The Utility of the Markers of Coagulation and Hemostatic Activation Profile in the Management of Embolic Strokes of Undetermined Source.

BACKGROUND: Potential causes of embolic stroke of undetermined source (ESUS) include occult malignancy, venous thrombosis (VTE) with paradoxical embolism, and hypercoagulable disorders. Given the association of markers of coagulation and hemostatic activation (MOCHA) with these causes, the objective of this study was to validate the utility of the MOCHA profile in identifying the underlying cause of stroke. METHODS: We prospectively identified ESUS patients from January 1, 2017 to December 1, 2019 who underwent MOCHA profile (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer) testing. Abnormal MOCHA profile was defined as ≥ 2 abnormal markers. New diagnoses of malignancy, VTE, hypercoagulable disorders and recurrent stroke were identified during routine clinical follow-up. RESULTS: Of 236 ESUS patients, 104 (44%) patients had an abnormal MOCHA profile. In multivariable analyses the number of MOCHA abnormalities was significantly associated with malignancy, VTE, and hypercoagulable disorders (OR 2.59, CI 95% 1.78-3.76, p<0.001). Sensitivity, specificity, positive predictive value, and negative predictive value of an abnormal MOCHA profile for the combined outcome of malignancy, VTE, and hypercoagulability was 96%, 62%, 23%, and 99% respectively. DISCUSSION: The MOCHA profile was able to identify ESUS patients more likely to have malignancy, VTE, and hypercoagulable disorders during follow-up. Our results show that a normal MOCHA profile in ESUS patients can effectively rule out these potential causes of ESUS.

Prospective Assessment of Biomarkers of Hypercoagulability for the Identification of Patients With Severe Coronary Artery Disease. The ROADMAP-CAD Study.

In patients with stable coronary artery disease (CAD) blood hypercoagulability figures among factors leading to thrombosis. Tissue factor (TF) exposure at ruptured plaque initiates blood coagulation and hypercoagulability is responsible for thrombus formation. Early identification of patients eligible for angiography is a challenging issue for effective prevention of ACS. This pilot study aimed to identify biomarkers of hypercoagulability that can be prospectively used in risk assessment tools for the evaluation of CAD severity. Biomarkers of hypercoagulability could be a used for the evaluation of CAD severity. Platelet-poor plasma from 66 patients who were referred to coronary angiography was assessed for thrombin generation, phospholipid-dependent clotting time (Procoag-PPL ® ) and D-Dimers, and evaluated against atherosclerotic burden. Patients with CAD, as compared to controls, showed attenuated thrombin generation lag time: 4.7 (3.8-5.4) min versus 2.5 (2.1-2.9) min; p < 0.0001, shorter Procoag-PPL® clotting time 55.0(32-66) s versus 62.8 (42-85) s; p = 0.001), and higher D-Dimer levels 0.509 (0.27-2.58) µg/ml versus 0.309 (0.23-0.39) µg/ml; p = 0.038. Multivariate logistic regression model showed excellent discriminatory value in predicting CAD severity. The ROADMAP-CAD study showed that the Procoag-PPL® clotting time and thrombin Peak are informative for the the burden of the coronary atherosclerotic disease. The clinical relevance of this observation in the development of a new clinic-biological risk assessment model for early diagnosis of severe CAD has to be examined in a prospective study.

Viscoelastic testing in liver transplantation.

Despite the lack of large randomized clinical studies, viscoelastic tests (VETs) have been a critical armamentarium for hemostatic control in liver transplantation (LT) since the 1960s. Many transplant institutions have adopted VETs in their clinical practice. Several small-size randomized clinical trials on LT patients have suggested that VET-guided hemostatic treatment algorithms have led to decreased indications for and amounts of transfused blood products, especially fresh-frozen plasma, compared to standard laboratory-based hemostatic management. VETs have also been reported to offer insight into the diagnosis and prediction of LT patients' development of hypercoagulability-related morbidity and mortality. There is still a need for VET device-specific hemostatic algorithms in LT, and clinicians must take into account the tendency to underestimate the coagulation capacity of VETs in patients with end-stage liver disease where hemostasis is rebalanced.

