thromboplastin and Wounds-and-Injuries

The increasing understanding of trauma-induced coagulopathy has led to an expansion of treatment strategies in the acute management of trauma patients. The aim of this manuscript is to give a summary of current recommendations for the treatment of trauma-induced coagulopathy based on current literature and valid guidelines. Thetrauma-induced coagulopathyis an independentacutemultifactorial diseasewith significantimpact on the mortalityof severelyinjured patients. Largely responsible for the occurrence and severity of trauma-induced coagulopathy seems to be tissue trauma and shock-induced hypoperfusion. Coagulopathy is amplified by accompanying factors such as hypothermia or dilution. Diagnosis and therapy of deranged coagulation should start as soon as possible. Routinely tested coagulation parameters are of limited use to confirm diagnosis. Therapy follows the concept of "damage control resuscitation". Infusion of large volumes should be avoided and a mean arterial pressure of 65mmHg (in consideration of contraindications!) may be aimed.A specific protocol for massive transfusion should be introduced and continued.Acidaemia should be prevented and treated by appropriate shock therapy.Loss of body temperature should be prevented and treated. Hypocalcaemia <0.9 mmol/l should be avoided and may be treated. For actively bleeding patients, packed red blood cells (pRBC) may be given at haemoglobin<10g/dl(0,62mmol/l). If massive transfusion is performed using fresh frozen plasma (FFP), a ratio of FFP to pRBC of 1:2 to 1:1 should be achieved.For treatment of hyperfibrinolysis after severe trauma the use of tranexamic acid should be considered at an early stage. Fibrinogen should be substituted at levels <1,5g/l (4,41μmol/l). Prothrombin complex concentrates may be helpfull for treatment of diffuse bleeding or anticoagulativemedikation. In acute bleeding, platelets may be transfused at a platet count <100000/μl. For diffuse bleeding or thrombocytopathic patients desmopressin might be a therapeutic option.If a factor XIII (FXIII) measurement is not promptly available, a factor XIII blind-dose should be considered in severe ongoing bleeding. The use of recombinant activated coagulation factor VII (rFVIIa) be considered if major bleeding persists despite standard attempts to control bleeding and best practice use of blood components.

Topics: Acidosis; Antifibrinolytic Agents; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Calcium; Evidence-Based Medicine; Hemodilution; Humans; Hypotension, Controlled; Hypothermia, Induced; Inflammation; Platelet Activation; Resuscitation; Thromboplastin; Wounds and Injuries

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality worldwide. However, the mechanisms by which clots are formed in the deep veins have not been determined. Tissue factor (TF) is the primary initiator of the coagulation cascade and is essential for hemostasis. Under pathological conditions, TF is released into the circulation on small-membrane vesicles termed microparticles (MPs). Recent studies suggest that elevated levels of MP TF may trigger thrombosis. This review provides an overview of the role of TF in VTE.

Topics: Animals; Biomarkers; Blood Coagulation; Cell-Derived Microparticles; Disease Models, Animal; Humans; Mice; Neoplasms; Thromboplastin; Venous Thrombosis; Wounds and Injuries

Recombinant activated factor VIIa (rFVIIa) has many clinical applications for patients with congenital bleeding disorders and in a variety of clinical settings. Additional studies in the future are ongoing and should provide the clinical anesthesiologist an additional option during certain bleeding states. Specific recommendations as to timing of administration and frequent monitoring of ionized calcium status are suggested at this time. Optimization of fibrinogen levels, platelet levels, pH, and body temperature will enhance efficacy of rFVIIa.

Topics: Cerebral Hemorrhage; Factor VIIa; Hemophilia A; Hemophilia B; Humans; Postpartum Hemorrhage; Recombinant Proteins; Thromboplastin; Warfare; Wounds and Injuries

Tissue factor (TF) performs an essential role in the blood clotting system by activating the extrinsic coagulation pathway following vascular injury. In addition to this physiological hemostatic role for wound repair, TF also plays pivotal roles in organ dysfunction in trauma patients by triggering pathological disseminated thrombosis and inflammation. Constitutively expressed TF in subendothelial cells is released into the circulation following trauma and can be detected as slightly elevated TF levels in the plasma. Liberation of constitutive TF into the blood and inducible tissue factor expression on monocytes and the other cells may synergistically increase plasma TF levels to higher values at the early stage of posttrauma, especially in patients with disseminated intravascular coagulation (DIC) in association with sustained systemic inflammatory response syndrome. Marked TF generation not adequately balanced by physiological coagulation inhibitors such as tissue factor pathway inhibitor in posttrauma DIC patients has been observed. Based on these pieces of evidence, it has now been accepted that combined activation of TF-dependent coagulation inadequately regulated by anticoagulant mechanisms and inflammation may synergistically play important roles in the pathogenesis of posttrauma multiple organ dysfunction syndrome.

Topics: Blood Coagulation; Disseminated Intravascular Coagulation; Gene Expression Regulation; Humans; Inflammation; Multiple Organ Failure; Thromboplastin; Wounds and Injuries

Topics: Animals; Blood Coagulation; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Butter; Chromatography, Thin Layer; Contraceptives, Oral, Synthetic; Dietary Fats; Female; Humans; Hypercholesterolemia; Hyperlipidemias; Male; Oils; Phosphatidylethanolamines; Phosphatidylinositols; Phosphatidylserines; Pregnancy; Rabbits; Rats; Thromboplastin; Thrombosis; Time Factors; Wounds and Injuries; Zea mays

Topics: Blood Coagulation Factors; Blood Coagulation Tests; Blood Transfusion; Cerebral Hemorrhage; Epistaxis; Factor VIII; Gastrointestinal Hemorrhage; Hemarthrosis; Hematuria; Hemophilia A; Hemorrhage; Humans; Oral Hemorrhage; Thromboplastin; Wounds and Injuries

Excessive bleeding is a major concern in scar debridement and grafting procedures. TT-173 is a new topical hemostatic agent based on recombinant human tissue factor that has shown promising results in patients who underwent tooth extraction. EHTIC study sought to evaluate the efficacy and safety of TT-173 to reduce the bleeding in donor sites of skin grafting procedures.. EHTIC study was a phase II, randomized, parallel, double blind, placebo controlled trial. Patients received TT-173 (n=38) or placebo (n=33) sprayed over donor site after graft harvest. Time to hemostasis and incidence of adverse events were recorded. Systemic absorption of the product and its immunogenicity were also measured during the follow up of the subjects.. Treatment with TT-173 significantly reduced the bleeding time from 7 to 3min (Log-Rank p<0.0001). Moreover, bleeding stopped within the 10min of evaluation period in all the patients that received TT-173. In contrast, 24.24% of patients from placebo group required additional measures to arrest hemorrhage (Fisher p=0.0013). Product related adverse events, systemic absorption into blood stream, interferences with the healing of the donor site or immunogenic reaction against TT-173 were not observed.. The new hemostatic agent TT-173 has proven efficacious and safe to reduce the bleeding from donor site. This study paves the way for further investigation of the product as topical hemostatic treatment in plastic surgery and other surgical indications.

