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At least 1,009 records · Page 56Linked to original sources
PubMed2006

Risk of rebleeding after treatment of acute hydrocephalus in patients with aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Cerebrospinal fluid drainage is often indicated in patients with acute hydrocephalus after aneurysmal subarachnoid hemorrhage but is believed to increase the risk of rebleeding. We studied the risk of rebleeding in patients with subarachnoid hemorrhage during treatment for acute hydrocephalus. METHODS: We included patients with hydrocephalus treated with external ventricular drainage or lumbar punctures within 4 days after the hemorrhage and before aneurysm occlusion. Each treated patient was matched with a control patient with untreated hydrocephalus and a control patient without ventricular enlargement. Patients and controls were matched for interval since subarachnoid hemorrhage, duration of exposure, use of tranexamic acid, clinical condition on admission, and age. We used Cox regression to calculate hazard ratios and we adjusted for rebleeding that had occurred before starting the cerebrospinal fluid drainage. RESULTS: In the group treated with external ventricular drainage, rebleeding occurred in seven of 34 patients (21%) with treatment, in seven of 34 controls (21%) with untreated hydrocephalus, and in six of 34 controls (18%) without hydrocephalus. In the group treated with one or more lumbar punctures, rebleeding occurred in one of 21 patients (5%) with treatment, in three of 21 controls (14%) with untreated hydrocephalus, and in none of the 21 controls without hydrocephalus. The hazard ratios for rebleeding were 1.0 (95% CI: 0.4 to 2.7) for external ventricular drainage treatment and 0.7 (95% CI: 0.1 to 6.4) for lumbar puncture treatment. CONCLUSIONS: This study does not confirm an importantly increased risk of rebleeding during external ventricular drainage or lumbar punctures for acute hydrocephalus after aneurysmal subarachnoid hemorrhage.

Acute Disease↗
PubMed1988

Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage.

Using logistic regression, we analyzed the predictive value of a number of entry variables with respect to the outcome variables delayed cerebral ischemia, rebleeding, and poor outcome (death or severe disability) in patients with aneurysmal subarachnoid hemorrhage. The entry variables were clinical condition on admission (grades on the Glasgow Coma Scale, Hunt and Hess system), the amount of subarachnoid and intraventricular blood and the presence of hydrocephalus on the admission computed tomogram, and antifibrinolytic treatment with tranexamic acid. We used data from a prospectively studied population of 176 patients admitted within 72 hours after subarachnoid hemorrhage. The risk of delayed cerebral ischemia was best predicted by the amount of subarachnoid blood, intraventricular blood, and antifibrinolytic treatment irrespective of clinical condition and hydrocephalus. The site of delayed cerebral ischemia was not related to the location of the subarachnoid hemorrhage. Antifibrinolytic treatment was the only entry variable (negatively) predicting the risk of rebleeding. Death or severe disability after 3 months was best predicted by the amount of subarachnoid blood and the initial clinical condition reflected by the grade on the Glasgow Coma Scale.

Blood↗
PubMed1989

Management problems in acute hydrocephalus after subarachnoid hemorrhage.

In a consecutive series of 473 patients admitted within 72 hours after a subarachnoid hemorrhage, 91 (19%) had hydrocephalus on the initial computed tomogram. Consciousness was unimpaired in 25 of the 91 (28%). In 11 more patients acute hydrocephalus developed within 1 week after subarachnoid hemorrhage. Thirty-eight (8%) of all 473 patients subsequently showed clinical deterioration because of acute hydrocephalus; 11 of these 38 had fluctuations in the level of consciousness. Of the 66 patients with acute hydrocephalus and impaired consciousness on admission, 26 (39%) spontaneously improved within 24 hours. Ventricular drainage was performed in 32 (31%) of the 102 patients with acute hydrocephalus (7% of all 473 patients). Consciousness improved after ventricular drainage in 25 (78%) of the 32 patients. Ventriculitis developed in 12 of the 24 patients with external drainage, mainly after greater than 3 days of drainage, and in none of the eight patients with an internal shunt. Among the 340 patients with aneurysmal subarachnoid hemorrhage and no long-term tranexamic acid treatment, the frequency of rebleeding in patients with ventricular drainage (43% of 23) was significantly higher than in hydrocephalic patients without drainage (15% of 52 patients; chi 2 = 5.009, p = 0.025) and patients without acute hydrocephalus (20% of 265 patients; chi 2 = 5.521, p = 0.019). We conclude that spontaneous improvement occurs in half of the patients with acute hydrocephalus and impaired consciousness on admission, which is usually apparent within 24 hours, and that the outcome of patients who need ventricular drainage will improve if rebleeding and infection after insertion of the ventricular drain can be prevented.

