Phospholipid inhibitors

2011 ◽  
Vol 31 (04) ◽  
pp. 243-250 ◽  
Author(s):  
M. Galli
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Anticardiolipin Antibodies ◽  
Low Molecular Weight ◽  
Obstetrical Complications ◽  
Glycoprotein I ◽  
Long Duration ◽  
Activity Dependent ◽  
Cerebral Arterial Thrombosis

SummaryThe antiphospholipid syndrome (APS) is defined by the association of arterial and/or venous thrombosis and/or pregnancy complications with the presence of at least one among the main antiphospholipid antibodies (aPL) (i. e., Lupus anticoagulants, LA, IgG and/ or IgM anticardiolipin antibodies, aCL, IgG and/or IgM antiβ2-glycoprotein I antibodies, aβ2-GPI). Several clinical studies have consistently reported that LA is a stronger risk factor for both arterial and venous thrombosis compared to aCL and aβ2-GPI. In particular, LA activity dependent on the first domain of β2-GPI and triple aPL positivity are associated with the risk of thrombosis and obstetrical complications.Asymptomatic aPL-positive subjects do not require primary thromboprophylaxis. Venous thromboembolism is the most common initial clinical manifestation of APS. To prevent its recurrence indefinite anticoagulation is recommended. Long duration treatment with warfarin or aspirin is used after a first cerebral arterial thrombosis. Low molecular weight heparin (LMWH) with or without aspirin is recommended to reduce the rate of obstetrical complications of APS pregnant women.

Protein Z Levels Could Help To Predict Obstetrical Complications and Arterial Thrombosis in Patients with Antiphospholipid Antibodies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4081-4081
Author(s):  
Annick Ankri ◽  
Isabelle Martin-Toutain ◽  
Kiarach Goldar ◽  
Marie-Claude Diemert ◽  
Danielle Vauthier-Brouze ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Plasma Protein ◽  
Plasma Levels ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Clinical Event ◽  
Protein Z ◽  
Thrombotic Risk ◽  
Obstetrical Complications ◽  
Thrombotic Tendency

Abstract Introduction: Protein Z (PZ) is a vitamin K dependant plasma protein synthesized by the liver. The precise physiological function of PZ is still unclear: - anticoagulant, the PZ-dependant protease inhibitor complex inhibits factor Xa and acts as a naturally occurring anticoagulant; - procoagulant, PZ promote the assembly of thrombin with PL vesicles- and promote coagulation. In clinical situations, low PZ plasma levels have been associated with bleeding and thrombotic tendency while elevated PZ plasma levels have been linked with ischemic stroke. Antiphospholipid syndrome (APS) is a complex autoimmune thrombotic disorder. Despite specific clinical and laboratory criteria, diagnostic and prognostic tools in patients with APS are limited in their ability to predict adverse outcome in patients with antiphospholipid antibodies (aPLA). Therefore, we hypothesized that PZ could play a role in the thrombotic tendency. Study: to evaluate our hypothesis, we measured PZ plasma concentrations in a case control study including 61 patients with confirmed aPLA with or without APS versus 53 controls. Among the group of patients with APS, 15 had obstetrical complications (OC), 16 had arterial thrombosis (AT) and 11 venous thrombosis (VT). Nineteen patients had aPLA without APS defining the APS(−) group. Plasma PZ antigen concentrations were measured on citrated plasma using the commercial ELISA kit, Asserachrom protein Z, (Diagnostica Stago). Results: PZ plasma levels were normally distributed. Normal PZ concentrations defined as mean ±2 SD were contained between 0.4 and 2.6 μg/mL. No difference was found in mean+ SD between male and female. Two per cents of controls and 18% of patients with venous thrombosis had PZ under 0.4 μg/mL. Forty per cents of patients with OC, 25% with AT and 18% with VT had PZ above 2.6 μg/mL. Plasma protein Z levels measured at least 6 month after any clinical event were significantly higher in APS patients than in controls and APS(−) patients [mean ± SD μg/mL, 2.0 ± 0.9 vs 1.5 ± 0.5 and 1.3 ± 0.5 respectively). According to the clinical complications, PZ concentrations were significantly greater in the group with OC (2.4+0.6 μg/mL) and AT (2.05+0.8 μg/mL) than in controls (1.5+0.5 μg/mL), VT(1.3+0.9 μg/mL) and APS(−) (1.3+0.5 μg/mL) patients [OC vs Controls: p<0.0001; AT vs Controls: p= 0.0047; OC vs AT: p= NS; OC vs APS(−):p< 0.0001; OC vs VT: p= 0.0016, APS(−) vs controls: NS; APS(−) vs VT: NS; VT vs Controls: NS; APS(−) vs AT: p=0.0034; AT vs VT: p= 0.05]. We found an increased relative risk of OC and AT with increasing PZ levels with odds ratios of 7.1 [95% CI: 2.1–23.7] for OC and 2.4 [95% CI: 1.1–5.4] for AT. Conclusion: our study retrospective on a small size sample, indicates that high protein Z plasma could be a high risk for obstetrical complications and a lower risk for arterial thrombosis in aPLA patients. Measure of PZ could help to evaluate obstetrical and thrombotic risk of patients with aPLA. Further prospective studies are needed to confirm our results.