The hypercoagulable state in COVID-19: Incidence, pathophysiology, and management.

The 2019 coronavirus disease (COVID-19) presents with a large variety of clinical manifestations ranging from asymptomatic carrier state to severe respiratory distress, multiple organ dysfunction and death. While it was initially considered primarily a respiratory illness, rapidly accumulating data suggests that COVID-19 results in a unique, profoundly prothrombotic milieu leading to both arterial and venous thrombosis. Consistently, elevated D-dimer level has emerged as an independent risk factor for poor outcomes, including death. Several other laboratory markers and blood counts have also been associated with poor prognosis, possibly due to their connection to thrombosis. At present, the pathophysiology underlying the hypercoagulable state is poorly understood. However, a growing body of data suggests that the initial events occur in the lung. A severe inflammatory response, originating in the alveoli, triggers a dysfunctional cascade of inflammatory thrombosis in the pulmonary vasculature, leading to a state of local coagulopathy. This is followed, in patients with more severe disease, by a generalized hypercoagulable state that results in macro- and microvascular thrombosis. Of concern, is the observation that anticoagulation may be inadequate in many circumstances, highlighting the need for alternative or additional therapies. Numerous ongoing studies investigating the pathophysiology of the COVID-19 associated coagulopathy may provide mechanistic insights that can direct appropriate interventional strategies.

Lymphocytic thrombophilic arteritis and cutaneous polyarteritis nodosa: Clinicopathologic comparison with blinded histologic assessment.

BACKGROUND: Lymphocytic thrombophilic arteritis (LTA), or macular lymphocytic arteritis, is defined by a primary lymphocytic vasculitis. However, the nosology of LTA has been controversial, with speculation that it may represent an indolent non-nodule-forming variant of cutaneous polyarteritis nodosa (cPAN). OBJECTIVE: This study compares the clinicopathologic features of patients with LTA or cPAN to assess if these conditions should be considered distinct entities. METHODS: This is a cross-sectional study of all LTA and cPAN cases at a single tertiary center using prospectively collected clinical data and blinded histologic assessment. RESULTS: The study included 17 patients with LTA and 13 patients with cPAN. Clinically, cases of LTA were distinguished by a more widespread pattern of livedo racemosa, which was noninfiltrated and asymptomatic. In contrast, cPAN was associated with localized starburst livedo, purpura, and episodic features including nodules, pain, and large inflammatory ulcers. When patients were separated according to the presence (>5%) or paucity (≤5%) of neutrophils on blinded histology review, they had distinct clinical features and differences in disease course. LIMITATIONS: This was a single-center study. CONCLUSION: Our data support the classification of LTA and cPAN as separate entities rather than a spectrum of the same disorder and highlight the importance of clinicopathologic correlation in distinguishing these conditions.

Appropriateness of thrombophilia testing in patients in the acute care setting and an evaluation of the associated costs.

Thrombophilia testing is rarely recommended in acute care settings due to the high likelihood of false-positive and false-negative results. Inappropriately performing these tests in the acute care setting is associated with inaccurate interpretation and an increased economic burden. In this retrospective analysis, the appropriateness of thrombophilia tests ordered for patients in an acute care setting was evaluated in terms of both clinical utility and economic costs. This analysis included adult inpatients discharged from an academic community medical center from November 1, 2016 to November 1, 2017 who received thrombophilia testing. Patients were stratified into two groups: appropriately tested and inappropriately tested based on data abstracted directly from the electronic health record. The primary outcome, the appropriateness of the tests, was based on published criteria for thrombophilia testing and included concurrent anticoagulation use, patient admitting diagnosis, and/or comorbidities associated with thrombosis risk. The secondary endpoint was the financial burden of inappropriate thrombophilia testing based on assay charges. The analytic sample included 200 patients and 1393 thrombophilia tests. In 179 patients (89.5%), 1168 tests (83.8%) were inappropriately conducted. From 179 patients, tests in 85 were inappropriate due to concurrent anticoagulant use and/or provoked venous thromboembolism (VTE), and tests in 94 were inappropriate due to a lack of 2 or more risk factors for thrombophilia. Only 21 patients (10.5%) had appropriate testing with 225 tests (16.2%). The financial impact of inappropriate testing was estimated as excess charges amounting to $148,151.16/year. Restricting testing to avoid unnecessary risks and costs warrants further analysis.

