Thrombotic Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung
Keyword(s):  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Screening Tests ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Complexes

The three main elements in the pathophysiology of thrombosis are endothelial injury, a decrease in blood flow, and an imbalance between procoagulant and anticoagulant factors. The latter element can be either hereditary (e.g., antithrombin deficiency) or acquired (e.g., antiphospholipid syndrome). This review details the assessment of patients with thrombotic disorders, hereditary and acquired hypercoagulable states, and the management of venous thromboembolism. Figures show how the degradation of thrombin-activated factor V Leiden by activated protein C (APC) is significantly slower than that of normal activated factor V (factor Va), leading to enhanced thrombin generation; how normal factor V serves as a cofactor of APC in the inhibition of factor VIIIa, whereas factor V Leiden has a poor cofactor function; and how IgG antibodies recognize platelet factor 4–heparin complexes in heparin-induced thrombocytopenia. Tables list inherited and acquired hypercoagulable states, questions for assessing thrombosis, screening tests for patients with suspected hypercoagulable states, clinical features that suggest thrombophilia, frequency and relative risk of venous thrombosis in selected hypercoagulable states, proposed clinical and laboratory criteria for antiphospholipid syndrome, the classification of antiphospholipid antibodies, the 4Ts scoring system for heparin-induced thrombocytopenia, and general guidelines for the management of patients with venous thromboembolism. This review contains 2 highly rendered figures, 9 tables, and 168 references.

Thrombotic Disorders

2015 ◽  
Author(s):  
Lawrence L K Leung
Keyword(s):  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Screening Tests ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Heparin Complexes

The three main elements in the pathophysiology of thrombosis are endothelial injury, a decrease in blood flow, and an imbalance between procoagulant and anticoagulant factors. The latter element can be either hereditary (e.g., antithrombin deficiency) or acquired (e.g., antiphospholipid syndrome). This review details the assessment of patients with thrombotic disorders, hereditary and acquired hypercoagulable states, and the management of venous thromboembolism. Figures show how the degradation of thrombin-activated factor V Leiden by activated protein C (APC) is significantly slower than that of normal activated factor V (factor Va), leading to enhanced thrombin generation; how normal factor V serves as a cofactor of APC in the inhibition of factor VIIIa, whereas factor V Leiden has a poor cofactor function; and how IgG antibodies recognize platelet factor 4–heparin complexes in heparin-induced thrombocytopenia. Tables list inherited and acquired hypercoagulable states, questions for assessing thrombosis, screening tests for patients with suspected hypercoagulable states, clinical features that suggest thrombophilia, frequency and relative risk of venous thrombosis in selected hypercoagulable states, proposed clinical and laboratory criteria for antiphospholipid syndrome, the classification of antiphospholipid antibodies, the 4Ts scoring system for heparin-induced thrombocytopenia, and general guidelines for the management of patients with venous thromboembolism. This review contains 2 highly rendered figures, 9 tables, and 168 references.

Is APC Resistance a Risk Factor for Venous Thromboembolism in Patients over 70 Years?

2002 ◽  
Vol 88 (10) ◽  
pp. 587-591 ◽  
Author(s):  
Karine Lacut ◽  
Grégoire Le Gal ◽  
Patrick Van Dreden ◽  
Luc Bressollette ◽  
Pierre-Yves Scarabin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Odds Ratio ◽  
Dna Analysis ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Factor V ◽  
Apc Resistance ◽  
Increased Risk ◽  
History Of

SummaryActivated protein C (APC) resistance is the most common risk factor for venous thromboembolism (VTE). Previous studies mostly analysed patients under 70 years and reported a four-to sevenfold increased risk. This case-control study included consecutive patients referred for a clinical suspicion VTE to our medical unit: 621 patients with a well-documented diagnosis (cases) and 406 patients for which the diagnosis was ruled out and who had no personal history of VTE (controls). APC resistance related to factor V Leiden was defined by either a positive DNA analysis or a positive STA® Staclot APC-R assay. Under 70 years, APC resistance was associated with a threefold increased risk of VTE (odds ratio 3.2, 95% CI, 1.7 to 6.0), whereas in patients over 70 years, it appeared to be no longer a strong risk factor (odds ratio 0.8, 95% CI, 0.4 to 1.7). Age appeared as an effectmeasure modifier with a significant interaction (p = 0.005). Our data suggest that APC resistance is not a risk factor for VTE in elderly.

