Development Of Venous Thromboembolic Complications Research Articles

The state of hemostasis system in patients after mild coronavirus infection

Introduction. One of the complications of the new coronavirus infection (COVID-19) is the development of venous thromboembolic complications. In this regard, changes in the hemostasis system that persist in the process of recovery in patients who have had a mild form of the disease are of interest.Aim. To evaluate plasma hemostasis in patients after mild coronavirus infection Materials and methods. 39 patients after mild coronavirus infection were examined. The following parameters were assessed: APTT, PT, fibrinogen, factor VIII, von Willebrand factor, D-dimer, proteins C and S, and thrombin generation. Results. In patients who underwent COVID-19, in comparison with healthy individuals, an increase in the plasma concentration of fibrinogen, von Willebrand factor antigen, and D-dimer was detected. Furthermore, increased activity of antithrombin III, decreased sensitivity to thrombomodulin, and an increase in the coagulation index were detected. Conclusion. Patients who have undergone COVID-19 are characterized by a procoagulant orientation of changes in plasma hemostasis that persist up to 3 months after the disease. It is necessary to take into account the state of the hemostasis system even in patients who have undergone COVID-19 in mild form.

The role of hereditary thrombophilia in the development of venous thrombosis in combat trauma

Introduction. Combat trauma is one of the factors causing hemostasis disorders in the wounded. Currently, there is insufficient information about the significance of hereditary thrombophilia in the development of venous thromboembolic complications in the wounded.Aim. To study the effect of polymorphism of genes of components of the hemostasis system on the development of venous thrombosis in wounded with combat trauma.Materials and methods. The prospective study included men (n = 81) of young age (the average age was 36.0 ± 8.5 years) who received a combat wound and were treated at the Military Medical Academy named after S.M. Kirov. The subjects were divided into 2 groups: the main group included 40 victims (49.4%) who were diagnosed with venous thrombosis during treatment, the control group included 41 patients without signs of thrombosis (50.6%). The study of allelic polymorphism of genes associated with the formation of blood clots was carried out using a real-time polymerase chain reaction based on the study of human DNA in peripheral blood material.Results. Comparative analysis revealed no statistically significant differences in the frequency of occurrence of the studied genetic variants between the study group and the control group. When assessing the prevalence of polymorphism of the MTHFR and MTRR genes, it was found that the combination of the genotypes “MTHFR 677 CT” and “MTRR 66 GG” is associated with an 8.5-fold increase in the risk of developing VTEO [OR = 8.5; p = 0.029].Conclusion. Analysis of the test results showed that no relationship was found between individual genetic variants and the risk of developing venous thrombosis in the studied group of wounded despite the high prevalence (prothrombogenic alleles of various genes were detected in 79 servicemen (97.5%)). At the same time, the combination of MTHFR 677 CT and MTRR 66 GG genotypes in that patient population was shown to be associated with a significant increase in the risk of thrombosis.