Topics: Adult; Blood Loss, Surgical; Burns; Double-Blind Method; Female; Hemostatics; Humans; Male; Middle Aged; Recombinant Proteins; Skin Transplantation; Thromboplastin; Treatment Outcome; Wounds and Injuries

Conventional clotting tests are not expeditious enough to allow timely targeted interventions in trauma, and current point-of-care analyzers, such as rotational thromboelastometry (ROTEM), have limited sensitivity for hyperfibrinolysis and hypofibrinogenemia.. To evaluate the performance of a recently developed global fibrinolysis capacity (GFC) assay in identifying fibrinolysis and hypofibrinogenemia in trauma patients.. Exploratory analysis of a prospective cohort of adult trauma patients admitted to a single UK major trauma center and of commercially available healthy donor samples was performed. Lysis time (LT) was measured in plasma according to the GFC manufacturer's protocol, and a novel fibrinogen-related parameter (percentage reduction in GFC optical density from baseline at 1 minute) was derived from the GFC curve. Hyperfibrinolysis was defined as a tissue factor-activated ROTEM maximum lysis of >15% or LT of ≤30 minutes.. Compared to healthy donors (n = 19), non-tranexamic acid-treated trauma patients (n = 82) showed shortened LT, indicative of hyperfibrinolysis (29 minutes [16-35] vs 43 minutes [40-47]; p < .001). Of the 63 patients without overt ROTEM-hyperfibrinolysis, 31 (49%) had LT of ≤30 minutes, with 26% (8 of 31) of them requiring major transfusions. LT showed increased accuracy compared to maximum lysis in predicting 28-day mortality (area under the receiver operating characteristic curve, 0.96 [0.92-1.00] vs 0.65 [0.49-0.81]; p = .001). Percentage reduction in GFC optical density from baseline at 1 minute showed comparable specificity (76% vs 79%) to ROTEM clot amplitude at 5 minutes from tissue factor-activated ROTEM with cytochalasin D in detecting hypofibrinogenemia but correctly reclassified >50% of the patients with false negative results, leading to higher sensitivity (90% vs 77%).. Severe trauma patients are characterized by a hyperfibrinolytic profile upon admission to the emergency department. The GFC assay is more sensitive than ROTEM in capturing hyperfibrinolysis and hypofibrinogenemia but requires further development and automation.

Topics: Adult; Afibrinogenemia; Blood Coagulation Disorders; Fibrinolysis; Humans; Prospective Studies; Thrombelastography; Thromboplastin; Wounds and Injuries

It has been observed that trauma patients often display elevated procoagulant activity that could be caused, in part, by tissue factor (TF). We previously observed that trauma patients with thermal, blunt, and penetrating injuries have active FIXa and FXIa in their plasma. In the current study, we evaluated the effect of injury severity, with or without accompanying shock, on the frequency and concentration of TF, FIXa, and FXIa in plasma from trauma patients.. Eighty trauma patients were enrolled and divided equally into four groups based on their Injury Severity Score and base deficit:Blood was collected at a 0 time-point (first blood draw upon arrival at hospital) and citrate plasma was prepared, frozen, and stored at -80 °C. FXIa, FIXa, and TF activity assays were based on a response of thrombin generation to corresponding monoclonal inhibitory antibodies.. The frequency and median concentrations of TF were relatively low in non-severe injury groups (17.5% and 0 pM, respectively) but were higher in those with severe injury (65% and 0.5 pM, respectively). Although FXIa was observed in 91% of samples and was high across all four groups, median concentrations were highest (by approximately fourfold) in groups with shock. FIXa was observed in 80% of plasma samples and concentrations varied in a relatively narrow range between all four groups. No endogenous activity was observed in plasma from healthy individuals.. (1) Frequency and concentration of TF is higher in patients with a higher trauma severity. (2) Concentration of FXIa is higher in patients with shock. (3) For the first time reported, the vast majority of plasma samples from trauma patients contain active FIXa and FXIa.. Prognostic/epidemiological study, level II.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Factor IXa; Factor XIa; Female; Humans; Injury Severity Score; Male; Middle Aged; Shock; Thromboplastin; Wounds and Injuries; Young Adult

Activated immune cells such as monocytes are key factors in systemic inflammatory response syndrome (SIRS) following trauma and sepsis. Activated monocytes induce almost all tissue factor (TF) expression contributing to inflammation and coagulation. TF and CD13 double-positive microparticles (TF/CD13MPs) are predominantly released from these activated monocytes. This study aimed to evaluate TF/CD13MPs and assess their usefulness as a biomarker of pathogenesis in early SIRS following trauma and sepsis. This prospective study comprising 24 trauma patients, 25 severe sepsis patients, and 23 healthy controls was conducted from November 2012 to February 2015. Blood samples were collected from patients within 24 h after injury and diagnosis of severe sepsis and from healthy controls. Numbers of TF/CD13MPs were measured by flow cytometry immediately thereafter. Injury Severity Score (ISS) and Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores were calculated at patient enrollment. APACHE II and SOFA scores and International Society of Thrombosis and Haemostasis (ISTH) overt disseminated intravascular coagulation (DIC) diagnostic criteria algorithm were calculated at the time of enrollment of severe sepsis patients. Numbers of TF/CD13MPs were significantly increased in both trauma and severe sepsis patients versus controls and correlated significantly with ISS and APACHE II score in trauma patients and with APACHE II and ISTH DIC scores in severe sepsis patients. Increased numbers of TF/CD13MPs correlated significantly with severities in the acute phase in trauma and severe sepsis patients, suggesting that TF/CD13MPs are important in the pathogenesis of early SIRS following trauma and sepsis.

Topics: Adult; Aged; APACHE; Biomarkers; CD13 Antigens; Cell-Derived Microparticles; Female; Humans; Injury Severity Score; Male; Middle Aged; Prospective Studies; Sepsis; Systemic Inflammatory Response Syndrome; Thromboplastin; Wounds and Injuries

We present a methodology for personalizing the clinical treatment of severely injured patients with acute traumatic coagulopathy (ATC), an endogenous biological response of impaired coagulation that occurs early after trauma and shock and that is associated with increased bleeding, morbidity, and mortality. Despite biological characterization of ATC, it is not easily or rapidly diagnosed, not always captured by slow laboratory testing, and not accurately represented by coagulation models. This lack of knowledge, combined with the inherent time pressures of trauma treatment, forces surgeons to treat ATC patients according to empirical resuscitation protocols. These entail transfusing large volumes of poorly characterized, nontargeted blood products that are not tailored to an individual, the injury, or coagulation dynamics. Massive transfusion mortality remains at 40 to 70% in the best of trauma centers. As an alternative to blunt treatments, time-consuming tests, and mechanistic models, we used dynamical systems theory to create a simple, biologically meaningful, and highly accurate model that (i) quickly forecasts a driver of downstream coagulation, thrombin concentration after tissue factor stimulation, using rapidly measurable concentrations of blood protein factors and (ii) determines the amounts of additional coagulation factors needed to rectify the predicted thrombin dynamics and potentially remedy ATC. We successfully demonstrate in vitro thrombin control consistent with the model. Compared to another model, we decreased the mean errors in two key trauma patient parameters: peak thrombin concentration after tissue factor stimulation and the time until this peak occurs. Our methodology helps to advance individualized resuscitation of trauma-induced coagulation deficits.

