Sclerotherapy of lower limb veins: Indications,contraindications and treatment strategies to prevent complications – A consensus document of the International Union of Phlebology-2023
Restricted accessReview articleFirst published online May, 2023
Sclerotherapy of lower limb veins: Indications,contraindications and treatment strategies to prevent complications – A consensus document of the International Union of Phlebology-2023
Sclerotherapy is a non-invasive procedure commonly used to treat superficial venous disease, vascular malformations and other ectatic vascular lesions. While extremely rare, sclerotherapy may be complicated by serious adverse events.
Objectives
To categorise contraindications to sclerotherapy based on the available scientific evidence.
Methods
An international, multi-disciplinary panel of phlebologists reviewed the available scientific evidence and developed consensus where evidence was lacking or limited.
Results
Absolute Contraindications to sclerotherapy where the risk of harm would outweigh any benefits include known hypersensitivity to sclerosing agents; acute venous thromboembolism (VTE); severe neurological or cardiac adverse events complicating a previous sclerotherapy treatment; severe acute systemic illness or infection; and critical limb ischaemia. Relative Contraindications to sclerotherapy where the potential benefits of the proposed treatment would outweigh the risk of harm or the risks may be mitigated by other measures include pregnancy, postpartum and breastfeeding; hypercoagulable states with risk of VTE; risk of neurological adverse events; risk of cardiac adverse events and poorly controlled chronic systemic illness. Conditions and circumstances where Warnings and Precautions should be considered before proceeding with sclerotherapy include risk of cutaneous necrosis or cosmetic complications such as pigmentation and telangiectatic matting; intake of medications such as the oral contraceptive and other exogenous oestrogens, disulfiram and minocycline; and psychosocial factors and psychiatric comorbidities that may increase the risk of adverse events or compromise optimal treatment outcomes.
Conclusions
Sclerotherapy can achieve safe clinical outcomes provided that (1) patient-related risk factors and in particular all material risks are (1a) adequately identified and the risk benefit ratio is clearly and openly discussed with treatment candidates within a reasonable timeframe prior to the actual procedure; (1b) when an individual is not a suitable candidate for the proposed intervention, conservative treatment options including the option of ‘no intervention as a treatment option’ are discussed; (1c) complex cases are referred for treatment in controlled and standardised settings and by practitioners with more expertise in the field; (1d) only suitable individuals with no absolute contraindications or those with relative contraindications where the benefits outweigh the risks are offered intervention; (1e) if proceeding with intervention, appropriate prophylactic measures and other risk-mitigating strategies are adopted and appropriate follow-up is organised; and (2) procedure-related risk factors are minimised by ensuring the treating physicians (2a) have adequate training in general phlebology with additional training in duplex ultrasound, procedural phlebology and in particular sclerotherapy; (2b) maintain their knowledge and competency over time and (2c) review and optimise their treatment strategies and techniques on a regular basis to keep up with the ongoing progress in medical technology and contemporary scientific evidence.
De MaeseneerMGKakkosSKAherneT, et al.Editor’s choice European Society for Vascular Surgery (ESVS) 2022 clinical practice guidelines on the management of chronic venous disease of the lower limbs. Eur J Vasc Endovasc Surg2022; 63: 184–267.
2.
BradburyAWBateGPangK, et al.Ultrasound-guided foam sclerotherapy is a safe and clinically effective treatment for superficial venous reflux. J Vasc Surg2010; 52: 939–945.
3.
BreuFXGuggenbichlerS. European consensus meeting on foam sclerotherapy, April, 4-6, 2003, Tegernsee, Germany. Dermatol Surg2004; 30: 709–717.
4.
CavezziAFrulliniARicciS, et al.Treatment of varicose veins by foam sclerotherapy: two clinical series. Phlebology2002; 17: 13–18.
5.
OuvryPAllaertF-ADesnosP, et al.Efficacy of polidocanol foam versus liquid in sclerotherapy of the great saphenous vein: a multicentre randomised controlled trial with a 2-year follow-up. Eur J Vasc Endovasc Surg2008; 36: 366–370.
6.
BlaiseSCharavin-CocuzzaMRiomH, et al.Treatment of low-flow vascular malformations by ultrasound-guided sclerotherapy with polidocanol foam: 24 cases and literature review. Eur J Vasc Endovasc Surg2011; 41: 412–417.
7.
ZucchiAMeariniLMeariniE, et al.Treatment of varicocele: randomized prospective study on open surgery versus Tauber antegrade sclerotherapy. J Androl2005; 26: 328–332.
8.
