Prothrombin Time (prothrombin + time)

Distribution by Scientific Domains
Distribution within Medical Sciences

Kinds of Prothrombin Time

  • prolonged prothrombin time

  • Selected Abstracts

    A two-step coagulation test to identify anti,2 -glycoprotein I lupus anticoagulants

    V. Pengo
    Summary., Lupus anticoagulants (LA) are immunoglobulins which inhibit phospholipid (PL)-dependent coagulation tests. LA are not specific, as they may reflect the presence of antibodies to human prothrombin, human ,2 -Glycoprotein I (,2GPI), an association of previous antibodies or other antibodies. Antibodies to human ,2GPI act as in vitro anticoagulants by enhancing the binding of ,2GPI to PL, and this binding may be influenced by calcium ion concentration. A reduction in final calcium concentration, from 10 mm to 5 mm, increased coagulation times in both dilute Russell Viper Venom Time (dRVVT) and dilute Prothrombin Time (dPT) when plasmas of patients with anti,2GPI antibodies were used. Ten LA patients showed increased dRVVT and dPT ratios from means of 1.5 to 1.7 (P < 0.001) and 2.4 to 4.3 (P = 0.002), respectively. Instead, all LA-positive anti,2GPI antibody-negative patients showed decreased coagulation times from mean ratios of 1.5 to 1.3 (P = 0.004) in dRVVT and from 2.0 to 1.5 (P = 0.01) in dPT. These results are confirmed by running dRVVT of normal plasma spiked with affinity purified IgG anti,2GPI antibodies. Therefore, when a PL,dependent coagulation test is run twice, at different final calcium concentrations, anti,2GPI LA can be identified. [source]

    Effect of diphacinone on blood coagulation in Spermophilus beecheyi as a basis for determining optimal timing of field bait applications

    Desley A Whisson
    Abstract The effect was determined of a single dose of 2,mg,kg,1 diphacinone on three blood-clotting parameters [Prothrombin Time (PT), Partial Thromboplastin Time (PTT), and Protein Induced by Vitamin K Absence or Antagonists (PIVKA)] over a 120-h period in California ground squirrels, Spermophilus beecheyi. Diphacinone resulted in elevated PT, PTT and PIVKA within 24,h of squirrels receiving the dose. The most significant change was observed 72,h after dosing. As time following diphacinone dosing increased, there was higher individual variation in blood-clotting time. We suggest that increasing the interval between field bait applications should still result in squirrel mortality but reduce the potential for secondary hazards that may occur when squirrels have the opportunity to consume more than one lethal dose of diphacinone. 2002 Society of Chemical Industry [source]

    Biocompatibility investigation and urea removal from blood by urease-immobilized HEMA incorporated poly(ethyleneglycol dimethacrylate) microbeads

    F. Ayhan
    Abstract The biocompatibility of modified and urease-immobilized poly(ethyleneglycol dimethacrylate/2-hydroxyethylmetacrylate) [poly(EGDMA/HEMA)] microbeads was tested through blood compatibility tests. Twelve percent HEMA incorporated nonporous particles of 105,125 ,m were used in the research. Hydroxyl groups on microbeads were chemically modified by following a three-step procedure that is composed of activation, spacer-arm incorporation (hexamethylene diamine) and, finally, glutaraldehyde bounding. Enzyme urease was immobilized on microbead surfaces, and adsorption of blood proteins in serum and plasma, blood coagulation time, and leukocyte and platelet adhesion were tested. Incubation of 1.5 cc of biological fluid with 100 mg of urease-immobilized poly(EGDMA/HEMA) microbeads at room temperature shows that protein adsorption on surfaces occurs, but protein content after treatment was in the range of healthy people. Adsorbed albumin and total globulin amounts per gram of microbeads is much greater than fibrinogen. Immobilization of urease reduced the protein adsorption and blood coagulation times compared with those of modified microbeads. Prothrombin time (PT) was not altered much, whereas poly(EGDMA/HEMA) microbeads induced a significant increase of activated partial thromboplastin time (APTT). The platelet and leukocyte adhesion slightly increased with the modification of poly(EGDMA/HEMA) and decreased with the introduction of urease. When blood samples were treated with urease-immobilized microbeads, BUN values of patients were lowered to almost acceptable amounts. 2002 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 64B: 13,18, 2003 [source]

    Effects of pentoxifylline on coagulation profile and disseminated intravascular coagulation incidence in Egyptian septic neonates

    M. Adel Msc
    Summary Background and objectives:, Neonatal sepsis is frequently associated with pathological activation of the coagulation system, leading to microcirculatory derangement and multiple organ dysfunction syndrome (MODS). The key role in the pathogenesis of sepsis has been attributed to proinflammatory cytokines. These trigger the development of disseminated intravascular coagulation (DIC) via the tissue factor-dependent pathway of coagulation. Pentoxifylline (PTX), a methylxanthine derivative that is used in peripheral vascular disease, has the potential to modify inflammatory response. The current work was designed to evaluate the potential protective effects of PTX against sepsis-induced microcirculatory derangement in Egyptian neonates. Methods:, A double-blind placebo-controlled quasi-randomized design was used. Thirty-seven neonates with sepsis were randomly allocated into two groups. Seventeen patients were given PTX (5 mg/kg/h for 6 h; for 6 successive days). Twenty patients received equivalent volume of normal saline and represented the placebo group. Prothrombin time (PT), Activated partial thromboplastin time (APTT), fibrinogen, d -dimer, C-reactive protein (CRP), complete blood count (CBC), also hemodynamic parameters comprising arterial blood pressure, heart rate, capillary refill and urinary output were assessed in both groups before and after treatment. Results:, Coagulation parameters in the two groups showed no significant differences. However, a higher incidence of DIC was observed in the placebo group neonates. PTX significantly lowered the percentage of bleeding (P = 00128) and less frequent use of FFP was observed in the PTX group (3553% in PTX group vs. 80% in placebo group, P = 0003). Incidence of MODS was significantly lower (P = 0037) and hospital stay duration of survivors was significantly shorter (P = 0044) in the PTX treated-infants. Conclusion:, Pentoxifylline protects against sepsis-induced microcirculatory derangement in neonates. It significantly lowered the incidence of bleeding and MODS and shortened the length of hospital stay. [source]

