT tests were carried out over 8 days on the same normal subjects (16) and patients on oral anticoagulants (48) in the 9 laboratories of the Bologna area. The use of customary thromboplastins and coagulometers was maintained in all labs throughout the study. The main results were: 1) the interlaboratory CV of the prothrombin ratios obtained for each sample with all customary thromboplastins (5 different brands) was 15%, but was reduced to levels of 5.8 to 8.9 when using constant thromboplastin brands and batches; 2) the International Sensitivity Index (ISI) values obtained in the different labs were only slightly influenced by the use of different coagulometers; 3) comparable ISI values were obtained through direct calibration with the international reference material and through intermediate calibration with a locally selected standard; 4) use of INR values instead of percentage activity greatly reduced interlaboratory variability and significantly improved uniformity of anticoagulation level measurements, thus reducing the possibility of erroneous prescriptions. The Bologna exercise is therefore of educational value for laboratory and community doctors of the area in understanding and accepting the INR system.

Administration, Oral↗

PubMed1977

[Hemarthroses complicating anticoagulant therapy (heparin, oral anticoagulants)].

Three patients with hemarthrosis complicating anticoagulant therapy are described. Two had acute hemarthrosis of the knee joint occurring during long term oral anticoagulant therapy for cardiovascular disorders. Joint symptoms disappeared rapidly after arthrocentesis and diminution of the dose of oral anticoagulant medication. The third patient has been on chronic hemodialysis for the last three years. After 2 years of this therapy he developed periarthritis of the right shoulder, followed suddenly by hemarthrosis of the right shoulder which remained symptomatic for 9 months in spite of several joint aspirations and reduction in the dosage of heparin administered during hemodialysis. Resolution of the hemarthrosis of the right shoulder occurred only when the vascular access for the dialysis sessions was displaced from the right to the left forearm. It is assumed that there was communication in the venous draining territories of the arterio-venous fistula and the shoulder articulation.

Acenocoumarol↗

PubMed1990

The functional site of placental anticoagulant protein: essential histidine residue of placental anticoagulant protein.

Placental anticoagulant protein (PAP) rapidly lost its anticoagulant effect due to photooxidation in the presence of methylene blue at pH 7.9 and 8 degrees C. Photooxidized PAP failed to bind the phospholipid vesicle. It seemed unlikely that the protein underwent a change in molecular size during the photooxidation on the basis of its behavior in electrophoresis and gel filtration. Photooxidized PAP had significantly decreased histidine contents, whereas the contents of other amino acids remained essentially unchanged. The peptide, SHLRKV, was included in the functional site of PAP and still showed an anticoagulant activity. On the other hand, the peptide which substituted histidine by alanine, SALRKV, no longer showed the activity. It was shown that the histidine residue is involved in Ca2+ or the phospholipid binding site of the protein.

Amino Acid Sequence↗

PubMed1990

Studies of natural anticoagulant proteins and anticardiolipin antibodies in patients with the lupus anticoagulant.

Components of the natural anticoagulant system (NAS) and anticardiolipin antibodies were examined in 21 patients with lupus anticoagulant (LA), 13 of whom had past histories of thrombotic episodes. No relationship could be shown between the antigenic levels of protein C and S (PC, PS) and a history of thrombosis. Inhibition of the anticoagulant activity of activated protein C (APC) was observed using plasma from 20/21 patients when phospholipid vesicles were used as the surface for the coagulation reaction. This effect was not affected by the addition of PS. When platelet membranes were employed only 2/21 patients demonstrated inhibition of APC. Under the latter condition, PS functional activity was inhibited in 7/21 patients, six of whom had a past history of thrombosis. Reduced antithrombin III or heparin cofactor II levels were observed in a total of 4/21 patients and may have contributed to the development of thrombosis in three of these patients. Antibodies specifically directed against these proteins were not detected suggesting the possibility of an associated constitutional deficiency. Anticardiolipin antibodies, though elevated in 17/21 patients, did not serve as a useful marker for an increased risk of thrombosis, and the level did not correlate with inhibition of the activity of APC or PS. We conclude that the mechanism of thrombosis in patients with LA is multi-factorial. A subset of patients in whom LA specifically inhibits PS function may represent patients who are at significant risk from thrombosis.

Antibodies↗

PubMed1991

Comparison of the in vivo anticoagulant properties of standard heparin and the highly selective factor Xa inhibitors antistasin and tick anticoagulant peptide (TAP) in a rabbit model of venous thrombosis.

An in vivo thromboplastin (TP)-induced venous stasis thrombosis model in rabbits was used to compare the efficacy of standard heparin with the selective factor Xa inhibitors, recombinant tick anticoagulant peptide (rTAP) and recombinant antistasin (rATS), in prophylactic prevention of thrombus formation. Heparin significantly reduced TP-induced clot formation at doses of 55 and 100 U kg-1h-1 yielding clot weights of 9 +/- 4 and 6 +/- 2%, respectively. Clot formation was significantly decreased by i.v. infusions of rTAP at doses of 21, 37 and 64 micrograms kg-1 min-1 resulting in normalized clot weights of 13 +/- 3, 8 +/- 2 and 2 +/- 1%, respectively. rATS was approximately 10-fold more potent than rTAP, reducing normalized clot weights to 16 +/- 5, 2 +/- 1 and 1 +/- 0.8% at rATS doses of 1.25, 2.5 and 5.0 micrograms kg-1 min-1, respectively. These data suggest that factor Xa-mediated inhibition of coagulation with rTAP and rATS is as effective as conventional anticoagulant treatment with heparin in preventing venous thrombosis.

Animals↗

PubMed1990

Detection of lupus anticoagulant by means of dilute Russell's viper venom time is affected by oral anticoagulant therapy.

The effects of oral anticoagulant therapy on the detection of lupus anticoagulant (LA) were studied in 110 patients with histories of thrombosis. LA was clearly positive in only two (2%) of the patients. Factor defects caused by warfarin therapy did not affect the kaolin clotting time (KCT) or recalcification time (RT) in mixing tests, but markedly affected the dilute Russell's viper venom time (DRVVT), resulting in 45 weak false-positive results. However, the problem was overcome in 93% of these cases by taking account of the basal prolongation of patients' DRVVT and the sensitivity of plasmas to dilution of the phospholipid reagent. A simple mathematical formula is suggested.

Administration, Oral↗