Evaluation of intravenous direct thrombin inhibitor monitoring tests: Correlation with plasma concentrations and clinical outcomes in hospitalized patients.

The parenterally administered direct thrombin inhibitors (DTIs) argatroban and bivalirudin are effective anticoagulants for acute heparin-induced thrombocytopenia (HIT) treatment. The activated partial thromboplastin time (aPTT) has classically been used as the monitoring test to assess degree of anticoagulation, however concerns exist with using aPTT to monitor DTI therapy. In this observational study plasma samples from DTI treated patients were analyzed by aPTT, dilute thrombin time (dTT) and ecarin chromogenic assay (ECA) to delineate results into concordant and discordant groups. Discordant samples were further analyzed via liquid chromatography with tandem mass spectrometry (LC MS/MS). In total 101 patients with 198 samples were evaluated. Discordance between tests were frequent (59% of DTI treated patients). Bivalirudin aPTT vs dTT discordance was observed in 45% (57/126) of samples. Amongst bivalirudin samples with test discordance dTT results were more likely to be concordant with LC MS/MS than the aPTT (77% vs 9%, p < 0.0001). Argatroban aPTT vs dTT discordance was observed in 43% (31/72) and aPTT vs ECA discordance was observed in 40% (29/72) of samples. Amongst argatroban samples with test discordance both the dTT and ECA tests were more likely to have concordant results with LC MS/MS than the aPTT (88% vs 9%, p < 0.0001 for both dTT and ECA tests). There were no differences between discordant and concordant patient groups in a composite outcome of bleeding/thrombosis rate (23% vs 27%, p = 0.689). Further investigation is warranted to elucidate the effect of suitable monitoring assays on patient outcomes in the setting of DTI therapy.

Structural Characteristics and Anticoagulant Property In Vitro and In Vivo of a Seaweed Sulfated Rhamnan.

Great diversity and metabolite complexity of seaweeds offer a unique and exclusive source of renewable drug molecules. Polysaccharide from seaweed has potential as a promising candidate for marine drug development. In the present study, seaweed polysaccharide (SPm) was isolated from Monostroma angicava, the polymeric repeat units and anticoagulant property in vitro and in vivo of SPm were investigated. SPm was a sulfated polysaccharide which was mainly constituted by 3-linked, 2-linked-α-l-rhamnose residues with partially sulfate groups at C-2 of 3-linked α-l-rhamnose residues and C-3 of 2-linked α-l-rhamnose residues. Small amounts of xylose and glucuronic acid exist in the forms of ß-d-Xylp(4SO4)-(1→ and ß-d-GlcA-(1→. SPm effectively prolonged clotting time as evaluated by the activated partial thromboplastin time and thrombin time assays, and exhibited strong anticoagulant activity in vitro and in vivo. The fibrin(ogen)olytic and thrombolytic properties of SPm were evaluated by plasminogen activator inhibitior-1, fibrin degradation products, D-dimer and clot lytic rate assays using rats plasma, and the results showed that SPm possessed high fibrin(ogen)olytic and thrombolytic properties. These results suggested that SPm has potential as a novel anticoagulant agent.

Laboratory Monitoring of Parenteral Direct Thrombin Inhibitors.

Argatroban and bivalirudin are parenteral direct inhibitors of the activity of thrombin, but, unlike heparin, can inhibit both soluble as well as clot-bound thrombin. These agents do not require antithrombin as a cofactor for activity. The parenteral direct thrombin inhibitors (DTIs) can be used in a variety of settings, including heparin-induced thrombocytopenia (HIT) or an allergy to heparin, and patients requiring anticoagulation for an invasive cardiovascular intervention. Both agents have a relatively short half-life in patients without organ system failure and are typically administered by continuous infusion. Argatroban is primarily eliminated by the liver, while bivalirudin is removed by a combination of proteolytic cleavage by thrombin and renal clearance mechanisms. Several laboratory tests are available for monitoring the anticoagulant effects of the DTIs: the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT) are the most commonly used assays, but on occasion, the thrombin time may be useful. Other coagulation assays such as the dilute thrombin time (dTT), chromogenic anti-IIa assays, and the ecarin clotting time (ECT) can be used. The intensity of anticoagulation with DTIs depends on the indication for use. For patients with HIT, the target aPTT is 1.5 to 3.0 and 1.5 to 2.5 times the patient's baseline value for argatroban and bivalirudin, respectively. DTI anticoagulation used during percutaneous coronary intervention can be measured using ACT. Both DTIs may cause an elevation in the international normalized ratio depending on their plasma concentration. This article will review the use of parenteral DTIs and related laboratory assays for assessing the anticoagulant effect of these drugs.

Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants.

BACKGROUND: Point-of-care testing (POCT) of coagulation has been proven to be of great value in accelerating emergency treatment. Specific POCT for direct oral anticoagulants (DOAC) is not available, but the effects of DOAC on established POCT have been described. We aimed to determine the diagnostic accuracy of Hemochron® Signature coagulation POCT to qualitatively rule out relevant concentrations of apixaban, rivaroxaban, and dabigatran in real-life patients. METHODS: We enrolled 68 patients receiving apixaban, rivaroxaban, or dabigatran and obtained blood samples at six pre-specified time points. Coagulation testing was performed using prothrombin time/international normalized ratio (PT/INR), activated partial thromboplastin time (aPTT), and activated clotting time (ACT+ and ACT-low range) POCT cards. For comparison, laboratory-based assays of diluted thrombin time (Hemoclot) and anti-Xa activity were conducted. DOAC concentrations were determined by liquid chromatography-tandem mass spectrometry. RESULTS: Four hundred and three samples were collected. POCT results of PT/INR and ACT+ correlated with both rivaroxaban and dabigatran concentrations. Insufficient correlation was found for apixaban. Rivaroxaban concentrations at <30 and <100 ng/mL were detected with >95% specificity at PT/INR POCT ≤1.0 and ≤1.1 and ACT+ POCT ≤120 and ≤130 s. Dabigatran concentrations at <30 and <50 ng/mL were detected with >95% specificity at PT/INR POCT ≤1.1 and ≤1.2 and ACT+ POCT ≤100 s. CONCLUSIONS: Hemochron® Signature POCT can be a fast and reliable alternative for guiding emergency treatment during rivaroxaban and dabigatran therapy. It allows the rapid identification of a relevant fraction of patients that can be treated immediately without the need to await the results of much slower laboratory-based coagulation tests. TRIAL REGISTRATION: Unique identifier, NCT02371070 . Retrospectively registered on 18 February 2015.

Thrombin Generation Assay as a Laboratory Monitoring Tool during Bypassing Therapy in Patients with Hemophilia and Inhibitors.

Hemophilia treatment relies upon replacement of the deficient factor to restore physiological levels in plasma. The development of inhibitors is the main complication of replacement therapy, which renders replacement therapy ineffective and requires the use of alternative hemostatic drugs known as bypassing agents. The hemostatic response to bypassing agents is different from patient to patient and even in the same patient during different bleeding episodes. Up to now, no routine laboratory test has been found suitable to monitor efficacy and safety of these drugs. The unpredictable clinical response to bypassing therapy and the lack of a monitoring laboratory tool renders surgery in inhibitor patients a big challenge for the risk of both bleeding and thromboembolic complications. The thrombin generation assay (TGA) has been proposed as a monitoring tool in this patient population on the basis of the results obtained both in vitro and ex vivo. This review aims to summarize the current published evidence on the use of TGA as a laboratory monitoring tool in patients with hemophilia complicated by inhibitors.

Alterations of the thrombin generation profile in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder resulting in the erosion of the cartilage and bone. Systemic involvement including the cardiovascular system with the risk of atherosclerosis may also occur. Calibrated automated thrombogram (CAT), a commercially available thrombin generation assay is suitable for the general assessment of the functionality of coagulation system. In this study we performed CAT assay in RA patients and in non-affected control subjects (matched for age, sex and comorbidities). Among the CAT parameters Velocity Index increased (from 60 to 83 nM/min), Lag Time and Time to Peak decreased (from 3.47 to 2.83 min and from 6.98 to 5.58 min respectively) in RA. On the other hand, Endogenous Thrombin Potential values decreased (from 1242 to 1108 nM min). The observed alterations were not associated with the applied therapy. These results indicate that the velocity of thrombin formation is increased, while the thrombin generating capability is reduced in RA.

Laboratory measurement of the non-vitamin K antagonist oral anticoagulants: selecting the optimal assay based on drug, assay availability, and clinical indication.