    Reproducibility and variability of activated clotting time measurements in the cardiac catheterization laboratory

    Terence M. Doherty
    Abstract The objective of this study was to characterize the reproducibility and variability in the measurement to the activated clotting time (ACT) when performed on two different types of instruments, the HemoTec ACT (Medtronic) and the Hemochron 801 (International Technidyne). The ACT has evolved into the most common point-of-care test used in the cardiac catheterization lab to manage patient heparinization. Since the test has not been standardized, different systems frequently produce different results under the same clinical conditions. Duplicate paired ACT tests (n = 885) from 359 patients were performed on both instruments. Prothrombin times (PT) and activated partial thromboplastin times (aPTT) were also determined on subsets of these same samples (PT = 533; aPTT = 487). The performance and relationships between the two tests were determined using a variety of statistical analytical techniques. The average difference between the ACT devices was only 8 sec, yet more than 60% of the measurements varied by more than 10%. Over one-fourth of measurements varied by more than 20%. The reproducibility to the HemoTec instrument was superior to the Hemochron instrument across the entire range of ACTs measured (mean coefficient of variation 2.4% 54 3.1% vs. 7.2% 54 6.1% for HemoTec and Hemochron, respectively; P < 0.00001; range = 65,555 sec). The relationship between the two ACTs was nonlinear. In therapeutic ranges used for interventional procedures (200,350 sec), HemoTec and Hemochron ACTs are not comparable to one another. Statistical comparative analysis indicated that the HemoTec ACT has better overall performance. 2005 Wiley-Liss, Inc. [source]

    Development of an inhibitory antibody fragment to human tissue factor using phage display technology

    S.M. Meiring
    Abstract Tissue factor is involved in the etiology of thrombotic diseases initiating the thrombosis associated with the inflammation that occurs during infection. The prevention of blood coagulation and inflammation is of primary importance in a number of pathological situations. A single-chain variable antibody fragment of molecular weight of 26,kD that inhibits the action of human tissue factor was selected by phage display technology, purified and tested for its tissue factor inhibitory effect, purified on a protein A column, and its purity evaluated on SDS-PAGE. The effects of the antibody fragment on prothrombin times, Factor Xa production, and thrombin generation were assessed with increasing fragment concentrations, using chromogenic and fluorometric substrates. The antibody fragment dose-dependently prolonged the prothrombin time (IC50=0.5,,M) and delayed the lag phase before the thrombin generation burst and the peak thrombin concentration in the thrombin generation assay. The effect on thrombin generation was more pronounced in thrombophilic plasma than in normal plasma. Antibody-based tissue factor inhibitors therefore may provide an effective treatment for thrombotic disease without serious bleeding complications. Drug Dev Res 2009. 2009 Wiley-Liss, Inc. [source]

    The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and l -selectin function in vivo

    Background Adhesion molecules of the selectin family (mainly P- and L-selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P-and/or L-selectin. Materials and Methods For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous (i.v.) injection of FITC-dextran. Results We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven- and nine-fold, respectively. In contrast, treatment with monoclonal antibodies against P- and L-selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti-P-selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P-selectin function. Importantly, fucoidan and the anti-P-selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. Conclusions Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L -selectin function but may instead be related to the anticoagulative capacity of fucoidan. [source]

    Disseminated intravascular coagulation in acute leukemia: clinical and laboratory features at presentation

    Masamitsu Yanada
    Abstract:,Background:,Although there are two major scoring systems for the clinical diagnosis of disseminated intravascular coagulation (DIC), the validity of these systems for leukemia-associated DIC remains to be confirmed. Methods:,By analyzing 125 newly diagnosed acute leukemia patients, we investigated clinical and laboratory features of leukemia-associated DIC, and determined the validity of the two established criteria. Results:,A total of 36 patients (29%) were diagnosed with DIC according to expert opinion, a method regarded as the de facto gold standard. Leukemia-associated DIC is characterized by rare manifestation of organ failure because of thrombosis and no relevance of the platelet count for the diagnosis. The results of receiver operating characteristics analysis favored fibrin degradation product (FDP) rather than D-dimer as the fibrin-related marker test. Although prothrombin time, plasma fibrinogen, and serum FDP levels were significantly different for patients with and without DIC, multivariate analysis identified FDP levels to be the only factor associated with DIC diagnosis. The cut-off level of 15 ,g/mL for FDP was found to be the most effective to differentiate DIC from non-DIC, resulting in diagnostic sensitivity and specificity of 92% and 96%, respectively. The diagnostic results for our patients produced with this FDP-based system were at least comparable with or superior to those obtained with the two currently available scoring systems. Conclusions:,Our findings suggest that an FDP-based criterion may be applicable for the diagnosis of leukemia-associated DIC. Although it appears to be simple and practicable enough for clinical use, prospective validation of this criterion is needed. [source]

    Hematology and coagulation parameters predict outcome in Taiwanese patients with spontaneous intracerebral hemorrhage