Assessment of hypercoagulability using thromboelastography predicts advanced status in renal cell carcinoma.

BACKGROUND: Thromboelastography (TEG) has been established as a sensitive method to assess the whole coagulation process. The aim of the study was to evaluate the diagnosis significance of TEG on hypercoagulability in patients suffering renal mass. METHODS: A total of 478 patients were diagnosed with renal tumor by histolopathologic examination and were assigned to three groups. Group A: 79 patients with benign renal tumor; Group B: 317 patients with renal cell carcinoma (RCC, Fuhrman grades I and II); Group C: 82 patients with high-risk RCC (Fuhrman grades III and IV). Subgroup analysis was performed in malignant renal tumor patients according to the TMN classification. The clinical data, whole blood TEG, and conventional coagulation tests were reviewed. RESULTS: There was no statistically significant difference between subgroups in respect to conventional coagulation tests. Hypercoagulablity was marked in Group C according to the TEG parameters. The elevated platelets and fibrinogen is linked with hypercoagulability in renal tumor. The positive correlation was between fibrinogen and MA value (r = .663, P < .05). The pathologic tumor stages were also associated with the TEG parameters. CONCLUSION: Patients suffering advanced RCC are hypercoagulable which can be identified by TEG. MA value could be potential diagnosis indicators for detecting high-grade RCC.

An Audit of Thrombophilia Testing in Patients with Ischemic Stroke or Transient Ischemic Attack: The Futility of Testing.

OBJECTIVES: Many patients admitted with an ischemic stroke or transient ischemic attack (TIA) undergo thrombophilia testing. There is limited evidence to support this practice. We examined the effect of thrombophilia testing on management of patients admitted with an ischemic stroke or TIA. MATERIALS AND METHODS: In this retrospective observational single-center study, we identified patients who were admitted with stroke or TIA and underwent thrombophilia testing over a 45-month period. We reviewed their electronic medical records to assess whether testing affected clinical management, defined as anticoagulation treatment by the time of discharge due to a positive test result. Secondary endpoints included potential misdiagnosis due to false positive results and cost of testing. RESULTS: Testing was performed in 143 patients with a stroke or TIA. Forty-four patients (31%) had at least 1 positive test result. The most common positive tests were an elevated factor VIII activity (18% of patients tested) and decreased protein S activity (11% of patients tested). Both of these tests are subject to acute phase effects. Testing altered clinical management in only 1 patient (1% of total patients tested). Thirty-three patients (75%) have the potential for carrying a misdiagnosis due to a positive test that was never repeated for confirmation or repeated too soon after the initial positive test. The annual cost of testing was approximately $62,000. CONCLUSIONS: Thrombophilia testing in the acute inpatient setting rarely impacted the clinical management of patients admitted with a stroke or TIA. By avoiding thrombophilia testing, both the potential for misdiagnosis and health care costs can be reduced. Therefore, we have discontinued thrombophilia testing in in-patients with a diagnosis of stroke.

Prospective Assessment of Clinical Risk Factors and Biomarkers of Hypercoagulability for the Identification of Patients with Lung Adenocarcinoma at Risk for Cancer-Associated Thrombosis: The Observational ROADMAP-CAT Study.