GuexJJAllaertFAGilletJL, et al.Immediate and midterm complications of sclerotherapy: report of a prospective multicenter registry of 12, 173 sclerotherapy sessions. Dermatol Surg2005; 31: 123–128. Discussion 128. Multicenter Study Research Support, Non-U.S. Gov’t.
9.
GilletJDonnetALauseckerM, et al.Pathophysiology of visual disturbances occurring after foam sclerotherapy. Phlebology2010; 25: 261–266.
10.
GilletJGuedesJGuexJ, et al.Side-effects and complications of foam sclerotherapy of the great and small saphenous veins: a controlled multicentre prospective study including 1025 patients. Phlebology2009; 24: 131–138.
11.
YiannakopoulouE. Safety concerns for sclerotherapy of telangiectases, reticular and varicose veins. Pharmacology2016; 98: 62–69.
12.
CavezziAParsiK. Complications of foam sclerotherapy. Phlebology2012; 27: 46–51.
13.
NguyenCNNguyenQ-BDSilapuntS. Analysis of adverse events with sclerosants reported to the United States food and drug administration. Phlebology2022; 37: 452–459.
14.
GrondinLSorianoJ. Duplex-echosclerotherapy, the quest for the safe technique. Phlebologie1992; 24(3): 824–825.
15.
SchadeckM. Doppler et Echotomographie dans la scle´rose des veines saphe`nes. Phlebologie1986; 39: 697–716.
LimSYTanJXD’CruzRT, et al.Catheter-directed foam sclerotherapy, an alternative to ultrasound-guided foam sclerotherapy for varicose vein treatment: a systematic review and meta-analysis. Phlebology2020; 35: 369–383.
CavezziAMostiGCampanaF, et al.Catheter foam sclerotherapy of the great saphenous vein, with perisaphenous tumescence infiltration and saphenous irrigation. Eur J Vasc Endovasc Surg2017; 54: 629–635.
20.
WhiteleyMSPatelSB. Modified Tessari Tourbillon technique for making foam sclerotherapy with silicone-free syringes. Phlebology2015; 30: 614–617.
21.
WhiteleyMSDos SantosSJLeeCT, et al.Mechanochemical ablation causes endothelial and medial damage to the vein wall resulting in deeper penetration of sclerosant compared with sclerotherapy alone in extrafascial great saphenous vein using an ex vivo model. J Vasc Surg Venous Lymphatic Disord2017; 5: 370–377.
22.
ThierensNHolewijnSVissersWH, et al.Five-year outcomes of mechano-chemical ablation of primary great saphenous vein incompetence. Phlebology2020; 35: 255–261.
23.
ParsiK. Interaction of detergent sclerosants with cell membranes. Phlebology2015; 30: 306–315. Review.
24.
ParsiKExnerTConnorDE, et al.The lytic effects of detergent sclerosants on erythrocytes, platelets, endothelial cells and microparticles are attenuated by albumin and other plasma components in vitro. Eur J Vasc Endovasc Surg2008; 36: 216–223. Research Support, Non-U.S. Gov’t.
25.
ConnorDECooley-AndradeOGohWX, et al.Detergent sclerosants are deactivated and consumed by circulating blood cells. Eur J Vasc Endovasc Surg2015; 49: 426–431. Research Support, Non-U.S. Gov’t.
26.
DabbsEBDos SantosSJMainsiouwLE, et al.Implication of foam sclerosant inactivation by human whole blood in a laboratory setting. Phlebology2018; 33: 338–343.
27.
TessariLCavezziAIzzoM, et al.In vivo demonstration of sodium tetradecyl sulphate sclerosant foam binding with blood proteins. In: 13th annual meeting of the European venous forum. Florence, Italy: Phlebology, 2012, pp. 307–326.
28.
WollmannJC. The history of sclerosing foams. Dermatol Surg2004; 30: 694–703.
29.
WatkinsMR. Deactivation of sodium tetradecyl sulphate injection by blood proteins. Eur J Vasc Endovasc Surg2011; 41: 521–525.
30.
TessariLCavezziAFrulliniA. Preliminary experience with a new sclerosing foam in the treatment of varicose veins. Dermatol Surg2001; 27: 58–60.
31.
RaoJGoldmanMP. Stability of foam in sclerotherapy: differences between sodium tetradecyl sulfate and polidocanol and the type of connector used in the double-syringe system technique. Dermatol Surg2005; 31: 19–22.
32.
WongKChenTConnorDE, et al.Basic physiochemical and rheological properties of detergent sclerosants. Phlebology2015; 30: 339–349.
33.
RedondoPCabreraJ. Microfoam sclerotherapy. Semin Cutan Med Surg2005; 24: 175–183.
34.