    H.-Y. Fang
    Volume of intracerebral hemorrhage (ICH), Glasgow Coma Scale (GCS) score, peripheral edema around the hematoma, and hydrocephalus are good predictors of mortality in patients with spontaneous ICH from western countries. However, the significance of hematologic and biochemical parameters associated with spontaneous ICH has not been extensively studied. This study was designed to determine prognostic factors for spontaneous ICH in Taiwanese patients. We prospectively studied 109 consecutive patients with spontaneous ICH admitted to Changhua Christian Medical Center. Clinical and laboratory data were collected and analyzed. Mean age was 62.3 years. There were 63 men (58%) and 46 women (42%). Differences in GCS score, ICH score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score between the survival and non-survival groups were statistically significant. Laboratory data were statistically different using multivariate analysis for platelet count, prothrombin time, and white cell count. This is the first study providing information on predictors of spontaneous ICH mortality in Taiwanese patients. The prothrombin time and platelet count on the first day were good early predictors of mortality. This finding in ethnically Chinese patients appears to be different from the profile for patients from western countries. [source]

    Abnormalities of prothrombin: a review of the pathophysiology, diagnosis, and treatment

    HAEMOPHILIA, Issue 6 2008
    S. L. MEEKS
    Summary., Prothrombin (factor II) deficiency is a rare autosomal recessive coagulation disorder that occurs in approximately 1 in 1,2 million people. Prothrombin is activated to thrombin, which in turn proteolytically cleaves fibrinogen to fibrin and contributes to forming a stable fibrin clot. The haemostatic level of prothrombin is thought to be between 20 and 40%, and the half-life is approximately 3 days. There are more than 40 known mutations in prothrombin. Both hypoprothrombinemia and dysprothrombinemia have been described. Low prothrombin activity typically prolongs both the activated partial thromboplastin time and prothrombin time. Clinical manifestations are predominantly mucosal or surgical- or trauma-associated bleeding, but joint bleeding and intracranial haemorrhages have been reported. No purified prothrombin products are available for replacement therapy. Both fresh frozen plasma and prothrombin complex concentrates contain prothrombin and may be used for treatment. [source]

    Successful outcome of a cirrhotic patient with postoperative haematuria treated with a single high dose of recombinant factor VIIa

    HAEMOPHILIA, Issue 6 2001
    J. F. Luca
    Recombinant factor VIIa (rfVIIa) has been widely used for the treatment and prevention of bleeding episodes in haemophiliacs with high-titre inhibitors. High single doses are the treatment of choice for joint and muscle bleeds in those patients. There are only a few reports on the value of rfVIIa in cirrhotic patients with haemostatic impairment but this drug can consistently correct the prothrombin time in these individuals. We report a case of a good response to a single high dose of rfVIIa in a patient with advanced liver disease who suffered from severe refractory postoperative haematuria. [source]

    Cholestasis enhances liver ischemia/reperfusion-induced coagulation activation in rats

    Jaap J. Kloek
    Aim:, Cholestasis is associated with increased morbidity and mortality in patients undergoing major liver surgery. An additional risk is induced when vascular inflow occlusion is applied giving rise to liver ischemia/reperfusion (I/R) injury. The role of the coagulation system in this type of injury is elusive. The aim of the current study was to assess activation of coagulation following hepatic I/R injury in cholestatic rats. Methods:, Male Wistar rats were randomized into two groups and subjected to bile duct ligation (BDL) or sham laparotomy. After 7 days, both groups underwent 30 min partial liver ischemia. Animals were sacrificed before ischemia or after 6 h, 24 h, and 48 h reperfusion. Results:, Plasma AST and ALT levels were higher after I/R in cholestatic rats (P < 0.05). Hepatic necrosis, liver wet/dry ratio and neutrophil influx were increased in the BDL group up to 48 h reperfusion (P < 0.05). Liver synthetic function was decreased in the BDL group as reflected by prolonged prothrombin time after 6 h and 24 h reperfusion (P < 0.05). I/R in cholestatic rats resulted in a 12-fold vs. 7-fold (P < 0.01) increase in markers for thrombin generation and a 6-fold vs. 2-fold (P < 0.01) increase in fibrin degradation products (BDL vs. control, respectively). In addition, the cholestatic rats exhibited significantly decreased levels of antithrombin (AT) III and increased levels of the fibrinolytic inhibitor plasminogen activator inhibitor (PAI-1) during reperfusion. Conclusions:, Cholestasis significantly enhances I/R-induced hepatic damage and inflammation that concurs with an increased activation of coagulation and fibrinolysis. [source]

    Interleukin-17 as a new marker of severity of acute hepatic injury

    Yuki Yasumi
    Aim:, To determine cytokines associated with the progression of acute hepatic injury (AHI), we comprehensively evaluated the serum levels of 17 cytokines. Methods:, We simultaneously measured serum levels of 17 cytokines on admission using a newly developed suspension array protein assay system in 51 patients with AHI, including 15 conventional AHI (CAHI), 15 severe AHI (SAHI) and 21 fulminant hepatic failure (FHF). Results:, Interleukin (IL)-6, IL-8 and IL-17 levels were significantly different among the three disease types as determined by one-way analysis of variance, and only the IL-17 level showed a significant elevation in SAHI and FHF than in CAHI. Namely, the IL-17 levels in SAHI and FHF patients were 4.4 (2.0,11.0) (mean [1 .s.d. range]) and 5.6 (2.0,18.5) pg/mL, respectively, whereas all CAHI patients showed levels lower than the lower limit of detection (2.0 pg/mL). In multiple regression analysis for each factor of model for end-stage liver disease (MELD) score, only IL-10 level was selected as the significant independent variable for total bilirubin level, only IL-17 level for prothrombin time, and TNF-, and IL-1, levels for creatinine level. Conclusion:, These data suggest the usefulness of serum IL-17 level in evaluating the severity of AHI, thus emphasizing the necessity for the basic investigation of the pathological role of IL-17 in acute hepatitis. [source]