ИЗУЧЕНИЕ ВЛИЯНИЯ НАСЛЕДСТВЕННЫХ ТРОМБОФИЛИЙ В РАЗВИТИИ ВЕНОЗНЫХ ТРОМБОЗОВ ПРИ БОЕВОЙ ТРАВМЕ

Introduction. Combat trauma is one of the factors that cause impaired hemostasis in the wounded. Currently, there is not enough information about the significance of hereditary thrombophilia in the development of venous thromboembolic complications in the wounded. Target. Study of the effect of polymorphism of the genes of the components of the hemostasis system on the development of venous thrombosis in the wounded with a combat injury. Materials and methods. The prospective study included young men (n=81) (mean age 36.0 ± 8.5 years) who received a combat wound and were treated at the Military Medical Academy. CM. Kirov. The subjects were divided into 2 groups: the main group included 40 patients (49.4%) who were diagnosed with venous thrombosis during treatment, the control group included 41 patients without signs of thrombosis (50.6%). The study of allelic polymorphism of genes associated with the process of thrombus formation was carried out using a real-time polymerase chain reaction based on the study of human DNA in peripheral blood material. Results. In a comparative analysis, no statistically significant differences were found in the frequency of occurrence of the studied genetic variants between the study group and the control group. When assessing the prevalence of polymorphisms in the MTHFR and MTRR genes, it was found that the combination of the MTHFR 677 CT and MTRR 66 GG genotypes is associated with an 8.5-fold increase in the risk of developing venous thromboembolic complications [OR=8.5; p=0.029]. Conclusion. The analysis of the obtained results showed that, despite the high prevalence (the presence of prothrombogenic alleles of various genes was detected in 79 military personnel (97.5%)), it was not possible to establish a relationship between individual genetic variants and the risk of developing venous thrombosis in the studied group of wounded. At the same time, it has been shown that the combination of the MTHFR 677 CT and MTRR 66 GG genotypes is associated with a significant increase in the risk of thrombosis.

Risks of thrombosis: genotype and phenotype of blood coagulation factor V

The review is devoted to the key component of plasma hemostasis — blood coagulation factor V. The structure of this protein and the F5 gene encoding it, its role in the hemostasis system, interaction with other coagulation factors and the natural anticulant protein C are considered. Particular attention is paid to the genetic defects of F5, which determine both hemorrhagic complications and a hereditary tendency to increased thrombus formation. Among the latter, the Leiden mutation of coagulation factor V (FV Leiden), which is hereditary thrombophilia and is considered as a risk factor for the development of venous thromboembolic complications, is described in detail.

Incidencia de eventos tromboembólicos venosos en pacientes hospitalizados con COVID-19

Background and objectiveSeveral studies have reported on the thromboembolic alterations developed in patients with SARS-CoV-2 pneumonia, however, there are no definitive data on the risk factors for the appearance of these events. The aim of this study was to analyse the relationship between personal, clinical, and paraclinical factors and the development of venous thromboembolic complications in hospitalized patients with COVID-19. MethodsFollow-up study of a retrospective cohort of COVID-19 patients admitted, from August 2020 to February 2021, to the Clínica Antioquia de Itagüí. 525 medical records of patients older than 18 years with a confirmed diagnosis of SARS-CoV-2 were included. ResultsThe presence of VTE was identified in 3% of hospitalized patients. Of the patients with COVID-19, 25.1% were admitted to the intensive care unit, 18.9% required invasive mechanical ventilation. Mortality from COVID-19 in our study was 18.1%. In patients hospitalized with SARS-CoV-2, an increased risk of development of thromboembolic events was identified in those with elevated levels of troponin I (HR 4.07; 95% CI 1.09-15.18), a history of prior thromboembolic events (HR 11.01; 95% CI 1.06-114.87), and thrombocytopenia (HR 6.47; 95% CI 2.05-20.44). ConclusionsAn association was found between thromboembolic complications and a history of VTE. Likewise, it was concluded that troponin values ≧ .03 ng/ml and platelet levels < 150,000/mm3 are associated with VTE.

ЭПИДЕМИОЛОГИЯ, ФАКТОРЫ РИСКА, ДИАГНОСТИКА И ПРОФИЛАКТИКА ТРОМБОЗА ГЛУБОКИХ ВЕН ПРИ ПЕРЕЛОМАХ ДЛИННЫХ КОСТЕЙ НИЖНИХ КОНЕЧНОСТЕЙ