Topics: Adult; Aged; Blood Coagulation; Blood Coagulation Disorders; Blood Transfusion; Calibration; Female; Hemorrhage; Humans; Male; Middle Aged; Prospective Studies; Thrombin; Thromboplastin; Thrombosis; Treatment Outcome; Wounds and Injuries

The aim of this study was to compare the efficacy, safety, and cost-effectiveness of 3-factor prothrombin complex concentrate (3F-PCC) vs 4-factor prothrombin complex concentrate PCC (4F-PCC) in trauma patients requiring reversal of oral anticoagulants.. All consecutive trauma patients with coagulopathy (international normalized ratio [INR] ≥1.5) secondary to oral anticoagulants who received either 3F-PCC or 4F-PCC from 2010 to 2014 at 2 trauma centers were reviewed. Efficacy was determined by assessing the first INR post-PCC administration, and successful reversal was defined as INR less than 1.5. Safety was assessed by reviewing thromboembolic events, and cost-effectiveness was calculated using total treatment costs (drug acquisition plus transfusion costs) per successful reversal.. Forty-six patients received 3F-PCC, and 18 received 4F-PCC. Baseline INR was similar for 3F-PCC and 4F-PCC patients (3.1 ± 2.3 vs 3.4 ± 3.7, P = .520). The initial PCC dose was 29 ± 9 U/kg for 3F-PCC and 26 ± 6 U/kg for 4F-PCC (P = .102). The follow-up INR was 1.6 ± 0.6 for 3F-PCC and 1.3 ± 0.2 for 4F-PCC (P = .001). Successful reversal rates in patients were 83% for 4F-PCC and 50% for 3F-PCC (P = .022). Thromboembolic events were observed in 15% of patients with 3F-PCC vs 0% with 4F-PCC (P = .177). Cost-effectiveness favored 4F-PCC ($5382 vs $3797).. Three-factor PCC and 4F-PCC were both safe in correcting INR, but 4F-PCC was more effective, leading to better cost-effectiveness. Replacing 3F-PCC with 4F-PCC for urgent coagulopathy reversal may benefit patients and institutions.

Topics: Aged; Anticoagulants; Blood Coagulation Disorders; Calcium; Cost-Benefit Analysis; Critical Care; Female; Hemostatics; Humans; International Normalized Ratio; Male; Retrospective Studies; Safety; Thromboplastin; Trauma Centers; Warfarin; Wounds and Injuries

The initiation of coagulation in trauma is thought to originate from exposed tissue factor (TF); recent data have led to the alternative hypothesis that damage-associated molecular patterns may contribute to postinjury coagulation. In acute traumatic coagulopathy, aberrant coagulation is mediated via the activated protein C (aPC) pathway; the upstream regulators of this process and its relation to TF remain uncharacterized. To examine the role of the TF pathway in mediating acute traumatic coagulopathy, we used specific antibody blockades in an established murine model of traumatic hemorrhagic shock, hypothesizing that both coagulation activation after injury and aPC-mediated coagulopathy are driven by TF via thrombin.. Mice underwent an established model of trauma and hemorrhage and were subjected to either sham (vascular cannulation) or trauma-hemorrhage (cannulation, laparotomy, shock to mean arterial pressure of 35 mm Hg); they were monitored for 60 minutes before sacrifice. Mice in each group were pretreated with either targeted anti-TF antibody to block the TF pathway or hirudin for specific blockade of thrombin. Plasma was assayed for thrombin-antithrombin (TAT) and aPC by enzyme-linked immunosorbent assay.. Compared with controls, trauma-hemorrhage mice treated with anti-TF antibody had significantly reduced levels of TAT (2.3 ng/mL vs. 5.7 ng/mL, p = 0.016) and corresponding decreases in aPC (16.3 ng/mL vs. 31.6 ng/mL, p = 0.034), with reductions to levels seen in sham mice. Direct inhibition of thrombin yielded similar results, with reduction in aPC to levels below those seen in sham mice.. In this study, blockade of the TF pathway led to the attenuation of both thrombin production and aPC activation observed in traumatic shock. Specific thrombin inhibition achieved similar results, indicating that aPC-related coagulopathy is mediated via thrombin activated by the TF pathway. The near-complete blockade of TAT and aPC observed in this model argues for a dominant role of the TF-thrombin pathway in both coagulation activation after injury and traumatic coagulopathy.

Topics: Animals; Blood Coagulation Disorders; Enzyme-Linked Immunosorbent Assay; Hirudins; Male; Mice; Mice, Inbred C57BL; Protein C; Shock, Hemorrhagic; Shock, Traumatic; Thrombin; Thromboplastin; Wounds and Injuries

The two sides of trauma-induced coagulopathy, the hypocoagulable and the hypercoagulable states, are poorly understood. To identify potential mechanisms for venous thromboembolism and bleeding after acute trauma, we estimated changes in circulating procoagulant microparticles (MPs) and thrombin activity during hospitalization for trauma.. Whole blood was collected by venipuncture into 3.2% trisodium citrate at 0, 6, 12, 24, and 72 hours after injury and discharge. Platelet-poor plasma was harvested and stored at -80°C until analysis. Thrombin generation was determined using the calibrated automated thrombogram (CAT), reported as lag time (minutes), peak height (nM thrombin), and time to reach peak height (ttPeak, minutes). The concentration of total procoagulant MPs (number/μL) was measured by flow cytometry. Data are presented as median (interquartile range [IQR]).. Among 443 trauma patients (1,734 samples; Injury Severity Score [ISS], 13.0 [IQR, 6.0-22.0]; hospital length of stay, 4.0 days [IQR, 2.0-10.0]; age, 48 years [IQR, 28-65]; 70.7% male; 95% with blunt mechanism; mortality, 3.2%), no discernable patterns in thrombin generation or MP concentration were observed over time. The peak height and MPs were significantly different from healthy volunteers and were 337 nM (IQR, 285-395) and 400/μL plasma (IQR, 211-772), respectively. Extreme (defined as highest or lowest 5%) values reflecting a possible "hypercoagulable state" (lag time ≤ 1.98, peak height ≥ 486.2, ttPeak ≤ 3.61, and total procoagulant MP ≥ 2,278) were reached within 12 hours after acute trauma, while extreme values representing a possible "hypocoagulable state" (lag time ≥ 18.6, peak height ≤ 17.8, and ttPeak ≥ 29.45) were not reached until 1 day to 3 days.. Although there was no predictable pattern of coagulopathy observed in each patient after trauma, those who reached extreme values did so relatively early after injury. These findings should be taken into account when designing risk model tools involving coagulation laboratory parameters.. Epidemiologic study, level III.

Topics: Acute Disease; Adult; Aged; Biomarkers; Blood Coagulation Tests; Blood Transfusion; Cell-Derived Microparticles; Cohort Studies; Emergency Service, Hospital; Female; Flow Cytometry; Follow-Up Studies; Humans; Injury Severity Score; Male; Middle Aged; Prospective Studies; Risk Assessment; Survival Analysis; Thrombin; Thromboplastin; Treatment Outcome; Wounds and Injuries

In trauma patients, resuscitation treatment of intravascular volume may cause haemodilution including blood cell- and plasma-dilution. After plasma-dilution, fibrinogen is the first factor that decreases to critically low concentrations. Fibrin formed in lowered levels is susceptible to fibrinolysis, a natural forerunner for bleeding. To assess whether a fibrinogen concentrate or a factor XIII (FXIII) concentrate can reverse the impairment of fibrin properties after plasma dilution, different laboratory methods were used to determine thrombin generation and fibrin quantity/quality in a normal plasma sample diluted in vitro. Coagulation and clot lysis by plasmin were triggered with tissue factor and rt-PA, respectively.We found that while the endogenous thrombin potential (ETP) was unaffected after plasma-dilution due to postponement of thrombin decay, levels of fibrinogen and hence fibrin were decreased in dilution degree-dependency. The imbalance between influence of the dilution on thrombin activity and fibrin formation brought unexpected outcomes of fibrin properties: the formed clots favoured the degradation by plasminbut the fibrin networks remained tighter/less permeable. This proteolytic tendency was partly overturned by the fibrinogen concentrate added (total fibrinogen ≥ 2 g/l), and much more affected if used in combination with tranexamic acid (a fibrinolysis inhibitor) at small doses. No reversal effect resulted from the FXIII concentrate added. We conclude that plasma-dilution did reduce the proteolytic resistance of formed clots. The fibrinogen concentrate, better together with small doses of tranexamic acid, may reverse the impairment of fibrin property.The FXIII concentrate is not effective in this regard in our in vitro model using platelet-poor plasma.

