https://journal.chestnet.org/article/S0012-3692(12)60129-9/pdf

Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

March 5, 2019 e1 WRITING GROUP MEMBERS Emelia J. Benjamin, MD, ScM, FAHA, Chair Paul Muntner, PhD, MHS, FAHA, Vice Chair Alvaro Alonso, MD, PhD, FAHA Marcio S. Bittencourt, MD, PhD, MPH Clifton W. Callaway, MD, FAHA April P. Carson, PhD, MSPH, FAHA Alanna M. Chamberlain, PhD Alexander R. Chang, MD, MS Susan Cheng, MD, MMSc, MPH, FAHA Sandeep R. Das, MD, MPH, MBA, FAHA Francesca N. Delling, MD, MPH Luc Djousse, MD, ScD, MPH Mitchell S.V. Elkind, MD, MS, FAHA Jane F. Ferguson, PhD, FAHA Myriam Fornage, PhD, FAHA Lori Chaffin Jordan, MD, PhD, FAHA Sadiya S. Khan, MD, MSc Brett M. Kissela, MD, MS Kristen L. Knutson, PhD Tak W. Kwan, MD, FAHA Daniel T. Lackland, DrPH, FAHA Tené T. Lewis, PhD Judith H. Lichtman, PhD, MPH, FAHA Chris T. Longenecker, MD Matthew Shane Loop, PhD Pamela L. Lutsey, PhD, MPH, FAHA Seth S. Martin, MD, MHS, FAHA Kunihiro Matsushita, MD, PhD, FAHA Andrew E. Moran, MD, MPH, FAHA Michael E. Mussolino, PhD, FAHA Martin O’Flaherty, MD, MSc, PhD Ambarish Pandey, MD, MSCS Amanda M. Perak, MD, MS Wayne D. Rosamond, PhD, MS, FAHA Gregory A. Roth, MD, MPH, FAHA Uchechukwu K.A. Sampson, MD, MBA, MPH, FAHA Gary M. Satou, MD, FAHA Emily B. Schroeder, MD, PhD, FAHA Svati H. Shah, MD, MHS, FAHA Nicole L. Spartano, PhD Andrew Stokes, PhD David L. Tirschwell, MD, MS, MSc, FAHA Connie W. Tsao, MD, MPH, Vice Chair Elect Mintu P. Turakhia, MD, MAS, FAHA Lisa B. VanWagner, MD, MSc, FAST John T. Wilkins, MD, MS, FAHA Sally S. Wong, PhD, RD, CDN, FAHA Salim S. Virani, MD, PhD, FAHA, Chair Elect On behalf of the American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee

Heart Disease and Stroke Statistics—2019 Update: A Report From the American Heart Association

https://www.onlinelibrary.wiley.com/doi/epdf/10.1111/j.1538-7836.2006.01753.x

International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).

ALAT
: alanine aminotransferase
ASAT
: aspartate aminotransferase
APAH
: associated pulmonary arterial hypertension
BAS
: balloon atrial septostomy
BMPR2
: bone morphogenetic protein receptor 2
BNP
: brain natriuretic peptide
BPA
: balloon pulmonary angioplasty
BREATHE
: Bosentan

/pdf/2015-esc-ers-guidelines-for-the-diagnosis-and-treatment-of-y26yabnnom.pdf

2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT).

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Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together in a single document the most up-to-date statistics related to heart disease, stroke, and the cardiovascular risk factors listed in the AHA’s My Life Check - Life’s Simple 7 (Figure1), which include core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure [BP], and glucose control) that contribute to cardiovascular health. The Statistical Update represents …

Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association.

background Chronic thromboembolic pulmonary hypertension (CTPH) is associated with considerable morbidity and mortality. Its incidence after pulmonary embolism and associated risk factors are not well documented. methods We conducted a prospective, long-term, follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism. Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and, if supportive findings were present, ventilation–perfusion lung scanning and pulmonary angiography. CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg, respectively; pulmonary-capillary wedge pressure was normal; and there was angiographic evidence of disease. results The cumulative incidence of symptomatic CTPH was 1.0 percent (95 percent confidence interval, 0.0 to 2.4) at six months, 3.1 percent (95 percent confidence interval, 0.7 to 5.5) at one year, and 3.8 percent (95 percent confidence interval, 1.1 to 6.5) at two years. No cases occurred after two years among the patients with more than two years of follow-up data. The following increased the risk of CTPH: a previous pulmonary embolism (odds ratio, 19.0), younger age (odds ratio, 1.79 per decade), a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion), and idiopathic pulmonary embolism at presentation (odds ratio, 5.70). conclusions CTPH is a relatively common, serious complication of pulmonary embolism. Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed.

Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism.

