| 1. |
- Ahmad, Abrar, et al.
(författare)
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Association between TLR9 rs5743836 polymorphism and risk of recurrent venous thromboembolism
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 44:1, s. 130-138
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Tidskriftsartikel (refereegranskat)abstract
- Recent gene knockout studies on mice have shown the role of toll-like receptor 9 (TLR9) in resolution of venous thromboembolism (VTE) through sterile inflammation. However, the role of a putative functional TLR9 polymorphism (rs5743836) in risk assessment of VTE recurrence remains unknown. The aim of our study was to investigate the TLR9 rs5743836 polymorphism in VTE patients and its association with the risk of VTE recurrence. We analyzed TLR9 rs5743836 polymorphism in Malmö thrombophilia study patients; a prospective follow-up study of 1465 VTE patients by Taqman PCR. From a total of 1465 VTE patients, those who had VTE before inclusion and those who died or had VTE recurrence during anticoagulant treatment were excluded (n = 415). Cox regression analyses were performed on the remaining 1050 VTE patients, including 126 (12.5%) patients that had recurrent VTE during follow-up period. TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 3.46, 95% CI 1.06-11.33) independent of acquired risk factors for VTE, family history, risk of thrombophilia and deep vein thrombosis (DVT) location. Similarly, in unprovoked VTE patients, TLR9 polymorphism was significantly associated with higher risk of VTE recurrence in female patients (HR 5.94, 95% CI 1.25-28.13) after adjusting for family history, risk of thrombophilia and DVT location. No association between TLR9 polymorphism and risk of VTE recurrence was found in male patients. Our results suggest that TLR9 rs5743836 polymorphism is an independent risk factor for VTE recurrence in female patients but not in males.
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| 2. |
- Ahmad, Abrar, et al.
(författare)
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Risk prediction of recurrent venous thromboembolism : a multiple genetic risk model
- 2019
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 47:2, s. 216-226
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Tidskriftsartikel (refereegranskat)abstract
- A single genetic biomarker is unable to accurately predict the risk for venous thromboembolism (VTE) recurrence. We aimed to: (a) develop a multiple single nucleotide polymorphisms (SNPs) model to predict the risk of VTE recurrence and (b) validate a previously described genetic risk score (GRS) and compare its performance with the model developed in this study. Twenty-two SNPs, including established and putative SNPs associated with VTE risk, were genotyped in the Malmö thrombophilia study cohort (MATS; n = 1465, follow-up ~ 10 years) by using TaqMan PCR. Out of 22-SNPs, 12 had an association with the risk of VTE recurrence and were included for calculating GRSs. The risk of VTE recurrence was calculated by stratifying patients according to number of risk alleles. In 12-SNP GRS, patients with ≥ 7 risk alleles were associated with higher risk of VTE recurrence compared to patients having ≤ 6 risk alleles. In a simplified model (8-SNP GRS), the discriminative power of 8-SNP GRS was similar to that of 12-SNP GRS based on post-test probabilities (PP). Furthermore, 8-SNP GRS further improved the risk prediction of VTE recurrence in unprovoked VTE and male patients (PP% = 15.4 vs 8.3, 17.1 vs 7.2 and 19.0 vs 7.1 for high risk groups vs low risk groups in whole population, males and unprovoked VTE patients respectively). In addition, we also validated previously described 5-SNP GRS in our cohort and found that the 8-SNP GRS performed better than the 5-SNP GRS in terms of higher PP. Our results show that a multiple SNP GRS consisting of 8-SNPs may be an effective model for prediction of VTE recurrence, particularly in unprovoked VTE and male patients.
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| 3. |
- Ahmad, Abrar, et al.
(författare)
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Thrombomodulin gene c.1418C>T polymorphism and risk of recurrent venous thromboembolism.
