Review Article Influence of Acquired and Genetic Risk ...downloads.hindawi.com/journals/ijvm/2014/859726.pdf · gene mutation is the most common predisposing factor, accounting for

Review ArticleInfluence of Acquired and Genetic Risk Factorson the Prevention Management and Treatment ofThromboembolic Disease

Raghid Kreidy

Department of Vascular Surgery Saint George Hospital University Medical Center University of Balamand Youssef Sursock StreetPO Box 166378 Achrafieh Beirut 1100 2807 Lebanon

Correspondence should be addressed to Raghid Kreidy docrkdyincocomlb

Received 22 December 2013 Accepted 11 June 2014 Published 26 June 2014

Academic Editor Robert M Schainfeld

Copyright copy 2014 Raghid KreidyThis is an open access article distributed under theCreative CommonsAttribution License whichpermits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Prevention management and treatment of venous thromboembolism requires understanding of the epidemiology and associatedrisk factors particularly in recognizing populations warranting prophylaxis in evaluating patients with high risk situations and indetermining the duration of anticoagulation required to minimize recurrent thrombosis and to avoid postthrombotic syndromeThe present paper reviews recent advances concerning acquired and genetic risk factors for venous thrombosis analyses individualrisks related to age and focuses on thrombotic genetic risk factors and the synergistic gene-environment and gene-gene interactionsand their importance in the management and treatment of venous thromboembolic disease

1 Introduction

Lower extremity deep vein thrombosis (DVT) remains acommon and serious medical condition manifesting inpatients with recognized or unrecognized risk factor orcomplicating the outcome of critical ill and surgical patientsWhen it is misdiagnosed or improperly treated DVT maylead to pulmonary embolism the most devastating compli-cation of acute DVT Pulmonary embolism is responsible for10 of death among hospitalized patients and is the mostcommon preventable cause of death in these patients Amer-ican Heart Association statistics document two million casesof DVT each year with the incidence of DVT increasing asthe population ages [1] Pulmonary embolism (PE) accountsfor 200 000 deaths each year and the annual cost of the treat-ment is measured in billions of dollars [2] Postthromboticsyndrome is also a costly andmorbid long term complicationof DVT with severe adverse socioeconomic impacts [3]

The appropriate management of venous thrombosisrequires a thorough knowledge of diagnostic and treatmentmodalities However an understanding of the underlyingepidemiology and associated risk factors is equally essentialOnce risk factors for venous thrombosis are recognized

appropriatemanagement and treatmentmay ensue Promptlydiagnosed and properly treated lower extremity DVT maybecome a benign disease [4]

The purpose of this review paper is to determine theinfluence of acquired and genetic risk factors on the preven-tion management and treatment of venous thromboembolicdisease andon reducing the incidence of PE recurrent venousthrombosis and postthrombotic syndrome Age-related riskfactors interaction between acquired and genetic risk factorsand the effect ofmultiple and complex prothrombotic geneticdefects on venous thromboembolism will be particularlydiscussed

2 Discussion

The development of clinically manifest venous thrombosismost often occurs with the convergence of multiple acquiredand genetic risk factors These factors vary according toethnic and geographic distribution of the populations [5]Thesimultaneous presence of multiple risk factors is a prereq-uisite for thrombosis with synergistic gene-gene and gene-environment interactions often increasing the risk above thesum of individual risk factors [6]

Hindawi Publishing CorporationInternational Journal of Vascular MedicineVolume 2014 Article ID 859726 5 pageshttpdxdoiorg1011552014859726

2 International Journal of Vascular Medicine

Lower extremity deep venous thrombosis (DVT) is pre-dominantly a disease of older age [7] The incidence of DVTincreases exponentially with age for both idiopathic andsecondary DVT rising nearly 90-fold between 15 and 80 yearsof age with a relative risk of 19 for each 10-year increase inage [5 8] DVT is uncommon in young adults and very rarebefore the age of 20 years [5]