Topics: Blood Coagulation; Factor XIII; Fibrinogen; Fibrinolysin; Fibrinolysis; Hemodilution; Hemorrhage; Humans; In Vitro Techniques; Plasma; Proteolysis; Resuscitation; Thromboplastin; Tranexamic Acid; Wounds and Injuries

Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding.. As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥ 35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)].. 21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001).. Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.

Topics: Adult; Biomarkers; Blood Coagulation; Blood Coagulation Disorders; Blood Transfusion; Cell-Derived Microparticles; Female; Hemorrhage; Humans; Injury Severity Score; Male; Middle Aged; Partial Thromboplastin Time; Phenotype; Predictive Value of Tests; Prospective Studies; Risk Factors; Thrombelastography; Thrombin; Thromboplastin; United States; Wounds and Injuries; Young Adult

Major trauma is an independent risk factor for developing venous thromboembolism. While increases in thrombin generation and/or procoagulant microparticles have been detected in other patient groups at greater risk for venous thromboembolism, such as cancer or coronary artery disease, this association has yet to be documented in trauma patients. This pilot study was designed to characterize and quantify thrombin generation and plasma microparticles in individuals early after traumatic injury.. Blood was collected in the trauma bay from 52 blunt injured patients (cases) and 19 uninjured outpatients (controls) and processed to platelet poor plasma to allow for (1) isolation of microparticles for identification and quantification by flow cytometry, and (2) in vitro thrombin generation as measured by calibrated automatic thrombography. Data collected are expressed as either mean ± standard deviation or median with interquartile range.. Among the cases, which included 39 men and 13 women (age, 40 ± 17 years), the injury severity score was 13 ± 11, the international normalized ratio was 1.0 ± 0.1, the thromboplastin time was 25 ± 3 seconds, and platelet count was 238 ± 62 (thousands). The numbers of total (cell type not specified) procoagulant microparticles, as measured by Annexin V staining, were increased compared to nontrauma controls (541 ± 139/μL and 155 ± 148/μL, respectively; P < .001). There was no significant difference in the amount of thrombin generated in trauma patients compared to controls; however, peak thrombin was correlated to injury severity (Spearman correlation coefficient R, 0.35; P = .02).. Patients with blunt trauma have greater numbers of circulating procoagulant microparticles and increased in vitro thrombin generation. Future studies to characterize the cell-specific profiles of microparticles and changes in thrombin generation kinetics after traumatic injury will determine whether microparticles contribute to the hypercoagulable state observed after injury.

Topics: Adult; Annexin A5; Biomarkers; Case-Control Studies; Cell-Derived Microparticles; Cohort Studies; Female; Humans; Male; Middle Aged; Partial Thromboplastin Time; Pilot Projects; Prospective Studies; Prothrombin Time; Risk Factors; Thrombin; Thrombophilia; Thromboplastin; Trauma Severity Indices; Venous Thromboembolism; Wounds and Injuries

Topics: Arachidonic Acid; Aspirin; Bleeding Time; Drug Combinations; Drug Resistance; Factor X; Fasting; Humans; Male; Middle Aged; Outpatients; Platelet Aggregation; Simvastatin; Thromboplastin; Time Factors; Wounds and Injuries

Elevated levels of circulating procoagulants like tissue factor may increase the risk of systemic coagulation activation, thrombin generation, and consumptive coagulopathy. I measured procoagulant activity in plasma by using a clot-based assay that incorporated normal plasma to replace missing factors, corn trypsin inhibitor to block contact activation, factor VIIa to improve sensitivity to tissue factor activity, and anti-tissue factor antibodies to measure tissue factor-specific activity. Procoagulant activity was evaluated in 58 trauma patients. Trauma patients without coagulopathy (n = 50) showed 5-fold higher procoagulant activity than did control subjects (P < .001), whereas trauma patients with coagulopathy (n = 8) showed 10-fold higher activity than control subjects (P < .001) and 2-fold higher activity than trauma patients without coagulopathy (P = .03). In control subjects, tissue factor activity was below the detection limit of the assay. Tissue factor activity was 3- to 4-fold higher in trauma patients with coagulopathy vs patients without coagulopathy (P = .002). Trauma patients with coagulopathy have increased circulating tissue factor activity.

Topics: Anticoagulants; Disseminated Intravascular Coagulation; Female; Humans; Male; Middle Aged; Thromboplastin; Wounds and Injuries

Progressive postinjury coagulopathy has become the fundamental rationale for damage control surgery, and the decision to abort operative intervention must occur prior to overt laboratory confirmation of coagulopathy. Current coagulation testing is most commonly performed for monitoring anticoagulation therapy, the results are delayed, and the applicability of these tests in the trauma setting is questionable. Point-of-care (POC) rapid thrombelastography (r-TEG) provides real time analysis of thrombostatic function, which may allow for accurate, goal directed therapy. The test differs from standard thrombelastography (TEG) because the clotting process and subsequent analysis is accelerated by the addition of tissue factor to the whole blood sample, but is limited by the requirement that the analysis be performed within 4 min of blood draw to prevent clot formation. Consequently, citrated specimens have been proposed to obviate this time limitation. We hypothesized that the speed of r-TEG analysis following tissue factor addition to citrated blood might compromise accurate determinations compared with noncitrated whole blood. Additionally, we sought to compare the use of r-TEG with conventional coagulation tests in analysis of postinjury coagulopathy.. We conducted a retrospective study of severely injured patients entered into our trauma database between January and June 2008 who were at risk for postinjury coagulopathy. Patients needed simultaneous conventional coagulation (INR, fibrinogen, platelet count) and r-TEG specimens with either fresh or citrated whole blood for inclusion in the study. kappa-Statistics were used to determine the agreement between the tests in predicting hypocoagulability. McNemar's chi(2) tests were used to compare theoretical blood product administration between r-TEG and conventional coagulation tests for noncitrated specimens. Therapeutic transfusion triggers were: INR (>1.5) and r-TEG ACT (>125 s) for FFP administration; fibrinogen (<133 mg/dL) and alpha-angle (<63 degrees ) for cryoprecipitate; and platelet count (<100K) and maximum amplitude (MA) (<52 mm) for aphaeresis platelets. Statistical significance was established as P<0.05 using two-sided tests.. Forty-four patients met the inclusion criteria. kappa-Values (correlation) were higher in noncitrated versus citrated specimens for all comparisons between conventional and r-TEG tests, indicating better performance of r-TEG with the noncitrated specimens. FFP would have been administered to significantly more patients based on conventional transfusion triggers (61.5% by INR transfusion triggers versus 26.9% by r-TEG-ACT triggers, P=0.003). There was no statistically significant difference in potential cryoprecipitate or aphaeresis platelet administration.. POC r-TEG is superior when performed with uncitrated versus citrated whole blood for evaluation of postinjury coagulation status. As a real time measure of total thrombostatic function, our preliminary data suggest that r-TEG may effectively guide transfusion therapy and result in reduced FFP administration compared with conventional coagulation tests.