- 2016
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 42:1, s. 135-141
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Tidskriftsartikel (refereegranskat)abstract
- Thrombomodulin gene (THBD) is a critical cofactor in protein C anticoagulant system. THBD c.1418C>T polymorphism is reported to be associated with higher risk of primary venous thromboembolism (VTE) but its role in VTE recurrence is unknown. The aim of this study was to investigate the role of THBD polymorphism in VTE recurrence. THBD c.1418C>T polymorphism was genotyped by using Taqman polymerase chain reaction in a prospective population based study of 1465 consecutive objectively verified VTE patients. Uni- and multivariate Cox regression were performed for the risk assessment of VTE recurrence. Patients who had VTE before inclusion or had recurrence or died during anticoagulant treatment were excluded. Among the remaining (N = 1046) patients, 126 (12.05 %) had VTE recurrence during the follow up period (from 1998 to 2008). THBD polymorphism was not significantly associated with risk of VTE recurrence in the univariate [Hazard ratio (HR) 1.11, 95 % confidence interval (CI) 0.78-1.59, p = 0.55] as well as the multivariate analysis adjusted for age, sex and thrombophilia (HR 1.11, 95 % CI 0.78-1.59, p = 0.54). Similarly, in unprovoked first VTE (n = 614), no association was observed between THBD polymorphism and risk of VTE recurrence (HR 1.22 and 95 % CI 0.78-1.89, p = 0.38). In this prospective study, our results do not suggest a predictive role for THBD c.1418C>T polymorphism in VTE recurrence.
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| 4. |
- Alhadad, Alaa, et al.
(författare)
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Iliocaval vein stenting: Long term survey of postthrombotic symptoms and working capacity.
- 2011
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 31, s. 211-216
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the long term effect on lower extremity function and working capacity after stenting of iliocaval vein segments for acute deep venous thrombosis (DVT) or chronic venous occlusive disease. During a 14 year period from November 1994 to October 2008, 114 patients with median age 36 (interquartile range [IQR], 27-48) years, 72 (63%) women, 72 (63%) with hypercoagulable disorders, with acute DVT (n = 44, 39%), or chronic occlusions (n = 70, 61%) in the iliocaval vein segment were treated with venous stent placement after catheter-directed thrombolysis, angioplasty or recanalization. The long term impact on lower extremity function and working capacity was evaluated through retrospective evaluation of a prospectively registered database in combination with a questionnaire sent to all 108 surviving patients. The questionnaire was returned by 91/108(84%) patients, 37 (86%) with acute DVT, and 54(83%) with chronic venous occlusions. After a median follow-up of 6.2 (IQR 3.8-10.5) years, 38 (42%) patients were without anticoagulation therapy. Among patients with acute DVT 29 (78%) reported no lower extremity pain, 31 (84%) reported no ulcerations, and 26 (70%) were without lower extremity swelling, and 33(89%) without pelvic or genital pain. In summary, 22 (59%) were free from any symptomatic postthrombotic symptoms (PTS). Among patients with chronic occlusions, corresponding figures were 22 (41%), 45 (80%), 13 (24%), 39 (72%), and 7 (13%). Among patients treated for acute DVT 27 (73%) were working full- or part time, and 2 (5%) were above retirement age. Corresponding figures among patients treated for chronic venous occlusions were 31 (57%), and 10 (19%). Stenting of iliocaval vein segments with or without catheter-directed thrombolysis is a promising treatment of both acute thrombosis and chronic iliocaval vein occlusion that requires further study in comparison to non-interventional treatment concerning long time effects on postthrombotic symptoms and working capacity.
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| 5. |
- Ali Abdi, Abshir, et al.
(författare)
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Prevalence of common hereditary risk factors for thrombophilia in Somalia and identification of a novel Gln544Arg mutation in coagulation factor V
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : SPRINGER. - 0929-5305 .- 1573-742X. ; 44:4, s. 536-543
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Tidskriftsartikel (refereegranskat)abstract
- Thrombophilia, commonly manifested as venous thromboembolism (VTE), is a worldwide concern but little is known on its genetic epidemiology in many parts of the globe particularly in the developing countries. Here we employed TaqMan genotyping and pyrosequencing to evaluate the prevalence of known common nucleotide polymorphisms associated with thrombophilia in a Somali population in the Puntland region of Somalia. We also employed next generation sequencing (NGS) to investigate other genetic variants in a Somali patient with deep venous thrombosis (DVT). As expected, we found no existence of factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) in the Somali population. The G allele of ABO [261G/delG] polymorphism (rs8176719) was found at a frequency of 29%, similar to that observed in other African populations. We found the lowest so far reported frequency of MTHFR C677T (rs1801133) polymorphism in the Somali population (T allele frequency 1.5%). A novel and deleterious single nucleotide variation in exon 11 of coagulation factor V (c.1631A amp;gt; G) causing Gln544Arg exchange in factor V was identified in a 29 years old Somali female with DVT. The same patient was heterozygous to VKORC1 Asp36Tyr polymorphism (rs61742245) that predisposes to warfarin resistance. In conclusion, this study shows that common hereditary factors for thromboembolism found in Caucasians are either less frequent or absent in the Somali population-similar to the situation in other Africans. NGS is possibly a better choice to detect genetic risk variants for thrombosis in this ethnic group.