Gene-Gene and Gene-Environment Interactions Determine Risk of Thrombosis in Families With Inherited Antithrombin Deficiency

Blood ◽  
1999 ◽  
Vol 94 (8) ◽  
pp. 2590-2594 ◽  
Author(s):  
H.H. van Boven ◽  
J.P. Vandenbroucke ◽  
E. Briët ◽  
F.R. Rosendaal
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Venous Thromboembolism ◽  
Genetic Risk ◽  
Factor V Leiden ◽  
Genetic Defects ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Gene Environment ◽  
Genetic And Environmental Factors

To analyze inherited antithrombin deficiency as a risk factor for venous thromboembolism in various conditions with regard to the presence or absence of additional genetic or acquired risk factors, we compared 48 antithrombin-deficient individuals with 44 nondeficient individuals of 14 selected families with inherited antithrombin deficiency. The incidence of venous thromboembolism for antithrombin deficient individuals was 20 times higher than among nondeficient individuals (1.1% v 0.05% per year). At the age of 50 years, greater than 50% of antithrombin-deficient individuals had experienced thrombosis compared with 5% of nondeficient individuals. Additional genetic risk factors, Factor V Leiden and PT20210A, were found in more than half of these selected families. The effect of exposure to 2 genetic defects was a 5-fold increased incidence (4.6% per year; 95% confidence interval [CI], 1.9% to 11.1%). Acquired risk factors were often present, determining the onset of thrombosis. The incidence among those with exposure to antithrombin deficiency and an acquired risk factor was increased 20-fold (20.3% per year; 95% CI, 12.0% to 34.3%). In conclusion, in these thrombophilia families, the genetic and environmental factors interact to bring about venous thrombosis. Inherited antithrombin deficiency proves to be a prominent risk factor for venous thromboembolism. The increased risks among those with exposure to acquired risk factors should be considered and adequate prophylactic anticoagulant therapy in high-risk situations seems indicated in selected families with inherited antithrombin deficiency.

Influence of thrombophilia on risk of recurrent venous thromboembolism while on warfarin: results from a randomized trial

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4432-4436 ◽  
Author(s):  
Clive Kearon ◽  
Jim A. Julian ◽  
Michael J. Kovacs ◽  
David R. Anderson ◽  
Philip Wells ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Warfarin Therapy ◽  
Factor V Leiden ◽  
International Normalized Ratio ◽  
Antiphospholipid Antibody ◽  
Factor V ◽  
Antithrombin Deficiency ◽  
Recurrent Venous Thromboembolism ◽  
Prothrombin Gene Mutation ◽  
Recurrent Vte

Abstract We sought to determine whether thrombophilic defects increase recurrent venous thromboembolism (VTE) during warfarin therapy. Six hundred sixty-one patients with unprovoked VTE who were randomized to extended low-intensity (international normalized ratio [INR], 1.5-1.9) or conventional-intensity (INR, 2.0-3.0) anticoagulant therapy were tested for thrombophilia and followed for a mean of 2.3 years. One or more thrombophilic defects were present in 42% of patients. The overall rate of recurrent VTE was 0.9% per patient-year. Recurrent VTE was not increased in the presence of factor V Leiden (hazard ratio [HR], 0.7; 95% CI, 0.2-2.6); the 20210G>A prothrombin gene mutation (HR, 0); antithrombin deficiency (HR, 0); elevated factor VIII (HR, 0.7; 95% CI, 0.1-5.4); elevated factor XI (HR, 0.7; 95% CI, 0.1-5.0), or elevated homocysteine (HR, 0.7; 95% CI, 0.1-5.3), but showed a trend to an increase with an antiphospholipid antibody (HR, 2.9; 95% CI, 0.8-10.5). Compared with patients with no thrombophilic defects, the rate of recurrence was not increased in the presence of one (HR, 0.7; 95% CI, 0.2-2.3) or more than one (HR, 0.7; 95% CI, 0.2-3.4) defect. We conclude that single or multiple thrombophilic defects are not associated with a higher risk of recurrent VTE during warfarin therapy.

