Reference values of coagulation assays performed for thrombophilia screening after a first venous thrombosis and their intra-patient associations

2022 ◽  
Author(s):  
Jean-Christophe Gris ◽  
Éva Cochery-Nouvellon ◽  
Chloé Bourguignon ◽  
Éric Mercier ◽  
Sylvie Bouvier ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Reference Values ◽  
Coagulation Assays ◽  
Thrombophilia Screening

scholarly journals A Female with Recurrent Venous Thrombosis

1970 ◽  
Vol 13 (1) ◽  
pp. 100-102
Author(s):  
Aparna Das ◽  
AKM Aminul Hoque ◽  
Ratan Dasgupta ◽  
Ahmedul Kabir ◽  
Gobinda Banik ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Venous Thrombosis ◽  
Protein S ◽  
Protein S Deficiency ◽  
Low Level ◽  
S Deficiency ◽  
Thrombophilia Screening ◽  
Recurrent Venous Thrombosis

A 50- year-old female was presented with recurrent venous thrombosis with ischemic stroke due to protein S deficiency. Other causes of recurrent venous thrombosis were excluded by different investigations. We only found low level of protein S. In most of the cases, thrombophilia screening is not usaally done. So, this report will illustrate the importance of thrombophlia screening in patient having recurrent venous thrombosis. DOI: http://dx.doi.org/10.3329/jom.v13i1.10085 JOM 2012; 13(1): 100-102

Thrombophilia screening in the acute phase of deep venous thrombosis

2009 ◽  
Vol 69 (6) ◽  
pp. 633-635
Author(s):  
Anna-Marie Bloch Munster ◽  
Johannes Jakobsen Sidelmann ◽  
Jørgen Gram
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Acute Phase ◽  
Thrombophilia Screening

Thrombophilia screening in the acute phase of deep venous thrombosis

2009 ◽  
Vol 69 (6) ◽  
pp. 633-635 ◽  
Author(s):  
Anna-Marie Bloch Münster ◽  
Johannes Jakobsen Sidelmann ◽  
Jørgen Gram
Keyword(s):  
Venous Thrombosis ◽  
Deep Venous Thrombosis ◽  
Acute Phase ◽  
Thrombophilia Screening

New Approach for Evaluation of Quantitative Risk Factors of Venous Thromboembolism Using Individualized Reference Values.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4022-4022
Author(s):  
Rainer B. Zotz ◽  
Andrea Gerhardt ◽  
Rudiger E. Scharf
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Venous Thrombosis ◽  
Reference Values ◽  
Protein S ◽  
Healthy Controls ◽  
New Approach ◽  
Increased Risk ◽  
Risk Determinants ◽  
Protein S Activity

Abstract The evaluation of quantitative risk factors of venous thromboembolism is characterized by several unsolved problems. The majority of quantitative components of hemostasis are dependent on age, sex, and hormone intake. The cut-off values determined in case-control studies depend on the specific patient/control group and can not be generalized on individuals with other characteristics. Furthermore, the approach does not give reference values dependent on age, sex, and hormone intake which are necessary for risk estimations in clinical practice. To overcome these disadvantages, we used a multiple regression analysis to create a system of reference values which change continuously depending on age, sex, and hormone intake according to the parameter distribution in healthy controls and calculated the relative risk of hemostatic components (729 patients with first VTE and 675 healthy controls). A significantly increased risk for venous thrombosis was associated with deficiency of protein S activity (odds ratio (OR) 2.8 to 6.1, p=0.0007), free protein S concentration (OR 2.7 to 20.4, p=0.0001), protein C activity (OR 3.2 to 9.4, p=0.0001), antithrombin activity (OR up to 75, p=0.0001), and increased levels of fibrinogen (OR 3.8, p=0.0001), factor VIII:C (OR 3.3, p=0.0001), factor IX (OR 2.3, p=0.0001), factor XI (OR 2.9, p=0.0001), vWF activity (OR 2.4, p=0.0001), and vWF antigen (OR 3.5, p=0.0001). In contrast to previously published studies, this new approach gives clinically important cut-off values dependent on age, sex, and hormone intake and allows to identify patients at increased risk for venous thrombosis on an individualized basis. Particularly parameters which are highly dependent on age and sex, like protein S activity, can be characterized more precisely using the described procedure. This comprehensive analysis demonstrates that, apart from well-known risk determinants, deficiency of protein S and increased values of FI, FVIII:C, FIX, FXI, vWF, and vWF-Ag are risk determinants predicting venous thrombosis.