Among the so called ‘antiphospholipid antibodies’, the presence of Lupus Anticoagulant (LA) is associated with thrombosis-related events and defines the antiphospholipid syndrome. The role of anti-cardiolipin (aCL) antibodies and anti-human s 2-glycoprotein I (a s 2GPI) antibodies is less striking. Since the problem of standardization for these tests is far from resolved, we evaluated whether the combination of results (antiphospholipid laboratory profiles) could help to better classify these patients. Over a 6-year period, 618 consecutive subjects (55% of whom had previous documented thrombosis-related events) were referred to our clinic for Antiphospholipid antibody detection. LA was detected according to internationally accepted recommendations. ACL and a s 2GPI antibodies were detected by Enzyme- Linked-Immunosorbent Assay (ELISA). Patients’ records were reviewed for the presence of previous thromboembolic events or obstetric complications according to Sapporo’s clinical criteria for the diagnosis of antiphospholipid syndrome (APS) and each patient underwent a physical examination.When individual tests were considered in a multivariate analysis which took into account age, gender, the presence of SLE or other autoimmune diseases and established risk factors for venous and arterial thromboembolism, LA (Odds Ratio 4.4, Confidence Interval 1.5–13.3) and a s 2GPI antibodies (Odds Ratio 2.9, Confidence Interval 1.1–7.5) but not aCL antibodies (Odds Ratio 1.2, Confidence Interval 0.5–2.7) were found to be independent risk factors for thrombosis-related events.When antiphospholipid antibody profiles instead of individual test positivity were analyzed in the above mentioned model, triple positivity resulted a strong independent risk factor (Odds Ratio 33.3, Confidence Interval 7.0–157.6), retaining its significance when the association with venous or arterial thromboembolism was considered. Double positivity with negative LA was close to significance for thrombosis- related events (Odds Ratio 2.2, Confidence Interval 1.0–5.2, p=0.056) and highly significant risk factor for obstetric complications (Odds Ratio 10.8, Confidence Interval 2.9–40.8). Other combinations did not reach statistical significance. The mean level of IgG a s 2GPI antibodies was statistically higher in triple positive profile and might account for positive LA. As compared to a single test, the analysis of a complete antiphospholipid antibody profile can better determine patients at risk.

Antibody profiles for the diagnosis of antiphospholipid syndrome.

Anti-phospholipid (aPL) antibodies are defined as antibodies detected in systems employing phospholipids (PL). This general definition is misleading as it comprises a large group of autoimmune phospholipid-reactive antibodies that are directed against specific phospholipid-binding plasma proteins, such as β2-glycoprotein I (β2GPI) and prothrombin. Definition of phospholipid-reacting antibodies according to the plasma protein against which they are directed appears more appropriate and could be useful in understanding clinical events and pathogenic mechanisms. Using ELISA systems we have studied the presence of antibodies directed against specific phospholipid-binding proteins in a series of 22 patients with thrombosis and phospholipid-reactive antibodies of the IgG isotype. High levels of anti-β2GPI IgG were detected in all 22 patients. Normal values were calculated on the basis of OD values at 405 nm (OD405) obtained for 22 age- and sex-matched healthy subjects (cut off value = 0.401). Levels of anti-β2GPI antibodies were linearly correlated with those of cardiolipin-reactive (aCL) antibodies. Eleven out of 22 patients (50%) had values of anti-prothrombin antibodies exceeding the cut-off value of 0.250. No relationship was found between the levels of anti-β2GPI and anti-prothrombin antibodies. Tests for antibodies against two natural inhibitors of blood coagulation, protein C and protein S, revealed elevated levels of anti-protein C IgG and anti-protein S IgG in 4 and 12 patients, respectively. A highly significant correlation between anti-protein C IgG and anti-protein S IgG values as well as between antibody titers against the two studied natural coagulation inhibitors and anti-prothrombin IgG was found. When comparing patients positive for aCL and presence or absence of a previous thrombotic episode (aCL+/T+ vs aCL+/T-), the positivity of anti-P2GPI IgG was found to be statistically associated with thrombosis. Conversely, among patients with previous thromboembolism with or without aCL (aCL+/T+ vs aCL-/T+) the positivity of anti-β2GPI IgG was strictly associated with the positivity of aCL, thus identifying the aPL antibody syndrome. These data demonstrate that anti-β2GPI antibodies are a marker of “autoimmune” thrombosis. Anti-prothrombin antibodies are not a marker of thrombosis and are closely associated with antibodies to protein C and protein S.

Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies

The antiphospholipid antibodies (aPL) present in autoimmune disorders are associated with thromboembolic episodes, and their binding to phospholipids (PL) is mediated by a plasma cofactor, beta 2-glycoprotein I (beta 2GPI). Both PL and beta 2GPI seem necessary for binding, thus indicating that the two components comprise the epitope against which aPL are directed. Using an anti-beta 2GPI antibody ELISA with the antigen adsorbed onto polyvinylchloride (PVC) plates, we detected high antibody titres in 12 out of 12 plasma from patients with the antiphospholipid syndrome. No or very low positivity was obtained when the same ELISA was carried out in polystyrene (PST) plates, while an increasing positivity was found when processed (i.e. more hydrophilic) or COOH-surface PST plates were used. When beta 2GPI dependent IgG-aPL were purified using agarose-immobilized cardiolipin, 4 out of 4 preparations were highly positive in anti-beta 2GPI antibody ELISA using PVC plates, while beta 2GPI was not fully recognized by aPL-IgG when adsorbed onto PST plates. These findings demonstrate that aPL are, in fact, anti-beta 2GPI antibodies directed against a cryptic epitope which is expressed when beta 2GPI is bound to anionic phospholipid, or another suitable surface.

Autoimmune antiphospholipid antibodies are directed against a cryptic epitope expressed when beta 2-glycoprotein I is bound to a suitable surface.

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2007.02454.x

Alessandra Biasiolo

Papers

Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism.

Antibody profiles for the diagnosis of antiphospholipid syndrome.

Autoantibodies to phospholipid-binding plasma proteins in patients with thrombosis and phospholipid-reactive antibodies

Autoimmune antiphospholipid antibodies are directed against a cryptic epitope expressed when beta 2-glycoprotein I is bound to a suitable surface.

Survey of lupus anticoagulant diagnosis by central evaluation of positive plasma samples