Acute Disease↗
PubMed1983

Thrombin-induced lung vascular injury. Roles of fibrinogen and fibrinolysis.

We examined the contributions of fibrin and the fibrinolytic mechanism in mediating the thrombin-induced lung vascular injury. Studies were made in sheep in which alterations in lung transvascular fluid and protein exchange were assessed using the lung lymph fistula preparation. Group I(n = 10) control sheep in which left atrial pressure was raised to increase pulmonary lymph flow (Qlym); Group II(n = 8) control sheep in which thrombin was infused intravenously (58.3 +/- 12.6 U/kg) to induce pulmonary thromboembolization; Group III (n = 6) sheep were defibrinogenerated using Ancrod (purified fraction of venom of Agkistrodon rhodostoma) prior to embolization with thrombin (124.5 +/- 2.5 U/kg); Group IV (n = 13) sheep were treated with tranexamic acid to inhibit fibrinolysis prior to embolization with thrombin (140.0 +/- 25.8 U/kg). In Group II, pulmonary thromboembolization increased Qlym without a change in the steady-state lymph-to-plasma protein concentration ratio (L/P). Raising left atrial pressure (increases Pla) postembolization to test for an increase in pulmonary vascular permeability to proteins further increased Qlym but did not alter L/P, indicating an increase in permeability. In Group III, the thrombin-induced increase in Qlym was blunted and the L/P decreased; increases Pla further increased Qlym but decreased L/P. In Group IV, Qlym also increased after thrombin-induced embolization and L/P decreased; increases Pla further increased Qlym but decreased L/P. The responses to increases Pla of Groups III and IV were similar to the response of Group I rather than to that of Group II, indicating that defibrinogenation and fibrinolytic inhibition prevented the increase in lung vascular permeability. The results indicate that circulating fibrinogen and activation of plasmin are necessary for development of lung vascular injury after pulmonary thromboembolization.

Animals↗
PubMed1989

Role of catalytic and lysine-binding sites in plasmin-induced neutrophil adherence to endothelium.

Plasmin resulted in increased neutrophil adherence to cultured ovine pulmonary artery endothelial cell monolayers in a concentration-dependent manner (10(-12)-10(-7) M). The adherence response increased fivefold above baseline within 60 min after addition of plasmin (10(-8) M) and the response persisted up to 30 min after removal of plasmin. The neutrophil adherence was mediated by the action of plasmin on neutrophils rather than endothelial cells. The response was the result of an increase in functional activity of CD18 neutrophil cell surface adhesive glycoprotein. Neutrophil adherence was inhibited by pretreatment of neutrophils with MAbs IB4 and 60.3 targeted against the beta chain of the CD18, whereas control isotypic MAb 60.5 against HLA class I antigen had no effect. The plasmin catalytic site was not involved in the response. Lys-plasminogen had reduced adherence-promoting activity relative to plasmin, whereas glu-plasminogen had no effect. Elastase-derived plasminogen fragments corresponding to kringle 1+2+3 and kringle 4 (both of which contained the lysine-binding sites) possessed neutrophil adherence-promoting activities similar to plasmin, whereas miniplasminogen (which contains the catalytic site but no lysine-binding sites) had minimal effect, indicating the involvement of lysine-binding sites in the response. Blocking lysine-binding sites of plasmin and elastase-derived plasminogen fragments with tranexamic acid (IC50 of 5 mM) inhibited neutrophil adherence. A monospecific polyclonal antibody against the lysine-binding sites also reduced the neutrophil adherence-promoting activity of plasmin. The results indicate that plasmin induces neutrophil adherence to the endothelium and that the effect is mediated by lysine-binding sites on plasmin.