Evidence-based indications for thrombophilia screening

VASA ◽  
2008 ◽  
Vol 37 (1) ◽  
pp. 19-30 ◽  
Author(s):  
Lindhoff-Last ◽  
Luxembourg
Keyword(s):  
Venous Thromboembolism ◽  
Family History ◽  
Venous Thrombosis ◽  
Arterial Thrombosis ◽  
Pregnancy Loss ◽  
Late Pregnancy ◽  
Evidence Based ◽  
Increased Risk ◽  
Thrombophilia Screening ◽  
History Of

Thrombophilic defects have been shown to be associated with an increased risk of venous thrombosis, fetal loss, and gestational complications. The knowledge about the clinical relevance of thrombophilic defects is increasing, and evidence-based indications for thrombophilia screening are therefore discussed in this review. Selective thrombophilia screening based on previous personal and/or family history of venous thromboembolism is more cost-effective than universal screening in all patient groups evaluated. In the majority of patients with acute venous thrombosis, the results of thrombophilia screening do not influence the duration of oral anticoagulation. The only patient population who clearly profits from thrombophilia screening in this situation are patients with a newly diagnosed antiphospholipid syndrome, because prolonged anticoagulation can avoid the high incidence of recurrence in this patient population. Because of the increased risk of venous thrombosis during pregnancy and the puerperium, thrombophilia screening is indicated in selected patients with a previous history of venous thrombosis or a positive family history. Significant associations with early and late pregnancy loss are observed for carriers of the heterozygous factor V Leiden mutation, the heterozygous prothrombin-mutation G20210A and anticardiolipin antibodies, while protein S deficiency is significantly associated with late pregnancy loss. Antithrombotic drugs like UFH, LMWH or low-dose aspirin may have a potential therapeutic benefit in patients with recurrent pregnancy loss and thrombophilia, but placebo-controlled, multicenter trials are urgently needed to clarify this issue. Although a supra-additive effect for the risk of venous thrombosis is observed between oral contraceptives and some thrombophilias, the absolute incidence of venous thromboembolism is low in premenopausal women and mass screening strategies are therefore unlikely to be effective. While antiphospholipid antibodies are known to be associated with arterial thrombosis, screening for heritable thrombophilias is not useful in arterial thrombosis, although subgroup analysis indicates that they may play a role particularly in young patients and children.

scholarly journals Methods to monitor the therapy oral anticoagulants: the current problems.

2018 ◽  
Vol 96 (2) ◽  
pp. 101-105
Author(s):  
J. Antovic ◽  
Tat'yana B. Kondratieva
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thrombosis ◽  
Gold Standard ◽  
Laboratory Tests ◽  
Oral Anticoagulants ◽  
Coagulation Assays ◽  
Urgent Surgery ◽  
Routine Monitoring ◽  
Highly Effective ◽  
Effective Drugs

Oral anticoagulants antivitamin-K (ОАС - AVК) are highly effective drugs that prevent the development of venous thrombosis, stroke in atrial fibrillation. Routine monitoring is not recommended for DOAC. If measurements are necessary LC-MS/MS is the gold standard. The classical coagulation assays, PT-INR and aPTT, have no or very limited utility. The absence of the ability of simple laboratory tests in emergent or urgent surgery or procedures still remains unresolved.

Plasma Constitutive Serum Amyloid A4 Is Procoagulant and Is Elevated in Venous Thrombosis Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3486-3486
Author(s):  
John H. Griffin ◽  
Jose A. Fernandez ◽  
Ranjeet Kumar Sinha ◽  
Darlene J. Elias ◽  
Hiroshi Deguchi
Keyword(s):  
Venous Thrombosis ◽  
Plasma Levels ◽  
Thrombin Generation ◽  
Conflicts Of Interest ◽  
Oxidized Ldl ◽  
Serum Amyloid ◽  
Procoagulant Activity ◽  
Clinical Event ◽  
Coagulation Assays ◽  
Sds Page