A literature review presents a data concerning the incidence and risk factors for development of venous thromboembolic complications (VTEC), as well as their diagnosis and prevention in long bones fractures of the lower extremities (LBFLE). Literature data show that, despite the widespread implementation of preventive measures in case of LBFLE, it is not always possible to completely avoid VTEC. The main risk factors for their development are the injuries’ severity, the location and nature of the extremity bone fracture, the duration of immobilization, the amount of surgery performed for bone fragments stabilization, as well as age and the presence of concomitant diseases. In the diagnosis of thrombotic process, laboratory and radiation research methods play an essential role, and according to data they has varying degrees of sensitivity and specificity. However, to date, none of them has absolute diagnostic accuracy. Complex thrombosis prophylaxis significantly reduces the risk of VTEC development, however, the choice of the type and dosage of anticoagulants, as well as the duration of their use, remain controversial, and some authors recommend different approaches in this issue. In addition, the diagnostic criteria and therapeutic tactics for embologenic floating thrombi remain open for discussion. In this regard, the conduct of large randomized scientific studies aimed at early diagnosis, prevention and treatment of VTEC using modern diagnostic tests and new generation anticoagulants is relevant and allows to minimize the risk of disability and death.

Venske tromboembolijske komplikacije kod pacijenata sa limfomom

Lymphomas represent a heterogeneous group of malignant hematological diseases with high risk for development of venous thromboembolic complications (VTE). Consequently, VTE significantly impacts morbidity and mortality in these patients. Another concern is the financial burden of the healthcare system caused by diagnostic and therapeutic procedures of cancer-associated thrombosis (CAT). The complex biology of lymphoma, in conjunction with patient and treatment related risk factors for the development of VTE, results in a procoagulant hemostatic dysregulation. Considering the incidence of VTE in patients with lymphoma, there is an emerging demand for both reliable risks assessment model (RAM) for prediction of VTE, as well as for effective VTE prophylaxis and treatment. The clinical course of patients with malignant diseases is accompanied by a wide range of potential treatment complications, making the task of prevention and treatment of VTE even more challenging. In recent years, great progress has been achieved in understanding the pathophysiological mechanisms of thrombotic complications, while the significant number of randomized controlled trials (RCT) have provided standards of prophylaxis and treatment of VTE complications in patients with malignancy. In comparison to previous recommendations and guidelines for CAT, the use of direct oral anticoagulants (DOAC) has been gradually approaching low molecular weight heparins (LMWH) in terms of efficacy and safety profile in these indications. This systematic review is focused on the latest pathophysiological advances, risk factors assessment, prophylactic and therapeutic recommendations and guidelines concerning VTE in patients with lymphoma.

PB2426 CLINICAL MANIFESTATION OF HEREDITARY THROMBOPHILIA IN CHILDREN

Background:Venous thromboembolism (VTE) in children is becoming a more frequent problem. The pathogenesis of thrombosis is complex: thrombophilia, background disease, trigger factor. Special attention should be deserved to hereditary thrombophilia (HT), which from childhood can be accompanied by persistent disorders in the hemostasis system and significantly increase the risk of thrombosis.Aims:To assess the influence of HT on the development of venous thromboembolic complications in children.Methods:We have examined 24 patients aged from 1 day to 18 years, who had various types of thrombotic manifestations (n = 20) or the threat thereof taking into account the family history (n = 4). The average age of children was 5.6 years, the ratio of girls to boys was 1.4 / 1.0. All patients underwent a full laboratory examination aimed at the diagnosis of HT and antiphospholipid syndrome (APS): levels of antithrombin III (ATIII), protein C and S, antibodies to β2‐glycoprotein and cardiolipin, lupus anticoagulant, homocysteine level. Molecular genetic testing included thrombogenic mutations and polymorphisms.Results:In half of the cases of VTE, the lower extremity deep vein thrombosis of was diagnosed. Venous sinus thrombosis ‐ in 20% of the examined (n = 4); pulmonary artery thromboembolism in one case; thrombosis in the pool of the portal and superior vena cava ‐ in 35%. VTE recurrences were observed in 20% of cases. The diagnosis of HT is verified in 62.5% of all examined children and in 55% of children with thrombosis. The HT variants were distributed in the following way: 33.3% ‐ mutation in the FV Leiden (het) gene; 20% ‐ in the prothrombin G20210A (het) gene; AT III deficiency was diagnosed in three patients (20%); combined mutations in MTHFRC‐677T (T/T) and PAI‐1 (4G/4G) genes‐ 26.7%. MTHFRC‐677T (T/T) mutations in two cases were accompanied by moderate hyperhomocysteinemia. Trigger factors for VTE not associated with HT were background diseases and its associated complications: acute lymphoblastic leukemia (n = 4); parenteral nutrition (n = 1); operative interventions (n = 2); autoimmune diseases (n = 2) and APS (n = 1). Clinical manifestation of HT in 63.3% of cases was observed in patients over 10 years old. In 72.7% of cases, VTE occurred spontaneously. The earliest spontaneous VTE was detected in a child at the age of 1 day (portal vein thrombosis). In 75% of cases of recurrent VTE, HT has occurred.Summary/Conclusion:Hereditary thrombophilia is a sign of the potential risk of thrombosis in children. Clinical manifestation of VTE occurs at any location, at any age, but significantly more often in children older than 10 years. The presence of HT is a high risk factor for recurrent and spontaneous VTE. Diagnosis of HT is reasonable to carry out in all cases of VTE in children, which is important not only for assessment of the risk of repeated thrombotic episodes, but also for selecting the antithrombotic therapy regimen and optimizing preventive measures.

