The Risk Factors of Thrombogenic, Thrombophilia, and the Principle for Heparin Prophylaxis in Personalized Medicine

Abstract Background: Little is known about the time of development and distribution pattern of venous thrombembolism (VTE) after radical prostatectomy (RPE) for malignancy. Patients and Methods: 415 consecutive patients undergoing standard RPE were prospectively assessed regarding the incidence and distribution pattern of VTE, the hemodynamic relevance of pelvic lymphoceles (LC) and other possible risk factors for VTE. All patients underwent RPE and received heparin prophylaxis until discharge, followed by acetylsalicylic acid 100 mg daily. On day -1, 8 and 21 complete compression ultrasound, measurement of pelvic vein flow and pelvic ultrasound were performed. Results: VTE was found in 17,3% of patients. Most thrombi were limited to calf muscle veins (55,5%). Isolated calf deep vein thrombosis (DVT) was found in 22,2% and proximal DVT in 12,5%. On day 8 and 21 the following incidences of VTE were found: calf muscle vein thrombosis 4.8 and 4.8%; isolated calf vein thrombosis 1.7% and 2.2%; proximal DVT 0.5% and 1.7%; pulmonary embolism 0.5% and 0.5%, respectively. Multivariate analysis revealed surgery time (OR 1.26), number of blood tranfusion (OR 1.73) and venous flow reduction (OR 2.83) as risk factors for the development of VTE. 33.3% of the patients developed a LC postoperatively; of these 5.3% showed a reduction of pelvic vein flow. A venous flow reduction was only seen with LC. Conclusion: The incidence and distribution pattern of VTE after RPE is comparable to major abdominal surgery for malignancy. The development of LC is a significant risk factor for VTE, when pelvic vein flow is impaired. Since the majority of proximal VTE developed between day 8 and day 21 when the patient is already discharged, the concept of a prolonged heparin prophylaxis after RPE should be evaluated prospectively.

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Norethisterone Treatment, a Major Risk-Factor for Veno-Occlusive Disease in the Liver After Allogeneic Bone Marrow Transplantation

Blood ◽

10.1182/blood.v92.12.4568.424k02_4568_4572 ◽

1998 ◽

Vol 92 (12) ◽

pp. 4568-4572

Author(s):

Hans Hägglund ◽

Mats Remberger ◽

Sven Klaesson ◽

Berit Lönnqvist ◽

Per Ljungman ◽

...

Keyword(s):

Risk Factors ◽

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Allogeneic Bone Marrow Transplantation ◽

Occlusive Disease ◽

Allogeneic Bone ◽

Hla Antigen ◽

Hematopoietic Stem ◽

Heparin Prophylaxis

In this single-center study, we retrospectively analyzed incidence and risk factors for hepatic veno-occlusive disease (VOD) in 249 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation between January 1990 and June 1995. Twenty-four of the 249 transplanted patients developed VOD. The probabilities of developing VOD were 17% among women and 7% in men (P = .01). In women treated with norethisterone, the incidence was 27% compared with 3% in women without this treatment (P = .007). One-year survival rates were 17% and 73% in patients with (n = 24) or without VOD (n = 225), respectively. The use of heparin prophylaxis (100 IE/kg/24 hours for 1 month) did not alter the incidence or 1-year mortality of VOD. In multivariate analysis, the following risk factors were significant: norethisterone treatment (P < .001), bilirubin >26 μmol/L before bone marrow transplantation (BMT) (P = .002), one HLA-antigen mismatch (P = .003), previous abdominal irradiation (P = .02), and conditioning with busulphan (P = .02). Our conclusion is that norethisterone treatment should not be used in patients undergoing BMT and heparin prophylaxis did not affect the incidence or mortality of VOD.

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Personalized medicine in glaucoma management

Russian Ophthalmological Journal ◽

10.21516/2072-0076-2019-12-3-95-100 ◽

2019 ◽

Vol 12 (3) ◽

pp. 95-100 ◽

Cited By ~ 1

Author(s):

A. N. Zhuravleva ◽

O. A. Kiseleva ◽

M. O. Kirillova

Keyword(s):

Risk Factors ◽

Personalized Medicine ◽

Multifactorial Disease ◽

Hereditary Predisposition ◽

P4 Medicine ◽

Prevention And Treatment ◽

Individualized Approach ◽

Primary Glaucoma ◽

Individual Strategies

The review addresses the management of primary glaucoma as a socially significant multifactorial disease. The main reasons that impede the timely diagnosis and treatment of patients with glaucoma are indicated: blurring of boundaries, conventionality of standards, and lack of individualized approach to treatment. The main risk factors for the development of glaucoma are highlighted, with special attention to hereditary predisposition and the role of “medicine of the future” in managing glaucoma. Four fundamental principles are described: personalization, prediction, prevention and participative attitude (P4 medicine). Advanced scientific understanding of the key risk factors for the development and progression of glaucoma, together with a modern personalized and personified approach will further develop precise individual strategies for the prevention and treatment of the disease.