Topics: Adult; Blood Coagulation Disorders; Citric Acid; Female; Humans; Male; Middle Aged; Pilot Projects; Point-of-Care Systems; Retrospective Studies; Thrombelastography; Thromboplastin; Wounds and Injuries; Young Adult

Trauma patients are at risk of developing an acute coagulopathy of trauma (ACT) related to tissue injury, shock, and hemodilution. ACT is incompletely understood, but is similar to disseminated intravascular coagulation (DIC) and is associated with poor outcome.. Thrombin generation assays were used to evaluate plasma hemostasis in 42 trauma patients, 25 normal subjects, and 45 patients on warfarin and in laboratory-prepared factor reduced plasma.. Prolonged prothrombin time (PT), more than 18 seconds, or an international normalized ratio of greater than 1.5 was present in 15 trauma patients indicating possible ACT. Native thrombin generation (no activator added, contact activation blocked) showed that Trauma with ACT patients had lag times 68% shorter and peak thrombin generation threefold higher than normal patients indicating the presence of circulating procoagulants capable of initiating coagulation systemically. Trauma patients had lower platelet counts and fibrinogen and Factor (F)II levels putting them at increased risk of bleeding. In laboratory-prepared isolated factor-reduced samples and in patients with vitamin K-dependent factor deficiency due to warfarin, thrombin generation decreased in direct proportion to FII levels. In contrast, in diluted plasma and in trauma patients with reduced factor levels, thrombin generation was increased and associated with slower inhibition of thrombin generation (prolonged termination time) and decreased antithrombin levels (43% of normal in Trauma with ACT).. Thrombin generation studies indicate that Trauma with ACT patients show dysregulated hemostasis characterized by excessive non-wound-related thrombin generation due to a combination of circulating procoagulants capable of activating coagulation systemically and reduced inhibitor levels allowing systemic thrombin generation to continue once started.

Topics: Adult; Anticoagulants; Antithrombins; Disseminated Intravascular Coagulation; Female; Hemostasis; Humans; Male; Middle Aged; Plasma; Prothrombin; Prothrombin Time; Thrombin; Thromboplastin; Vitamin K; Warfarin; Wounds and Injuries

Healing of skin wounds is delayed in hemophilia B (HB) mice. HB mice do not bleed excessively at wounding, yet rebleed hours to days later. Tissue factor (TF) expression is up-regulated by inflammatory cytokines and has been linked to angiogenesis. We hypothesized that impaired thrombin generation in HB leads to impaired TF expression following injury. Punch biopsies were placed on wild-type (WT) and HB mice. Tissues from wound sites were immunostained for TF. Blood vessels are normally surrounded by a coat of pericytes expressing TF. Surprisingly, within a day after wounding TF disappeared from around nearby vessels; returning after 8 days in WT and 10 days in HB mice. The granulation tissue filling the wound during healing also lacked TF around angiogenic vessels. Thus, perivascular TF expression is down-regulated during wound healing. This may prevent thrombosis of neovessels during angiogenesis but renders hemophiliacs vulnerable to hemorrhage during healing.

Topics: Animals; Biopsy; Disease Models, Animal; Down-Regulation; Factor X Deficiency; Gene Expression Regulation; Hemophilia B; Humans; Mice; Mice, Knockout; Skin; Thromboplastin; Wound Healing; Wounds and Injuries

Mechanical ventilation can induce organ injury associated with overwhelming inflammatory responses. Excessive activation of poly(adenosine diphosphate-ribose) polymerase enzyme after massive DNA damage may aggravate inflammatory responses. Therefore, the authors hypothesized that the pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase by PJ-34 would attenuate ventilator-induced lung injury.. Anesthetized rats were subjected to intratracheal instillation of lipopolysaccharide at a dose of 6 mg/kg. The animals were then randomly assigned to receive mechanical ventilation at either low tidal volume (6 ml/kg) with 5 cm H2O positive end-expiratory pressure or high tidal volume (15 ml/kg) with zero positive end-expiratory pressure, in the presence and absence of intravenous administration of PJ-34.. The high-tidal-volume ventilation resulted in an increase in poly(adenosine diphosphate-ribose) polymerase activity in the lung. The treatment with PJ-34 maintained a greater oxygenation and a lower airway plateau pressure than the vehicle control group. This was associated with a decreased level of interleukin 6, active plasminogen activator inhibitor 1 in the lung, attenuated leukocyte lung transmigration, and reduced pulmonary edema and apoptosis. The administration of PJ-34 also decreased the systemic levels of tumor necrosis factor alpha and interleukin 6, and attenuated the degree of apoptosis in the kidney.. The pharmacologic inhibition of poly(adenosine diphosphate-ribose) polymerase reduces ventilator-induced lung injury and protects kidney function.

Topics: Animals; Bronchoalveolar Lavage Fluid; Cytokines; Lung; Male; Poly(ADP-ribose) Polymerase Inhibitors; Positive-Pressure Respiration; Rats; Rats, Sprague-Dawley; Respiration, Artificial; Thromboplastin; Tidal Volume; Wounds and Injuries

Topics: Animals; Atherosclerosis; Humans; Neoplasms; Sepsis; Thromboplastin; Wounds and Injuries

Topics: Animals; Hemostasis; Humans; Skin; Thromboplastin; Thrombosis; Wounds and Injuries

The initial phase of wound repair involves inflammation, induction of tissue factor (TF), formation of a fibrin matrix, and growth of new smooth muscle actin (alpha-SMA)-positive vessels. In diabetes, TF induction in response to cutaneous wounding, which ordinarily precedes increased expression of vascular endothelial growth factor (VEGF) and alpha-SMA transcription, is diminished, though not to a degree causing excessive local bleeding. Enhanced TF expression in wounds of diabetic mice caused by somatic TF gene transfer increased VEGF transcription and translation and, subsequently, enhanced formation of new blood vessels and elevated blood flow. Furthermore, increased levels of TF in wounds of diabetic mice enhanced wound healing; the time to achieve 50% wound closure was reduced from 5.5 days in untreated diabetic mice to 4.1 days in animals undergoing TF gene transfer (this was not statistically different from wound closure in nondiabetic mice). Thus, cutaneous wounds in diabetic mice display a relative deficiency of TF compared with nondiabetic controls, and this contributes to delayed wound repair. These data establish TF expression as an important link between the early inflammatory response to cutaneous wounding and reparative processes.