BACKGROUND: The aim of this prospective study was to identify the most clinically relevant hypercoagulability biomarkers in lung adenocarcinoma patients for elaboration of an improved risk assessment model (RAM) for venous thromboembolism (VTE). SUBJECTS, MATERIALS, AND METHODS: One hundred fifty ambulatory patients with lung adenocarcinoma were prospectively enrolled. Thrombin generation, procoagulant phospholipid-dependent clotting time (Procoag-PPL), tissue factor activity (TFa), factor VIIa (FVIIa), factor V (FV), antithrombin, D-Dimers, P-selectin, and heparanase levels were assessed in platelet-poor plasma at inclusion (baseline) and at the end of the third chemotherapy cycle (third chemotherapy). Cox regression analysis was used to identify independent VTE predictors. RESULTS: At baseline, patients had significantly attenuated thrombin generation, shorter Procoag-PPL, higher levels of TFa, D-Dimers, and heparanase, and lower levels of FVIIa and P-selectin, compared with controls. A significant increase in Procoag-PPL, FV, and FVIIa and a decrease of P-selectin levels were observed between baseline and third chemotherapy. Hospitalization within the last 3 months prior to assessment, time since cancer diagnosis less than 6 months, mean rate index (MRI) of thrombin generation, and Procoag-PPL were independently associated with symptomatic VTE. Accordingly, a prediction model including Procoag-PPL and MRI showed significant discriminating capacity (area under the curve: 0.84). CONCLUSION: Ambulatory patients with lung adenocarcinoma may display pronounced blood hypercoagulability due to decreased Procoag-PPL, increased endothelial cell activation, and increased degradation of fibrin. Incorporation of Procoag-PPL and MRI of thrombin generation may improve the accuracy of a VTE-RAM in the above setting. IMPLICATIONS FOR PRACTICE: The prospective ROADMAP-CAT study identified two biomarkers of hypercoagulability, the procoagulant phospholipid-dependent clotting time (Procoag-PPL) and the mean rate index (MRI) of the propagation phase of thrombin generation assessed with the Calibrated Automated Thrombinoscope, as being clinically relevant for the classification of ambulatory patients with lung adenocarcinoma receiving a maximum of one cycle of chemotherapy into high and intermediate/low risk for venous thromboembolism. Measurement of Procoag-PPL and MRI within 1 month after the administration of the first chemotherapy cycle provides significant accuracy of the assessment. Association of the Procoag-PPL and MRI with the clinical risk assessment model for cancer-associated thrombosis in ambulatory patients with solid tumors (COMPASS-CAT RAM) further improved its accuracy.

Assessment of Hereditary Thrombophilia: Performance of Protein C (PC) Testing.

Protein C (PC) is a plasma Vitamin K-dependent pro-enzyme protein that is synthesized in the liver. Upon activation, PC regulates the coagulation process by neutralizing the procoagulant activities of factors V and VIII in the presence of the cofactor Protein S. PC is a major regulator of the coagulation process. The clotting based Protein C assay, the protocol described in this chapter, quantitates the amount of functional PC present in the specimen in a proportional fashion based on the prolongation of the Activated Partial Thromboplastin Time (APTT). Other methods for assessing PC are also available, including chromogenic and antigenic assays, but protocols for these assays are not provided.

Assessment of Hereditary Thrombophilia: Performance of Protein S (PS) Testing.

Protein S (PS) is a Vitamin K-dependent protein that functions as a cofactor for the regulation of the coagulation system. PS works in conjunction with Activated Protein C to inactivate factors V and VIII. PS circulates in plasma either complexed to the complement protein, C4b Binding Protein or unbound. The unbound (or free) component is the functional form for the regulation of the coagulation system. PS can be measured in plasma by functional activity, the free (or unbound form) or both free and bound fractions (Total PS). The test most widely used for clinical evaluations is the Free PS Antigen assay (which is the surrogate of PS anticoagulant activity) and represents the protocol described in this chapter. The Free PS Antigen assay is an immunologic assay which specifically measures the unbound fraction of PS in test plasma. Other methods for assessing PS are also available, including PS activity and total PS Antigen assays, but protocols for these assays are not provided.