Although the non-vitamin K antagonist oral anticoagulants (NOACs) do not require routine monitoring, there are special circumstances in which laboratory measurement may be warranted. The objectives of this review are to summarize evidence on the influence of the NOACs on coagulation tests and provide practical guidance to clinicians on measurement and interpretation of coagulation assays in NOAC-treated patients. Selection of an appropriate assay for NOAC measurement depends on the drug, clinical objective, and assay availability. Separate suggestions for assay selection are provided depending on whether specialized assays are available or whether choice is limited to conventional coagulation assays such as the prothrombin time (PT) and activated partial thromboplastin time (APTT). The dilute thrombin time (TT) and ecarin-based assays are able to quantify dabigatran across a broad range of concentrations, but are not widely available. A normal TT excludes clinically relevant levels. A normal APTT probably excludes excess levels of dabigatran, but does not rule out typical on-therapy drug concentrations. The PT is insufficiently sensitive to dabigatran to be useful in most situations. Factor Xa inhibitors may be quantified with an anti-Xa assay calibrated with drug-specific standards. A normal PT probably excludes excess levels of rivaroxaban and edoxaban, but not typical on-therapy levels of these agents. The PT is less sensitive to apixaban. Depending on the sensitivity of the thromboplastin reagent, a normal PT may not exclude excess levels of apixaban. The APTT has inadequate sensitivity to factor Xa inhibitors and is not recommended for their measurement.

Tigecycline treatment causes a decrease in fibrinogen levels.

The objective of this study was to assess the impact of tigecycline treatment on coagulation parameters, specifically fibrinogen, in patients with severe infections. We examined 20 cases of tigecycline-treated patients with severe infections, including hospital-acquired pneumonia, complicated intra-abdominal infections, complicated skin and soft tissue infections, and bloodstream infections. We monitored the relative markers of coagulation and renal and liver function before, during, and after treatment. Fibrinogen (FIB) levels decreased significantly after the use of tigecycline and normalized after the cessation of treatment. FIB levels significantly decreased in the patients treated with the recommended dose or a higher treatment dose. The FIB levels decreased more in the higher-treatment-dose group. There was no difference in the decrease in FIB levels or the FIB level recovery by age. Prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) were prolonged after tigecycline use. The TT decreased after the cessation of treatment, and the PT and APTT also decreased but not to a significant level. There was no change in platelet, alanine aminotransferase (ALT), or creatinine (Cr) levels associated with treatment. The use of tigecycline was associated with decreased FIB levels, which returned to normal after the cessation of treatment. A high-dose treatment group showed greater decreases in FIB levels than did patients treated with the recommended dose. The decline in FIB was not related to patient age. The use of tigecycline was associated with prolonged PT, APTT, and TT.

Thrombin generation assay identifies individual variability in responses to low molecular weight heparin in pregnancy: implications for anticoagulant monitoring.

Low molecular weight heparin (LMWH) given to inhibit coagulation and reduce the risk of thrombosis, is typically monitored by anti-Xa assay. However, anti-Xa levels may not necessarily provide an accurate measure of coagulation inhibition. Moreover, pregnancy is associated with hypercoagulability, which may compromise the efficacy of LMWH. We looked at the association between anti-Xa levels and parameters of thrombin generation assay [TGA; area under the curve (AUC), peak height (PH) and time to peak (ttP)] using samples from 41 pregnant women receiving LMWH and 40 normal pregnant women controls. TGA results confirmed the physiological hypercoagulability of normal pregnancy (mean normalised values: AUC 119%; PH 157%; ttP 72%). Although anti-Xa measures correlated with all three TGA parameters, this group correlation masked significant inter-individual variability, demonstrated by the R(2) value or coefficient of determination. Anti-Xa levels contributed to 74% of variation in AUC values, 63% of variation in PH values and only 53% of variation in ttP values. The remainder reflects the contribution of patients' intrinsic coagulation status. Hence, some patients with 'safe' anti-Xa levels may potentially be under-anticoagulated, particularly in pregnancy. Measuring coagulability directly with TGA may lower the risk of adverse events due to under-anticoagulation in selected patients.

[THE TEST OF GENERATION OF THROMBIN IN DYNAMICS IN PATIENTS AFTER TRANSCUTANEOUS CORONARY INTERVENTION].