Animals↗
PubMed1998

Activated human protein C prevents thrombin-induced thromboembolism in mice. Evidence that activated protein c reduces intravascular fibrin accumulation through the inhibition of additional thrombin generation.

Activated protein C (APC) is a potent physiologic anticoagulant with profibrinolytic properties, and has been shown to prevent thrombosis in different experimental models. We investigated the effect of human APC on thrombin-induced thromboembolism in mice, a model of acute intravascular fibrin deposition leading to death within minutes. APC given intravenously (i.v.) as a bolus 2 min before thrombin challenge (1,250 U/kg) reduced mortality in a dose-dependent manner despite the lack of thrombin inhibitor activity. Significant inhibition of thrombin-induced death was observed at the dose of 0.05 mg/kg, and maximal protection was obtained with 2 mg/kg (> 85% reduction in mortality rate). Histology of lung tissue revealed that APC treatment (2 mg/kg) reduced significantly vascular occlusion rate (from 89.2 to 46.6%, P < 0.01). The protective effect of APC was due to the inhibition of endogenous thrombin formation as indicated by the fact that (a) the injection of human thrombin caused a marked decrease in the coagulation factors of the intrinsic and common pathways (but not of Factor VII), suggesting the activation of blood clotting via the contact system; (b) APC pretreatment reduced markedly prothrombin consumption; (c) the lethal effect of thrombin was almost abolished when the animals were made deficient in vitamin K-dependent factors by warfarin treatment, and could be restored only by doubling the dose of thrombin, indicating that the generation of endogenous thrombin contributes significantly to death; and (d) APC failed to protect warfarin-treated animals, in which mortality is entirely due to injected thrombin, even after protein S supplementation. Other results suggest that APC protects from thrombin-induced thromboembolism by rendering the formed fibrin more susceptible to plasmin degradation rather than by reducing fibrin formation: in thrombin-treated mice, fibrinogen consumption was not inhibited by APC; and inhibition of endogenous fibrinolysis by epsilon-aminocaproic or tranexamic acid resulted in a significant reduction of the protective effect of APC. Since APC did not enhance plasma fibrinolytic activity, as assessed by the measurement of plasminogen activator (PA) or PA inhibitor (PAI) activities, PAI-1 antigen, or 125I-fibrin degrading activity, we speculate that the inhibition of additional (endogenous) thrombin formation by APC interrupts thrombin-dependent mechanisms that make fibrin clots more resistant to lysis, so that the intravascular deposited fibrin can be removed more rapidly by the endogenous fibrinolytic system.

Animals↗
PubMed1990

Management of multiple cholesterol embolization syndrome--a case report.

A sixty-two-year-old man who underwent coronary angiography and received acute thrombolytic and anticoagulant therapy for acute myocardial infarction developed multisystemic injury, including renal insufficiency and cutaneous manifestations. Fundoscopic examination and skin biopsy specimen led to the diagnosis of multiple cholesterol embolization syndrome (MCES). Discontinuation of anticoagulants and administration of hemostatic (carbazochrome, tranexamic acid, reptilase, and vitamin K) and antihyperlipidemic (cholestyramine and probucol) drugs resulted in temporary improvement of cutaneous and renal disorders and extended survival for about one year. Besides severe aortic atherosclerosis, postmortem examination revealed numerous cholesterol emboli to multiple organs. MCES is a rare but serious complication of left heart catheterization and anticoagulant therapy, and the optimal treatment remains to be established. The authors suggest here that the above-mentioned therapy might be effective for management of MCES.

Anticoagulants↗
PubMed1987

Characterization of plasminogen activators in unstimulated and stimulated human whole saliva.

