scholarly journals Role of ADAMTS13, VWF and F8 genes in deep vein thrombosis

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258675
Author(s):  
Maria Teresa Pagliari ◽  
Andrea Cairo ◽  
Marco Boscarino ◽  
Ilaria Mancini ◽  
Emanuela Pappalardo ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Low Frequency ◽  
Activity Levels ◽  
Adamts13 Activity ◽  
Common Variants ◽  
Single Nucleotide Variants ◽  
Variable Threshold ◽  
Vein Thrombosis ◽  
Deep Vein

Background We previously described the association between rare ADAMTS13 single nucleotide variants (SNVs) and deep vein thrombosis (DVT). Moreover, DVT patients with at least one rare ADAMTS13 SNV had a lower ADAMTS13 activity than non-carriers. Aims To confirm ADAMTS13 variants association with DVT and reduced plasma ADAMTS13 activity levels in a larger population. To investigate the role of VWF and F8 variants. Methods ADAMTS13, VWF and F8 were sequenced using next-generation sequencing in 594 Italian DVT patients and 571 controls. Genetic association testing was performed using logistic regression and gene-based tests. The association between rare ADAMTS13 variants and the respective plasmatic activity, available for 365 cases and 292 controls, was determined using linear regression. All analyses were age-, sex- adjusted. Results We identified 48 low-frequency/common and 272 rare variants. Nine low-frequency/common variants had a P<0.05, but a false discovery rate between 0.06 and 0.24. Of them, 7 were found in ADAMTS13 (rs28641026, rs28503257, rs685523, rs3124768, rs3118667, rs739469, rs3124767; all protective) and 2 in VWF (rs1800382 [risk], rs7962217 [protective]). Rare ADAMTS13 variants were significantly associated with DVT using the burden, variable threshold (VT) and UNIQ (P<0.05), but not with C-ALPHA, SKAT and SKAT-O tests. Rare VWF and F8 variants were not associated with DVT. Carriers of rare ADAMTS13 variants had lower ADAMTS13 activity than non-carriers (ß -6.2, 95%CI -11,-1.5). This association was stronger for DVT patients than controls (ß -7.5, 95%CI -13.5,-1.5 vs. ß -2.9, 95%CI -10.4,4.5). Conclusions ADAMTS13 and VWF low-frequency/common variants mainly showed a protective effect, although their association with DVT was not confirmed. DVT patients carrying a rare ADAMTS13 variants had slightly reduced ADAMTS13 activity levels, but a higher DVT risk. Rare VWF and FVIII variants were not associated with DVT suggesting that other mechanisms are responsible for the high VWF and FVIII levels measured in DVT patients.

Rare Coding Single Nucleotide Variants of ADAMTS13 Are Associated with Deep Vein Thrombosis in a Next-Generation Sequencing Association Study

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 107-107
Author(s):  
Luca Andrea Lotta ◽  
Giacomo Tuana ◽  
Jin Yu ◽  
Ida Martinelli ◽  
Mark Wang ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Allele Frequency ◽  
Genomic Dna ◽  
Low Frequency ◽  
Adamts13 Activity ◽  
Single Nucleotide Variants ◽  
Base Pairs ◽  
Single Nucleotide ◽  
Vein Thrombosis ◽  
Deep Vein

