Thrombotic events in rare kinds of genetic thrombophilias

Author(s):  
М.Г. Николаева ◽  
А.П. Момот ◽  
А.Н. Мамаев ◽  
Н.Г. Хорев ◽  
Н.М. Пасман ◽  
...  

Цель исследования: изучить лабораторный фенотип редких мутаций Лейдена [FVL А(1961)A] и гена протромбина [FII А(20210)A] при их клинической реализации в виде тромбозов. Материалы и методы. Проведено многоцентровое проспективное наблюдательное исследование, включающее 80 носителей редких генетических форм тромбофилий: FVL А(1961)A (n = 31), FII А(20210)A (n = 10) и компаунд FII G(20210)A + FVL G(1691)A (n = 39). У всех пациентов исследована резистентность фактора Va к активированному протеину С (APC-R) по нормализованному отношению (НО) и уровень активности протромбина в плазме крови в состоянии физического здоровья и в случае эпизода тромботического события. Результаты. Определена ассоциативная связь развития тромботических событий со снижением НО при оценке APC-R как у гомозиготных носителей мутации Лейден (Ме = 0,35; 95% ДИ = 0,31–0,37 по НО), так и гетерозиготных компаундов (Ме = 0,43; 95% ДИ = 0,42–0,45 по НО). Заключение. Лабораторный мониторинг пациентов с редкими формами генетических тромбофилий позволяет выделить группу высокого тромбогенного риска, нуждающуюся в пролонгированной тромбопрофилактике. Objectives: to study the laboratory phenotype of rare Leiden mutation [FVL A(1961)A] and the prothrombin gene mutation [FII А(20210)A] implementating clinically as thrombosis. Patients / Methods. A multicenter prospective observational study included 80 carriers of rare genetic kinds of thrombophilia: FVL A(1961)A (n = 31), prothrombin FII А(20210)A (n = 10) and the compound FII G(20210)A + FVL G(1691)A (n = 39). All patients were tested for the factor Va resistance to activated protein C (APC-R), normalized ratio (NR), and the plasma prothrombin activity (%) in healthy conditions and in the case of thrombotic event. Results. An associative relation between the development of thrombotic events and a decrease in NR was determined when assessing APC-R, both in homozygous carriers of the Leiden mutation (Me = 0.35; 95% CI = 0.31–0.37 in NR) and heterozygous compounds (Me = 0.43; 95% СI = 0.42–0.45 in NR). Conclusions. Laboratory follow up for patients with rare kinds of genetic thrombophilias allows to identify a group at high thrombogenic risk requiring prolonged thromboprophylaxis.

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Carola Gianni ◽  
Tamara Metz ◽  
Luigi Di Biase ◽  
Sanghamitra Mohanty ◽  
Chintan Trivedi ◽  
...  

Introduction: Focal impulse and rotor modulation (FIRM)-guided ablation targets localized sources that are thought to sustain AF. We sought to evaluate if acute success of FIRM-guided ablation in patients with non-paroxysmal AF influenced the mid-term ablation outcomes. Methods: This was a multicenter prospective observational study of persistent and LSP AF patients undergoing FIRM ablation in 3 centers. Patients with at least 2 months follow-up were included in the analysis. FIRM was performed alone or in addition to conventional ablation and rotors were ablated as confirmed by their absence during remapping. Acute success was defined as AF termination, organization or slowing 10%. Mid-term success was defined as freedom from AT/AF off antiarrhythmic drugs (AADs) and after a single procedure during the initial follow-up (excluding the 2-month blanking period). Results: A total of 43 patients were enrolled (mean age 62 ± 10; 91% persistent, 9% LSP). Rotors-only ablation was performed in 65% of patients, and in addition to conventional ablation in the remaining 35%. Overall, acute success was achieved in 33% of patients. During a mean follow-up of 5.5 ± 2.4 months, 35% of patients were free of AT/AF off AADs after a single procedure. When comparing patients who underwent rotors-only ablation with those who received additional conventional ablation, mid-term success rates were respectively 25% vs. 53% (P = NS). There was no statistical difference in SR maintenance between patients with and without acute success during FIRM ablation (29% vs. 38%, P = NS). Conclusion: FIRM-guided ablation in persistent and LSP AF was not effective in obtaining AF slowing/organization/termination during the procedure and in preventing mid-term AT/AF recurrences. Acute success did not impact the mid-term success rate.


2001 ◽  
Vol 86 (09) ◽  
pp. 804-808 ◽  
Author(s):  
Alberto Tosetto ◽  
Monica Simioni ◽  
Marco Ruggeri ◽  
Domenico Madeo ◽  
Francesco Rodeghiero ◽  
...  