Topics: Animals; Diabetes Mellitus, Type 1; DNA Primers; Inflammation; Mice; Mice, Inbred NOD; Polymerase Chain Reaction; Skin; Thromboplastin; Vascular Endothelial Growth Factor A; Wound Healing; Wounds and Injuries

Activated monocytes are able to express tissue factor (TF), a potent procoagulant. The effect of injury on monocyte TF expression is not known. We have found that patients with head injury (HI) have increased antithrombin activity and decreased platelet function compared with non-head-injured trauma patients. Our objective was to determine whether injury increases TF expression by monocytes and whether this increased TF expression is attenuated in patients with HI.. We prospectively enrolled 37 trauma patients (meeting the entry criterion of an Injury Severity Score [ISS] > or = 9) and 11 healthy control subjects. We sampled blood on arrival and then at 24, 48, and 72 hours. We performed flow cytometry with antibody markers for monocytes (CD14), platelets (CD42a), and TF. We compared results of patients with HI (Glasgow Coma Scale score < or = 9 and Abbreviated Injury Scale Head/Neck score > or = 3) with patients without HI and with controls.. Patients had a mean ISS of 23.9 +/- 2.3 (+/- SEM), mean age of 45 +/- 3 years, and mean length of stay of 17.9 +/- 3.2 days. Seventy-six percent were men, and 97% had blunt trauma. The overall mortality rate was 11%. Trauma patients had greater monocyte TF expression than controls for all time periods (p < 0.05). Trauma patients with HI had elevated monocyte TF expression compared with controls for the initial and 24-hour time periods, but they subsequently had more rapid return of monocyte TF expression to baseline (despite a higher ISS) than trauma patients without HI. Trauma patients both with and without HI had increased platelet-monocyte binding at each time versus controls.. Trauma induces TF expression on monocytes. Patients with HI have attenuation of this expression by 24 hours after injury. The attenuation of TF expression by monocytes in HI parallels the increase in AT and the decrease in platelet function seen after HI. The correlation of TF expression with platelet-monocyte binding suggests that platelet binding may lead to monocyte activation.

Topics: Adult; Blood Transfusion; Case-Control Studies; Craniocerebral Trauma; Female; Flow Cytometry; Hemostatics; Humans; Injury Severity Score; Male; Middle Aged; Monocytes; Thromboplastin; Wounds and Injuries

Intravenous infusion of recombinant tissue factor pathway inhibitor (rTFPI) for 24 hours decreases neointimal thickening and luminal stenosis 1 month after balloon-induced injury to the carotid arteries in minipigs. This study was designed to determine whether the effect of rTFPI is accounted for by early decreases in procoagulant activity and thrombosis on the injured vessel wall. Vascular injury was induced by balloon hyperinflations in both carotid arteries of anesthetized pigs given no anticoagulant as a control (n=16), an intravenous infusion for 24 hours of rTFPI (0.5 mg/kg bolus and 25 microg. kg(-1). min(-1), n=14), or an intravenous infusion of unfractionated heparin (100 U. kg(-1). h(-1), n=19). Accumulation of radiolabeled autologous platelets was markedly decreased over 24 hours on injured arteries from animals given rTFPI (0.6x10(6)/cm(2)) compared with controls (2.5x10(6)/cm(2), P=0.0004). Deposition of radiolabeled fibrin was also decreased in rTFPI-treated animals (269+/-266 microg/cm(2)) compared with controls (2389+/-1673 microg/cm(2), P=0.04). Similar effects were observed with heparin. However, factor Xa activity, assayed after 24 hours by incubation of the injured arterial segments with the chromogenic substrate S-2222, was decreased more markedly on arteries from rTFPI-treated animals (0.14+/-0.13 OD) than those from heparin-treated animals (0.29+/-0.18 OD) compared with controls (0. 47+/-0.24 OD, P=0.0007). In addition, arteries from rTFPI-treated animals showed a 4-fold lower induction of tissue factor protein compared with controls (P=0.0002). Attenuation of procoagulant activity and tissue factor-mediated thrombin generation in response to injury may account for the promising results with rTFPI in the porcine angioplasty model.

Topics: Animals; Blood Coagulation; Carotid Arteries; Carotid Artery Injuries; Catheterization; Factor Xa Inhibitors; In Vitro Techniques; Lipoproteins; Male; Recombinant Proteins; Swine; Thromboplastin; Thrombosis; Wounds and Injuries

To determine the role of plasma tissue factor on disseminated intravascular coagulation (DIC) in trauma and septic patients, and also to investigate the relationships between tissue factor and various thrombin markers, we made a prospective cohort study. Forty trauma patients and 20 patients with sepsis were classified into subgroups according to the complication of DIC. Plasma tissue factor antigen concentration (tissue factor), prothrombin fragment F1+2 (PF1+2), thrombin antithrombin complex (TAT), fibrinopeptide A (FPA), and D-dimer were measured on the day of admission (day 0), and on days 1, 2, 3, and 4 after admission. The levels of plasma tissue factor in the DIC group were more elevated than those of the non-DIC group in both the trauma and the septic patients. In patients with sepsis, tissue factor levels on days 0 through 4 in the non-DIC group showed markedly higher values than those in the control patients (135 +/- 8 pg/ml). Significant correlations between tissue factor and PF1+2, TAT, FPA, and D-dimer were observed in the DIC patients, however, no such correlations were found in the non-DIC patients. These results suggest that elevated plasma tissue factor in patients with trauma and sepsis gives rise to thrombin generation, followed by intravascular coagulation.

Topics: Adult; Aged; Aged, 80 and over; Antithrombin III; APACHE; Biomarkers; Disseminated Intravascular Coagulation; Endothelium, Vascular; Female; Fibrin Fibrinogen Degradation Products; Fibrinopeptide A; Humans; Male; Middle Aged; Monocytes; Peptide Fragments; Peptide Hydrolases; Prospective Studies; Prothrombin; Sepsis; Thrombin; Thromboplastin; Wounds and Injuries

Tissue factor (TF) is a transmembrane glycoprotein that, after binding to factor VII/VIIa, initiates the extrinsic coagulation pathway, resulting in thrombin generation and its sequelae. Thrombin has been shown to induce TF mRNA in endothelium, monocytes, and smooth muscle cells, further perpetuating the thrombogenic cycle. This study was designed to determine the effect of specific inhibition of thrombin by recombinant hirudin (r-hirudin) on TF distribution after balloon angioplasty in the cholesterol-fed rabbit femoral artery and porcine coronary artery models.. Thirty-five femoral arteries from 32 cholesterol-fed New Zealand White rabbits and 84 coronary arteries from 55 Yorkshire-Albino swine were studied by use of a recently developed in situ method of TF localization based on digoxigenin labeling of recombinant factor VIIa (Dig-VIIa), with correlative studies of TF immunoreactivity by use of anti-rabbit (AP-1) or anti-human (sTF) antibodies. At sites of balloon angioplasty in rabbit femoral or pig coronary arteries (double or single injury), TF-antibody and Dig-VIIa staining were noted in association with endothelial cells, smooth muscle cells, and foam cells and within the fibrous tissue matrix primarily of the adventitia and neointima. Staining was significantly greater after balloon angioplasty than in vessels that had not undergone angioplasty but was similar after single and double balloon injury. Animals treated with r-hirudin (rabbits, 1 mg/kg bolus plus 2-hour infusion; pigs, 1 mg/kg bolus plus 0.7 mg x kg(-1) x d(-1) infusion for 14 days with implantable pump) had diminished TF-antibody and Dig-VIIa staining 28 days after balloon angioplasty compared with controls (bolus heparin only). This effect was more prominent on the neointima and was more striking in the porcine than the rabbit model.. TF expression, persistent 1 month after balloon angioplasty in rabbit femoral arteries and porcine coronary arteries, is attenuated by specific thrombin inhibition with hirudin. These results suggest that thrombin inhibition, in addition to its effect on acute thrombus formation and its effect on luminal narrowing by plaque in experimental animals, may result in a prolonged reduction in thrombogenicity of the restenotic plaque through this effect on TF expression.