The article presents results of observation of generation of thrombin in patients with ischemic heart disease in different terms after transcutaneous coronary intervention. The sampling included 37 patients with stable ischemic heart disease. The control group included 30 healthy individuals. To study system of hemostasis of this category of patients the test of generation of thrombin and its modification with added thrombomodulin were applied for evaluating anti-coagulant activity of system of protein C. The comparison of indicators of test of generation of thrombin in patients with ischemic heart disease before operation and in individuals of control group revealed no reliable differences (p > 0.05). The observation of patients with stable ischemic heart disease in various time-frame after mechanical re-vascularization of myocardium established significant increasing of generation of thrombin and decreasing of anticoagulant activity of system of protein C at 1-3 day after operation (p < 0.05). The positive correlation was established between endogenous thrombin potential and annexin 5, an early marker of dysfunction of endothelium in mentioned time-frame after operation (p = 0.0008; r = 0.57). The significant increasing of content of anti-inflammatory markers of C-reactive protein and fibrinogen was observed at 1-3 day after transcutaneous coronary intervention (p < 0.05). In that way, the study data give evidence to hyper-coagulation in patients with stable ischemic heart disease in early time-frame after operation despite normal values of activated partial thromboplastin time, prothrombin time, D-dimer and applied standard disaggregant therapy.

The effect of the REG2 Anticoagulation System on thrombin generation kinetics: a pharmacodynamic and pharmacokinetic first-in-human study.

The REG2 Anticoagulation System consists of pegnivacogin, a subcutaneously administered aptamer factor IXa inhibitor, and its intravenous active control agent, anivamersen. Its effect on thrombin generation is unknown. A prospectively designed thrombin generation study was conducted within the phase 1 ascending dose study of REG2 to assess the effect of REG2 on thrombin generation kinetics. A total of 32 healthy volunteers were recruited into four cohorts of ascending dose pegnivacogin for the phase 1 study. In this pre-specified substudy, blood samples were drawn in the presence or absence of corn trypsin inhibitor at specified times within each dosing cohort. Thrombin generation was initiated with tissue factor and thrombin generation kinetics were measured using the Calibrated Automated Thrombogram (CAT). REG2 attenuated thrombin generation in a dose-dependent manner. All parameters of the CAT assay, except for lag time, showed a dose and concentration-dependent response to pegnivacogin [time to peak thrombin generation (PTm), endogenous thrombin potential, peak thrombin generation, and velocity index (VIx)]. Reversal of the effect of pegnivacogin with anivamersen demonstrated restoration of thrombin generation without rebound effect. This first-in-human study of the effect of the REG2 Anticoagulation System on thrombin generation demonstrates concentration-dependent suppression of thrombin generation that is reversible without rebound effect, as measured by the CAT assay.

Urgent monitoring of direct oral anticoagulants in patients with atrial fibrillation: a tentative approach based on routine laboratory tests.

The number of patients diagnosed with atrial fibrillation who will be candidates for antithrombotic therapy with direct oral anticoagulants (i.e., dabigatran, rivaroxaban, apixaban and edoxaban) is exponentially arising worldwide, thus posing substantial economic and organizational challenges for their urgent monitoring. Due to long turnaround time and inherent technical complexity, liquid chromatography techniques are unsuitable for rapid assessment of their concentration. Even the use of surrogate tests such as thrombin clotting time or anti-factor Xa activity carries some economic and technical drawbacks. Based on literature data, we have hence developed an algorithm based on first-line tests for urgent screening of the anticoagulant effect of direct oral anticoagulants, which entails activated partial thromboplastin time (aPTT) for dabigatran and prothrombin time (PT) for rivaroxaban. Although these tests also display a concentration-dependent prolongation in patients taking apixaban and edoxaban, neither of them is sufficiently sensitive for providing accurate estimation of the pharmacodynamic effect, so that the measurement of anti-factor Xa activity remains the most suitable approach in patients taking these drugs. According to literature data, this strategy appears suitable to reliably define the thrombotic or bleeding risk in an urgent setting, contextually saving precious laboratory resources.

Clinical judgment when using coagulation tests during direct oral anticoagulant treatment: a concise review.

Because their anticoagulant effect is dose predictable, steady, and little influenced by diet and drugs, laboratory monitoring was deemed unnecessary in trials on venous and arterial thromboprophylaxis with the direct oral anticoagulant drugs (DOACs) rivaroxaban, apixaban, edoxaban, or dabigatran. However, there are special clinical settings in which measurement of their anticoagulant effect may be clinically desired. Because of lack of standardization between reagents employed and their global nature, the activated partial thromboplastin time (APTT) and the prothrombin time (PT) are not generally suitable for accurately assessing the anticoagulant effect of DOACs. The modified (diluted) PT reliably quantifies the anticoagulant effect of rivaroxaban or of apixaban. However, a higher intraindividual variability from one PT reagent to another is found when the data are compared with those obtained with standard PT. The HEMOCLOT (HYPHEN BioMed, France) assay is a modified (diluted) thrombin time (TT) provided with dabigatran calibrators. However, it is performed only in few specialized centers. Anti-factor Xa (anti-FXa) chromogenic assays employ routine automated coagulometers or manual spectrometers, and kits for anti-FIIa assays that measure dabigatran levels and kits for anti-Xa with rivaroxaban calibrators are commercially available. However, no correlation has been identified between any of these tests and clinical outcomes in patients taking any of the DOACs. Thus, currently, there are evidence gaps regarding the role of laboratory testing for surveillance and management of adverse events associated with DOACs. In view of this, in addition to standardization, validation of such assays is mandatory before they can be used to make clinical decisions.