APC-resistance as a possible predictor of recurrent thrombosis in women with Factor V Leiden

Hypothesis/aims of study. The current analysis was undertaken to elucidate the role of Factor Va resistance to proteolytic cleavage by activated protein C in FVL(1691)GA female carriers in the development of acute and recurrent thromboses.&#x0D; Study design, materials and methods. A prospective clinical cohort study of 1100 women of reproductive age was conducted, with the course and outcomes of 2,707 pregnancies analyzed. Two cohorts were specified: the main group consisted of 500 patients with FV(1691)GA genotype, and the control group consisted of 600 patients with FVL(1691)GG genotype.&#x0D; Results. FVL(1691)GA genotype was significantly associated with the development of venous thromboembolic complications (VTEC) compared to FVL(1691)GG genotype (OR 9.3; p &lt; 0.0001). Episodes of recurrent thrombosis during and outside of pregnancy were registered only in FVL(1691)GA patients (OR 5.7, p = 0.2). In all cases, at the time of the thrombotic event and during the period before the episode of acute or recurrent thrombosis, an APC resistance normalized ratio (NR) value was ≤ 0.49, with no episodes of VTEC registered with an APC resistance NR value ≥ 0.5.&#x0D; Conclusion. Venous thromboses occur under the condition of expressed APC resistance with underlying FVL(1691)GA carriage. The APC resistance index can serve as an objective biochemical marker to determine the feasibility of thromboprophylaxis within the framework of personalized medicine.

Risk of postoperative venous thromboembolic complication development in elderly patients

Aim. To evaluate venous thromboembolic complication risk in elderly patients admitted to trauma and orthopedics departments, prevalence of comorbidity, its impact on the risk of thrombotic events, efficacy and safety of prophylactic anticoagulant therapy. Materials and methods. Authors performed a retrospective analysis of medical records of 120 patients aged 65 years and over. Analyzed data included demographic data, main diagnosis, co-existing pathology according to International Classification of Diseases X, type of surgery and anticoagulant prophylaxis. Risk of development of venous thromboembolic complications was assessed by the Caprini scale. Potential drug-drug interactions were checked using Drug Interaction Checker available, created by company Cerner Multum according to FDA recommendations. Results. The most frequent causes of hospitalization were destructive large joint arthritis (40%) and fractures of lower extremities (21.7%). Surgeries with an average duration of 87 ± 31.4 min were performed in 85% of patients, of which major surgery – 68.6%, minor – 31.4%. Comorbidity was detected in 90% of elderly patients admitted to hospital because of pathology of the musculoskeletal system. Pathology of musculoskeletal system most often was combined with cardiovascular diseases (81.7%). A moderate risk of venous thromboembolic complications was detected in 10% patients, high risk in 75%. Anticoagulant prophylaxis with a direct factor Xa inhibitor rivaroxaban or low-molecular weight heparin enoxaparine sodium was performed in 80% of patients. Conclusion. The study demonstrated that 75% of elderly patients with pathology of the musculoskeletal system are at high risk for the development of venous thromboembolic complications. The main risk factors include the type and duration of surgery and comorbidity.