Central Nervous System Infections

2016 ◽  
pp. 453-460
Author(s):  
Pritish K. Tosh ◽  
M. Rizwan Sohail
Keyword(s):  
Risk Factors ◽  
Central Nervous System ◽  
Nervous System ◽  
Venous Thromboembolism ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Lupus Anticoagulant ◽  
Anticardiolipin Antibodies ◽  
Central Nervous System Infections ◽  
Glycoprotein I

Thrombophilia refers to the tendency for thromboembolism (ie, having risk factors for thromboembolism), which may be inherited or acquired. The presence of increasing numbers of risk factors further increases the risk of venous thromboembolism (VTE). Antiphospholipid antibodies (lupus anticoagulant, anticardiolipin antibodies, and anti–β‎2-glycoprotein I antibodies) and hyperhomocysteinemia are risk factors not only for VTE but also for arterial thrombosis.

Lupus Anticoagulants and Thrombosis: Clinical Association of Different Coagulation and Immunologic Tests

2000 ◽  
Vol 84 (12) ◽  
pp. 1012-1016 ◽  
Author(s):  
Jeffrey Dlott ◽  
Francesca Norbis ◽  
Luisa Ruggeri ◽  
Linda Cler ◽  
Douglas Triplett ◽  
...  
Keyword(s):  
At Risk ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Colloidal Silica ◽  
Anticardiolipin Antibodies ◽  
Clotting Time ◽  
Lupus Anticoagulants ◽  
Glycoprotein I ◽  
Patients At Risk ◽  
Kaolin Clotting Time

SummaryThe dilute Russell’s viper venom time (dRVVT) and the kaolin clotting time (KCT) are two among the most commonly used coagulation tests for the detection of lupus anticoagulants. The dRVVT seems superior to the KCT in identifying LA-positive patients at risk of thrombosis. However, this relationship is greatly influenced by both the source of reagents and the instrumentation employed to carry out the assays. Therefore, 4 dRVVTs (“home-made” dRVVT, DVV test, Bioclot LA, LA Screen), and one KCT (Kaoclot) were performed in two centers and compared for their retrospective correlation with the thrombotic complications of 72 patients with a previously established diagnosis of lupus anticoagulants. Two other assays (“home-made” KCT, and Colloidal Silica Clotting Time, CSCT) were performed in one of the two centers, and compared with Kaoclot for their clinical correlations in the same population of patients, 44 of whom (61%) had suffered from arterial and/or venous thrombosis. A rather good degree of inter-laboratory and inter-assay correlations of the different tests was found. However, a statistically significant association with thrombosis was found only with the coagulation profile generated using the “homemade” dRVVT. When the commercially available dRVVTs were used, none of the coagulation profiles remained associated with thrombosis. When the assays were analyzed separately, the association with thrombosis was statistically significant for LA screen (p = 0.0019), DVV test (p = 0.0043), and Bioclot (p = 0.0255), and of borderline significance for the “home-made” dRVVT (p = 0.0503) in one center. This last assay was also significantly associated with thrombosis in the other center (p = 0.0139). When venous and arterial thrombosis were considered separately, DVV test was statistically associated with venous thrombosis in both centers (p = 0.0076 and p = 0.0187, respectively), and LA screen in one center (p = 0.0303). No dRVVT was found to correlate with arterial thrombosis. Kaoclot, Colloidal Silica Clotting Time, and the “home-made” KCT did not correlate with thrombosis. The prevalence of IgG and/or IgM antibodies to cardiolipin, β2-glycoprotein I and prothrombin were 74%, 86% and 85%, respectively. Increased titers of IgG anticardiolipin antibodies were associated with arterial thrombosis (p = 0.0375), whereas IgM anti-β2-glycoprotein I antibodies were associated with venous thrombosis (p = 0.0433). In conclusion, these retrospective data support the notion that the dRVVT, rather than other coagulation or ELISA tests, are able to identify lupus anticoagulant-positive patients at risk of thrombosis. This property appears common to several commercially available dRVVT kits, making this type of assay the ideal target of future efforts of laboratory standardization.