The fibrinolytic activity of saliva from healthy males was studied on plasminogen-free and plasminogen-rich fibrin plates. A cell-bound plasminogen activator in human unstimulated and stimulated whole saliva was demonstrated. The assessed fibrinolytic activities could always be quenched by incorporation into the fibrin plates of IgG antibodies raised against human two-chain tissue-plasminogen activator (t-PA), while additional experiments indicated the absence in normal human saliva of urokinase-like and factor XII-dependent plasminogen activators as well as the absence of inhibitors of fibrinolysis. Thus, t-PA is the only type of plasminogen activator in normal human saliva. The present findings seem to support our recent clinical observations of a decrease in the incidence of bleeding complications and need for replacement therapy in hemophiliacs undergoing oral surgery during local antifibrinolytic therapy with tranexamic acid. Whether the findings might also be of importance in other pathological conditions of the oral cavity, such as impaired wound healing, remains to be elucidated.

Factor XII↗
PubMedDate not supplied

Computed chest tomography in rats with pulmonary damage due to microembolism.

Computed chest tomography was performed in 13 rats with pulmonary damage due to microembolism, caused by injection of thrombin (500 NIH/kg body weight) and tranexamic acid, a fibrinolytic inhibitor (200 mg/kg body weight), and in 9 control rats. The purpose of the investigation was to perform attenuation measurements at two levels of the right lung, each with three regions of interest (anterior, mid and posterior). Alterations in attenuation, compared with controls, were correlated with lung weight. Compared with controls, the attenuation was significantly increased in the anterior and posterior regions at both levels in animals with pulmonary damage, but not in the mid regions. There was a statistically significant correlation between increasing attenuation and increasing lung weight. A significant difference was found between damaged and control lungs regarding the microscopic grade of interstitial oedema, alveolar oedema and fibrin. Histograms of attenuation values in computed tomograms might be of value in detecting alveolar oedema. It is concluded that computed chest tomography is a good method for detecting pulmonary oedema at an early stage of experimental microembolism in the rat.

Animals↗
PubMed1985

Accidental massive IV administration of cyclosporine in man.

A 23-year-old female patient being treated for Hodgkin's disease (pulmonary) received by mistake cyclosporine iv instead of tranexamic acid. We followed the evolution of the clinical signs, which were interpreted as possible signs of acute toxicity, and monitored the plasma concentrations over an 84-hour period.

Adult↗
PubMed2000

Simple and safe method to prepare patients with prosthetic heart valves for surgical dental procedures.

Temporary discontinuation of high-intensity oral anticoagulant treatment is not recommended in patients undergoing dental surgery. This policy is not based on solid data from randomized clinical trials but on expert consensus. The alternative, i.e., to continue treatment and treat patients with tranexamic acid mouthwash, often is not applicable. A prospective cohort study was carried out to evaluate bleeding and thromboembolic complications in patients bearing prosthetic heart valves and registering International Normalized Ratio (INR) values between 2.0 and 4.5, who underwent dental procedures after a 2-day suspension of warfarin treatment. One hundred four consecutive patients receiving high-intensity anticoagulation underwent 123 dental procedures after 2 days' warfarin withdrawal. No major bleeding complications occurred in the week after the procedure; minor bleeding requiring local measures occurred in two patients. No thromboembolic events and no cases of bacterial endocarditis were recorded in the 3 months after the procedure. A mean decrease in INR by approximately 1.0 U (from 2.95+/-0,59 to 1.87+/-0,46) occurred after 2 days' warfarin suspension. Seven days after reinitiation of warfarin, INR values returned to the therapeutic range in 90% of cases. The calculated average time spent at INR less than 2.0 (critical value) was 28 hours. Two days' warfarin suspension is a simple and safe policy for patients with prosthetic heart valves undergoing dental surgery.

Adult↗
PubMed2004

Characterization of plasminogen as an adhesive ligand for integrins alphaMbeta2 (Mac-1) and alpha5beta1 (VLA-5).