A recent study demonstrated that inherited throm-bophilia is the most common risk factor for venous throm-bosis among patients younger than 50 years with prevalenceof at least threefold increase comparing to the control group[9 10] Thrombophilia should be screened in patients underthe age of 50 even with the presence of a transient riskfactor Young adults present usually with severe forms ofvenous thrombosisThey should be assessed for acquired andparticularly for genetic factors This permits to extend theduration of anticoagulant therapy in high risk patients reduc-ing the incidence of postthrombotic syndrome and venousthromboembolic recurrence Pregnancy and treatment withoral contraceptives or estrogen drugs especially when associ-ated with inherited thrombophilia represent a frequent causeof DVT among young female patients [9 10] Screeningfor thrombophilia among young females with strong familyhistory of venous thromboembolism (VTE) before startingestrogen therapy is warranted Congenital abnormalities ofthe inferior vena cava (IVC) essentially when associatedwith inherited thrombophilia are an underdiagnosed causeof venous thrombosis [11] They are responsible for 14 ofiliac vein thrombosis among young adults and should beexcluded in young patients with spontaneous iliofemoralvenous thrombosis especially when recurrent venous orthrombosis resistance to anticoagulants is observed ForIVC congenital anomalies without thrombophilia at least6-month treatment with anti-vitamin K is required Longterm and sometimes life-long oral anticoagulation are recom-mended if IVC congenital abnormalities are associated withsevere thrombophilia or with recurrent DVT [12]

Elderly patients tend to have all the usual risk factorsassociated with VTE but also face additional risk conferredfrom a higher incidence of comorbidities immobility andthe hypercoagulability associated with aging In the elderlypatient clinical diagnosis can represent a challenge becauseclinical symptoms and signs are subtle atypical nonsensitiveand nonspecific Advanced age is an independent risk factorfor VTE [13] and has been reported in some series to bethe most frequent risk factor for VTE [14] Hospitalizationimmobility hip fracture heart failure and chronic renalfailure increase considerably the risk for venous thrombosisin the geriatric age group [15 16] Unless contraindicatedevery elderly patient bedridden or having multiple comor-bid conditions admitted for sepsis cancer critical medicalcondition or surgery must receive thromboprophylaxis withdose adjustment according to creatinin clearance if requiredEarly ambulation strict control of heart failure and chronicrenal failure and aggressive treatment of hip fractures arehighly recommended for these geriatric patients [16]

Obesity has been associated with increased thromboticrisk particularly in patients admitted for acute medicalillness trauma or surgery [17] Mechanical prophylaxis

and thromboprophylaxis with adjusted dose according toincreased bodyweight must be considered in this high riskgroup

The risks for VTE increase essentially when surgery isperformed in patients with advanced age under generalanesthesia for trauma cancer and major orthopedic dis-abling diseases [18]Thromboprophylaxis should be extendedfor five weeks postoperatively in patients undergoing majororthopedic surgery or abdominopelvic surgery for cancer[19]

The incidence of recurrent DVT is higher among patientsless than 65 years of age and patients with idiopathic DVTirreversible thrombotic risk primary hypercoagulopathyessentially factor V R 506 Q-Leiden (FVL) mutation andhyperhomocysteinemia [20]

In a recent published study the authors detected FVLmutation among 257 of all patients with recurrent DVTand among 666 of patients with recurrent DVT youngerthan 60 years [14] Prolonged duration of oral anticoagulationis suggested when patients carriers for FVLmutation developiliofemoral venous thrombosis or severe postthromboticsyndrome

Oger et al suggested that varicose veins are an inde-pendent risk factor for DVT only among women and thosegreater than 65 years of age [21] In a previous publishedstudy the author did not observe a significant difference inthe incidence of DVT related to varicose veins with gender[14] However 77 of the patients reported with varicoseveins were above 65 years of age emphasizing the importanceof thromboprophylaxis in this particular risk group [14]

Venous thrombosis following immobilization and bedrest is frequently bilateral In chronically immobilized per-sons residing at home or at a nursing home with no otherrisk factor for VTE recent guidelines do not suggest routinethromboprophylaxis [19]