Abstract Regulation of thrombin generation by the factors (F) Xa:Va complex is key for achieving hemostasis and avoiding thrombosis, i.e., for the hemostatic balance. Plasma lipoproteins and minor abundance lipids can influence the hemostatic balance. For example, oxidized LDL is procoagulant, HDL is anticoagulant as an APC:protein S cofactor, certain glycosphingolipids are anticoagulant cofactors, and acyl carnitines and lysosulfatides inhibit the FXa;Va complex. To identify novel lipoprotein factors that affect FXa:Va activity (prothrombinase (IIase) activity), lipoprotein fractions from ten adult varied subjects were made by ultracentrifugation and, following dialysis into Hepes-buffered saline, screened for their procoagulant activity in purified IIase assays. Each lipoprotein fraction, except that from one subject (#939) with only 22% activity, similarly enhanced thrombin generation by IIase. SDS page analysis of these lipoprotein fractions showed a very low level of one protein band (14 kDa) for subject #939. Proteomics analysis of that band from normal lipoprotein fractions implied this 14 kDa band was constitutive serum amyloid A4 (SAA4). The biologic functions of SAA4 are unclear. To assess its procoagulant activity, recombinant 14 kDa SAA4 was studied in various coagulation assays. When SAA4 was added to IIase assays, it caused a robust procoagulant activity in the presence of FVa but not in the absence of FVa. Plasma-based coagulation assays, done without phospholipids added, were also used, including FXIa-induced thrombin generation, and FXa-1-stage clotting assays. Recombinant SAA4 was mildly or strongly procoagulant in these plasma-based assays. SAA4 dose-dependently shortened the FXa-induced clotting time from 320 sec to 55 sec; and SAA4 increased thrombin generation by 15 % in normal plasma and by 85 % in plasma from subject #939. Direct interactions between recombinant SAA4 and purified FXa were studied using SPR (Octet Red™) with immobilized-FXa subjected to titrations of SAA4. Kinetic constants gave a value for Kd apparent of 25 nM for SAA4 binding to FXa. Thus, SAA4 binds FXa and is procoagulant by enhancing IIase activity. We then assessed potential clinical relevance of SAA4's procoagulant activity. SAA4 is a plasma apolipoprotein, mainly made in the liver, with a constant plasma level of 4 µM. It is not an acute phase protein, unlike SAA1 and SAA2. SAA4 contains 112 residues and plasma contains two monomeric isoforms (14 kDa and 19 kDa) due to the absence or presence of N-glycosylation at Asn-76. The plasma levels of monomeric SAA4 (combined 14 and 19 kDa isoforms) were determined by quantitative IR immunoblotting (non-reduced SDS PAGE) using the Odyssey IR imaging system (Li-Cor Biosciences) for 110 venous thrombosis (VTE) subjects and 110 matched controls from the Scripps Venous Thrombosis Registry. The Registry samples were from male and female adults without cancer or lipid altering drugs who were < 55 yrs old and gave fasting blood samples > 3 months after the clinical event (see H. Deguchi et al, BLOOD 2015). When the relative fluorescence unit (RFU) values for SAA4 14 and 19 kDa monomer bands for 110 normal subjects were normalized to a median of 100 %, patients with VTE had significantly higher plasma levels of monomeric SAA4 (median 116.4 RFU vs median 100 RFU, p=0.0005) (see median values in Figure). The odds ratio (OR) for the 75%-ile cut-off was 2.1 (95% CI = 1.2 - 3.8, p=0.01) (see Figure). Thus, SAA4 monomers are elevated in VTE patients compared to matched controls for the Scripps Venous Thrombosis Registry. Further studies are needed to replicate this finding and to gather more data towards deciphering whether the link between elevated SAA4 and VTE is causal, consequential or coincidental. However, the fact that recombinant 14 kDa SAA4 binds FXa and is procoagulant in purified IIase assays and in plasma-based clotting assays provides biological plausibility for a causal prothrombotic role for SAA4. These findings also raise the possibility that SAA4 procoagulant activity might contribute to normal hemostasis. Further studies are needed to clarify the details for the procoagulant effects of SAA4 on coagulation pathways. In summary, these results show that elevated monomeric plasma levels of SAA4 are strongly linked to VTE in adults (< 55 yrs old) and that SAA4 itself is a potential enhancer of thrombin generation in plasma. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

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