    Ischaemic preconditioning of the graft in adult living related right lobe liver transplantation: impact on ischaemia,reperfusion injury and clinical relevance

    HPB, Issue 7 2010
    Paola Andreani
    Abstract Background:, Ischaemic preconditioning (IPC) of the right liver graft in the donor has not been studied in adult-to-adult living related liver transplantation (LRLT). Objective:, To assess the IPC effect of the graft on ischaemia reperfusion injury in the recipient and compare recipient and donor outcomes with and without preconditioned grafts. Patients and methods:, Alternate patients were transplanted with right lobe grafts that were (n= 22; Group Precond) or were not (n= 22; Group Control) subjected to IPC in the living donor. Liver ischaemia,reperfusion injury, liver/kidney function, morbidity/mortality rates and outcomes were compared. Univariate and multivariate analyses were performed to identify factors predictive of the aspartate aminotransferase (AST) peak and minimum prothrombin time. Results:, Both groups had similar length of hospital stay, morbidity/mortality, primary non-function and acute rejection rates. Post-operative AST (P= 0.8) and alanine aminotransferase (ALT) peaks (P= 0.6) were similar in both groups (307 189 and 437 302 vs. 290 146 and 496 343, respectively). In univariate analysis, only pre-operative AST and warm ischemia time (WIT) were significantly associated with post-operative AST peak (in recipients). In multivariate analysis, the graft/recipient weight ratio (P= 0.003) and pre-operative bilirubin concentration (P= 0.004) were significantly predictive of minimum prothrombin time post-transplantation. Conclusions:, Graft IPC in the living related donor is not associated with any benefit for the recipient or the donor and its clinical value remains uncertain. [source]

    Effects of fibrinogen concentrate administration during severe hemorrhage

    Background: Fibrinogen concentrate has been shown to improve coagulation in dilutional coagulopathy in experimental studies, but clinical experience is still scarce. The aim of this study was to evaluate laboratory data and the clinical outcome of fibrinogen administration in patients suffering from severe hemorrhage. Materials and methods: A retrospective study over a 3-year observation period of consecutive patients who received a single dose of fibrinogen concentrate but not recombinant factor VIIa as part of their treatment of severe hemorrhage, defined as >6 U of packed red blood cells (PRBCs). Results: Thirty-seven patients were included, most of them suffering from severe hemorrhage following open heart surgery (68%). After a median fibrinogen dose of 2 g (range 1,6 g), an absolute increase in the plasma fibrinogen concentration of 0.6 g/l was observed (P<0.001). The activated partial thromboplastin time (APTT) decreased significantly (P<0.001), from 52 to 43 s and the prothrombin time (PT) decreased from 20 to 17 s, respectively. The transfusion requirement for PRBCs decreased from 6 to 3 U (P<0.01) in the 24 h after fibrinogen administration, but fresh-frozen plasma and platelet concentrate transfusions did not change significantly. Eight patients (22%) died in intensive care unit and the pre-operative fibrinogen concentration was not significantly different in these patients. Conclusion: Administration of fibrinogen for severe hemorrhage was associated with an increased fibrinogen concentration and a significant decrease in APTT, PT and the requirement for PRBCs. [source]

    Influence of temperature and time before centrifugation of specimens for routine coagulation testing

    Summary The accurate standardization of the preanalytical phase is of pivotal importance for achieving reliable results of coagulation tests. Because information on the suitable storage conditions for coagulation testing is controversial, we aimed at investigating the sample stability with regard to the temperature and time before centrifugation. The activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen and D-dimer were assayed in specimens collected from 26 consecutive patients on antivitamin K therapy on the ACL TOP analyzer. Three primary 3.6-ml siliconized evacuated tubes containing 0.109 mol/l buffered trisodium citrate were sequentially collected from each patient. These three tubes were mixed, pooled and divided into seven identical aliquots. The first aliquot was immediately centrifuged according to the standard protocol [1500 g for 15 min at room temperature (RT)] and analyzed. The other aliquots were left for 3, 6 and 24 h, respectively, at RT or 4 C, and then centrifuged and analyzed. Test results were compared with those obtained on the reference specimen. Statistically significant prolongations were observed for aPTT in all the samples. Such differences exceeded the analytical quality specifications for desirable bias in the samples stored for 24 h. A significant reduction, yet comprised within the desirable bias, was observed for PT and fibrinogen in uncentrifuged specimens stored at RT for 3 and 6 h. No significant biases could be recorded in D-dimer. In conclusion, a 6-h storage of uncentrifuged specimens at either RT or 4 C may still be suitable to achieve results of routine coagulation testing comprised within the analytical quality specifications for desirable bias. [source]

    Establishing an oral anticoagulant monitoring service in a multiethnic developing country

    Summary We describe the establishment of an International Normalized Ratio (INR)-based system for monitoring oral anticoagulant therapy in a multiethnic developing country. There was significant variation in geometric mean normal prothrombin time among ethnic groups: 12.7 s for Indians, 13.4 s for Africans and 13.7 s for subjects of mixed ancestry. About 4129 INR measurements were performed in the first 2 years. The majority (55.2%) of achieved INRs were subtherapeutic. We found 31 (0.8%) instances of severe overanticoagulation (INR > 8.0). There were no bleeding manifestations in 24 (77%) of them. Only two experienced life-threatening haemorrhage. The management of bleeding and excessive anticoagulation was not always in accordance with international recommendations. The high incidence of underanticoagulation in Trinidad and Tobago may be due to genetically determined warfarin resistance or underdosing. Oral anticoagulant monitoring in Trinidad and Tobago could benefit from the centralization of such services to designated clinics with specialized staff and computer-assisted dosing which adopt internationally accepted guidelines for practice. [source]

    Waveform analysis of clotting test optical profiles in the diagnosis and management of disseminated intravascular coagulation (DIC)