Venous Thrombogenesis and Functional State of the Hemorheology and Hemostasis System in Stroke Patients

Investigation of the hemorheology and hemostasis system in patients with stroke of various types, location, and severity as well as with and without venous thromboembolic complications (VTECs), who were treated at critical and intensive care units, demonstrated the significance of impairments in the hemorheology and hemostasis system for VTEC pathogenesis in stroke patients. Despite ongoing anticoagulant therapy, aggravation of the prothrombogenic state was observed in VTEC patients. Ischemic stroke was associated with more severe changes compared to hemorrhagic stroke. Hemostasiological predictors of VTEC were identified. In patients without VTEC, both the coagulation and anticoagulation systems as well as the fibrinolysis system were preserved. The D-dimer and thrombophilia markers, such as hyperhomocysteinemia and antiphospholipid syndrome, were shown not to contribute to the development of VTEC in stroke patients.

Oral Contraceptives and HRT Risk of Thrombosis.

Estrogen-containing medication, prescribed either for contraception in women of reproductive age or for prevention of cardiovascular events and osteoporosis as well as for alleviation of symptoms related to menopause, is associated with changes in the hemostatic balance and contributes to increased risk of development of venous thromboembolic complications. This risk is dose and medication dependent, increases with age, congenital and/or acquired predisposition to thrombosis, and mode of administration. This review attempts to summarize the current knowledge regarding the pathophysiology of oral contraceptive (OC) and hormone replacement therapy (HRT) -induced prothrombotic state in women, the risk of thrombosis associated with administration of various commercially available OCs and HRT, the additional risk in women with hereditary or acquired thrombophilia, and the currently available recommendations regarding massive screening of women for thrombophilia prior to initial prescription or continuation of treatment with OCs and HRT preparations.

THROMBOSIS IN CANCER. PART 2

Cancer is one of the most significant risk factors for the development of venous thromboembolic complications, and also increases the risk of arterial thrombosis mainly in the coronary and cerebrovascular arteries. The article aimed to examine the direct toxic effects on vascular endothelium demonstrated by specific classes of chemotherapeutic drugs, tumor procoagulant effect, inhibition of endogenous fibrinolysis, and increased platelet aggregation among the pathogenetic mechanisms of these complications. The article is presented in two parts. The first part examines the traits of the hemostasis state in cancer, some pathogenetic mechanisms of arterial and venous thrombosis, and the management of cancer patients with the arterial thrombosis. The second part provides a review of the literature on the prevention and treatment of cancer-associated venous thromboembolic complications.

PREVENTION OF VENOUS THROMBOEMBOLIC COMPLICATIONS IN TRAUMAS OF LOCOMOTOR SYSTEM

Therapy of patients with disturbances of the locomotor system requires use of drugs to prevent venous thromboembolic complications. In addition to non-drug measures low-molecular heparins are the drugs of choice among coagulants at conservative therapy of traumas and in the post- operative period. The second generation low-molecular heparin – bemirin sodium – demonstrates high effectiveness and safety and might be applied by patients with medium and high degree of development of venous thromboembolic complications (VTEC).