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| 6. |
- Almskog, LM, et al.
(författare)
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Rotational thromboelastometry results are associated with care level in COVID-19
- 2021
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Ingår i: Journal of thrombosis and thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 51:2, s. 437-445
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Tidskriftsartikel (refereegranskat)abstract
- High prevalence of thrombotic events in severely ill COVID-19 patients have been reported. Pulmonary embolism as well as microembolization of vital organs may in these individuals be direct causes of death. The identification of patients at high risk of developing thrombosis may lead to targeted, more effective prophylactic treatment. The primary aim of this study was to test whether rotational thromboelastometry (ROTEM) at admission indicates hypercoagulopathy and predicts the disease severity, assessed as care level, in COVID-19 patients. The study was designed as a prospective, observational study where COVID-19 patients over 18 years admitted to hospital were eligible for inclusion. Patients were divided into two groups depending on care level: (1) regular wards or (2) wards with specialized ventilation support. Conventional coagulation tests, blood type and ROTEM were taken at admission. 60 patients were included; age 61 (median), 67% men, many with comorbidities (e.g. hypertension, diabetes). The ROTEM variables Maximum Clot Firmness (EXTEM-/FIBTEM-MCF) were higher in COVID-19 patients compared with in healthy controls (p < 0.001) and higher in severely ill patients compared with in patients at regular wards (p < 0.05). Our results suggest that hypercoagulopathy is present early in patients with mild to moderate disease, and more pronounced in severe COVID-19 pneumonia. Non-O blood types were not overrepresented in COVID-19 positive patients. ROTEM variables showed hypercoagulopathy at admission and this pattern was more pronounced in patients with increased disease severity. If this feature is to be used to predict the risk of thromboembolic complications further studies are warranted.
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| 7. |
- Becker, Richard C., et al.
(författare)
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Chromogenic laboratory assays to measure the factor Xa-inhibiting properties of apixaban-an oral, direct and selective factor Xa inhibitor
- 2011
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 32:2, s. 183-187
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Tidskriftsartikel (refereegranskat)abstract
- An ability to readily determine an anticoagulant effect with an emerging class of direct, active site, oral factor Xa inhibitors is viewed by the medical community as attractive and by some as an absolute requirement for their use in clinical practice. We performed a pharmacokinetic and pharmacodynamic substudy in APPRAISE-1-a study of apixaban in patients with acute coronary syndrome(ACS). A total of 1691 patients had blood sampled for apixaban plasma concentrations using mass spectrometry/high performance liquid chromatography and anti-Xa activity using a chromogenic assay employing either low molecular weight heparin or apixaban as reference standards. Anti-Xa activity, determined by either anti-Xa-LMWH (r = 0.9671; P < 0.0001) or anti-Xa-apixaban (r = 0.9669; P < 0.0001) correlated strongly and in a linear fashion with apixaban plasma concentrations. The correlations for each method were equally strong at low (< 100 ng/ml) (r = 0.86, P < 0.0001; r = 0.85, P < 0.0001), intermediate(100-200 ng/ml) (r = 0.73, P < 0.0001; r = 0.69, P < 0.0001) and high (> 200 ng/ml) (r = 0.91, P < 0.0001; r = 0.91, P < 0.0001) plasma concentrations of apixaban, respectively. Our pharmacokinetic and pharmacodynamic substudy suggests that an apixaban-mediated anticoagulant effect can be detected even at very low plasma concentrations using a standard laboratory chromogenic anti-Xa assay with either LMWH or apixaban calibrators. While establishing parameters for safety and efficacy will require further investigation, an ability to discern the presence of a drug effect may provide clinically useful information.
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| 8. |
- Björck, Fredrik, 1974-, et al.
