Arterial and Venous Thrombosis as a Symptom of Antiphospholipid Syndrome – A Noticeable Analysis from the Past.

Antiphospholipid syndrome (APS), defined as combination of venous and/or arterial thrombosis as well as obstetric complications with antiphospholipid antibodies presence in blood, is an example of acquired thrombophilia. The thrombotic episodes in the APS course are highly recurrent, with an increasing incidence with years after secondary anticoagulant prophylaxis cessation. In between 2005-2011 a study was conducted in Poznań, Poland, with the aim to find a correlation between actual APS diagnostic guidelines (criteria from Sydney’2006) and the clinical feature of thrombosis in this syndrome with coexistence of inherited thrombophilia and risk factors for cardio-vascular disease included. Additionally, a selection of the highest thromboembolic risk group was made among asymptomatic patients with antiphospholipid antibodies (APA) detected to compare with APS patients. An association between a type of laboratory test confirming the longtime APA presence and thrombotic risk was analyzed as well. The follow up had lasted for meanly 47 months and included 75 patients (50 females and 25 males) at the mean age of 43, divided into three groups (25 persons each): I – with asymptomatic APA, IIA – with arterial episodes in the history and IIB – with past venous complications in the course of APS. The majority of them comprised persons with primary APS or with asymptomatic APA (aAPA) - without any other autoimmune diseases. The laboratory tests included: lupus anticoagulant (LA) according to the 3-step procedure recommended by ISTH (International Society on Thrombosis and Hemostasis), anticardiolipin (ACA) – of IgG and IgM class and anti-β2-glycoprotein I (aβ 2 GPI) – of IgG class, both with the cut-off value of 99 percentile. D-dimer and fibrinogen concentration, protein C and antithrombin activity, activated protein C resistance, free protein S concentration, factor VIII were further analyzed. Among comorbidities and risk factors for venous and arterial thrombosis, there was significantly more frequent incidence of autoimmune diseases in the asymptomatic group of people compared to patients after thromboembolic episodes. Most often the aAPA presence was confirmed in the LA tests – the majority of positive results appeared among patients with asymptomatic course and with past venous thrombosis as well and less frequently - in the group of arterial episodes in the history. Any significant differences were found in the reference to the incidence of thrombotic episodes in the retrospective assessment of symptomatic patients and prospective – in the whole investigated group, although the time of their occurrence after beginning of observation period almost doubled in people with past thromboembolic episodes, comparing to the earlier asymptomatic persons.

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

Thrombosis and Haemostasis ◽

10.1160/th04-03-0138 ◽

2004 ◽

Vol 92 (12) ◽

pp. 1312-1319 ◽

Cited By ~ 11

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.

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

The Journal of Rheumatology ◽

10.3899/jrheum.081194 ◽

2009 ◽

Vol 36 (6) ◽

pp. 1195-1199 ◽

Cited By ~ 105

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.

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Prevention of thrombosis in antiphospholipid syndrome

Hematology ◽

10.1182/asheducation-2016.1.707 ◽

2016 ◽

Vol 2016 (1) ◽

pp. 707-713 ◽

Cited By ~ 7

Author(s):

Wendy Lim

Keyword(s):

Risk Factors ◽

Primary Prevention ◽

Secondary Prevention ◽

Antiphospholipid Syndrome ◽

Antithrombotic Therapy ◽

Thrombotic Risk ◽

Pregnancy Morbidity ◽

Asymptomatic Patients ◽

Risk Patients ◽

Thrombotic Complications

Abstract Antiphospholipid syndrome (APS) is an acquired autoimmune condition characterized by thrombotic events, pregnancy morbidity, and laboratory evidence of antiphospholipid antibodies (aPL). Management of these patients includes the prevention of a first thrombotic episode in at-risk patients (primary prevention) and preventing recurrent thrombotic complications in patients with a history of thrombosis (secondary prevention). Assessment of thrombotic risk in these patients, balanced against estimated bleeding risks associated with antithrombotic therapy could assist clinicians in determining whether antithrombotic therapy is warranted. Thrombotic risk can be assessed by evaluating a patient’s aPL profile and additional thrombotic risk factors. Although antithrombotic options for secondary prevention of venous thromboembolism (VTE) have been evaluated in clinical trials, studies in primary prevention of asymptomatic aPL-positive patients are needed. Primary prevention with aspirin may be considered in asymptomatic patients who have a high-risk aPL profile, particularly if additional risk factors are present. Secondary prevention with long-term anticoagulation is recommended based on estimated risks of VTE recurrence, although routine evaluation of thrombotic risk can assist in determining whether ongoing anticoagulation is warranted. Studies that stratify thrombotic risk in aPL-positive patients, and patients with APS evaluating antithrombotic and non-antithrombotic therapies will be useful in optimizing the management of these patients.