    C. H. Toh
    Summary Transmittance waveform charts the changes in light transmittance on standard coagulation assays, such as the prothrombin time (PT) and activated partial thromboplastin time (APTT). Analysis and characterization of these data on photo-optical coagulation analysers provides additional qualitative and quantitative information to that obtained using the clotting time alone. The most thoroughly evaluated clinical application is that of the biphasic APTT waveform with disseminated intravascular coagulation (DIC). The degree of waveform abnormality correlates directly with the severity of haemostatic dysfunction and allows for both the prediction and monitoring from non-overt to overt DIC. As its performance is simple and rapid, this provides the means for targeting therapeutic intervention to an earlier stage of DIC. The recent identification that the mechanism underlying the biphasic waveform is a complex that exists in vivo between C reactive protein with very low density lipoprotein, provides potentially important insights into the molecular pathogenesis of DIC. Thus, in addition to the immediate clinical utility in diagnostic practice, it has important applications as a research tool. Preliminary experience in the application of this technology to the diagnosis and management of the haemophilias and the lupus anticoagulant syndrome has also provided evidence of the power and utility of waveform analysis in essentially simple clotting assays. [source]

    Clinical approach to the patient with unexpected bleeding

    J. M. Teitel
    Bleeding can be considered unexpected if it is disproportionate to the intensity of the haemostatic stress in a patient with no known haemorrhagic disorder or if it occurs in a patient in whom a bleeding disorder has been characterized but is adequately treated. A thorough history usually allows the clinician to predict reasonably accurately whether the patient is likely to have a systemic haemostatic defect (and if so whether it is congenital or acquired), or whether the bleeding likely has a purely anatomical basis. The nature of bleeding is instructive with respect to preliminary categorization. Thus, mucocutaneous bleeding suggests defects of primary haemostasis (disordered platelet,vascular interactions). Bleeding into deeper structures is more suggestive of coagulation defects leading to impaired fibrin clot formation, and delayed bleeding after primary haemostasis is characteristic of hyperfibrinolysis. Localized bleeding suggests an anatomical cause, although an underlying haemostatic defect may coexist. Where bleeding is so acutely threatening as to require urgent intervention, diagnosis and treatment must proceed simultaneously. In the case of minor haemorrhage (not threatening to life or limb) it may be preferable to defer therapy while the nature of the bleeding disorder is methodically investigated. Initial laboratory evaluation is guided by the preliminary clinical impression. The amount of blood loss can be inferred from the haematocrit or haemoglobin concentration, and the platelet count will quickly identify cases in which thrombocytopenia is the likely cause of bleeding. In the latter instance, examination of the red cell morphology, leucocyte differential, and mean platelet volume may allow the aetiological mechanism to be presumptively identified as hypoproliferative or consumptive. With regard to coagulation testing, the activated PTT, prothrombin time, and thrombin time usually constitute an adequate battery of screening tests, unless the clinical picture is sufficiently distinctive to indicate the immediate need for more focused testing. In any event, sufficient blood should be taken to allow more detailed studies to be done based on the results of these screening tests. These results will direct the need for further assays, such as specific clotting factor activity levels, von Willebrand factor assays, tests for coagulation inhibitors, platelet function assays, and markers of primary or secondary fibrinolytic activity. [source]

    Hemostatic Defect in Baboons Autotransfused Treated Plasma to Simulate Shed Blood

    C. Robert Valeri M.D.
    This study was done to determine how autotransfusion of nontreated plasma and plasma treated with urokinase with and without aprotinin affected hemostasis in healthy baboons. Methods: A 500-mL volume of blood was collected from the baboon, a 250-mL volume of plasma was isolated, and the RBCs were reinfused. Three baboons were autotransfused untreated plasma. Four baboons received plasma that had been treated with 3000 IU/mL urokinase at +37C for 30 minutes. Eight baboons received plasma that had been treated first with urokinase 3000 IU/mL at +37C for 30 minutes and then with aprotinin (1000 KIU/mL). Bleeding time, fibrinogen degradation products (FDP), D-dimer, and alpha-2 antiplasmin levels were measured. Results: During the 4-hour period following autotransfusion of the urokinase-aprotinin-treated plasma, the levels of D-dimer and FDP were significantly higher and fibrinogen and alpha-2 antiplasmin levels were significantly lower than those levels seen after the autotransfusion of nontreated plasma. FDP and D-dimer levels showed significant positive correlations with prothrombin time (PT) and activated partial thromboplastin time (aPTT). A significant negative correlation was observed between thrombin time (TT) and fibrinogen level. A significant positive correlation was observed between bleeding time and D-dimer level and a significant negative correlation between the bleeding time and the fibrinogen level. Conclusions: The infusion of a volume of urokinase or urokinase-aprotinin treated autologous plasma equivalent to 15% of the blood volume was not associated with a bleeding diathesis in healthy baboons. [source]

    Comparison of two blood sampling methods in anticoagulation therapy: venipuncture and peripheral venous catheter

    Neriman Zengin MScN
    Aim., To compare prothrombin time and activated partial thromboplastin time values in concurrent blood samples obtained by direct venipuncture and from a peripheral venous catheter. Method., Concurrent blood samples obtained from catheters and by direct venipuncture were studied. Venipuncture samples were labelled as the reference (control) group and the peripheral venous catheter samples as the experimental group. A 21-gauge needle was used in the venipuncture method and 18G, 20G, 22G catheters were used in the peripheral venous catheters method. In each case, after the blood samples were drawn by venipuncture and peripheral venous catheter the needles were drawn out, 18 ml of blood was added to 02 ml of citrate to give a 2 ml sample. The tube was shaken gently to mix the blood and citrate well. Results., No clinically significant difference between prothrombin time and activated partial thromboplastin time values were seen in the blood samples drawn by venipuncture and peripheral venous catheter methods. Discussion., It is recommended that peripheral venous catheter can be used for patients with high bleeding risk if they have a long hospital stay and frequent blood samples are needed. Relevance to clinical practice., In clinical applications, nurses may prefer the use of peripheral venous catheter to venipuncture both for the comfort of the patients who get anticoagulation therapy and for the prevention of the risks as a result of venipuncture. Application of peripheral venous catheter eliminates the risks of superficial bleeding, irritation, pain and anxiety caused by venipuncture. [source]