Тромбоэмболия легочной артерии у раненого с сочетанной минно-взрывной травмой на фоне проведения антикоагулянтной профилактики (клинический случай)

Venous thrombosis and pulmonary embolism in healthy military are rare. Fighting surgical trauma is the trigger of a cascade of defense reactions of the body and the blood coagulation system, leading to stop bleeding. Hemostatic disorders, shifting the equilibrium toward hypercoagulable state, the emergence of the risk factors associated with the injury, lead to uncontrolled thrombosis with subsequent development of venous thromboembolic complications. We present the case of the left pulmonary artery thromboembolism in 41 year old wounded with a gunshot fracture of the right femur, obtained by blowing an unknown explosive device. Medical assistance was provided in three stages of evacuation. In order to stabilize a femur fracture the external fixation device was used. According coagulogram thrombinemia persisted for more than 30 days. Prevention of thrombosis carried LMWH (Clexane), with 9 days after injury. 31 day angiography was performed computer, identified thrombus by 70% ceiling clearance left pulmonary artery; by ultrasound scanning of the veins of the lower limbs was diagnosed asymptomatic thrombosis of the right iliofemoral. Against the background of complex treatment for 67 hours after the injury occurred recanalization. This case shows that the injured limb wound clinical symptoms of the disease symptoms negate venous thrombosis, which becomes the only manifestation of pulmonary embolism. Prevention of venous thromboembolic events, as well as monitoring of its effectiveness, should be carried out at all stages of the evacuation of the wounded and for the entire period of the presence of risk factors for their development.

Clinical outcomes and factors predicting development of venous thromboembolic complications in patients with advanced refractory cancer in a Phase I Clinic: The M. D. Anderson Cancer Center experience

Venous thromboembolism (VTE) is common in patients with advanced cancer and may influence patient eligibility for clinical studies, quality of life, and survival. We reviewed the medical records of 220 consecutive patients seen in the Phase I Clinical Trials Program at M. D. Anderson Cancer Center to determine the frequency of VTE, associated characteristics, and clinical outcomes. Twenty-three (10.5%) patients presenting to the Phase I Clinic had a history of VTE; 26 (11.8%) patients subsequently developed VTE, with a median follow-up of 8.4 months. These included nine (39%) patients with and 17 (8.6%) without a history of VTE (P < 0.0001). The most common events were deep venous thromboses of the extremities and pulmonary emboli. The median survival of patients with and without a history of VTE was 4.7 and 10.9 months, respectively (P = 0.0002). Multivariate analysis demonstrated that a history of VTE (P < 0.0001), pancreatic cancer (P = 0.007), and platelet count >440 x 10(9)/L (P = 0.026) predicted new VTE episodes. In conclusion, this retrospective analysis demonstrated that a history or new development of VTE was noted in 40 (18%) of 220 patients seen in our Phase I Clinic. A prognostic score that can be used to predict time to development of and frequency of VTE is proposed. Am. J. Hematol. 2009. (c) 2009 Wiley-Liss, Inc.

Clinical Outcomes and Factors Predicting Development of Venous Thromboembolic Complications in Patients with Advanced Refractory Cancer in a Phase I Clinic: The M. D. Anderson Cancer Center Experience