Alternative monitoring of argatroban using plasma-diluted thrombin time.

OBJECTIVE: To report a case of heparin-induced thrombocytopenia (HIT) in a patient with concurrent liver dysfunction and a prolonged baseline activated partial thromboplastin time (aPTT) in whom argatroban therapy was monitored with aPTT and a novel plasma-diluted thrombin assay. CASE SUMMARY: An 80-year-old man with HIT and liver dysfunction was treated with argatroban, which was initiated at a dose of 0.5 µg/kg/min and gradually decreased to 0.09 µg/kg/min. The patient had a mildly prolonged aPTT at baseline (37.5 seconds). He was concurrently monitored with aPTT, per institution protocol, and plasma-diluted thrombin time. Plasma-diluted thrombin times were consistently lower than aPTTs, but mirrored the trend of the aPTTs. Eleven hours after argatroban was stopped, the aPTT remained elevated (53.9 seconds), while the plasma-diluted thrombin time returned to normal range (26.4 seconds). The patient's therapy was transitioned to warfarin and he had a hospital course with no thrombotic or bleeding complications. DISCUSSION: Plasma-diluted thrombin time is a novel laboratory test consisting of 1 part patient plasma diluted with 3 parts normal plasma. Plasma-diluted thrombin time has been shown to blunt the sensitivity of the thrombin time and may be more accurate for drug monitoring. A MEDLINE search revealed 2 studies using the plasma-diluted thrombin time assay. The first study compared aPTT and plasma-diluted thrombin times in blood samples mixed with argatroban, bivalirudin, or lepirudin at 3 different concentrations. Blood samples contained lupus inhibitors, vitamin k deficiency, or normal baseline aPTTs. The aPTT overestimated drug concentrations in all samples with lupus anticoagulant and vitamin k deficiency, while the plasma-diluted thrombin time correctly estimated drug concentrations in nearly all samples. The second study looked at monitoring dabigatran with plasma-diluted thrombin time and found a linear relationship between the plasma-diluted thrombin time and the dabigatran dose-response curve. CONCLUSIONS: Plasma-diluted thrombin time may be an alternative for direct thrombin inhibitor monitoring in patients with elevated aPTT values at baseline. Further randomized control trials are needed to determine its applicability in clinical practice.

Stroke thrombolysis in patients taking dabigatran.

Stroke thrombolysis is becoming a common practice in Australian and New Zealand hospitals. There are no established guidelines for thrombolysis of patients who are taking dabigatran, and accurate medication reconciliation may not be possible. Patients with normal activated partial thromboplastin time are unlikely to have clinically significant dabigatran concentration in the blood. For safest outcomes, we suggest incorporating thrombin time assay for acute stroke patients suspected to be taking dabigatran.

A randomized, double blind, placebo and active comparator controlled pilot study of UP446, a novel dual pathway inhibitor anti-inflammatory agent of botanical origin.