Topics: Angioplasty, Balloon; Animals; Cholesterol, Dietary; Coronary Vessels; Digoxigenin; Factor VIIa; Femoral Artery; Hirudins; Male; Rabbits; Recombinant Proteins; Swine; Thrombin; Thromboplastin; Tunica Intima; Wounds and Injuries

To determine the roles of tissue factor and thrombin on the systemic inflammatory response syndrome (SIRS) in posttrauma patients, as well as to investigate the relationship between SIRS and sepsis.. Prospective, cohort study.. General intensive care unit of a tertiary care emergency department.. Forty trauma patients were classified into subgroups, according to the duration of SIRS: non-SIRS patients (n = 9); patients with SIRS for < 2 days (n = 15); and patients with SIRS for > 3 days (n = 16).. None.. Tissue factor antigen concentration, prothrombin fragment F1+2, thrombin antithrombin complex, fibrinopeptide A, and cross-linked fibrin degradation products (D-dimer) were measured on the day of admission, and on days 1 through 4 after admission. Simultaneously, the number of SIRS criteria that the patients met and the disseminated intravascular coagulation score were determined. The results of these measurements, frequency of acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome, sepsis, and outcome were compared among the groups. The values of all five hemostatic molecular markers in the patients with SIRS for > 3 days were significantly more increased than those molecular marker values measured in the other groups on the day of admission. These values continued to be markedly high up to day 4 of admission. The occurrence rates of disseminated intravascular coagulation in these patient groups were significantly higher than those rates in the other two groups (p = .0001), and the disseminated intravascular coagulation scores did not improve during the study period. The occurrence rates of ARDS (p < .05) and multiple organ dysfunction syndrome (p < .01) were higher in patients with SIRS for > 3 days compared with those rates in the other groups, and the patients with SIRS for > 3 days had a poor outcome. No significant difference was noted in the frequency of sepsis among the groups.. Sustained SIRS is the main determinant for ARDS, multiple organ dysfunction syndrome, and outcome in posttrauma patients. Disseminated intravascular coagulation associated with massive thrombin generation and its activation is involved in the pathogenesis of sustained SIRS. Sepsis has a small role in early posttrauma multiple organ dysfunction syndrome.

Topics: Abbreviated Injury Scale; Adult; Analysis of Variance; Anticoagulants; Blood Coagulation Factors; Disseminated Intravascular Coagulation; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Respiratory Distress Syndrome; Systemic Inflammatory Response Syndrome; Thrombin; Thromboplastin; Wounds and Injuries

This study was conducted to identify a relationship between anatomical trauma severity and immunologic function. Four milliliters of citrated whole blood (CWB) was obtained from 14 multiply traumatized patients and their Injury Severity Score (ISS) was calculated. Each CWB sample was divided into four 1 ml aliquots with 1 microgram of E. coli endotoxin (ECE) (Difco) being added to the first, 10 micrograms of ECE to the second, 10 micrograms of pokeweed mitogen (PWM) to the third, and 20 microliters of saline to the fourth. Following a 2 hr incubation at 37 degrees C the recalcification time (RT) was determined on a Hepcon-B10. Percent shortening was calculated as the difference in the RT between the stimulated sample and the saline control. There was a significant correlation between ISS and % shortening of the ECE stimulated samples at both concentrations (for 1 microgram ECE r = 0.59, P = 0.02, and for 10 micrograms ECE r = 0.81, P = 0.00025), and also in the PWM sample (R = 0.79, P = 0.00071). This study demonstrates a significant and direct relationship between trauma severity and the patient's monocytes' ability to generate thromboplastin following ECE or PWM stimulation.

Topics: Adult; Calcium; Citrates; Citric Acid; Endotoxins; Escherichia coli; Female; Humans; Injury Severity Score; Leukocyte Count; Male; Middle Aged; Monocytes; Pokeweed Mitogens; Thromboplastin; Wounds and Injuries

Yucatan miniature swine were the experimental model used to examine the effect of ischemia-injury on post-ischemic monocyte (MO) and immune function. Monocyte plasminogen activator (PA) was depressed while MO tissue factor activity was increased. The ability of porcine monocytes to generate a primary in vitro antibody forming cell (AFC) response to sheep red blood cells (SRBC) also was depressed by ischemic injury. The mechanism by which ischemic injury modulated immunosuppression appeared to be through generation of immunosuppressive serum substances.

Topics: Animals; Antibody Formation; Disease Models, Animal; Extremities; Female; Immune Tolerance; Immunity, Cellular; Ischemia; Lymphocytes; Monocytes; Plasminogen Activators; Swine; Swine, Miniature; Thromboplastin; Wounds and Injuries

Topics: Cell Communication; Humans; Lymphocyte Activation; Monocytes; Muramidase; Phagocytes; Phytohemagglutinins; Plasminogen Activators; Splenectomy; T-Lymphocytes; Thromboplastin; Wounds and Injuries

Topics: Blood Coagulation; Complement Activation; Humans; Lymphocytes; Macrophages; Monocytes; Neutrophils; Phytohemagglutinins; Plasminogen Activators; Risk; Sepsis; Thromboplastin; Wounds and Injuries

Thromboembolic complications are often a common pathological consequence of severe soft tissue trauma. Recent demonstration that monocytes (M0) produce tissue factor (TF) has led to the suggestion that these TF producing M0 might play a role in coagulopathy. We have previously demonstrated that trauma patients with splenectomy develop aberrant monocyte function and this patient group is also known to be at high risk of hypercoagulability episodes. This paper is an initial report on the use of M0 TF as an indicator of and/or correlated to clotting episodes. Monocytes isolated form the Ficoll-Hypaque purified mononuclear cells of 46 normal individuals, 17 trauma patients and 6 surgical controls were assayed at 3 day post-injury intervals for their levels of TF activity. Changes in monocyte TF activity were correlated to increases in the fractional catabolic rate (FCR) of 125 I-fibrinogen. Trauma patients were retrospectively divided into those whose FcR was elevated to a level indicative of coagulopathy and those whose FCR levels were not associated with coagulation abnormalities. All trauma patients who exhibited significantly increased FCR experienced thromboembolic episodes and had monocytes whose TF activity was increased an average of 300% (mean = 47 units vs mean = 12 units) over surgical controls. These increase in monocyte TF activity occurred at 6-13 days post injury and preceded clinical manifestation of coagulopathy by 4-6 days. The increased monocyte TF activity demonstrated in this study was significantly correlated to detection of pathologically increased FCR (R = 0.850) and compared to other indices of hypercoagulability.