Plasminogen (Pg) has been implicated in many biologic processes involving extracellular proteolysis. We investigated whether Pg, by virtue of its capacity to be deposited within the extracellular matrix, can serve as a ligand for cell surface integrins. We report here that Pg supports cell adhesion by engaging integrins alphaMbeta2 and alpha5beta1. The immobilized Glu-Pg, but not its derivatives with the N-terminal peptide lacking, plasmin and Lys-Pg, supported efficient adhesion that was abolished by anti-alphaMbeta2 and anti-alpha5beta1 integrin-specific monoclonal antibodies (mAbs). In addition, lysine binding sites of Glu-Pg contributed to cell adhesion inasmuch as tranexamic acid and epsilon-aminocaproic acid inhibited cell adhesion. The involvement of alphaMbeta2 and alpha5)beta1 in adhesion to Glu-Pg was demonstrable with blood neutrophils, U937 monocytoid cells, and genetically engineered alphaMbeta2-transfected human embryonic kidney (HEK) 293 cells. In alphaMbeta2, the alphaMI-domain is the binding site for Glu-Pg because the "I-less" form of alphaMbeta2 did not support cell adhesion and the recombinant alphaMI-domain bound Glu-Pg directly. In comparison with cell adhesion, the binding of soluble Glu-Pg to cells and the concomitant generation of plasmin activity was inhibited by anti-alpha5beta1 but not by anti-alphaMbeta2. These findings identify Glu-Pg as an adhesive ligand for integrins alphaMbeta2 and alpha5beta1 and suggest that alpha5beta1 may participate in the binding of soluble Glu-Pg and assist in its activation.

Amino Acid Sequence↗
PubMed2006

Ineffective off-label use of recombinant activated factor VII in a case of bone-marrow transplantation-related gastrointestinal bleeding.

BACKGROUND: For patients with a normal coagulation system, who experience serious bleeding, sound evidence for recombinant activated factor VII (rFVIIa) as an effective haemostatic agent is only scarcely available so far from controlled clinical trials. In systematic reviews on the clinical use of rFVIIa, treatment failures were only rarely reported. CASE PRESENTATION: We present a 45-year old, Caucasian male with persistent intestinal bleeding due to enterocolitis associated with cytomegalovirus infection and acute graft-versus-host-disease. He had received allogeneic peripheral blood stem cell transplantation from an unrelated HLA-identical donor because of chronic myelogenous leukaemia diagnosed two years earlier. Bleeding started at day 18 after transplantation with bloody diarrhea, which was treated with multiple transfusions of fresh frozen plasma, platelet, and red blood cell concentrates, and continued relentlessly, despite all efforts, including continued transfusions, high-dose prednisolone, broad antibiotic and antiviral coverage, and tranexamic acid. Recombinant FVIIa was started at boluses of 90-120 mug/kg every 4-8 hours. Despite more than 10 doses, recurrent severe bleeding progressed to refractory shock, multiorgan failure and death. CONCLUSIONS: Little can be concluded from single case reports of clinical improvement, because publication bias in favour of positive effects is likely. Our case suggests that rFVIIa is not a panacea, in particular for severe bleeding after bone-marrow transplantation. As long as rigorous, controlled studies or comprehensive registries are lacking, conventional interventions remain the standard of care in non-haemophilic patients with severe bleeding.

Journal Article↗
PubMed2025

Integrative analyses of mendelian randomization and bioinformatics reveal casual relationship and genetic links between COVID-19 and knee osteoarthritis.