BACKGROUND: Current use of prescribed or over the counter non-steroidal anti-inflammatory drugs (NSAIDs) for pain and osteoarthritis (OA) have untoward gastrointestinal and cardiovascular related side effects, as a result the need for a safe and effective alternative has become unequivocally crucial. METHOD: A randomized, double blind, placebo and active controlled pilot study of a novel dual pathway, COX1/2 and LOX, inhibitor anti-inflammatory agent of botanical origin, UP446 was conducted. Sixty subjects (age 40-75) with symptomatic OA of the hip or knee were assigned to 4 treatment groups (n = 15); Group A0 (Placebo, CMC capsule), Group A1 (UP446 250 mg/day), Group A2 (UP446 500 mg/day) and Group A3 (Celecoxib, 200 mg/day). MOS-SF-36 and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) data were collected at baseline and after 30, 60 and 90 days of treatment as a measure of efficacy. Erythrocyte sedimentation rate, C-reactive protein, plasma thrombin time (PTT), fructosamine, Hematology, clinical chemistry and fecal occult blood were monitored for safety. RESULTS: Statistically significant decrease in WOMAC pain score were observed for Group A1 at day 90, Group A2 at 30 and 90 days and Group A3 at 60 and 90 days. Statistically significant decrease in WOMAC stiffness score were observed for Group A1 and Group A2 at 30, 60 and 90 days; but not for Group A0 and Group A3. The mean change in WOMAC functional impairment scores were statistically significant for Group A1 and Group A2 respectively at 30 days (p = 0.006 and p = 0.006), at 60 days (p = 0.016 and p = 0.002) and at 90 days (p = 0.018 and p = 0.002), these changes were not significant for Group A0 and Group A3. Based on MOS -SF-36 questionnaires, statistically significant improvements in physical function, endurance and mental health scores were observed for all active treatment groups compared to placebo. No significant changes suggestive of toxicity in routine hematologies, serum chemistries, liver enzymes or PTT were noted in any of the treatment groups. CONCLUSION: Based on current findings UP446 is safe and efficacious alternative to established anti-inflammatory medications for alleviating OA symptoms as measured by the WOMAC Index.

A modified thrombin clotting time test as a quality control marker for heparin contamination in obstetric intraoperative cell salvage.

OBJECTIVE: To assess if a modified thrombin clotting time test could be used as a simple quality control (QC) method to screen for unfractionated heparin in the product obtained from obstetric intraoperative cell salvage cases before re-infusion. BACKGROUND: A national QC scheme has recently been piloted to monitor the quality of autologous blood being returned to the patient. Laboratory tests include full blood count and microalbumin. Unfractionated heparin testing should be performed to ensure that there is no gross contamination of heparin in the final product; however, presently, there is no quick cheap test available suitable for heparin detection. MATERIALS AND METHODS: Samples were collected into plain non-anticoagulated tubes and centrifuged at 2500 × g for 5 min. Supernatant was mixed with commercially available coagulated normal plasma and a thrombin clotting time test performed. RESULTS: Calibration runs demonstrated that our system was sensitive up to 0 · 14 IU mL(-1) heparin, linear between 0 · 08 and 0 · 14 IU mL(-1). CONCLUSION: We have shown that the thrombin clotting time test can be modified and used as a cheap and reliable marker for heparin contamination. We have successfully incorporated this modified test into our hospital's obstetric QC scheme.

Prognosis analysis and risk factors related to progressive intracranial haemorrhage in patients with acute traumatic brain injury.

BACKGROUND: Since progressive intracranial haemorrhage (PIH) was introduced in neurosurgical literatures, several studies have been performed. PIH has been shown to be associated with a high increase in the risk of clinical worsening and related to morbidity and mortality as well. So, early detection and prediction of PIH is practically important in a clinical situation. OBJECTIVES: To investigate the risk factors related to PIH in patients with acute traumatic brain injury (TBI) and analyse their clinical significances. METHODS: PIH was confirmed by comparing the first and repeated CT scans. Data compared included gender, age, mechanism of injury, Glasgow Coma Score (GCS) at admission, timing from injury to the first CT, the signs of the initial CT scan, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fg), thrombin time (TT), platelet (PLT) and D-dimer (D-D) values. Logistic regression analysis was used to show the risk factors related to PIH. RESULTS: A cohort of 498 patients with TBI was evaluated, and there were 139 (27.91%) patients who suffered from PIH. The differences between PIHs and non-PIHs were significant in age, GCS at admission, the signs of the initial CT scan (fracture, subarachnoid haemorrhage, brain contusion and primary haematoma), PT, Fg and D-D values (p < 0.001). Logistic regression analysis was used to identify that CT scans (subarachnoid haemorrhage, brain contusion and primary haematoma) and plasma D-D values as the most important predictors of PIH (p < 0.001). CONCLUSIONS: For patients with the initial CT scan showing subarachnoid haemorrhage, brain contusion and primary haematoma with abnormal D-D levels, an earlier and dynamic CT scan should be performed, for the detection of PIH as early as possible and the medical intervention would be enforced in time.

[Endogenous thrombin potential in practical use]. / Anwendungen des endogenen Thrombinpotenzials.

An overview is given on the method and the applications of thrombin generation assays. Thrombin generation assays provide a tool which can be used to trace the entire thrombin formation and inactivation of a plasma sample. Therefore they are principally different from traditional global assays like PT and aPTT and promise new opportunities for the assessment of bleeding or thrombotic risks.