scholarly journals Antiphospholipid antibodies and thrombosis: association with acquired activated protein C resistance in venous thrombosis and with hyperhomocysteinemia in arterial thrombosis

2004 ◽  
Vol 92 (12) ◽  
pp. 1312-1319 ◽  
Author(s):  
Jeannine Kassis ◽  
Carolyn Neville ◽  
Joyce Rauch ◽  
Lambert Busque ◽  
Erika Chang ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Protein C ◽  
Complete Blood Count ◽  
Tertiary Care ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Activated Protein C Resistance ◽  
Increased Risk

SummaryAlthough antiphospholipid antibodies (aPL) are associated with thrombosis, it is not known who with aPL is at higher risk for thrombosis. It was the aim of this cross-sectional study to investigate how thrombophilic factors contribute to venous or arterial thrombosis in aPL-positive individuals. In outpatient test centres at two tertiary care hospitals, two hundred and eight (208) persons requiring aPL testing were matched by age, gender and centre to 208 persons requiring a complete blood count. Persons were classified as aPL-positive (having anticardiolipin, lupus anticoagulant and/or anti-β2-glycoprotein I antibodies) or aPL-negative. Several thrombophilic factors were studied using logistic regression modelling. Results showed that the aPL-positive group had three-fold more events (37%) than the aPL-negative group (12%). In unadjusted analyses, clinically important associations were observed between factor V Leiden and venous thrombosis, hyperhomocysteinemia and arterial thrombosis, and activated protein C resistance (APCR) and venous thrombosis (OR, 95% CI = 4.00, 1.35-11.91; 4.79, 2.03-11.33; and 2.03, 1.03-3.97, respectively). After adjusting for recruitment group, persons with both APCR and aPL had a three-fold greater risk (OR, 95% CI = 3.31, 1.30-8.41) for venous thrombosis than those with neither APCR nor aPL. Similarly, after adjusting for hypertension, family history of cardiovascular disease, gender and recruitment group, persons with both hyperhomocysteinemia and aPL had a five-fold increased risk (OR, 95% CI = 4.90, 1.37-17.37) for arterial thrombosis compared to those with neither risk factor. In conclusion, APCR phenotype and hyperhomocysteinemia are associated with a higher risk of venous and arterial thrombosis, respectively, in the presence of aPL.

scholarly journals Hemostasis system and immunomorphologic state of placenta under presence of antiphospholipid antibodies in plasma with consideration of their class and pregnancy outcome

2004 ◽  
Vol 53 (1) ◽  
pp. 22-26
Author(s):  
N. G. Kosheleva ◽  
L. В. Zubzhitskaia ◽  
О. N. Arzhanova ◽  
О. V. Tyshkevich ◽  
Y. Gromyko ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Recurrent Miscarriage ◽  
Anticardiolipin Antibodies ◽  
Research Groups ◽  
Hemostasis System ◽  
Autoimmune Antibodies ◽  
Glycoprotein I ◽  
Tissue Damages

The present study was undertaken to investigate hemostasis system of 197 women with recurrent miscarriage: Analysis placentas by immunomorphology are studied of 41 women and of 52 women with autoimmune antibodies to 2-glycoprotein-I (2-GPI) in placenta. There was exposed hyperactivation platelets blood of all women with antiphospholipid antibodies irrespective of groups with significantly was increased at the beginning of pregnancy and progressed with growing gestation. As result of investigation it is determined certain connection between outcome of pregnancy and activation degree platelets blood in vasculars. Was found absence influence anticardiolipin antibodies (aCL) on plasmocoagulative link hemostasis. The circulation of lupus anticoagulant (LA) was accompanied indication of hypercoagulation. In all research groups was determined significant oppression of fibrinolisis. Analysis placentas by immunomorphology was determined significantly tissue damages with LA and 2-GPI-dependent aCL.