BACKGROUND: Clinical and epidemiological analyses have found an association between coronavirus disease 2019 (COVID-19) and knee osteoarthritis (KOA). Infection with COVID-19 may increase the risk of developing KOA. OBJECTIVES: This study aimed to investigate the potential causal relationship between COVID-19 and KOA using Mendelian randomization (MR) and to explore the underlying mechanisms through a systematic bioinformatics approach. METHODS: Our investigation focused on exploring the potential causal relationship between COVID-19, acute upper respiratory tract infection (URTI) and KOA utilizing a bidirectional MR approach. Additionally, we conducted differential gene expression analysis using public datasets related to these three conditions. Subsequent analyses, including transcriptional regulation analysis, immune cell infiltration analysis, single-cell analysis, and druggability evaluation, were performed to explore potential mechanisms and prioritize therapeutic targets. RESULTS: The results indicate that COVID-19 has a one-way impact on KOA, while URTI does not play a causal role in this association. Ribosomal dysfunction may serve as an intermediate factor connecting COVID-19 with KOA. Specifically, COVID-19 has the potential to influence the metabolic processes of the extracellular matrix, potentially impacting the joint homeostasis. A specific group of genes (COL10A1, BGN, COL3A1, COMP, ACAN, THBS2, COL5A1, COL16A1, COL5A2) has been identified as a shared transcriptomic signature in response to KOA with COVID-19. Imatinib, Adiponectin, Myricetin, Tranexamic acid, and Chenodeoxycholic acid are potential drugs for the treatment of KOA patients with COVID-19. CONCLUSIONS: This study uniquely combines Mendelian randomization and bioinformatics tools to explore the possibility of a causal relationship and genetic association between COVID-19 and KOA. These findings are expected to provide novel perspectives on the underlying biological mechanisms that link COVID-19 and KOA.

Humans↗
PubMed2001

Prevention of the adverse effects of aprotinin in autologous fibrin glue.

To avoid the adverse effects of aprotinin (Apr) in autologous fibrin glue, we compared the inhibitory properties of four commercial anti-fibrinolytic agents (tranexamic acid (Tra), epsilon-aminocaproic acid (Ips), gabexate mesilate (Gab) and nafamostat mesilate (Naf)). The optimum conditions for the lysing of fibrin glue were an incubation temperature of 37 degrees C, and incubation medium containing urokinase at 100 U/ml and plasminogen at 100 mU/ml (for the washed glue), or neither (for unwashed glue). Fibrin glues without an anti-fibrinolytic agent were quickly lysed in the incubation medium, while those with an anti-fibrinolytic agent were slowly lysed dose-dependently. Naf was the most potent inhibitor and had high affinity for the glue, but the other agents were poor inhibitors and had low affinity. The inhibition potency (IP) of each agent did not correlate with hydrophobicity, but a good correlation was obtained between the remaining coefficient (RC) and hydrophobicity. Naf did not affect the adhesive strength of the glue. These results indicate that Naf is the most suitable anti-fibrinolytic agent to replace Apr.

Aprotinin↗
PubMed1989

A comparison of bovine serum albumins, modified with a variety of carboxyl group agents, as stimulators of tissue-type plasminogen activator-catalyzed activation of plasminogen.

Bovine serum albumins (BSA), modified with a variety of carboxyl group agents, stimulated the tissue-type plasminogen activator (t-PA)-catalyzed activation of human plasminogen. Modification with taurine (tau) and putrescine (put) provided the best stimulants. The tauBSA and putBSA were effective at a concentration of 5 micrograms/ml and enhanced the Lys-plasminogen activation by two-chain t-PA in a dose-dependent manner to a maximum of 44- to 46-fold at 200 micrograms/ml. The Km values for the activation of Glu-plasminogen by t-PA in the presence of tauBSA and putBSA (100 micrograms/ml) were 1.7 and 1.8 microM, while the kcat values were 0.059 and 0.062 s-1, respectively. T-PA was bound to both tauBSA and putBSA, which were immobilized on agarose beads, with KD values of 163 and 138 nM, respectively. The two modified BSAs were good substrates for plasmin and were hydrolyzed by the enzyme to small peptides. All of these modified BSA-related actions were inhibited by lysine analogs (e.g. tranexamic acid) which were adjusted to the concentrations required for the inhibition of the plasminogen (Kringle 1 domain) binding to fibrin. On the other hand, acetylation or succinylation of the amino groups of BSA was not effective, while alkylation of the thiol groups of this protein resulted in a moderate stimulation of the plasmin generation. The present results show that t-PA and plasminogen form complexes with certain charge-modified BSAs via their lysine-binding sites. The different stimulation potency of modified BSAs may provide a model for in vivo counterparts of fibrin.