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

Blood ◽

10.1182/blood.v108.11.4081.4081 ◽

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.

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Identifying additional risk factors for arterial and venous thrombosis among pediatric antiphospholipid antibodies carriers

Lupus ◽

10.1177/09612033211002256 ◽

2021 ◽

pp. 096120332110022

Author(s):

Elizabeth Sloan ◽

Tracey Wright ◽

Yu Zuo

Keyword(s):

Risk Factors ◽

Connective Tissue ◽

Venous Thrombosis ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Pediatric Patients ◽

Univariate Analysis ◽

Connective Tissue Diseases ◽

Additional Risk ◽

Potential Predictor

Background Antiphospholipid antibodies (aPL) have been extensively reported in children, but investigations into thrombotic risks associated with aPL positivity in pediatric patients is scarce. Positive aPL are not uncommon in pediatric connective tissue diseases (CTD), but identification and management of these patients is challenging due to lack of validated criteria and a paucity of data. In this study, we identify potential additional risk factors for thrombosis in a unique cohort of pediatric aPL positive carriers. Methods Retrospective chart review was performed on 491 pediatric patients with CTD seen in our institution from 2001 to 2019. Patients without persistently moderate to high titer aPL at least 12 weeks apart were excluded. Univariate analysis was performed to evaluate correlation between different risk factors and thrombotic events. Results Seventy-one aPL positive children with underlying CTD are included in this cohort. The majority (87%) are female and of Hispanic ethnicity (56%). Mean age of the cohort at the diagnosis of connective tissue disease is 12.7 (SD 2.6) years, and mean age of first positive aPL is 13.3 (SD 2.5) years. Average length of follow-up is 4.3 (SD 2.5) years. Four (5.6%) patients experienced arterial thrombosis, and 11 (15.5%) had venous thrombosis. Fifty-seven (80.3%) patients did not have any thromboembolic events. Among traditional risk factors and signs of endothelial injury, only Raynaud’s phenomena demonstrated significant association with arterial thrombosis (OR = 8.4, 95%CI 1.13–111, P = 0.039), and hypertension or anti-hypertensive use demonstrated significant association with venous thrombosis (OR = 8.387, 95%CI 1.2 – 94, P = 0.02). Conclusion Data from our cohort suggest that Raynaud’s phenomenon is a potential predictor of arterial thrombosis while the presence of hypertension or anti-hypertensive medication use is a potential predictor of venous thrombosis in aPL positive pediatric carriers. Further studies investigating pediatric aPL profiles and risk factors for development of thrombosis are needed to help guide clinicians in caring for these challenging patients.

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State-of-the-Art Review: Activated Protein C Resistance: Clinical Implications

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/107602969700300103 ◽

1997 ◽

Vol 3 (1) ◽

pp. 25-32 ◽

Cited By ~ 7

Author(s):

Bengt Zöller ◽

Andreas Hillarp ◽

Björn Dahlbäck

Keyword(s):

Risk Factors ◽

Venous Thrombosis ◽

Protein C ◽

Activated Protein C ◽

Protein S ◽

Factor V ◽

Thrombotic Risk ◽

Western Countries ◽

Apc Resistance ◽

Increased Risk

The discovery of inherited resistance to activated protein C (APC) as a major risk factor for venous thrombosis has dramatically improved our understanding of the pathogenesis of venous thrombosis. In a majority of cases, APC resistance is associated with a single point mutation in the factor V gene (FV) that results in substitution of arginine, R, at position 506 by glutamine, Q. (FV:Q506). The mutation renders factor Va partially resistant to degradation by APC. A functional APC resistance test, which includes predilution of the patient plasma with factor V-deficient plasma, is found to be 100% sensitive and specific for the presence of FV:Q506 and is useful as a screening assay. Carriers of the FV:Q506 allele have increased thrombin generation, resulting in hypercoagulability and a lifelong increased risk of venous thrombosis. In Western countries, APC resistance due to the FV mutation is present in 20-60% of thrombosis patients and in 1-15% of healthy controls, whereas the mutation is virtually absent from ethnic groups other than Caucasians. This may explain the high incidence of venous thrombosis in Western countries. The thrombotic risk in APC-resistant individuals may be further increased by other genetic defects, e.g., protein C or protein S deficiency, and by exposure to circumstantial risk factors, e.g., oral contraceptives, pregnancy, immobilization, and surgery. The question is thus raised as to whether general screening for APC resistance before circumstantial risk factors occur is warranted in Western countries. Key Words: Factor V—APC resistance-Protein C-Protein S—Thrombosis—Mutation.