    Impact of the Tokyo guidelines on the management of patients with acute calculous cholecystitis

    Shou-Wu Lee
    Abstract Background and Aim:, Prompt treatments for acute calculous cholecystitis can reduce both mortality and morbidity. The aim of this retrospective study was to assess the impact of the Tokyo guidelines on management of patients with acute cholecystitis. Methods:, The records of patients admitted due to acute calculous cholecystitis were collected between January 2007 and June 2008. Exclusion criteria included acalculous, hepatobiliary malignancy, younger than 18 years old and mortality unrelated to cholecystitis. These 235 patients were classified into three groups; grade I, grade II and grade III, according to the severity grading in the Tokyo guidelines for acute cholecystitis. They were further classified into two subgroups; those compatible with and incompatible with managements suggested in the Tokyo guidelines, for comparison. Results:, Lower levels of platelets, lower blood pressure, higher levels of C-reactive protein, blood urine nitrogen, prothrombin time, bilirubin, alkaline phosphatase, and more incidences of positive microorganisms cultured in bile or blood, were found in patients as the severity of disease progressed. Shorter mean length of hospital stay was compatible with the Tokyo guidelines, but no significant differences in outcomes, including incidences of survival, post-surgery complications and mortality, were found between the two subgroups. Conclusion:, No significant benefit of the application of the Tokyo guidelines in the management of patients was found between the two subgroups except for reduced mean length of hospital stay. The application of the Tokyo guidelines for improving the outcomes of patients with acute cholecystitis needs further investigation and evaluation. [source]

    Value of regional cerebral blood flow in the evaluation of chronic liver disease and subclinical hepatic encephalopathy

    Abstract Aims:, Regional changes in cerebral blood flow in patients with chronic hepatitis, cirrhosis and subclinical hepatic encephalopathy were investigated in the present study using single photon emission computed tomography (SPECT). Methods:, Twenty patients with cirrhosis, 11 patients with chronic hepatitis, and nine healthy controls were included in the study. Cerebral SPECT were obtained for all patients. The percentages of cerebral blood flow of 14 regions to the cerebellar blood flow were determined. Only the patients with cirrhosis underwent psychometric evaluation: visual evoked potentials (VEP) measurements and electroencephalogram (EEG) recordings along with blood levels of albumin, bilirubin, and ammonia were measured and prothrombin time was determined in cirrhotic patients. These patients were classified according to the Child,Pugh classification. Results:, Among cirrhotic patients, six had abnormal results in VEP studies, 11 in psychometric tests and with six in EEG evaluation. Any abnormality in psychometric tests and/or VEP studies is taken as the main criterion; subclinical hepatic encephalopathy was detected in 12 of 20 patients. According to SPECT results in patients with subclinical encephalopathy, a statistically significant decrease in cerebral blood flow in right thalamus and nearly significant decrease in left thalamus were observed. Regional blood flow was significantly higher in the frontal lobes of patients with cirrhosis when compared with healthy controls. Similarly, cerebral blood flow in frontal and cingulate regions was significantly higher in patients with chronic hepatitis than in healthy controls. There was no relationship between cerebral blood flow and blood levels of ammonia or Child,Pugh score, in cirrhotic patients. Conclusion:, Significant changes in cerebral blood flow may be present in chronic liver diseases and the authors suggest that the measurement of changes in cerebral blood flow might be useful in detecting subclinical hepatic encephalopathy. [source]

    Plasma and urine levels of urinary trypsin inhibitor in patients with acute and fulminant hepatitis

    Abstract Background and Aim Urinary trypsin inhibitor (UTI) is synthesized by hepatocytes and excreted into urine. Plasma and urine UTI levels have been measured to evaluate whether these levels may be useful markers in various pathological conditions. However, there has been no study on plasma and urine UTI levels in patients with acute liver diseases. The aim of the present study was to evaluate plasma and urine UTI levels and their relationship with the severity of hepatic damage in patients with acute liver diseases. Methods Plasma and urine UTI levels were measured by newly developed enzyme-linked immunosorbent assay in 15 patients with acute hepatitis (AH), 12 patients with acute severe hepatitis (ASH) and 10 patients with fulminant hepatitis (FH), as assessed on admission. The serial changes in plasma and urine UTI were also observed in some patients with AH and ASH. Results Plasma UTI levels (U/mL, median [25,75th percentile]) were: 11.0, (9.5,16.1) in patients with AH; 7.8 (5.6,11.5) in those with ASH; 6.5 (4.0,9.5) in patients with FH; and 9.7 (7.3,11.0) in normal controls. Plasma UTI levels in patients with FH were significantly lower than in those with AH. Plasma UTI levels showed significant positive correlations with the levels of prothrombin time (PT), hepaplastin test, antithrombin III, ,2-plasmin inhibitor, plasminogen (Plg) and fibrinogen. After the recovery of liver dysfunction, increased plasma UTI levels in patients with AH were decreased, whereas previously decreased plasma UTI levels in patients with ASH were increased. Urine UTI levels were significantly increased in patients with AH compared with those of normal controls. In patients with ASH and FH, urine UTI levels were increased but not significantly. Urine UTI levels significantly positively correlated with PT and Plg. After the recovery of liver dysfunction, previously increased urine UTI levels in patients with AH were decreased. The correlation between plasma UTI and urine UTI levels was not significant. Conclusions The findings of the present study suggested that the levels of plasma and urine UTI changed in patients with AH and were closely related to the abnormalities of coagulo-fibrinolysis, including PT. Further studies are needed to clarify whether these levels may be useful markers to predict the prognosis of acute hepatitis. [source]