Venous thrombosis increases with malignant tumors andincreases much more with metastasis with chemotherapyand particularly with thrombophilia However in outpatientswith cancer and indwelling central venous catheters and withno additional risk factors for VTE recent recommendationsdo not suggest routine prophylaxis with lowmolecular weightheparin [19]

Air travel is associated with a threefold higher risk forVTEwith an 18higher risk for each 2-hour increase in travelduration [22] This risk increases significantly when additiveknown risk factors including severe obesity advanced agelimited mobility previous VTE recent surgery or traumaactivemalignancy pregnancy estrogen use or known throm-bophilic disorder are reported For high risk patients hydra-tion avoiding drinking alcohol frequent ambulation calfmuscle exercise sitting in an aisle seat if feasible wear-ing graduated compression stockings putting comfortableclothes and using anticoagulants in some selected cases arehighly suggested [19]

A fine balance exists between anticoagulantprocoagulant and fibrinolytic factors A hypercoagulationstate or thrombophilia is common and is observed among50 to 70 of patients with unexplained VTE [23]395 to 535 of pregnant women [24 25] and 72

International Journal of Vascular Medicine 3

of individuals with travel-related VTE [26] In somecountries with high prevalence of prothrombotic geneticpolymorphism thrombophilia was reported to be thesecond most common cause of VTE [14] Recent studiessuggested that thrombophilia not only predisposes tothe development of venous thrombosis but also seems tointerfere in the development of postthrombotic syndromeeither directly by prolonging residual venous thrombosisor indirectly by increasing venous thrombotic recurrencerate [27 28] Assessment for genetic risk factors for VTEallows to avoid thrombogenic treatment (estroprogestativetreatment) and to prevent venous thrombosis in highrisk conditions (pregnancy trauma surgery and long-haul air travel) [29] Oral anticoagulation should beextended for prolonged periods among patients with severethrombophilia which ultimately reduces venous recurrencerate and postthrombotic syndrome [29]

Among the inherited thrombophilias factor V-Leidengene mutation is the most common predisposing factoraccounting for 10 to 20 of VTE in large populationstudies [30] The prevalence rate of factor V-Leiden inthe general population varies from 0 to 15 accordingto ethnicity [5 31] The allele mutation is low in AfricanAsian and South European populations (1ndash3) and highin Mediterranean populations (136 in Syria and 134in Greece) [32] Lebanon exhibits one of the highest fre-quencies of FVL mutation in the eastern Mediterraneanand in the world with a prevalence of 144 in the gen-eral population [33] The prevalence of FVL mutation isparticularly increased when venous thrombosis occurs inchildren young patients pregnant patients patients withfamily history of VTE and patients with spontaneousextended DVT resistant to anticoagulation [14 34] FVLmutation should be screened in this high risk subgroupof patients FVL mutation interacts with other concurrentacquired and thrombophilic conditions such as cancer oralcontraceptive use hormonal replacement therapy pregnancysurgery long-haul air travel and associated prothromboticgenetic abnormalities and essentially prothrombin G 20210Amutation to increase the risk of incident venous thrombosis[35] The relative risk for venous thrombosis is calculatedto be 2- to 3-fold for the prothrombin mutation aloneand 20-fold for a combination with FVL mutation [36]In a recent study the author reported three young adultpatients harboring this combination [36] Two of themcarriers for an additive MTHFR mutation with increasedhomocysteine level presenting for bilateral extensive lowerextremity venous thrombosis and severe PE were extremelyresistant to anticoagulant therapy and required IVC filterinsertion aggressive and prolonged anticoagulation FVLacts as a concurrent risk factor in individuals with otherprothrombotic polymorphisms and hyperhomocysteinemialeading to a synergistic gene-gene interaction increasing thepotential risk for venous thrombosis [37] The duration ofanticoagulant therapy among patients carriers for FVLmuta-tion depends on the nature and extension of the thrombosisthe underlying risk factors the presence of a previous VTEand the presence and severity of concurrent prothromboticgenetic mutation [36] Patients with homozygote mutation

for FVL and patients with combined heterozygote mutationfor FVL and prothrombin are considered for extended longterm treatment with anticoagulant therapy [38]