Animals↗
PubMed1978

Pharmacological studies on experimental nephritic rats (2). Antinephritic effect of various drugs on Masugi's nephritis.

Masugi's nephritis was induced in rats by a single i.v. injection of antikidney serum from rabbits immunized with the homogenate of rat whole kidneys. The antinephritic effect of drugs was evaluated through determination of biochemical parameters such as contents of protein and enzymes excreted into the urine and serum cholesterol content by the preadministration and intermittent administration tests. In the preadministration test, of test drugs, betamethasone (0.2 mg/kg +/- 3 p.o.) and azathioprine (25 mg/kg +/- 3 p.o.) showed an antinephritic effect. Betamethasone in particular resulted in normalization of urine and serum parameters. In the intermittent test, all drugs tested were effective. Significant recovery effects were observed with betamethasone (0.1 mg/kg +/- 6 p.o.),, prednisolone (5 mg/kg +/- 6 p.o.), azathioprine (30 mg/kg +/- 6 p.o.), tranexamic acid (200 mg/kg +/- 6 i.p.) and cetraxate (100 mg/kg 6 i.p.) on urinary protein excretion and with all test drugs including indomethacin (5 mg/kg +/- 6 p.o.) and cyclophosphamide (2.5 mg/kg +/- 6 p.o.) on urinary exzyme excretions. Serum cholesterol levels reverted to normal levels after administration of betamethasone. Using this nephritic model, the antinephritic effect of drugs could be tentatively evaluated.

Alkaline Phosphatase↗
PubMed2004

The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.

This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) is part of the Seventh American College of Chest Physicians Conference on Antithrombotic and Thrombolytic Therapy: Evidence-Based Guidelines. The article describes the antithrombotic effect of VKAs, the monitoring of anticoagulation intensity, the clinical applications of VKA therapy, and the optimal therapeutic range of VKAs, and provides specific management recommendations. Grade 1 recommendations are strong, and indicate that the benefits do, or do not, outweigh the risks, burdens, and costs. Grade 2 suggests that individual patient's values may lead to different choices (for a full understanding of the grading see Guyatt et al, CHEST 2004; 126:179S-187S). Among the key recommendations in this article are the following: for dosing of VKAs, we suggest the initiation of oral anticoagulation therapy with doses between 5 and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 2B). In the elderly and in other patient subgroups with an elevated bleeding risk, we suggest a starting dose at < or = 5 mg (Grade 2C). We recommend basing subsequent doses after the initial two or three doses on the results of INR monitoring (Grade 1C). The article also includes several specific recommendations for the management of patients with INRs above the therapeutic range and for patients requiring invasive procedures. For example, in patients with mild to moderately elevated INRs without major bleeding, we suggest that when vitamin K is to be given it be administered orally rather than subcutaneously (Grade 1A). For the management of patients with a low risk of thromboembolism, we suggest stopping warfarin therapy approximately 4 days before they undergo surgery (Grade 2C). For patients with a high risk of thromboembolism, we suggest stopping warfarin therapy approximately 4 days before surgery, to allow the INR to return to normal, and beginning therapy with full-dose unfractionated heparin or full-dose low-molecular-weight heparin as the INR falls (Grade 2C). In patients undergoing dental procedures, we suggest the use of tranexamic acid mouthwash (Grade 2B) or epsilon amino caproic acid mouthwash without interrupting anticoagulant therapy (Grade 2B) if there is a concern for local bleeding. For most patients who have a lupus inhibitor, we suggest a therapeutic target INR of 2.5 (range, 2.0 to 3.0) [Grade 2B]. In patients with recurrent thromboembolic events with a therapeutic INR or other additional risk factors, we suggest a target INR of 3.0 (range, 2.5 to 3.5) [Grade 2C]. As models of anticoagulation monitoring and management, we recommend that clinicians incorporate patient education, systematic INR testing, tracking, and follow-up, and good communication with patients concerning results and dosing decisions (Grade 1C+).

Administration, Oral↗