    Glucose-6-phosphate dehydrogenase deficiency is associated with increased initial clinical severity of acute viral hepatitis A

    Israel Gotsman
    Abstract Background and Aim: In glucose-6-phosphate dehydrogenase (G6PD) deficiency, the enzyme is deficient in liver cells as well as in erythrocytes. It has been suggested that this may be associated with a more severe clinical presentation of acute viral hepatitis A. The aim of this study is to determine the severity of liver disease in patients with viral hepatitis and G6PD deficiency. Methods: Eighteen patients with diagnosed G6PD deficiency and acute hepatitis A were compared with 18 matched control patients with hepatitis A in a university hospital for liver disease severity and clinical outcome. Results: Two of 18 patients with G6PD deficiency had neurological deterioration. Patients with G6PD deficiency had a mean peak prothrombin time (PT) that was significantly prolonged as compared with the control group (15.5 3.7 vs 12.9 2.0 s, respectively, P < 0.02), and a significantly higher proportion had an abnormal PT (PT > 13.3 s): 61 versus 11% (P < 0.0001). Hemolysis occurred in 44% of the G6PD deficiency patients. Total and direct bilirubin were significantly higher in all patients with G6PD deficiency, including patients without hemolysis. There was no significant difference in liver enzyme levels between the two groups. Patients with G6PD deficiency had a longer average hospital stay (9.5 4.8 vs 3.4 0.8 days, respectively, P < 0.001). There was no difference in the final clinical outcome between the two groups, and recovery of liver function was seen in all patients. Conclusions: Glucose-6-phosphate dehydrogenase deficiency in patients with hepatitis A causes a more severe initial clinical presentation, but does not alter the final clinical outcome. [source]

    Ex vivo inhibition of thrombus formation by an anti-glycoprotein VI Fab fragment in non-human primates without modification of glycoprotein VI expression

    Summary.,Objectives:,Glycoprotein (GP)VI is an attractive target for the development of new antithrombotic drugs. Its deficiency protects animals in several models of thrombosis, arterial stenosis and ischemia-,reperfusion while inducing no major bleeding tendency. The Fab fragment of one anti-GPVI monoclonal antibody (9O12.2) inhibits all GPVI functions in vitro. The aim of this study was to determine the ex vivo effects of 9O12.2 Fab on hemostasis, coagulation and thrombosis in non-human primates. Methods and results:,Blood samples were collected from cynomolgus monkeys before and after (30, 90 and 150 min, 1 and 7 days) a bolus injection of 9O12.2 Fab (4 mg kg,1) or vehicle. Platelet counts and coagulation tests (prothrombin time, activated partial thromboplastin time) were not modified following Fab injection. The PFA-100 closure time increased during the first hours and returned to initial values on day + 1. Platelet-bound Fab was detected from 30 min to 24 h after Fab injection without GPVI depletion at any time. Collagen-induced platelet aggregation was selectively and fully inhibited at 30 min. Thrombus formation on collagen in flowing whole blood (1500 s,1) was delayed and decreased, and collagen-induced or tissue factor-induced thrombin generation in platelet-rich plasma was profoundly inhibited. Conclusion:,The anti-GPVI 9O12.2 Fab inhibits thrombus formation ex vivo in non-human primates with a composite effect on platelet activation and thrombin generation in the absence of GPVI depletion. [source]

    Apixaban, an oral, direct and highly selective factor Xa inhibitor: in vitro, antithrombotic and antihemostatic studies

    P. C. WONG
    Summary.,Background:,Apixaban is an oral, direct and highly selective factor Xa (FXa) inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. Objective:,We evaluated the in vitro properties of apixaban and its in vivo activities in rabbit models of thrombosis and hemostasis. Methods:,Studies were conducted in arteriovenous-shunt thrombosis (AVST), venous thrombosis (VT), electrically mediated carotid arterial thrombosis (ECAT) and cuticle bleeding time (BT) models. Results:,In vitro, apixaban is potent and selective, with a Ki of 0.08 nm for human FXa. It exhibited species difference in FXa inhibition [FXa Ki (nm): 0.16, rabbit; 1.3, rat; 1.7, dog] and anticoagulation [EC2 (,m, concentration required to double the prothrombin time): 3.6, human; 2.3, rabbit; 7.9, rat; 6.7, dog]. Apixaban at 10 ,m did not alter human and rabbit platelet aggregation to ADP, ,-thrombin, and collagen. In vivo, the values for antithrombotic ED50 (dose that reduced thrombus weight or increased blood flow by 50% of the control) in AVST, VT and ECAT and the values for BT ED3 (dose that increased BT by 3-fold) were 0.27 0.03, 0.11 0.03, 0.07 0.02 and > 3 mg kg,1 h,1 i.v. for apixaban, 0.05 0.01, 0.05 0.01, 0.27 0.08 and > 3 mg kg,1 h,1 i.v. for the indirect FXa inhibitor fondaparinux, and 0.53 0.04, 0.27 0.01, 0.08 0.01 and 0.70 0.07 mg kg,1 day,1 p.o. for the oral anticoagulant warfarin, respectively. Conclusions:,In summary, apixaban was effective in the prevention of experimental thrombosis at doses that preserve hemostasis in rabbits. [source]

    Recombinant activated factor VII efficacy and safety in a model of bleeding and thrombosis in hypothermic rabbits: a blind study