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SAT0194 LACK OF EFFICACY OF RIVAROXABAN IN THE TREATMENT OF ANTIPHOSPHOLIPID SYNDROME AND CLINICAL SIGNIFICANCE OF ANTIPHOSPHOLIPID ANTIBODIES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3822 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1039.2-1039

Author(s):

S. Vardanyan ◽

K. Ginosyan ◽

V. Vardanyan ◽

A. Sargsyan ◽

A. Simonyan

Keyword(s):

Venous Thrombosis ◽

Antiphospholipid Syndrome ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Pregnancy Loss ◽

Positive Association ◽

Recurrent Thrombosis ◽

Double Positive ◽

Increased Risk ◽

Single Positive

Background:Chronic anticoagulation with vitamin K antagonists (VKA) is the standard treatment to prevent thrombotic events in antiphospholipid syndrome (APS). But in recent years treatment schemes began to include rivaroxaban. Use of direct oral anticoagulants (DOAC) is an attractive and often preferred alternative to VKAs in other medical settings owing to greater ease of use, fewer food and drug interactions, and lower bleeding risks [1].However, according to last guidelines, rivaroxaban should not be used in patients with triple aPL positivity due to the high risk of recurrent events [2].Objectives:1.To determine the risk of recurrent thrombosis in single or double positive APS patients treated with rivaroxaban.2.Find out possible association between presence of particular antiphospholipid antibodies or high level of lupus anticoagulant (LA) and type of vascular events.Methods:33 patients with confirmed APS (25 female (75.8%), 8 male (24.2%), mean age 43.2±11.6 years) were included in the study. 17 (51.5%) of investigated patients had primary APS, in remaining 16 (48.5%) APS was included in the framework of SLE. 18 (54.5%) patients were treated with warfarin 2.5-7.5 mg/daily, 15 (45.5%) patients - with rivaroxaban 20mg/daily for a follow-up period of 12 months. The data is introduced as odds ratios (OR) with 95% confidence interval (CI). The results were considered significant when p <0.05.Results:At baseline 21 (63.6%) patients had history of arterial thrombosis, 10 (30.3%) - venous thrombosis, 17 (51.5%) - pregnancy loss. According to results of serum immunology check, 29 (87.9%) patients were anticardiolipin antibody (ACA) positive, 9 (27.3%) - LA positive, 19 (57.6%) - anti-ß2-glycoprotein antibodies (anti-ß2-gp) positive; 20 (60.6%) patients were double positive (12 (36.4%) of them had positive ACA and anti-ß2-gp, 6 (18.2%) - ACA and LA, and 2 (6.1%) - anti-ß2-gp and LA), 4 (12.1%) patients were triple positive.No association between vascular event and/or pregnancy loss in patients with single positive ACA was found. We have found positive association between arterial thrombosis and single positive anti-ß2-gp (OR /CI 95%/ = 5.0 /2.08 – 23.06/, p< 0.05), positive association between positive LA and venous thrombosis (OR /CI 95%/ = 10 /1.7-57.7/, p< 0.05), strong positive association between positive LA and thromboembolism of pulmonary artery (OR /CI 95%/ = 46.0 /4.0-525.1/, p< 0.001), negative association between positive LA and pregnancy loss (OR /CI 95%/ =0.06 /0.03 – 0.1/, p< 0.01).Risk of thrombosis and/or pregnancy loss was not significantly increased in double positive patients, but triple positive patients had increased risk of venous thrombosis (OR /CI 95%/ =9.4 /3.2 – 105.8/, p<0.04).Recurrent thrombosis was detected in 16 patients: 2 patients (12.5%) were on warfarin, 14 (87.5%) - on rivaroxaban (10 (71.4%) arterial thrombosis, 4 (28.6%) venous thrombosis).No association between warfarin 2.5-7.5 mg/daily and occurrence of recurrent thrombosis was detected. An association between use of warfarin and increased risk of bleeding was found, but the risk was not significant (OR /CI 95%/ = 7.0 /0.7 – 66/, p= 0.09). Rivaroxaban 20 mg/daily was associated with recurrent thrombosis not only for triple positive patients (p< 0.02), but also in double positive patients (OR /CI 95%/ = 21.3 /1.8 – 251/, p< 0.04).Conclusion:Rivaroxaban does not prevent recurrent thrombosis not only in triple positive patients, but also in single and double positive APS patients. Type of antiphospholipid antibodies can be predictive for the type of further vascular event.References:[1]Vittorio Pengo, Gentian Denas, Giacomo Zoppellaro et al.Rivroxaban vs warfarin in high risk patients with antiphospholipid syndrome, Blood. 2018 Sep 27; 132(13); 1357-1358.[2]EULAR recommendations for the management of antiphospholipid syndrome in adults, Annals of the Rheumatic Diseases/ Volume 78: Issue 10:1296-1304.Disclosure of Interests:None declared

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Factor VII and Fibrinogen Levels as Risk Factors for Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1642511 ◽

1994 ◽

Vol 71 (06) ◽

pp. 719-722 ◽

Cited By ~ 182

Author(s):

T Koster ◽

F R Rosendaal ◽

P H Reitsma ◽

P A van der Velden ◽

E Briët ◽

...