Abstract Abstract 107 The considerable genetic predisposition to deep vein thrombosis (DVT) is only partially accounted for by known genetic risk variants. Genome-wide association studies investigating hundreds of thousands of common single nucleotide variants (SNVs) identified a number of associations, but missing heritability remains. Rare (i.e. minor allele frequency below 1%) and low-frequency (i.e. minor allele frequency below 5%) SNVs of the coding area may be responsible for at least part of this missing heritability. In order to investigate this, we sequenced 700,000 base pairs of genomic DNA including the protein coding exons and intron-exon boundaries of 186 hemostatic/pro-inflammatory genes. Indexed genomic DNA libraries were co-captured on NimbleGen HD2 2.1M-probe chips and capture products were sequenced on SOLiD 4 platforms. More than 70 billion base-pairs of raw sequence data were produced to sequence the target area with a median redundancy of 45X in 94 thrombophilia-negative patients with DVT and 98 controls. Most of the 4366 SNVs identified were rare, novel and nonsynonymous indicating pathogenetic potential. We tested the association of coding SNVs in the ADAMTS13 and VWF genes, encoding two interconnected proteins with fundamental roles in hemostasis. Sequencing of the two genes yielded 109 variants, 108 SNVs and a c.8241_8442del frameshift deletion in exon 51 of VWF. Being a carrier of rare coding (prevalence in DVT: 17% [n=16]; prevalence in controls 4% [n=4]; odds ratio [OR]: 4.8; 95% confidence interval [CI]: 1.6–15.0), rare nonsynonymous (prevalence in DVT: 11% [n=10]; prevalence in controls 3% [n=3]; OR: 3.8; 95% CI: 1.0–14.2) or low-frequency coding (prevalence in DVT: 36% [n=34]; prevalence in controls 23% [n=23]; OR: 1.9; 95% CI: 1.0–3.5) SNVs of ADAMTS13 was associated with DVT. Carrying rare or low-frequency SNVs of VWF was not associated with DVT. The 11 different rare missense variants of ADAMTS13 found in DVT patients had never been described in association with congenital thrombotic thrombocytopenic purpura. Patients carrying at least one ADAMTS13 mutation of the categories associated with DVT had lower plasmatic levels of ADAMTS13 activity compared to patients without mutations. The change in ADAMTS13 activity was −7% (95% CI: −24 to 10%) for patients with rare coding ADAMTS13 mutations, −12% (95% CI: −30 to 6%) for patients with rare nonsynonymous mutations and −29% (95% CI: −52 to −6%) for patients with missense mutations predicted to be damaging for protein function by SIFT. Our results uncover for the first time a link between ADAMTS13, an important regulator of hemostasis implicated in microvascular thrombosis, and DVT. Disclosures: No relevant conflicts of interest to declare.

Post-thrombotic syndrome after deep vein thrombosis: The role of follow-up Doppler ultrasound

2021 ◽  
Vol 156 (5) ◽  
pp. 251-252
Author(s):  
Francisco Galeano-Valle ◽  
Jorge del-Toro-Cervera ◽  
Pablo Demelo-Rodríguez
Keyword(s):  
Deep Vein Thrombosis ◽  
Doppler Ultrasound ◽  
Vein Thrombosis ◽  
Post Thrombotic Syndrome ◽  
Deep Vein

scholarly journals ROLE OF COLOUR DOPPLER IN EVALUATION OF ACUTE DEEP VEIN THROMBOSIS OF LOWER LIMB

2019 ◽  
Vol 8 (8) ◽  
pp. 512-516
Author(s):  
Vijay Bahadur Singh ◽  
Punya Pratap Singh ◽  
Rajesh Malik ◽  
Lovely Kaushal ◽  
Vijay Verma ◽  
...  
Keyword(s):  
Deep Vein Thrombosis ◽  
Lower Limb ◽  
Colour Doppler ◽  
Vein Thrombosis ◽  
Acute Deep Vein Thrombosis ◽  
Deep Vein

Role of D-Dimer Assay in Diagnosis of Deep Vein Thrombosis

2014 ◽  
Vol 9 (4) ◽  
pp. 187-194
Author(s):  
M.G. Vashist ◽  
S. Deswal ◽  
M. Verma ◽  
S. Kharb
Keyword(s):  
Deep Vein Thrombosis ◽  
Vein Thrombosis ◽  
Deep Vein ◽  
D Dimer

scholarly journals Clot retraction facilitates clot lysis

Blood ◽  
1981 ◽  
Vol 57 (1) ◽  
pp. 44-48 ◽  
Author(s):  
RC Carroll ◽  
JM Gerrard ◽  
JM Gilliam
Keyword(s):  
Deep Vein Thrombosis ◽  
Cytochalasin B ◽  
Platelet Rich Plasma ◽  
Clot Lysis ◽  
Clot Retraction ◽  
Similar Extent ◽  
Platelet Poor Plasma ◽  
Vein Thrombosis ◽  
Deep Vein