Topics: Blood Coagulation; Fibrinogen; Humans; Monocytes; Postoperative Complications; Splenectomy; Thromboembolism; Thromboplastin; Wounds and Injuries

On the basis of a series of clinical investigations, our present viewpoints on posttraumatic pulmonary insufficiency due to the microembolism syndrome may be summarized as follows. Two forms of this syndrome exist: 1. An early microembolism syndrome caused by transient deposition of fibrin-rich microemboli in the pulmonary microcirculation, giving rise to a temporarily low ventilation/perfusion ratio. This pulmonary reaction pattern is often subclinical. 2. A delayed microembolism syndrome caused by persistent fibrin-rich microemboli due to fibrinolysis inhibition, giving rise to increased vascular permeability and progressive interstitial and alveolar oedema. This pulmonary reaction pattern leads to pulmonary insufficiency with the characteristic radiographic changes and clinical symptoms of respiratory distress. Whether the early syndrome will develop into the delayed form may depend mainly upon the severity of the trauma, the capacity of the fibrinolytic system to clear the lungs, the form of treatment given, and the cardiopulmonary state of the patients.

Topics: Fibrinolysis; Humans; Pulmonary Embolism; Respiratory Distress Syndrome; Thromboplastin; Wounds and Injuries

A summarized account of our experiences over 1 1/2 years is given, in relation to a minimum heparinisation technique during haemodialysis. This novel technique was made possible by the introduction of an APTT bedside method. In a comparison between the techniques employed so far for preventing a heparin-caused risk of haemorrhage and our method, the clear advantage of our method was apparent. In addition to a discussion of our methods, we describe the cases treated so far. The amounts of heparin required for dialysis are so small that a necessary coagulation can occur even in a part of the organism where there is a danger of haemorrhage. Thereby it was possible to extend the range of indication for haemodialysis substantially. By using minimum heparinisation, it is possible to perform an immediate postoperative haemodialysis. The healing of wounds, which is impaired in cases of renal insufficiency, may be improved by early dialysis without the risk of haemorrhage. Our results show that the minimum heparinisation signifies a decisive achievement in acute dialysis therapy.

Topics: Acute Kidney Injury; Adult; Aged; Blood Coagulation Tests; Female; Hemorrhage; Heparin; Humans; Kidney Failure, Chronic; Male; Middle Aged; Monitoring, Physiologic; Renal Dialysis; Risk; Thromboplastin; Wounds and Injuries

Topics: Animals; Disseminated Intravascular Coagulation; Male; Phospholipases; Rats; Thromboplastin; Wounds and Injuries

Recovery of intrathoracic and intraperitoneal blood and reinfusion by autotransfusion has been demonstrated to be safe and practical in selected trauma patients. Autotransfusion is ideally applicable to the trauma patient in whom replacement of six or fewer units of blood is required. In addition, autotransfusion provides readily available blood for patients with unusual blood types and for those in whom multiple transfusions may rapidly deplete available stores. The properties of an ideal autotransfusion device include rapid assembly, relatively low cost, ease of operation, in-line filtration, minimized air blood interface, simplified anticoagulation, and safety from air embolism and coagulopathies.

Topics: Bilirubin; Blood Banks; Blood Cell Count; Blood Coagulation Tests; Blood Platelets; Blood Transfusion, Autologous; Fibrinogen; Hematocrit; Hemoglobins; Hemolysis; Hemorrhage; Humans; Leukocyte Count; Liver; Liver Function Tests; Postoperative Complications; Prothrombin Time; Thoracic Surgery; Thorax; Thromboplastin; Wounds and Injuries

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Disseminated Intravascular Coagulation; Embolism; Female; Humans; Leukemia; Male; Postoperative Complications; Pregnancy; Pregnancy Complications, Hematologic; Shock; Thromboplastin; Thrombosis; Wounds and Injuries

Topics: Aminocaproates; Animals; Blood Coagulation; Hemorrhage; Hemostatics; Peptide Hydrolases; Rats; Snakes; Thromboplastin; Venoms; Vitamin K; Wounds and Injuries

Utilizing a disposable unit, intraoperative autotranfusion was employed during surgery in 53 patients admitted to the Bexar County Teaching Hospital at the University of Texas Health Science Center at San Antonio. During the two-year period of study, 26 patients underwent surgery for major traumatic injuries, 8 for ruptured ectopic pregnancy and 19 for miscellaneous emergency or elective conditions. The indication for intraoperative autotransfusion was an anticipated blood loss of 1,000 ml or more. Contraindications for its use were colon injury or localized infection. Over 325 units of blood were salvaged and returned directly to these patients during surgery. One death related to the use of the autotransfusor unit was due to massive air embolism. Twenty other deaths were associated with severe injuries and irreversible shock requiring greater than 3,600 ml of both autologous and homologous blood. Eight of these patients demonstrated severe pancoagulopathies. In the remaining patients, clotting factors and plasma or urine hemoglobin levels were transiently abnormal. However, there were no clinically apparent bleeding defects or renal problems detected. Postoperative blood cultures were consistently negative. It is concluded that intraoperative autotransfusion, when properly employed, is a safe, practical and technically feasible procedure.

Topics: Abdominal Injuries; Adult; Blood Cell Count; Blood Coagulation Disorders; Blood Platelets; Blood Transfusion, Autologous; Blood Volume; Disposable Equipment; Emergencies; Female; Humans; Male; Pregnancy; Pregnancy, Ectopic; Prothrombin Time; Rupture, Spontaneous; Surgical Procedures, Operative; Thoracic Injuries; Thromboplastin; Time Factors; Wounds and Injuries; Wounds, Gunshot

Topics: Adolescent; Adult; Aged; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Child; Disseminated Intravascular Coagulation; Factor IX; Factor V Deficiency; Factor VII; Factor VIII; Factor X; Fibrinolysin; Humans; Middle Aged; Plasminogen; Prognosis; Prothrombin Time; Thromboplastin; Wounds and Injuries

Topics: Blood Cell Count; Blood Coagulation; Blood Platelets; Burns; Craniocerebral Trauma; Fibrinogen; Fibrinolysin; Fibrinolysis; Humans; Prothrombin Time; Thromboplastin; Wounds and Injuries

Topics: Adult; Blood Cell Count; Blood Coagulation Disorders; Blood Coagulation Tests; Blood Platelets; Blood Transfusion; Fibrinogen; Fibrinolysis; Humans; Male; Military Medicine; Plasma; Prothrombin Time; Thrombin; Thromboplastin; Time Factors; United States; Vietnam; Wound Infection; Wounds and Injuries

Topics: Acute Kidney Injury; Anemia, Hemolytic; Blood Coagulation Disorders; Blood Coagulation Factors; Blood Transfusion; Coronary Disease; Female; Heart Arrest; Hemorrhagic Disorders; Humans; Hyaline Membrane Disease; Infant, Newborn; Ischemia; Kidney Transplantation; Male; Obstetric Labor Complications; Pregnancy; Shock, Septic; Shwartzman Phenomenon; Thrombocytopenia; Thromboembolism; Thromboplastin; Toxemia; Wounds and Injuries

Topics: Animals; Blood Coagulation; Blood Platelets; Catecholamines; Humans; Hypoxia; Microscopy, Electron; Shock; Shock, Septic; Thromboembolism; Thromboplastin; Wounds and Injuries

Topics: Blood Coagulation; Blood Platelets; Hemorrhage; Microscopy, Electron; Models, Theoretical; Thromboplastin; Thrombosis; Wounds and Injuries

Topics: Animals; Coloring Agents; Lagomorpha; Liver Cirrhosis; Pathology; Pharmacology; Rabbits; Research; Spleen; Splenic Vein; Staining and Labeling; Thromboplastin; Wounds and Injuries

Topics: Blood Coagulation; Humans; Skin; Skin Transplantation; Thromboplastin; Wound Healing; Wounds and Injuries