Keyword(s):

Risk Factors ◽

Deep Vein Thrombosis ◽

Venous Thrombosis ◽

Arterial Thrombosis ◽

Plasma Fibrinogen ◽

Factor Vii ◽

Thrombotic Risk ◽

Vein Thrombosis ◽

Thrombosis Risk ◽

Deep Vein

SummaryThe plasma levels of coagulation factor VII and fibrinogen are well known risk factors for arterial thrombosis. We tested the hypothesis that this association also exists for venous thrombosis. Additionally, MspI and Haelll polymorphisms in the factor VII and fibrinogen genes have recently been reported to be associated with the concentration of both proteins in the plasma. However, no conclusion could be drawn with respect to an increase or decrease in thrombosis risk. We undertook a population-based case-control study, in which 199 patients with a first, objectively confirmed episode of deep vein thrombosis, aged less than 70, and without a known malignant disorder were compared to 199 age-and sex-matched healthy controls, to evaluate the clinical importance of these reported findings.For fibrinogen we found a positive level-related association between the plasma fibrinogen level and thrombotic risk. Subjects with a plasma fibrinogen greater than 5 g/1 had an almost 4-fold increase of thrombosis risk. The frequencies of the different Haelll genotypes were out of balance only for the thrombosis patients, with a deficit of the H1H2 genotype. Possession of an H1H2 genotype was associated with a 40% reduction in thrombosis risk.For factor VII, neither the plasma level nor the MspI genotypes were related to deep vein thrombosis, although possession of a M2 allele was clearly associated with significantly lower factor VII levels. The frequencies of the Mspl-genotypes were the same for patients and control subjects and, exhibited Hardy-Weinberg equilibrium.Our results support that plasma fibrinogen, a determinant of arterial thrombosis is also a risk factor for venous thrombosis, while factor VII plasma concentration is unrelated to deep vein thrombosis, which is supported by the data from the DNA analysis of polymorphisms.

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Identifying Additional Risk Factors for Thrombosis and Pregnancy Morbidities Among Antiphospholipid Antibodies Carriers

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029618755946 ◽

2018 ◽

Vol 24 (6) ◽

pp. 980-985 ◽

Cited By ~ 3

Author(s):

Yu Zuo ◽

Jennifer Fan ◽

Ravi Sarode ◽

Song Zhang ◽

Una E. Makris ◽

...

Keyword(s):

Risk Factors ◽

Venous Thrombosis ◽

Antiphospholipid Antibodies ◽

Arterial Thrombosis ◽

Clinical Manifestations ◽

Reproductive Age ◽

Potential Candidate ◽

Additional Risk ◽

Potential Predictor ◽

Independent Association

The evaluation of thrombotic and pregnancy risks associated with antiphospholipid antibodies (aPL)in individual patients without antiphospholipid syndrome (APS) clinical manifestation is challenging. Our aim is to identify additional risk factors or potential candidate “second hits” for APS clinical events in a large cohort of ethnically diverse aPL-positive patients. We included 219 consecutive aPL-positive patients who attended clinic at our institution. All patients had at least 1 persistent high titer (≥99 percentiles) aPL. Independent risk factors for thrombosis and pregnancy morbidities among patients with positive aPL were evaluated. When assessing risk factors associated with pregnancy morbidities, only female controls of reproductive age (age ≤45) were used. Pearson χ2 analysis and multivariable logistic regression were used to evaluate correlation between different risk factors and clinical manifestations. Of the 219 aPL-positive patients, 120 (54.8%) patients had criteria APS clinical manifestations and 99 patients did not. A total of 46.1% were Caucasian, 26.4% of African descent, 16.9% Hispanic, 1.8% Asian, and 8.7% were unspecified. Among traditional risk factors and signs of endothelial injury, only hypertension demonstrated an independent association with arterial thrombosis (odds ratio [OR] = 3.826, 95% confidence interval [CI]: 1.597-9.167, P = .0026), and lupus anticoagulant (LA) demonstrated an independent association with venous thrombosis (OR = 3.308, 95% CI: 1.544-7.085, P = .0021). None of the evaluated risk factors demonstrated a significant association with pregnancy morbidity. Hypertension is a potential predictor of arterial thrombosis and the presence of LA is a potential predictor of venous thrombosis in aPL-positive patients.

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