Increased homocysteine plasmatic level is associated withboth arterial and venous thrombosis and results essentiallyfrom MTHFR C 677 T and MTHFR A 1298 C mutationThese mutations may or may not lead to hyperhomocys-teinemia depending on the homozygosity or heterozygosityof the mutation coinheritance with another mutation orthe presence of concurrent B vitamin deficiency [39] Theassociation between MTHFR C 677 T and MTHFR A 1298C genetic polymorphism and the increased risk for VTE isstill controversial [40 41] Ray et al suggest that the risk ofthese mutations is weak and is increasing in older patientsand with coinheritance with other mutations [42] Akar etal confirmed that MTHFR A 1298 C is an independent riskfactor for venous thrombosis and thatMTHFRC677 T andA1298Cmutation are associatedwith 3- to 5-fold increased riskfor thrombosis [43] Our findings suggest thatMTHFRC 677T and MTHFR A 1298 C mutation either alone or associatedwith other prothrombotic genetic defects essentially FVLincrease the risk for venous thrombosis [14]

Factor V H 1299 R polymorphism has been reported tobe a possible risk factor for the development of VTE with ahigh prevalence in the world (95ndash1 5) [44] We suggest toscreen understudied polymorphism such as MTHFR A 1298C and factor V H 1299 R in severe extended cases of VTEresistant to anticoagulation and not explained by the mostusual mutations [45]

3 Conclusion

Recognizing acquired and genetic risk factors allows forbetter prevention management and treatment of venousthromboembolic disease Risk stratification is important indetermining which patient requires prophylaxis in highrisk situations in counseling patients related to their riskassociated with contraception pregnancy and hormonalreplacement and in understanding who requires furtherconsideration because of young or advanced age malignancyand recent surgery The number of acquired factors pre-disposing to thrombosis usually outweighs the number ofprothrombotic genetic factors Few thromboses are generallycaused by inherited thrombophilia alone The finding thatpatients with thrombophilia can harbor more than oneprothrombotic state have further increased the relevance ofthe congenital thrombophilic states The association of twoor more prothrombotic genetic defects to FVL mutationincreases considerably the risks and the severity of venousthrombosis

Thrombophilia screening should be tailored to accom-modate a populationrsquos risk factor In countries with highprevalence of prothrombotic genetic polymorphism throm-bophilia should be tested among patients younger than 50years even with a transient risk factor and patients withconditions highly suggestive of hypercoagulation state Thispermits to stratify individual patients in to high and low riskfor incident and recurrent venous thromboembolism target-ing prophylaxis to those who would benefit most extending


the duration of anticoagulation therapy in high risk patientsand ultimately reducing the occurrence of recurrent venousthromboembolism and postthrombotic syndrome

Conflict of Interests

The author declares that there is no conflict of interestsregarding the publication of this paper

References

[1] J Hirsh and J Hoak ldquoManagement of deep vein thrombosis andpulmonary embolism a statement for healthcare professionalsrdquoCirculation vol 93 no 12 pp 2212ndash2245 1996

[2] J Avorn and W C Winkelmayer ldquoComparing the costs risksand benefits of competing strategies for the primary preventionof venous thromboembolismrdquo Circulation vol 110 supplement1 pp IV25ndashIV32 2004

[3] M McGuckin R Waterman J Brooks et al ldquoValidation ofvenous leg ulcer guidelines in the United States and UnitedKingdomrdquo American Journal of Surgery vol 183 no 2 pp 132ndash137 2002

[4] R Kreidy andN I Hakime ldquoDeep vein thrombosis of the lowerextremities a benign diseaserdquoChirurgia vol 22 no 3 pp 143ndash147 2009