Abstract Platelet facilitation of clot lysis was studied using the dilute clot lysis assay, a standardized assay for fibrinolysis shown to correlate with the development of postoperative deep vein thrombosis. Clots prepared from dilute platelet poor plasma showed prolonged clot lysis when compared with clots prepared in a similar fashion from dilute platelet rich plasma. Since in the presence of platelets clot retraction or contraction occurred, we evaluated a possible direct contribution of retraction to clot lysis. Dilute platelet poor plasma clots were compacted by centrifugation, to a similar extent as that achieved during clot retraction in dilute platelet rich plasma. These clots now lysed at a rate that approached that seen with dilute platelet rich plasma clots. Using an alternate alternate approach, dilute platelet rich plasma clots were treated with cytochalasin B to prevent clot retraction. Such clots now showed prolonged lysis similar to that seen with dilute platelet poor plasma. The prolonged lysis of cytochalasin B treated dilute platelet rich plasma clots was corrected by artificial compaction of the clots. The results suggest that clot retraction markedly facilitates clot lysis, and shows that a major role of platelets to facilitate clot lysis is the effect of these cells to cause clot retraction.

Treatment Of Venous Thromboembolism - Case For Thrombolytic Therapy

1981 ◽  
Author(s):  
V V Kakkar
Keyword(s):  
Deep Vein Thrombosis ◽  
Thrombolytic Therapy ◽  
Massive Pulmonary Embolism ◽  
Vein Thrombosis ◽  
Physiological Processes ◽  
Large Numbers ◽  
Complete Lysis ◽  
Thrombus Removal ◽  
Deep Vein

Thrombolytic therapy has a unique advantage in the treatment of patients suffering from thrombotic disease, since it is capable of inducing the dissolution of intravascular fibrin and thus causing the reduction or elimination of thrombi. The rapidity of thrombus removal distinguishes this form of treatment from anticoagulant therapy, in which normal physiological processes are allowed to restore the obstructed circulation. By quickly removing the obstruction, it should be possible to reduce the mortality arising from acute thromboembolic episodes.The results of therapy for deep-vein thrombosis have been fairly uniform. The published studies can be broadly classified into two main groups; in uncontrolled trials, partial or complete lysis of thrombi was obtained in approximately 65-80% of the patients who received streptokinase, while only 10-25% of the patients receiving heparin showed this change.In patients suffering from acute major or massive pulmonary embolism, a number of trials have demonstrated a more rapid resolution of the embolus than would be expected by treatment with heparin alone.The role of lytic therapy in preventing the late sequelae of deep vein thrombosis at present remains uncertian. Studies involving large numbers of patients and longer periods of follow-up are required to determine the extent to which post phlebitic venous insufficiency is reduced by early thrombolytic therapy.

The Role of Stanozolol in the Treatment of the Postphlebitic Syndrome

1981 ◽  
Vol 26 (1_suppl) ◽  
pp. S81-S83 ◽  
Author(s):  
P. E. Jarrett
Keyword(s):  
Deep Vein Thrombosis ◽  
Side Effects ◽  
Fibrinolytic Activity ◽  
Double Blind ◽  
Vein Thrombosis ◽  
Postphlebitic Syndrome ◽  
Deep Vein ◽  
Blind Crossover Study ◽  
Double Blind Crossover Study

The postphlebitic syndrome is a result of previous deep vein thrombosis and presents with oedema, pain, induration, pigmentation and ulceration. Extravascular deposition of fibrin is associated with reduced fibrinolytic activity in these patients. In a double-blind crossover study there was evidence of benefit from stanozolol which enhanced fibrinolytic activity. No side effects of any consequence were noted with a dosage of 5 mg twice per day.

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