Assessment of Hereditary Thrombophilia: Performance of Antithrombin (AT) Testing.

Antithrombin (AT) is a naturally occurring plasma inhibitor of coagulation, which is a synthesized in the liver. AT inhibits coagulation serine proteases (the enzymatically activated forms of the clotting factors), mainly thrombin (factor IIa) and factor Xa, but also to a lesser extent factors IXa, XIa, and XIIa. Acting alone, AT inhibits coagulation factors, but does this very slowly; however, when coupled with heparin as a cofactor, the speed of inhibition is increased many fold. The AT/Heparin complex is the most powerful naturally occurring anticoagulant in blood. AT levels of <70% of normal can cause significant thrombosis. Low levels of AT are caused by inherited genetic defects or acquired causes from other disease states. Plasma AT levels can be determined using a chromogenic assay with either bovine thrombin or human factor Xa as the enzyme. The generated color generated in the assay is inversely proportional to the concentration of AT in the plasma.

When children become adults and adults become most hypercoagulable after trauma: An assessment of admission hypercoagulability by rapid thrombelastography and venous thromboembolic risk.

BACKGROUND: Thrombelastography (TEG) maximal amplitude (mA) has also been shown to reflect hypercoagulability and increased venous thromboembolism (VTE) risk in adult trauma patients. Based on these previous works, we sought to identify when children become adults with respect to TEG mA values and whether this correlated with VTE risk. METHODS: We evaluated all trauma patients admitted from January 2010 to December 2013 who were highest-level activations. Age was evaluated as a continuous variable, followed by a categorical evaluation. TEG mA values were evaluated as continuous and dichotomous (hypercoagulable, mA ≥ 65 mm). Logistic regression was then constructed controlling for age categories, sex, and injury severity to assess the association with TEG mA values and VTE risk. RESULTS: A total of 7,194 Level 1 trauma patients were admitted during this time frame (819 were <18 years of age). The likelihood of mA equal to or greater than 65 mm remained at 35% to 37% through age 30 years with significant increases observed at ages 31 years to 35 years (45%) and 46 years to 50 years (49%), both p < 0.01. When controlling for injury severity, race, and sex, logistic regression demonstrated that every 5-year increase in age (after age 30 years) was associated with a 16% increased likelihood of hypercoagulability at admission. Beginning with age 1 year, VTE risk remained at 1.5% or less until age 13 years where it increased to 2.3%, increasing again at age 15 years to 5.1%. Two additional significant increases were identified between ages 31 years and 35 years (5.5%) as well as 46 years and 50 years (7.6%), both p < 0.001. Logistic regression demonstrated a 3.4-fold increased risk for VTE among those aged 31 years to 50 years compared with those who are younger than 30 years. The same model noted a 2.3-fold increased risk compared with those who are older than 50 years. CONCLUSION: Beginning at age 13 years, children transition toward adult hypercoagulability, as evidenced by elevated TEG mA values and VTE risk. However, the greatest VTE risk (and highest likelihood of hypercoagulable mA) is among those adults 31 years to 50 years of age. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Thromboelastographic assessment of the contribution of platelets and clotting proteases to the hypercoagulable state of dogs with immune-mediated hemolytic anemia.