[5] M Montagnana E J Favaloro M Franchini G C Guidiand G Lippi ldquoThe role of ethnicity age and gender in venousthromboembolismrdquo Journal of Thrombosis and Thrombolysisvol 29 no 4 pp 489ndash496 2010

[6] F R Rosendaal ldquoVenous thrombosis amulticausal diseaserdquoTheLancet vol 353 no 9159 pp 1167ndash1173 1999

[7] P D Stein R D Hull F Kayali W A Ghali A K Alshab andR E Olson ldquoVenous thromboembolism according to age theimpact of an aging populationrdquo Archives of Internal Medicinevol 164 no 20 pp 2260ndash2265 2004

[8] I ANaeligss S CChristiansen P Romundstad S CCannegieterF R Rosendaal and J Hammerstroslashm ldquoIncidence andmortalityof venous thrombosis a population-based studyrdquo Journal ofThrombosis and Haemostasis vol 5 no 4 pp 692ndash699 2007

[9] R Kreidy P Salameh andMWaked ldquoLower extremity venousthrombosis in patients younger than 50 years of agerdquo VascularHealth and Risk Management vol 8 no 1 pp 161ndash167 2012

[10] R Kreidy ldquoVenous thrombosis of lower extremities in youngpatientsrdquo Phlebolymphology vol 20 no 1 p 30 2012

[11] R Kreidy ldquoUnderdiagnosed cause of lower extremity venousthrombosis in the young patientrdquo International Angiology vol32 supplement 1 p 66 2013

[12] J G Schneider M V Eynatten K A Dugi M Duex and P PNawroth ldquoRecurrent deep venous thrombosis caused by con-genital interruption of the inferior vena cava and heterozygousfactorVLeidenmutationrdquo Journal of InternalMedicine vol 252no 3 pp 276ndash280 2002

[13] R Alikhan A T Cohen S Combe et al ldquoRisk factors forvenous thromboembolism in hospitalized patients with acutemedical illness analysis of the MEDENOX Studyrdquo Archives ofInternal Medicine vol 164 no 9 pp 963ndash968 2004

[14] R Kreidy M Waked E Stephan et al ldquoAcquired and geneticrisk factors for deep vein thrombosis of lower extremitiesamong Lebanese patientsrdquo Le Journal Medical Libanais vol 60no 1 pp 24ndash29 2012

[15] R Kreidy E Stephan P Salameh and M Waked ldquoValue ofvenous color flow duplex as initial screening test for geriatricinpatients with clinically suspected pulmonary embolismrdquoVascular Health and Risk Management vol 7 pp 585ndash589 2011

[16] R Kreidy E Stephan P Salameh and M Waked ldquoLowerextremity venous thrombosis in the elderly patientrdquo Interna-tional Angiology vol 32 supplement 1 p 53 2013

[17] J A Heit ldquoVenous thromboembolism disease burden out-comes and risk factorsrdquo Journal ofThrombosis and Haemostasisvol 3 no 8 pp 1611ndash1617 2005

[18] R H White H Zhou and P S Romano ldquoIncidence ofsymptomatic venous thromboembolism after different electiveor urgent surgical proceduresrdquo Thrombosis and Haemostasisvol 90 no 3 pp 446ndash455 2003

[19] G H Guyatt E A Akl M Crowther D D Gutterman and HJ Schunemann ldquoExecutive summary antithrombotic therapyand prevention of thrombosis 9th ed American College ofChest Physicians evidence-based clinical practice guidelinesrdquoChest vol 141 no 2 pp 7Sndash47S 2012

[20] AMarchiori LMosenaMH Prins andP Prandoni ldquoThe riskof recurrent venous thromboembolism among heterozygouscarriers of factor V Leiden or prothrombin G20210A mutationA systematic review of prospective studiesrdquoHaematologica vol92 no 8 pp 1107ndash1114 2007

[21] E Oger C Leroyer E Le Moigne et al ldquoThe value of a riskfactor analysis in clinically suspected deep venous thrombosisrdquoRespiration vol 64 no 5 pp 326ndash330 1997