Venous thromboembolism (VTE) is common in patients with advanced cancer and may influence patient eligibility for clinical studies, quality of life, and survival. We reviewed the records of 220 consecutive patients seen in the Phase I Program at M. D. Anderson Cancer Center to determine the frequency of VTE, associated characteristics and clinical outcomes. Of 220 patients, 23 (10.5%) presented to the Phase I clinic with a history of VTE. Twenty-six patients (11.8%) subsequently developed a venous thromboembolic event, with a median follow-up of 8.4 months. These included 9 of 23 patients (39%) with and 17 of 197 (8.6%) without a history of VTE (p < 0.0001). The median time from the first visit to the Phase I clinic to a new thromboembolic episode in the 26 patients was 5.1 months (range, 0 to 27 months). The respective times to development of new thromboembolic events for patients with and without a history of thromboembolism were 3.1 months (n = 9) and 5.3 months (n = 17). Four (15%) of the 26 patients developed venous thromboembolism within one month after their first visit to the Phase I clinic. Among the remaining 22 patients, 18 (69%) developed venous thromboembolism within the first year following their initial visit to the Phase I clinic, and 4 patients developed it after 2.5 years. Fifteen patients developed DVT, seven pulmonary embolism (PE), and one patient each developed one of the following thromboembolic episodes: concurrent DVT and PE; right atrial thrombus; thrombus in the abdominal aorta and DVT; and isolated thrombus in an abdominal aortic aneurysm. The median survival in patients with and without a history of VTE were 4.7 and 10.9 months, respectively (p = 0.0002). Multivariate analysis demonstrated that a history of VTE (hazard ratio 6.2; 95% C.I. 2.6–14.7; p < 0.0001), diagnosis of pancreatic cancer (hazard ratio 4.0; 95% C.I. 1.5–11.2; p=0.007) and platelet count >440 × 109/L (hazard ratio 3.1; 95% C.I. 1.1–8.2; p = 0.026) predicted the development of new venous thromboembolic episodes. These three parameters were used to design a predictive model. Based on the relative risks of the independent covariates, the relative risk of a new thromboembolic episode could be characterized by summing the weighted number of risk factors present at first visit to the Phase I clinic. History of venous thromboembolism was given a score of 2 because the hazard ratio was 6.3, whereas the diagnosis of pancreatic cancer and elevated platelet counts had hazard ratios of 4.7 and 3.0, respectively, and were each given a score of 1. Therefore, patients could have a score ranging from 0 to 4 (no patients had a score of 4). Patients were assigned to one of three risk groups on the basis of their weighted number of presenting risk factors: 0, low risk; 1, medium risk; 2–3, high risk. At 6 months, the rates of a new thromboembolic episode were 3.5%, 12.5%, and 28% for patients with scores 0, 1, or 2–3, respectively (p<0.0001). The median time to a new thromboembolic episode was not reached for patients with a score 0 or 1, and it was 9.1 months for patients with a score of 2–3. In conclusion, a history of VTE or new development of VTE was noted in 40 (18%) of 220 patients seen in our Phase 1 clinic. Our study suggests the need to closely monitor individuals with advanced cancer for the development of venous thromboembolic events. The high risk of recurrent venous thromboembolism in patients with a prior history of venous thromboembolism, whose anticoagulation therapy was discontinued before clinic referral, supports long-term continued prophylaxis in these patients. A prognostic score to predict for time to and frequency of venous thromboembolic events is thereby proposed.

Hemostasis and Thrombosis in Critically Ill Patients

A large number of critically ill patients will develop hemostasis and thrombosis issues during their clinical course. These problems may vary from excessive blood loss due to a myriad of causes; to widespread intravascular fibrin formation and consequent multiple organ dysfunction as a result of systemic inflammation; to the development of venous thromboembolic complications. Some patients will present with simultaneous bleeding and thrombotic complications, which will render the appropriate treatment even more complex. Both anticoagulant and prohemostatic drugs belong to the most frequently prescribed agents for patients in the intensive care unit (ICU).[1] [2] In addition, in critically ill patients, coagulation abnormalities often occur. A variety of changes, such as thrombocytopenia, prolonged global coagulation tests, reduced levels of coagulation inhibitors, or high levels of fibrin split products, may reflect various disease mechanisms. Also, some patients may have a marked coagulopathy that is not readily revealed by routine coagulation tests. In all cases, a proper differential diagnosis is required, as various underlying causes may require totally different therapeutic approaches. In this issue of Seminars in Thrombosis and Hemostasis, various topics regarding the diagnostic and therapeutic management of hemostasis and thrombosis issues in critically ill patients are discussed.