StarPConnorDEParsiK. Novel developments in foam sclerotherapy: Focus on Varithena(R) (polidocanol endovenous microfoam) in the management of varicose veins. Phlebology2018; 33: 150–162.
35.
RocheEPonsRRocheO, et al.A new automated system for the preparation of sclerosant foam: a study of the physical characteristics produced and the device settings required. Phlebology2020; 35: 724–733.
36.
WongKConnorDEAndradeOC, et al.Foam bubble size is significantly influenced by sclerosant concentration for polidocanol but not sodium tetradecyl sulphate. Phlebology2021; 36: 576–587.
37.
MorrisonNNeuhardtDLRogersCR, et al.Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation. J Vasc Surg2008; 47: 830–836. Comparative Study.
38.
MorrisonNNeuhardtDLRogersCR, et al.Incidence of side effects using carbon dioxide-oxygen foam for chemical ablation of superficial veins of the lower extremity. Eur J Vasc Endovasc Surg2010; 40: 407–413.
39.
MorrisonNNeuhardtD. Foam sclerotherapy: cardiac and cerebral monitoring. Phlebology2009; 24: 252–259.
40.
ReganJDGibsonKDRushJE, et al.Clinical significance of cerebrovascular gas emboli during polidocanol endovenous ultra-low nitrogen microfoam ablation and correlation with magnetic resonance imaging in patients with right-to-left shunt. J Vasc Surg2011; 53: 131–137.
41.
MyersKARobertsS. Evaluation of published reports of foam sclerotherapy: what do we know conclusively?Phlebology2009; 24: 275–280.
42.
WongM. Should foam made with physiologic gases be the standard in sclerotherapy?Phlebology2015; 30: 580–586.
43.
WatkinsMROliverRJ. Physiochemical properties and reproducibility of air-based sodium tetradecyl sulphate foam using the Tessari method. Phlebology2017; 32: 390–396.
44.
ParsiKExnerTLowJ, et al.In Vitro effects of detergent sclerosants on clot formation and fibrinolysis. Eur J Vasc Endovasc Surg2011; 41: 267–277.
45.
ParsiKExnerTConnorDE, et al.In vitro effects of detergent sclerosants on coagulation, platelets and microparticles. Eur J Vasc Endovasc Surg2007; 34: 731–740.
46.
CameronEChenTConnorDE, et al.Sclerosant foam structure and stability is strongly influenced by liquid air fraction. Eur J Vasc Endovasc Surg2013; 46: 488–494.
47.
TanLWongKConnorD, et al.Generation of sclerosant foams by mechanical methods increases the foam temperature. Phlebology2017; 32: 501–505.
48.
ParsiK. Paradoxical embolism, stroke and sclerotherapy. Phlebology2012; 27: 147–167. Review.
49.
CavezziATessariL. Foam sclerotherapy techniques: different gases and methods of preparation, catheter versus direct injection. Phlebology2009; 24: 247–251. Comparative Study Review.
50.
MeloGBEmersonGGDiasCSJr., et al.Release of silicone oil and the off-label use of syringes in ophthalmology. Br J Ophthalmol2020; 104: 291–296.
51.
McMasterS. Sodium tetradecyl sulphate foam stability prior to injection: Factors affecting liquid reformation. Phlebology/Venous Forum Royal Soc Med2011; 26: 222–226.
52.
BreuFXGuggenbichlerSWollmannJC. 2nd European consensus meeting on foam sclerotherapy 2006, Tegernsee, Germany. Vasa2008; 37(Suppl 71): 1–29.
53.
PatelSBOstlerAEDos SantosSJ, et al.The effects of environmental and compositional manipulations on the longevity of Tessari-made foam for sclerotherapy. J Vasc Surg Venous Lymphat Disord2015; 3: 312–318.
54.
ConnorDEJosephJEExnerT, et al.Infusion of foam sclerosants results in a distance-dependent procoagulant activity, haemoconcentration and elevation of D-dimer levels. Phlebology2014; 29: 677–687. Comparative Study Randomized Controlled Trial.
55.
McMasterPEverettWG. Fatal pulmonary embolism following compression sclerotherapy for varicose veins. Postgrad Med J1973; 49: 517–518.
56.
KangMYangAHannafordP, et al.Skin necrosis following sclerotherapy. Part 1: differential diagnosis based on classification of pathogenic mechanisms. Phlebology2022; 37: 409–424.
57.
MaRWPilotelleAParaskevasP, et al.Three cases of stroke following peripheral venous interventions. Phlebology2011; 26: 280–284.
58.
RayhillMBurchR. PFO and migraine: is there a role for closure?Curr Neurol Neurosc Rep2017; 17: 20.
59.
HahnMSchulzTJungerM. Late stroke after foam sclerotherapy. Vasa2010; 39: 108–110.