[22] D Chandra E Parisini and D Mozaffarian ldquoMeta-analysistravel and risk for venous thromboembolismrdquo Annals of Inter-nal Medicine vol 151 no 3 pp 180ndash190 2009

[23] M Cushman ldquoInherited risk factors for venous thrombosisrdquoHematology vol 2005 no 1 pp 452ndash457 2005

[24] I Martinelli V de Stefano E Taioli K Paciaroni E Rossiand P M Mannucci ldquoInherited thrombophilia and first venousthromboembolism during pregnancy and puerperiumrdquoThrom-bosis and Haemostasis vol 87 no 5 pp 791ndash795 2002

[25] S M Bates ldquoManagement of pregnant women with throm-bophilia or a history of venous thromboembolismrdquo Hematol-ogyAmerican Society of Hematology Education Program pp143ndash150 2007

[26] K A Parsi M A McGrath and R S A Lord ldquoTravellerrsquosvenous thromboembolismrdquo Cardiovascular Surgery vol 9 no2 pp 157ndash158 2001

[27] R Kreidy ldquoPathophysiology of post-thrombotic syndrome theeffect of recurrent venous thrombosis and inherited throm-bophiliardquo ISRN Vascular Medicine vol 2011 Article ID 5135034 pages 2011

[28] R Kreidy ldquoContribution of recurrent venous thrombosis andinherited thrombophilia to the pathogenesis of postthromboticsyndromerdquo Clinical Applied Thrombosis and Haemostasis 2013

[29] R Kreidy and N Irani-Hakime ldquoIs thrombophilia a major riskfactor for deep vein thrombosis of the lower extremities amongLebanese patientsrdquoVascular Health and Risk Management vol5 pp 627ndash633 2009

[30] S Moll ldquoThrombophiliasmdashpractical implications and testingcaveatsrdquo Journal of Thrombosis and Thrombolysis vol 21 no 1pp 7ndash15 2006

[31] L N Roberts R K Patel and R Arya ldquoVenous thromboem-bolism and ethnicityrdquo British Journal of Haematology vol 146no 4 pp 369ndash383 2009


[32] WHGeerts J AHeit G P Clagett et al ldquoPrevention of venousthromboembolismrdquo Chest vol 119 no 1 supplement pp 381Sndash175S 2001

[33] H Irani-Hakimeh H Tamim R Kreidy and W Y AlmawildquoThe prevalence of factor V R506Q mutation-Leiden amongapparently healthy Lebaneserdquo The American Journal of Hema-tology vol 65 no 1 pp 45ndash49 2000

[34] I Aschka V Aumann F Bergmann et al ldquoPrevalence offactor V leiden in children with thrombo-embolismrdquo EuropeanJournal of Pediatrics vol 155 no 12 pp 1009ndash1014 1996

[35] R Kreidy ldquoFactor V-Leidenmutation a common risk factor forvenous thrombosis among Lebanese patientsrdquoThrombosis vol2012 Article ID 380681 4 pages 2012

[36] S R Poort F R Rosendaal P H Reitsma and R M BertinaldquoA common genetic variation in the 31015840-untranslated regionof the prothrombin gene is associated with elevated plasmaprothrombin levels and an increase in venous thrombosisrdquoBlood vol 88 no 10 pp 3698ndash3703 1996

[37] V De Stefano P Chiusolo K Paciaroni and G Leone ldquoEpi-demiology of factor V leiden clinical implicationsrdquo Seminars inThrombosis and Hemostasis vol 24 no 4 pp 367ndash379 1998

[38] G Palareti ldquoCurrent criteria to determine the duration ofanticoagulant therapyrdquo Recent Progress in Medicine vol 98 no12 pp 603ndash606 2007

[39] M A Crowther and J G Kelton ldquoCongenital throm-bophilic states associated with venous thrombosis a qualitativeoverview and proposed classification systemrdquoAnnals of InternalMedicine vol 138 no 2 pp 128ndash134 2003