Determinants of Risk for Venous and Arterial Thrombosis in Primary Antiphospholipid Syndrome and in Antiphospholipid Syndrome with Systemic Lupus Erythematosus

2009 ◽  
Vol 36 (6) ◽  
pp. 1195-1199 ◽  
Author(s):  
ADRIANA DANOWSKI ◽  
MARIO NEWTON LEITÃO de AZEVEDO ◽  
JOSE ANGELO de SOUZA PAPI ◽  
MICHELLE PETRI
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Venous Thrombosis ◽  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Arterial Thrombosis ◽  
Pregnancy Loss ◽  
Fold Increase ◽  
Systemic Lupus ◽  
Hereditary Thrombophilia

Objective.Antiphospholipid syndrome (APS) is characterized by thrombosis (venous and arterial) and pregnancy loss in conjunction with the lupus anticoagulant, IgG or IgM anticardiolipin, or IgG or IgM anti-ß2-glycoprotein I. In most series, only a minority of patients with antiphospholipid antibodies develop a clinical manifestation.Methods.A cross-sectional study of consecutive patients in the Hopkins Lupus Center was performed. Interviews were done and records were reviewed for the following variables: gender, ethnicity, hypertension, triglycerides, cholesterol, smoking, diabetes mellitus, homocysteine, cancer, hepatitis C, hormone replacement therapy/oral contraceptives, hereditary thrombophilia, anticardiolipin antibodies IgG, IgM and IgA, and lupus anticoagulant (LAC). Our aim was to identify risk factors associated with thrombosis and pregnancy loss in patients with antiphospholipid antibodies.Results.A total of 122 patients (84% female, 74% Caucasian) were studied. Patients were divided into 3 groups: primary APS, APS associated with systemic lupus erythematosus, and patients with systemic lupus erythematosus (SLE) with antiphospholipid antibodies but no thrombosis or pregnancy loss. Venous thrombosis was associated with high triglycerides (p = 0.001), hereditary thrombophilia (p = 0.02), anticardiolipin antibodies IgG > 40 (p = 0.04), and LAC (p = 0.012). Hypertriglyceridemia was associated with a 6.4-fold increase, hereditary thrombophilia with a 7.3-fold increase, and anticardiolipin IgG > 40 GPL with a 2.8-fold increase in the risk of venous thrombosis. Arterial thrombosis was associated with hypertension (p = 0.008) and elevated homocysteine (p = 0.044). Hypertension was associated with a 2.4-fold increase in the risk of arterial thrombosis. No correlations were found for pregnancy loss.Conclusion.The frequency of thrombosis and pregnancy loss is greater in APS associated with SLE than in primary APS. Risk factors differ for venous and arterial thrombosis in APS. Treatment of hypertension may be the most important intervention to reduce arterial thrombosis. Elevated triglycerides are a major associate of venous thrombosis, but the benefit of treatment is not known. Hereditary thrombophilia is an associate of venous but not arterial thrombosis, making it cost-effective to investigate only in venous thrombosis.

scholarly journals Spontaneous arterial thrombosis in a patient with advanced ovarian clear cell cancer: a case report and literature review

2020 ◽  
Vol 48 (6) ◽  
pp. 030006052092674
Author(s):  
Jing Chen ◽  
Huimin Sun ◽  
Minrong Wu ◽  
Xiaolin Zhong ◽  
Yuqin Zhang
Keyword(s):  
Ovarian Cancer ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Clear Cell ◽  
Clear Cell Carcinoma ◽  
Cell Cancer ◽  
Underlying Disease ◽  
Low Molecular Weight ◽  
Vein Thrombosis ◽  
Deep Vein

Patients with ovarian cancer are often in a hypercoagulable state and have a high risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. However, arterial thrombosis is relatively rare in ovarian cancer. We report a case a 46-year-old woman with ovarian clear cell carcinoma who developed arterial and venous thrombosis in the lower extremities as the first manifestation. Her arterial thrombosis-related ischemic symptoms were not responsive to anticoagulant treatment of low-molecular-weight heparin, but improved after neoadjuvant chemotherapy and surgery. Therefore, we hypothesize that the optimal therapy for arterial thrombosis in ovarian cancer is treatment for the underlying disease (i.e., ovarian cancer). A thorough investigation is required to determine the relationships between arterial thrombosis and ovarian cancer and antithrombotic treatments for ovarian cancer related-arterial thrombosis.

scholarly journals Concomitant Deep Venous Thrombosis, Femoral Artery Thrombosis, and Pulmonary Embolism after Air Travel

2014 ◽  
Vol 2014 ◽  
pp. 1-4
Author(s):  
Salim Abunnaja ◽  
Marshall Clyde ◽  
Andrea Cuviello ◽  
Robert A. Brenes ◽  
Giuseppe Tripodi
Keyword(s):  
Pulmonary Embolism ◽  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Femoral Artery ◽  
Arterial Thrombosis ◽  
Arterial Occlusion ◽  
Air Travel ◽  
Artery Thrombosis ◽  
Long Duration ◽  
Paradoxical Embolus