SummaryWe hypothesized that increased prothrombin levels associated with G20210A prothrombin gene mutation could affect the results of activated protein C (APC) resistance phenotype and increase the risk of venous thrombosis (VT). The increasing addition of purified prothrombin in plasma of 90 normal subjects resulted in a parallel significant increase of APC resistance. Significantly different mean n-APC-SR in 879 GG20210 subjects compared to 27 heterozygous carriers of isolated G20210A mutation was observed (1.0 ± 0.12 vs. 0.95 ± 0.11; P = 0.02) in a random sample of 906 normal population subjects. Twenty-seven families with VT and isolated G20210A mutation consecutively diagnosed during 1998-1999 were evaluated. Mean n-APC-SR was significantly lower in the 80 G20210A carriers compared to 58 GG 20210 relatives investigated, even after sex and age adjustment (0.92 ± 0.08 vs. 1.05 ± 0.13; P < 0.0001). A strong relationship between plasma prothrombin level and n-APC-SR was observed in the families. When n-APC-SR values were grouped in tertiles, the odds ratio for VTE, after exclusion of the index cases and adjustment for 20210 status, for subjects in the lowest tertile (n-APC-SR 0.73-0.90) was 4.58 (95% CI 0.78-26.88) compared to upper tertile (n-APC-SR 1.01-1.30). In conclusion, in subjects with G20210A mutation APC resistance is significantly increased, correlates with plasma prothrombin level and the carriers with the lowest APC resistance values have an increased risk of VTE.


1999 ◽  
Vol 82 (11) ◽  
pp. 1462-1468 ◽  
Author(s):  
José Fernández ◽  
Jari Petäjä ◽  
John Griffin

SummaryUnfractionated heparin potentiates the anticoagulant action of activated protein C (APC) through several mechanisms, including the recently described enhancement of proteolytic inactivation of factor V. Possible anticoagulant synergism between APC and physiologic glycosaminoglycans, pharmacologic low molecular weight heparins (LMWHs), and other heparin derivatives was studied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs showed differing abilities to promote APC activity, and the molecular weight of LMWHs correlated with enhancement of APC activity. Degree of sulfation of the glycosaminoglycans influenced APC enhancement. However, because dextran sulfates did not potentiate APC action, the presence of sulfate groups per se on a polysaccharide is not sufficient for APC enhancement. As previously for unfractionated heparin, APC anticoagulant activity was enhanced by glycosaminoglycans when factor V but not factor Va was the substrate. Thus, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that could be of physiologic and pharmacologic significance.


1992 ◽  
Vol 67 (01) ◽  
pp. 046-049 ◽  
Author(s):  
H A Guglielmone ◽  
M A Vides

SummaryA simple and fast method for the quantitative determination of protein C activity in plasma is here described. The first step consists in the conversion of protein C in the test sample into activated protein C by means of an activator isolated from Southern Copperhead venom. Subsequently, the degradation of factor Va, in presence of protein C-deficient plasma, is measured by the prolongation of the prothrombin time which is proportional to the amount of protein C in the sample. The dose-response curve showed a linear relationship from 6 to 150% protein C activity and the inter- and intra-assay reproducibility was 3.5% and 5.6% respectively. In normal subjects, a mean of protein C level of 98 ± 15% of normal pooled plasma was found. Comparison with the anticoagulant assay in samples of patients with oral anticoagulant, liver cirrhosis, disseminated intravascular coagulation and severe preeclampsia revealed an excellent correlation (r = 0.94, p <0.001). Also, a similar correlation (r = 0.93, p <0.001) existed between amidolytic assay and the method here proposed for all the samples studied without including the oral anticoagulant group. These results allowed us to infer that this method evaluates the ability of protein C to interact with protein S, phospholipids, calcium ions and factor Va.


Author(s):  
Erhan Okuyan ◽  
Emre Gunakan ◽  
Sertaç Esin

Covid outbreak has been getting worse and spread affected all over the world. Pregnant patients are also vulnerable to respiratory diseases. We aimed to evaluate the awareness, emotional status, and behavior of pregnant during the COVID outbreak. This study's main benefit is to analyze the knowledge and understanding of pregnant women about the pandemic and draw attention to the prevention issues that need improvement. This research is a prospective observational study that 199 patients subjected to a questionnaire including 29 questions about patient characteristics, pregnancy information, knowledge about COVID19-infection, behavioral and emotional changes. 130 (65.3) of the patients stated an above-average knowledge level. Television was the most frequent information source (75.4%, n:150) and was the only information source for 90 (45.1%) of the patients. Sixty-nine patients used more than one information source. More than one prevention method uses by 149 (75%) of the patients. Washing hands (n:183, 92.0%) and cleaning the house (n:122, 61.3%) were the most preferred methods. Only 55 (27.6%) of the patients used a mask for prevention. 88(44.2%) of the patients stated that they preferred a shorter hospital stay, and 75 (37.7%) of the patients indicated that they postponed or avoided the pregnancy follow-up visits due to the COVID-19 issue. Pregnant women seem to be aware and stressed of COVID-19, but knowledge of what to do seems insufficient. Patients informed of risks of COVID infection, unplanned hospital admission, and chances of avoiding necessary visits and home birth demands.


2019 ◽  
Vol 130 (5) ◽  
pp. 1218-1226 ◽  
Author(s):  
Jin Pyeong Kim ◽  
Dong Kun Lee ◽  
Jeong Hwan Moon ◽  
Jun Sun Ryu ◽  
Seung Hoon Woo

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