[40] S M Naushad M N J Jamal R Angalena C K Prasadand A R R Devi ldquoHyperhomocysteinemia and the compoundheterozygous state for methylene tetrahydrofolate reductase areindependent risk factors for deep vein thrombosis among SouthIndiansrdquo Blood Coagulation and Fibrinolysis vol 18 no 2 pp113ndash117 2007

[41] I Spiroski S Kedev S Antov et al ldquoAssociation ofmethylenete-trahydrofolate reductase (MTHFR-677 and MTHFR-1298)genetic polymorphisms with occlusive artery disease and deepvenous thrombosis in Macedoniansrdquo Croatian Medical Journalvol 49 no 1 pp 39ndash49 2008

[42] J G Ray D Shmorgun and W S Chan ldquoCommon C677Tpolymorphismof themethylenetetrahydrofolate reductase geneand the risk of venous thromboembolism Meta-analysis of 31studiesrdquo Pathophysiology of Haemostasis and Thrombosis vol32 no 2 pp 51ndash58 2002

[43] N Akar E Akar R Akcay F Avcu A Yalcin and S CinldquoEffect Of metylenetetrahydrofolate reductase 677 C-T 1298 A-C and 1317 T-C on factor V 1691 mutation in Turkish deep veinthrombosis patientsrdquo Thrombosis Research vol 97 no 3 pp163ndash167 2000

[44] G S Zaatari Z K Otrock A S Sabbagh and R A RMahfouzldquoPrevalence of factor V R2 (H1299R) polymorphism in theLebanese populationrdquo Pathology vol 38 no 5 pp 442ndash4442006

[45] R Kreidy M Waked E Stephan I Jureidini and N Irani-Hakime ldquoContribution of factor V R 506 Q-Leiden prothrom-bin G 20210 A and MTHFR C 677 T mutation to the geneticsusceptibility of deep vein thrombosis of lower extremitiesIs screening for factor V H 1299 R and MTHFR A 1298 Cjustifiedrdquo International Angiology vol 28 supplement 1 no 4pp S123ndashS124 2009

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Lower extremity deep venous thrombosis (DVT) is pre-dominantly a disease of older age [7] The incidence of DVTincreases exponentially with age for both idiopathic andsecondary DVT rising nearly 90-fold between 15 and 80 yearsof age with a relative risk of 19 for each 10-year increase inage [5 8] DVT is uncommon in young adults and very rarebefore the age of 20 years [5]

A recent study demonstrated that inherited throm-bophilia is the most common risk factor for venous throm-bosis among patients younger than 50 years with prevalenceof at least threefold increase comparing to the control group[9 10] Thrombophilia should be screened in patients underthe age of 50 even with the presence of a transient riskfactor Young adults present usually with severe forms ofvenous thrombosisThey should be assessed for acquired andparticularly for genetic factors This permits to extend theduration of anticoagulant therapy in high risk patients reduc-ing the incidence of postthrombotic syndrome and venousthromboembolic recurrence Pregnancy and treatment withoral contraceptives or estrogen drugs especially when associ-ated with inherited thrombophilia represent a frequent causeof DVT among young female patients [9 10] Screeningfor thrombophilia among young females with strong familyhistory of venous thromboembolism (VTE) before startingestrogen therapy is warranted Congenital abnormalities ofthe inferior vena cava (IVC) essentially when associatedwith inherited thrombophilia are an underdiagnosed causeof venous thrombosis [11] They are responsible for 14 ofiliac vein thrombosis among young adults and should beexcluded in young patients with spontaneous iliofemoralvenous thrombosis especially when recurrent venous orthrombosis resistance to anticoagulants is observed ForIVC congenital anomalies without thrombophilia at least6-month treatment with anti-vitamin K is required Longterm and sometimes life-long oral anticoagulation are recom-mended if IVC congenital abnormalities are associated withsevere thrombophilia or with recurrent DVT [12]