BACKGROUND: Hypercoagulability is a well-known feature of canine immune-mediated hemolytic anemia (IMHA) and is believed to increase the risk of thrombosis. This study was undertaken to differentiate the relative contribution of platelets and clotting proteases to this hypercoagulability using thromboelastography (TEG). STUDY DESIGN: Retrospective observational study. METHODS: Thromboelastograms from 27 dogs with IMHA were retrospectively evaluated. Standard TEG parameters (R, K, α, MA), the G value, and the novel parameter delta (Δ) were determined. Hypercoagulability was attributed to the platelet component of hemostasis when there was an increased G value with a normal Δ value. KEY FINDINGS: Nineteen of 27 dogs (70.4%) had ≥ 2 TEG variables suggestive of hypercoagulability, 18 (66.7%) had a hypercoagulable G value, and 11 (40.7%) had a hypercoagulable Δ value. Ten of 27 (37%) samples met the criteria for platelet hypercoagulability. SIGNIFICANCE: Our report documents the derivation and application of the Δ value to differentiate enzymatic from platelet hypercoagulability. Further studies are required to validate the use of these TEG variables in this manner. The hypercoagulable tendency in dogs with IMHA is complex and multifactorial, and in some dogs this hypercoagulability may be attributed primarily to platelet hyper reactivity. Our findings may support the use of anti-platelet drugs in some dogs with IMHA.

Prominent protein Z-induced thrombin inhibition in cirrhosis: a new functional assay for hypercoagulability assessment.

BACKGROUND AND AIMS: Protein Z (PZ) is an anticoagulant that accelerates the inhibitory effect of PZ-dependent protease inhibitor (ZPI) on coagulation factor Xa. We assessed functional status of PZ system in 158 patients with liver cirrhosis and 59 healthy controls. METHODS: Plasma PZ and ZPI levels were measured by enzyme immunoassay. Thrombin generation assays (TGA) were performed with and without thrombomodulin (TM) or PZ, and the ratios were calculated by dividing TGA values with TM or PZ by values without TM or PZ. RESULTS: PZ and ZPI levels were reduced and elevated in advanced cirrhosis, respectively. The lag time ratio-PZ was significantly higher in cirrhosis patients than controls and correlated with the model for end-stage liver disease score. The peak thrombin ratio-PZ and endogenous thrombin potential (ETP) ratio-PZ were significantly lower in cirrhosis patients than controls and correlated with the severity of liver cirrhosis. The peak thrombin ratio-PZ was dramatically reduced in advanced cirrhosis. Cirrhosis patients had a significantly higher ETP ratio-TM than the controls, although the ratio was not correlated with cirrhosis severity. The lag time ratio-PZ and peak time ratio-PZ were significantly correlated with the levels of all coagulation and anticoagulation factors. Interestingly, the lag time ratio-PZ and peak thrombin ratio-PZ were significantly associated with thrombotic events. CONCLUSION: The anticoagulant role of PZ is insufficient in advanced stages of cirrhosis. Our newly developed functional assay for measuring the PZ system is expected to reflect the ongoing hypercoagulability of cirrhosis.

Assessment of coagulation and potential biochemical markers for hypercoagulability in canine hyperadrenocorticism.

BACKGROUND: Anecdotal accounts and limited research suggest that dogs with spontaneous hyperadrenocorticism (HAC) are at risk of developing thromboembolic complications. Detailed description of coagulation status and identification of subsets of dogs at greatest risk would impact therapeutic recommendations for these patients. HYPOTHESIS: A subset of dogs with HAC will have a hypercoagulable tendency as identified by increased procoagulant activity, decreased fibrinolysis, or both. Objective 1: To document the existence of this hypercoagulable tendency in HAC dogs using assays of individual coagulation factors, fibrinolytic activity, and systemic coagulation. Objective 2: To evaluate clinical and biochemical markers in HAC dogs to identify a subset of HAC patients at increased risk of this hypercoagulable tendency. ANIMALS: Seventeen dogs newly diagnosed with HAC. METHODS: Prospective study. Medical history, physical examination findings, routine diagnostic tests, and comprehensive coagulation testing were performed at the time of HAC diagnosis. Coagulation parameters were assessed individually and as panels for each dog. Historical and clinical variables were correlated with coagulation parameters to identify risk factors. RESULTS: The majority (88.2%) of HAC dogs exhibited a hypercoagulable tendency. Abnormalities in 1 coagulation assay did not predict abnormalities in others. Duration of clinical signs of HAC did not predict hypercoagulability. Comorbid conditions or abnormal clinicopathologic parameters that predicted hypercoagulability were not identified. CONCLUSIONS AND CLINICAL IMPORTANCE: Although HAC dogs may demonstrate a hypercoagulable tendency individually and as a group, comorbid conditions or biochemical variables that would predict more severe coagulation abnormalities were not identified.