The association between air travel and deep venous thrombosis and/or pulmonary embolism “economy-class syndrome” is well described. However, this syndrome does not describe any association between long duration travel and arterial thrombosis or coexistence of venous and arterial thrombosis. We present a case of concomitant deep venous thrombosis, acute femoral artery thrombosis, and bilateral pulmonary embolisms in a patient following commercial air travel. Echocardiogram did not reveal an intracardiac shunt that may have contributed to the acute arterial occlusion from a paradoxical embolus. To our knowledge, this is the first report in the literature that associates air traveling with both arterial and venous thrombosis.

Anticardiolipin Antibodies Block the Inhibition by β2-Glycoprotein I of the Factor Xa Generating Activity of Platelets

1993 ◽  
Vol 70 (02) ◽  
pp. 342-345 ◽  
Author(s):  
Wei Shi ◽  
Beng H Chong ◽  
Philip J Hogg ◽  
Colin N Chesterman
Keyword(s):  
Antiphospholipid Antibodies ◽  
Lupus Anticoagulant ◽  
Fetal Loss ◽  
Factor Xa ◽  
Anticardiolipin Antibodies ◽  
Recurrent Fetal Loss ◽  
Glycoprotein I ◽  
Activated Platelets ◽  
Inhibit Factor

SummaryAntiphospholipid antibodies, defined either by lupus anticoagulant (LA) activity or positive anticardiolipin immunoabsorbent assay (ACA) are associated with a predisposition to thromboses, recurrent fetal loss or thrombocytopenia. The mechanisms for these predispositions remain undefined. We have enriched immunoglobulin fractions from two patient plasmas to obtain antibodies with LA activity but no ACA, or conversely, with ACA positivity but no LA, in order to investigate in vitro characteristics which might explain a thrombotic propensity. β2-glycoprotein I (β2-GPI), the plasma cofactor required for ACA binding to negatively charged phospholipid, has previously been shown to inhibit prothrombinase generation in the presence of activated platelets (8). We now report that β2-GPI, at physiological concentrations, inhibits the generation of factor Xa in the presence of activated gel-filtered platelets. Further, ACA interferes with this inhibition, resulting in protracted, unopposed factor Xa generation. This interference with β2-GPI, a natural anticoagulant component of plasma, is potentially prothrombotic. LA immunoglobulins behave differently and inhibit factor Xa generation in a manner similar to β2-GPI. These findings provide the basis for a previously unsuspected mechanism for thrombosis in patients with aPL.

Antiphosphatidylinositol Antibody in Deep Venous Thrombosis Patients

2003 ◽  
Vol 16 (1) ◽  
pp. 61-66 ◽  
Author(s):  
P. Panarelli ◽  
M.P. Viola-Magni ◽  
E. Albi
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Solid Phase ◽  
Protein Complexes ◽  
Anticardiolipin Antibodies ◽  
Anionic Phospholipids ◽  
Positive Antibody

Antiphospholipid antibodies are a heterogeneous group of immunoglobulins with specificity for a number of phospholipids, phospholipid-binding proteins and phospholipid-protein complexes. The association between antiphospholipid antibodies and a variety of pathologic disorders, such as arterial and venous thrombosis and recurrent pregnancy loss is recognized as Antiphospholipid Syndrome. The immunoassay currently used to detect antiphospholipid antibodies is the anticardiolipin test. Anticardiolipin antibodies are believed to be polyspecific antibodies that cross-react with all the anionic phospholipids. Therefore, testing only for anticardiolipin antibodies does not always permit detection of all antiphospholipid antibodies, specially when only IgG are evaluated. In a selected population of 74 idiopathic and secondary deep venous thrombosis patients, IgG anticardiolipin, antiphosphatidylinositol and antiphosphatidylserine antibodies were detected by solid-phase immunoassays. Our results show that by testing for each antiphospholipid family, many patients, not evidenced by the standard anticardiolipin assay, were found to be antiphospholipid-positive. The anticardiolipin positive patients have always low, moderate or high levels of antiphospholipid antibodies, suggesting that the antiphospholipid positivity is predictive of anticardiolipin positivity. It should be noted that the patients with only antiphosphatidylinositol positive antibody have a story of nervous system pathology. The meaning of these results is at present under discussion.

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