Co-inheritance of the 20210A Allele of the Prothrombin Gene Increases the Risk of Thrombosis in Subjects with Familial Thrombophilia

1997 ◽  
Vol 78 (06) ◽  
pp. 1426-1429 ◽  
Author(s):  
M Makris ◽  
F E Preston ◽  
N J Beauchamp ◽  
P C Cooper ◽  
M E Daly ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Protein C ◽  
Factor V Leiden ◽  
Protein S ◽  
Factor V ◽  
Protein C Deficiency ◽  
Antithrombin Deficiency ◽  
Control Subjects ◽  
Increased Risk ◽  
Venous Thromboembolic

SummaryThe presence of the 20210A allele of the prothrombin (PT) gene has recently been shown to be a risk factor for venous thromboembolism. This is probably mediated through increased plasma prothrombin levels. The aim of this study was to compare the prevalence of the prothrombin 20210A allele in control subjects and in subjects with recognised thrombophilia and to establish whether the additional inheritance of the PT 20210A allele is associated with an increased risk of venous thromboembolism. 101 subjects with a history of venous thromboembolism and diagnosed as having either factor V Leiden (R506Q) or heritable deficiencies of protein C, protein S or antithrombin were studied. The prevalence of the PT 20210A allele in this group was compared with the results obtained for 150 control subjects. In addition, the relationships were examined between genetic status and the number of documented thromboembolic episodes, and between plasma prothrombin levels and possession of the PT 20210A allele. 8 (7.9%) of the 101 patients were also heterozygous for the PT 20210A allele. This compares with 0.7% in the control subjects (p = 0.005). After exclusion of patients on warfarin, the mean plasma prothrombin of 113 subjects without 20210A was 1.09 U/ml, as compared with 1.32 U/ml in 8 with the allele (p = 0.0002). Among the 101 patients with either factor V Leiden, protein S deficiency, protein C deficiency or antithrombin deficiency, the age adjusted mean (SD) number of venous thromboembolic episodes at diagnosis was 3.7 (1.5) in those with the PT 20210A allele, as compared with 1.9 (1.1) in those without (p = 0.0001). We have demonstrated that the prevalence of the PT 20210A allele is significantly greater in subjects with venous thrombosis and characterised heritable thrombophilia than in normal control subjects and that the additional inheritance of PT 20210A is associated with an increased risk of venous thromboembolism. We have also confirmed that plasma prothrombin levels are significantly greater in subjects possessing the PT 20210A compared with those who do not.

scholarly journals Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism

2017 ◽  
Vol 2017 ◽  
pp. 1-4
Author(s):  
Samuel Adediran ◽  
Nicole Agostino
Keyword(s):  
Adverse Drug Reaction ◽  
Drug Reaction ◽  
Venous Thromboembolism ◽  
Antiphospholipid Syndrome ◽  
Platelet Factor 4 ◽  
Antiphospholipid Antibody ◽  
Antiphospholipid Antibody Syndrome ◽  
Platelet Factor ◽  
Heparin Induced Thrombocytopenia ◽  
Recurrent Venous Thromboembolism

Heparin-induced thrombocytopenia (HIT) is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS) is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

scholarly journals A Retrospective Cross-sectional Study on Activated Protein C Resistance (Factor V Leiden): an Independent, Gender-dependent Risk Factor for Venous Thromboembolism

2021 ◽  
Author(s):  
Vahideh Takhviji ◽  
Kazem Zibara ◽  
Asma Maleki ◽  
Ebrahim Azizi ◽  
Sanaz Hommayoun ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Protein C ◽  
Activated Protein C ◽  
Factor V Leiden ◽  
Control Group ◽  
Factor V ◽  
Activated Protein C Resistance ◽  
Cross Sectional ◽  
Factor V Leiden Mutation

Abstract Background: Activated protein C resistance (APCR) due to factor V R506Q (Leiden) mutation is a major risk factor in patients with venous thromboembolism. The present study investigated the symptoms patterns and the risk for venous thromboembolism regarding multiple clinical, laboratory, and demographic properties in APCR patients.Material and Methods: A retrospective cross-sectional analysis was conducted on a total of 288 APCR patients with age interval ranging between 1 to 80 years. In addition, 288 control samples, reported healthy after confirmatory tests, were also randomly selected. Demographic information, clinical manifestations, family and treatment history were recorded, and specific tests applied.Results: APCR was found to be 2.3 times significantly more likely in men (OR: 2.1, p < 0.05) than women. The risk of DVT and PE in APCR patients was 4.5 and 3.2 times more than the normal group, respectively (p < 0.05). However, APCR could not be an independent risk factor for arterial thrombosis and pregnancy complications. Moreover, patients were evaluated for thrombophilia panel tests and showed significantly lower protein C and S than the control group and patients without DVT (p<0.0001).Conclusion: Factor V Leiden mutation and APCR abnormality are noticeable independent risk factors for venous thromboembolism. Screening strategies for factor V Leiden mutation in patients undergoing surgery, oral contraceptive medication, and pregnancy cannot be recommended, but a phenotypic test for activated protein C resistance should be endorsed in patients with venous thromboembolism.

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