Etiology and assessment of hypercoagulability with lessons from heparin-induced thrombocytopenia.

Hypercoagulability, or thrombophilia, is a condition associated with an abnormally increased tendency toward blood clotting. Affected individuals are prone to developing venous or arterial thrombosis and often require thromboprophylaxis. Hypercoagulability can be generally classified as either an inherited or acquired condition. Patients with an inherited thrombophilia have genetic variances that alter the quality or quantity of proteins involved with hemostasis. Hypercoagulability may also be acquired and develop as an exaggeration of normal physiologic responses to major tissue injury, or an abnormal response to various prothrombotic clinical factors. Careful assessment for hypercoagulability is important because effective management strategies, often involving anticoagulation, may be available. Heparin-induced thrombocytopenia is an example of an acquired hypercoagulable state that has been well studied and, when recognized, responds to appropriate therapy. In this article, we review the etiology, risks, and assessment of thrombophilia, with emphasis on the clinical lessons learned from heparin-induced thrombocytopenia.

[Cardiovascular risk assessment and intervention in HIV-infected patients]. / Evaluación del riesgo cardiovascular e intervención en los pacientes con VIH.

Because of the increased cardiovascular risk (CVR) in HIV-positive patients, preventive measures are essential, requiring algorithms for risk estimation, such as the Framingham risk equation, the Prospective Cardiovascular Munster Study (PROCAM) algorithm and the Systematic Coronary Risk Evaluation (SCORE) chart. Classical cardiovascular risk factors (CVRF) are closely related to CVR in HIV-infected patients but whether this risk is comparable to that in the general population is unknown. Therefore, these algorithms probably underestimate the risk in these patients. Currently, application of the same strategies as those used in the general population is recommended, without forgetting the specific characteristics of HIV positive patients or the importance of their inflammatory status, which can accelerate the development of arteriosclerosis and lead to an increase in cardiovascular morbidity and mortality. Therefore, in addition to traditional CVRF, biological markers of inflammation could help to identify the patients most at risk of a cardiovascular event. These markers, as well as the diverse techniques for assessment of subclinical atherosclerosis that could help in the early identification of at-risk patients, are reviewed in the present study. Lifestyle changes (healthy diet, smoking cessation, maintaining a healthy weight and daily physical exercise) reduce the probability of a coronary event by up to 80% in the general population. Traditional therapeutic measures (dyslipidemia, hypertension, diabetes mellitus) and those specific to HIV infection (viral suppression, discontinuous treatment, etc.) are reviewed.

Assessment of hypercoagulability markers and lipid levels in postmenopausal women undergoing either oral or transdermal hormone replacement therapy.

BACKGROUND: This study investigated the effect of either oral or transdermal hormone replacement therapy (HRT) on haemostatic, fibrinolytic and lipid profiles in a group of Brazilian women 3 months after beginning treatment by comparing these results with those obtained immediately before HRT. METHODS: Plasma levels of TAT, DDi, F1+2, PC, PS, AT, PAI-1 and serum lipids were determined in blood samples collected from 24 women undergoing oral HRT and from 11 women undergoing transdermal HRT. RESULTS: Significant increases in DDi and F1+2 plasma levels were observed after 3 months of oral HRT, while PS levels decreased. After transdermal HRT, a significant decrease was observed only for AT levels. CONCLUSION: After 3 months of oral HRT and in the absence of major genetic and acquired risk factors, women displayed a predisposition for activation of blood coagulation, and an increased activity of the fibrinolytic system. Oral HRT seemed to be more effective in predisposing haemostatic changes as compared to transdermal.