(författare)
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Predictors for INR-control in a well-managed warfarin treatment setting
- 2019
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer. - 0929-5305 .- 1573-742X. ; 47:2, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- Warfarin is well studied in patients with non-valvular atrial fibrillation (AF). It has low complication rates for patients achieving individual Time in Therapeutic Range (iTTR)>70%. The risk scores SAMe-TT2R2 and PROSPER are designed to predict future TTR, but are derived from a heterogeneous population with generally low iTTR. The aim of this study was to evaluate predictors for high and low iTTR in an AF population in Sweden, where there is a generally good anticoagulation control. A retrospective register study based on Swedish warfarin dosing system AuriculA, including 28,011 AF patients starting treatment during 1 January 2006 to 31 December 2011. Complications and risk factors were analysed and related to iTTR. Mean age was 73.7 (SD +/- 9.5) years, with 42.0% women. Mean CHA(2)DS(2)-VASc score (SD) was 3.6 (+/- 1.7). For patients with iTTR<60% there were over three times higher prevalence of excessive alcohol consumption than for patients with iTTR>70% (3.7% vs. 1.1%). Previous stroke were more prevalent for patients with high than low iTTR (17.1% vs. 20.3%). Concomitant comorbidities were associated with increased risk of poor iTTR. In Swedish AF patients, excessive alcohol use is clearly associated with iTTR below 60%. Patients with previous stroke are more likely to get iTTR above 70%, unlike those with concomitant disorders who more often have poor anticoagulation control. The SAMe-TT2R2-score cannot be applied in Sweden.
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| 9. |
- Butt, Talha, et al.
(författare)
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Outcome of intra-arterial thrombolysis in patients with diabetes and acute lower limb ischemia : a propensity score adjusted analysis
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 44:4, s. 475-480
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Tidskriftsartikel (refereegranskat)abstract
- The presence of diabetes mellitus is rarely addressed in acute lower limb ischaemia (ALLI). The aim of this study was to evaluate the outcome of local intra-arterial thrombolysis for ALLI in patients with diabetes mellitus (DM). Outcome of all thrombolytic events performed in an endovascular first-strategy centre during a 13-year period between 2001 and 2013 in patients with ALLI were followed to January 2017. A propensity score adjusted analysis was performed to evaluate results in patients with (n = 83) versus without (n = 316) DM. Patients with DM were younger (p = 0.001), more often women (p = 0.014), more often had renal insufficiency (p = 0.041), foot ulcers (p < 0.001), and thrombosis (p = 0.032) than the patients without DM. At presentation, patients with DM had a lower degree of ischemia judged by the Rutherford classification, compared to those without DM (p = 0.023). None of the 83 diabetic patients had a popliteal artery aneurysm, compared to 25 (7.9%) of the 316 patients without DM (p = 0.008). The amount of tPA administered to patients with DM was higher than to patients without DM (p = 0.03). In the propensity score adjusted analysis, patients with DM had a higher rate of major amputation at 1 (OR 2.52; 95% CI 1.22–5.20) and 3 years (OR 2.52; 95% CI 1.26–5.04), and a lower amputation-free survival at 3 years (OR 0.46; 95% CI 0.25–0.85), than those without DM. Patients with DM presenting with ALLI differ in clinical characteristics, presentation, and aetiology compared to patients with DM, and have a higher rate of major amputation and lower amputation-free survival rate after intra-arterial thrombolysis.
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| 10. |
- Damman, Peter, et al.
(författare)
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P2Y12 platelet inhibition in clinical practice
- 2012
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 33:2, s. 143-153
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Tidskriftsartikel (refereegranskat)abstract
- Platelet adhesion, activation and aggregation play a pivotal role in atherothrombosis. Intracoronary atherothrombosis is the most common cause of the development of acute coronary syndrome (ACS), and plays a central role in complications occurring around percutaneous coronary intervention (PCI) including recurrent ACS, procedure-related myocardial infarction or stent thrombosis. Inhibition of platelet aggregation by medical treatment impairs formation and progression of thrombotic processes and is therefore of great importance in the prevention of complications after an ACS or around PCI. An essential part in the platelet activation process is the interaction of adenosine diphosphate (ADP) with the platelet P2Y12 receptor. The P2Y12 receptor is the predominant receptor involved in the ADP-stimulated activation of the glycoprotein IIb/IIIa receptor. Activation of the glycoprotein IIb/IIIa receptor results in enhanced platelet degranulation and thromboxane production, and prolonged platelet aggregation. The objectives of this review are to discuss the pharmacological limitations of the P2Y12 inhibitor clopidogrel, and describe the novel alternative P2Y12 inhibitors prasugrel and ticagrelor and the clinical implications of the introduction of these new medicines.
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