Use of spiral computed tomography contrast angiography and ultrasonography to exclude the diagnosis of pulmonary embolism in the emergency department

Spiral computed tomography (CT) contrast angiography is a promising imaging modality for the diagnosis of pulmonary embolism but the negative predictive value of this test remains controversial. We performed a multi-center prospective cohort study to determine the safety of relying on a negative spiral CT contrast angiography scan to exclude pulmonary embolism. Patients presenting to the Emergency Departments of three tertiary care institutions with clinically suspected pulmonary embolism were potentially eligible for the study. Patients underwent a clinical evaluation to categorize pretest probability into low, moderate, and high categories, and had D-dimer testing performed. Patients at low pretest probability with normal D-dimer were considered to have pulmonary embolism excluded. The remaining patients underwent spiral CT contrast angiography scan of the pulmonary arterial circulation and bilateral venous ultrasound of the proximal leg veins. Patients who were confirmed to have pulmonary embolism or deep vein thrombosis were treated with anticoagulant therapy. Patients in whom the diagnosis of pulmonary embolism was excluded did not receive anticoagulant therapy and were followed for a 3-month period for the development of venous thromboembolic complications. Eight hundred fifty-eight (858) patients were enrolled in this study. Three-hundred sixty-nine (369) patients had low pretest probability and negative D-dimer results and no further diagnostic tests were performed. None of these patients subsequently developed venous thromboembolic complications (0%, 95% confidence interval [CI] 0% to 1.0%). The remaining 489 were referred for spiral CT contrast angiography scan and ultrasound. Sixty-seven patients were confirmed to have pulmonary embolism and an additional 15 patients with negative CT scans had proximal deep vein thrombosis (DVT) on ultrasound for a total prevalence of venous thromboembolism of 82/489 (16.8%). Two of 409 patients who had pulmonary embolism excluded in the initial evaluation phase developed proximal venous thromboembolism (0.5%; 95% CI 0% to 1.8%) in the 3-month follow-up period. These findings suggest that the combination of a negative spiral CT contrast angiography scan and normal venous ultrasound imaging safely excludes the diagnosis of pulmonary embolism in the Emergency Department setting.

Rapid D-dimer test combined a clinical model for deep vein thrombosis. Validation with ultrasonography and clinical follow-up in 383 patients.

An optimal approach to the diagnosis of deep vein thrombosis (DVT) in lower limbs in the emergency department is still unknown. In this prospective cohort study, we aimed to evaluate the accuracy of the widely available plasma D-dimer test (VIDAS) and establish the usefulness of combining D-dimer testing with a clinical model to reduce the need for serial ultra-sonographies and improve the diagnostic strategy of DVT. We performed a cohort study in 383 consecutive outpatients referred to the emergency department of Hospital La Princesa, with clinical suspicion of DVT. The patients were stratified into three pre-test probability categories using an explicit clinical model (Wells score), and underwent a quantitative automated ELISA D-dimer assay (VIDAS D-Dimer bioMérieux). Patients were managed according to the diagnostic strategy based on clinical probability and compression ultrasonography (CU). Patients for whom DVT was considered a high pre-test probability with negative ultrasonographic findings in the initial CU, returned the following week for repeat ultrasonography. All patients with DVT excluded did not receive anticoagulant therapy, and were followed up for three months to monitor the development of venous thromboembolic complications. DVT was confirmed in 102 patients (26.6%): 95 in the initial test, four in the second test, and three who developed venous thromboembolic complications in the three-month follow-up period. The calculated D-dimer cut-off level was 1 micro g/ml. One hundred patients (98%) with DVT had positive D-dimer. D-dimer had a sensitivity of 98% and a negative predictive value of 98.6%. Among the high-probability patients with positive D-dimer tests and initial negative CU, 9.75% had DVT on repeat CU at one week. The study results suggest that the addition of VIDAS D-dimer to this diagnostic algorithm could improve the management of patients with suspected DVT in daily practice. A diagnostic approach of DVT based on D-dimer (cut-off > or =1 microg/ml) as the first diagnostic tool for the exclusion of DVT, and the clinical probability model as the tool that identifies those patients requiring a second ultrasonography is useful and suitable for daily medical practice.