    Summary.,Background:,Recombinant activated factor VII (rFVIIa) is increasingly used to secure hemostasis in hemorrhagic situations in trauma and surgical patients. Hypothermia is often observed in these clinical settings. Objective:,To study the efficacy and safety of rFVIIa in hypothermia in a rabbit model of bleeding and thrombosis. Methods:,Sixty-nine rabbits were anesthetized, ventilated and monitored for blood pressure, temperature and carotid flow. The Folts model was used: a stenosis (75%) and an injury were carried out on the carotid artery, inducing thrombosis. Blood flow decreased as thrombus size increased until the pressure gradient was such that the thrombus was released and local arterial blood flow was suddenly restored. This is known as a cyclic flow reduction (CFR). After counting baseline CFRs during a 20-min period (P1), rabbits were randomized blindly to one of four groups: normothermic (NT) placebo or rFVIIa (150 ,g kg,1), hypothermic (HT) (34 C) placebo or rFVIIa. Then CFRs were recorded over a second period (P2). At the end of the experiment, a hepato-splenic section was performed and the amount of blood loss was recorded. After each period, the following were measured: ear immersion bleeding time (BT), hemoglobin, platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and fibrinogen. Results:,Hypothermia increased BT and blood loss. These effects were reversed by rFVIIa. In NT rabbits, rFVIIa shortened BT but did not reduce blood loss. rFVIIa-treated rabbits bled similarly regardless of temperature. The incidence of CFRs was higher in treated than placebo animals regardless of temperature. rFVIIa decreased PT and aPTT without modifying platelet count or fibrinogen level. Conclusion:,Hemostatic efficacy of rFVIIa was maintained in hypothermia. However, the number of CFRs was higher in the rFVIIa-treated group than in the placebo groups, whether for NT or HT rabbits. [source]

    Evaluation of low PAI-1 activity as a risk factor for hemorrhagic diathesis

    A. GREN
    Summary.,Background: Prospective studies of the epidemiology and clinical significance of low plasminogen activator inhibitor type 1 (PAI-1) activity are lacking. Objective: To evaluate the prevalence of low PAI-1 activity in patients with a bleeding tendency in comparison with a normal population. Methods: In 586 consecutive patients, referred because of bleeding symptoms, we added analyses of PAI-1 activity and tissue plasminogen activator complex with PAI-1 (t-PA,PAI-1) to the routine investigation, consisting of platelet count, bleeding time, prothrombin time, activated partial thromboplastin time, fibrinogen, factor VIII, von Willebrand factor activity, and antigen. Controls were 100 blood donors and 100 age- and sex-matched healthy individuals. The latter were also evaluated regarding the previous bleeding episodes. The bleeding history was classified as clinically significant or not, and the criteria were fulfilled in 75% of the patients and 18% of the healthy controls. Results: The routine laboratory investigation of the patients was negative in 57%. Low PAI-1 activity, defined as <1.0 U mL,1, was found in 23% of the patients and in 13% and 10% of the blood donors and healthy controls, respectively (odds ratio and 95% CI, 2.04; 1.11,3.77 and 2.75; 1.39,5.42, respectively). The difference remained statistically significant after the adjustment for body mass index, use of estrogens, sex and age (odds ratio for patients vs. healthy controls 3.23; 95% CI, 1.22,8.56, P = 0.019). The distribution of the 4G/5G genotypes in the patients was not different from that of two control populations. No specific symptom predicted for low PAI-1, which did not aggravate the clinical picture in association with the other hemostatic defects. Low tPA,PAI-1 was not associated with the increased bleeding tendency. Conclusion: Low PAI-1 activity is common in patients with a bleeding diathesis, but it is a risk factor of minor clinical importance and not associated with specific bleeding manifestations. [source]

    Guidelines for the use of recombinant activated factor VII (rFVIIa) in uncontrolled bleeding: a report by the Israeli Multidisciplinary rFVIIa Task Force

    Summary.,Background:,Recombinant activated factor VII (rFVIIa) has been approved by the U.S. Food and Drug Administration (FDA) for almost a decade for hemophilic patients with inhibitors. Its off-label use as a hemostatic agent in massive bleeding caused by a wide array of clinical scenarios is rapidly expanding. While evidence-based guidelines exist for rFVIIa treatment in hemophilia, none are available for its off-label use. Objectives:,The aim of this study is to develop expert recommendations for the use of rFVIIa in patients suffering from uncontrolled bleeding (with special emphasis on trauma) until randomized, controlled trials allow for the introduction of more established evidence-based guidelines. Methods:,A multidisciplinary task force comprising representatives of the relevant National Medical Associations, experts from the Medical Corps of the Army, Ministry of Health and the Israel National Trauma Advisory Board was established in Israel. Recommendations were construed based on the analysis of the first 36 multi-trauma patients accumulated in the prospective national registry of the use of rFVIIa in trauma, and an extensive literature search consisting of published and prepublished controlled animal trials, case reports and series. The final consensus guidelines, together with the data of the first 36 trauma patients treated in Israel, are presented in this article. Results:,Results of the first 36 trauma patients: The prolonged clotting assays [prothrombin time (PT) and partial thromboplastin time (PTT)] shortened significantly within minutes following administration of rFVIIa. Cessation of bleeding was achieved in 26 of 36 (72%) patients. Acidosis diminished the hemostatic effect of the drug, while hypothermia did not affect it. The survival rate of 61% (22/36) seems to be favorable compared with published series of similar, or less severe, trauma patients (range 30%,57%). Conclusions:,As a result of the lack of controlled trials, our guidelines should be considered as suggestive rather than conclusive. However, they provide a valuable tool for physicians using rFVIIa for the expanding off-label clinical uses. [source]