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Norethisterone Treatment, a Major Risk-Factor for Veno-Occlusive Disease in the Liver After Allogeneic Bone Marrow Transplantation

Blood ◽

10.1182/blood.v92.12.4568 ◽

1998 ◽

Vol 92 (12) ◽

pp. 4568-4572 ◽

Cited By ~ 68

Author(s):

Hans Hägglund ◽

Mats Remberger ◽

Sven Klaesson ◽

Berit Lönnqvist ◽

Per Ljungman ◽

...

Keyword(s):

Risk Factors ◽

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Allogeneic Bone Marrow Transplantation ◽

Occlusive Disease ◽

Allogeneic Bone ◽

Hla Antigen ◽

Hematopoietic Stem ◽

Heparin Prophylaxis

Abstract In this single-center study, we retrospectively analyzed incidence and risk factors for hepatic veno-occlusive disease (VOD) in 249 consecutive patients who underwent allogeneic hematopoietic stem cell transplantation between January 1990 and June 1995. Twenty-four of the 249 transplanted patients developed VOD. The probabilities of developing VOD were 17% among women and 7% in men (P = .01). In women treated with norethisterone, the incidence was 27% compared with 3% in women without this treatment (P = .007). One-year survival rates were 17% and 73% in patients with (n = 24) or without VOD (n = 225), respectively. The use of heparin prophylaxis (100 IE/kg/24 hours for 1 month) did not alter the incidence or 1-year mortality of VOD. In multivariate analysis, the following risk factors were significant: norethisterone treatment (P < .001), bilirubin >26 μmol/L before bone marrow transplantation (BMT) (P = .002), one HLA-antigen mismatch (P = .003), previous abdominal irradiation (P = .02), and conditioning with busulphan (P = .02). Our conclusion is that norethisterone treatment should not be used in patients undergoing BMT and heparin prophylaxis did not affect the incidence or mortality of VOD.

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Risk stratification and heparin prophylaxis to prevent venous thromboembolism in pregnant women

Thrombosis and Haemostasis ◽

10.1160/th07-05-0329 ◽

2007 ◽

Vol 98 (12) ◽

pp. 1237-1245 ◽

Cited By ~ 66

Author(s):

Joachim Dudenhausen ◽

Andree Faridi ◽

Thorsten Fischer ◽

Samson Fung ◽

Ulrich Geisen ◽

...

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Pregnant Women ◽

Management Strategies ◽

Prospective Trial ◽

High Risk Group ◽

Group I ◽

Increased Risk ◽

History Of ◽

Heparin Prophylaxis

SummaryWomen with a history of venous thromboembolism (VTE), thrombophilia or both may be at increased risk of thrombosis during pregnancy, but the optimal management strategy is not well defined in clinical guidelines because of limited trial data. A strategy of risk assessment and heparin prophylaxis was evaluated in pregnant women at increased risk of VTE. In a prospective trial (Efficacy of Thromboprophylaxis as an Intervention during Gravidity [EThIG]), 810 pregnant women were assigned to one of three management strategies according to pre-defined risk factors related to history of VTE and thrombophilic profile. Low-risk women (group I), received 50–100 IU dalteparin/ kg body weight/ day for 14 days postpartum, or earlier when additional risk factors occurred. Women at high (group II) or very high risk (group III) received dalteparin from enrolment until six weeks postpartum (50–100 IU and 100–200 IU/ kg/ day, respectively). Objectively confirmed, symptomatic VTE occurred in 5/810 women (0.6%; 95% confidence interval [CI], 0.2 to 1.5%) (group I, 0 of 225; II, 3/469; III, 2/116). The rate of serious bleeding was 3.0% (95 % CI, 1.9 to 4.4%); 1.1% (95 % CI, 0.5 to 2.2%) was possibly dalteparin-related. There was no evidence of heparin- induced thrombocytopenia, one case of osteoporosis, and rates of miscarriage and stillbirth were similar to previous, retrospective studies. Risk-stratified heparin prophylaxis was associated with a low incidence of symptomatic VTE and few clinically important adverse events. Antepartum heparin prophylaxis is, therefore, warranted in pregnant women with idiopathic thrombosis or symptomatic thrombophilia.