Elderly patients tend to have all the usual risk factorsassociated with VTE but also face additional risk conferredfrom a higher incidence of comorbidities immobility andthe hypercoagulability associated with aging In the elderlypatient clinical diagnosis can represent a challenge becauseclinical symptoms and signs are subtle atypical nonsensitiveand nonspecific Advanced age is an independent risk factorfor VTE [13] and has been reported in some series to bethe most frequent risk factor for VTE [14] Hospitalizationimmobility hip fracture heart failure and chronic renalfailure increase considerably the risk for venous thrombosisin the geriatric age group [15 16] Unless contraindicatedevery elderly patient bedridden or having multiple comor-bid conditions admitted for sepsis cancer critical medicalcondition or surgery must receive thromboprophylaxis withdose adjustment according to creatinin clearance if requiredEarly ambulation strict control of heart failure and chronicrenal failure and aggressive treatment of hip fractures arehighly recommended for these geriatric patients [16]

Obesity has been associated with increased thromboticrisk particularly in patients admitted for acute medicalillness trauma or surgery [17] Mechanical prophylaxis

and thromboprophylaxis with adjusted dose according toincreased bodyweight must be considered in this high riskgroup

The risks for VTE increase essentially when surgery isperformed in patients with advanced age under generalanesthesia for trauma cancer and major orthopedic dis-abling diseases [18]Thromboprophylaxis should be extendedfor five weeks postoperatively in patients undergoing majororthopedic surgery or abdominopelvic surgery for cancer[19]

The incidence of recurrent DVT is higher among patientsless than 65 years of age and patients with idiopathic DVTirreversible thrombotic risk primary hypercoagulopathyessentially factor V R 506 Q-Leiden (FVL) mutation andhyperhomocysteinemia [20]

In a recent published study the authors detected FVLmutation among 257 of all patients with recurrent DVTand among 666 of patients with recurrent DVT youngerthan 60 years [14] Prolonged duration of oral anticoagulationis suggested when patients carriers for FVLmutation developiliofemoral venous thrombosis or severe postthromboticsyndrome

Oger et al suggested that varicose veins are an inde-pendent risk factor for DVT only among women and thosegreater than 65 years of age [21] In a previous publishedstudy the author did not observe a significant difference inthe incidence of DVT related to varicose veins with gender[14] However 77 of the patients reported with varicoseveins were above 65 years of age emphasizing the importanceof thromboprophylaxis in this particular risk group [14]

Venous thrombosis following immobilization and bedrest is frequently bilateral In chronically immobilized per-sons residing at home or at a nursing home with no otherrisk factor for VTE recent guidelines do not suggest routinethromboprophylaxis [19]

Venous thrombosis increases with malignant tumors andincreases much more with metastasis with chemotherapyand particularly with thrombophilia However in outpatientswith cancer and indwelling central venous catheters and withno additional risk factors for VTE recent recommendationsdo not suggest routine prophylaxis with lowmolecular weightheparin [19]

Air travel is associated with a threefold higher risk forVTEwith an 18higher risk for each 2-hour increase in travelduration [22] This risk increases significantly when additiveknown risk factors including severe obesity advanced agelimited mobility previous VTE recent surgery or traumaactivemalignancy pregnancy estrogen use or known throm-bophilic disorder are reported For high risk patients hydra-tion avoiding drinking alcohol frequent ambulation calfmuscle exercise sitting in an aisle seat if feasible wear-ing graduated compression stockings putting comfortableclothes and using anticoagulants in some selected cases arehighly suggested [19]

A fine balance exists between anticoagulantprocoagulant and fibrinolytic factors A hypercoagulationstate or thrombophilia is common and is observed among50 to 70 of patients with unexplained VTE [23]395 to 535 of pregnant women [24 25] and 72







3 Conclusion







References




















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of






















3 Conclusion







References




















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















References




















































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





















of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















Documents

Review Article Influence of Acquired and Genetic Risk ...downloads.hindawi.com/journals/ijvm/2014/859726.pdf · gene mutation is the most common predisposing factor, accounting for