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EPC Dysfunction and Immune Networks: Translating Opportunities for Clinical Setting in Personalized Medicine

Current Medicinal Chemistry ◽

10.2174/0929867324666170606101823 ◽

2018 ◽

Vol 25 (35) ◽

pp. 4497-4506 ◽

Cited By ~ 5

Author(s):

Javier Rodríguez-Carrio ◽

Patricia López ◽

Ana Suárez

Keyword(s):

Risk Factors ◽

Personalized Medicine ◽

Risk Stratification ◽

Current Evidence ◽

Novel Biomarkers ◽

Endothelial Homeostasis ◽

And Oxidative Stress ◽

Insight Into ◽

Similar Risk ◽

Gaining Insight

Background: Cardiovascular (CV) risk stratification is suboptimal if solely based on traditional CV risk factors, since individuals with similar risk profiles could exhibit diverging CV outcomes. Thus, there is a need for new risk factors to be identified. Recent studies emphasize the relevance of the endothelial homeostasis in the control of CV risk, but the clinical relevance of these findings is starting to be appreciated. Gaining insight into the actual players involved in this phenomenon would lead to the identification of novel biomarkers. Due to their central role in vascular repair, Endothelial Progenitor Cells (EPC) are promising candidates for this issue. <P> Objective: Since excessive inflammation or imbalanced immune responses are known to underlie numerical or functional alterations of EPC, it can be speculated that these mediators may be considered as biomarkers for risk stratification. In the present narrative review, we aimed to compile and critically appraise all the current evidence linking inflammation and immune pathways with a compromised EPC functionality. <P> Results: A mounting body of evidence points to an inflammation-driven traditional CV risk factorsrelated EPC dysfunction. The effect of aging on EPC was associated with the CXCR4 pathway, whereas that of hypertension was related to TNFα. Activation of Akt/eNOS was observed in response to diabetes- and dyslipidemia-related traits. Inflammation and oxidative stress underlie the EPC dysfunction during smoking. <P> Conclusion: Inflammatory and immune networks can be proposed as feasible biomarkers for risk stratification in personalized medicine schemes.

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Towards Personalized Medicine: Non-Coding RNAs and Endometrial Cancer

Healthcare ◽

10.3390/healthcare9080965 ◽

2021 ◽

Vol 9 (8) ◽

pp. 965

Author(s):

Anna Franca Cavaliere ◽

Federica Perelli ◽

Simona Zaami ◽

Roberto Piergentili ◽

Alberto Mattei ◽

...

Keyword(s):

Risk Factors ◽

Endometrial Cancer ◽

Personalized Medicine ◽

Early Stage ◽

Classification Systems ◽

Clinical Staging ◽

Prediction Function ◽

Current Classification ◽

Non Coding Rnas

Endometrial cancer (EC) is the most frequent female cancer associated with excellent prognosis if diagnosed at an early stage. The risk factors on which clinical staging is based are constantly updated and genetic and epigenetic characteristics have recently been emerging as prognostic markers. The evidence shows that non-coding RNAs (ncRNAs) play a fundamental role in various biological processes associated with the pathogenesis of EC and many of them also have a prognosis prediction function, of remarkable importance in defining the therapeutic and surveillance path of EC patients. Personalized medicine focuses on the continuous updating of risk factors that are identifiable early during the EC staging to tailor treatments to patients. This review aims to show a summary of the current classification systems and to encourage the integration of various risk factors, introducing the prognostic role of non-coding RNAs, to avoid aggressive therapies where not necessary and to treat and strictly monitor subjects at greater risk of relapse.

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Subpopulation Discovery in Epidemiological Data with Subspace Clustering

Foundations of Computing and Decision Sciences ◽

10.2478/fcds-2014-0015 ◽

2014 ◽

Vol 39 (4) ◽

pp. 271-300 ◽

Cited By ~ 3

Author(s):

Uli Niemann ◽

Myra Spiliopoulou ◽

Henry Völzke ◽

Jens-Peter Kühn

Keyword(s):

Risk Factors ◽

Personalized Medicine ◽

Quality Assessment ◽

Cluster Structure ◽

Subspace Clustering ◽

Ground Truth ◽

Epidemiological Data ◽

Clustering Methods ◽

Class Skew ◽

Epidemiological Cohort

Abstract A prerequisite of personalized medicine is the identification of groups of people who share specific risk factors towards an outcome. We investigate the potential of subspace clustering for finding such groups in epidemiological data. We propose a workflow that encompasses clusterability assessment before cluster discovery and quality assessment after learning the clusters. Epidemiological usually do not have a ground truth for the verification of clusters found in subspaces. Hence, we introduce quality assessment through juxtaposition of the learned models to “models-of-randomness”, i.e. models that do not reflect a true cluster structure. On the basis of this workflow, we select subspace clustering methods, compare and discuss their performance. We use a dataset with hepatic steatosis as outcome, but our findings apply on arbitrary epidemiological cohort data that have tenths of variables and exhibit class skew.

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