60.
ForleeMVGroudenMMooreDJ, et al.Stroke after varicose vein foam injection sclerotherapy. J Vasc Surg2006; 43: 162–164.
61.
HanischFMullerTKrivokucaM, et al.Stroke following variceal sclerotherapy. Eur J Med Res2004; 9: 282–284.
62.
DraiEFerrariEBedouchaP, et al.[Sclerosis of varicose veins of the lower limbs causing ischemic cerebral accident]. Presse Med1994; 23: 182.
BushRGDerrickMManjoneyD. Major neurological events following foam sclerotherapy. Phlebology2008; 23: 189–192.
65.
PotterBGobeilFOiknineA, et al.The first case of takotsubo cardiomyopathy associated with sodium tetradecyl sulphate sclerotherapy. Can J Cardiol2010; 26: 146–148.
66.
CifuentesJUlloaJPintoP, et al.Takotsubo Syndrome induced by sclerotherapy with polidocanol. Acta Phlebologica2020; 21: 48–51.
67.
McGivernPIvolginaN. Legal liablity in informed consent cases: What are the rules of the game?McGill J Law Health2013; 139: 129–143.
68.
SkeneLSmallwoodR. Informed consent: lessons from Australia. BMJ2002; 324: 39–41.
ButterworthJFMackeyDCWasnickJD. Anesthetic complications. Morgan and Mikhail’s clinical anesthesiology. 5th ed.New York, USA: McGraw-Hill Education, 2013, pp. 1199–1229.
71.
ThibaultPK. Sclerotherapy of varicose veins and telangiectasias: a 2-Year experience with Sodium Tetradecyl Sulphate. ANZ J Phleb1999; 3: 25–30.
72.
GoldmanMPBennettRG. Treatment of telangiectasia: a review. J Am Acad Dermatol1987; 17: 167–182. Research Support, Non-U.S. Gov’t Review.
73.
GoldmanMPGuexJJWeissRA. Sclerotherapy: treatment of varicose and telangiectatic leg veins. 5th ed.Philadelphia: Saunders Elsevier, 2011.
74.
GoldmanMPBerganJJGuexJJ. Sclerotherapy: treatment of varicose veins and telangiectatic leg veins. 4thed.Philadephia: Mosby Elsevier, 2007.
75.
VarcoePF. Ultrasound guided sclerotherapy: efficacy, adverse events and dosing – an international survey. ANZ J Phleb2003; 7: 17–24.
76.
CavezziAParsiK. Complications of foam sclerotherapy. Phlebology2012; 27(Suppl 1): 46–51.
77.
Bunke-PaquetteN. Complications of liquid sclerotherapy. In: BerganJBunke-PaquetteN (eds) The vein book. 2 ed.New York: Oxford University Press, 2014, pp. 115–126.
78.
MuraroARobertsGWormM, et al.Anaphylaxis: guidelines from the European Academy of Allergy and Clinical Immunology. Allergy2014; 69: 1026–1045. Practice Guideline.
79.
WormMEdenharterGRueffF, et al.Symptom profile and risk factors of anaphylaxis in Central Europe. Allergy2012; 67: 691–698.
80.
KumarVAbbasAKAsterJC, et al.Robbins basic pathology. 10th ed.Philadelphia, PA: Elsevier, 2018.
81.
KolawoleHMarshallSDCrillyH, et al.Australian and New Zealand anaesthetic allergy group/Australian and New Zealand college of anaesthetists perioperative anaphylaxis management guidelines. Anaesth Intensive Care2017; 45: 151–158.
82.
KearonCAklEA. Duration of anticoagulant therapy for deep vein thrombosis and pulmonary embolism. Blood2014; 123: 1794–1801. Review.
83.
ChiYWWoodsTC. Clinical risk factors to predict deep venous thrombosis post-endovenous laser ablation of saphenous veins. Phlebology2014; 29: 150–153. Clinical Trial.
84.
PuggioniAMarksNHingoraniA, et al.The safety of radiofrequency ablation of the great saphenous vein in patients with previous venous thrombosis. J Vasc Surg Venous Lymphatic Disord2009; 49: 1248–1255.
85.
DecoususHQuereIPreslesE, et al.Superficial venous thrombosis and venous thromboembolism: a large, prospective epidemiologic study. Ann Intern Med2010; 152: 218–224. Multicenter Study Research Support, Non-U.S. Gov’t.
86.
HansonJNAscherEDePippoP, et al.Saphenous Vein Thrombophlebitis (SVT): a deceptively benign disease. J Vasc Surg1998; 27: 677–680.
87.
LitzendorfMESatianiB. Superficial venous thrombosis: disease progression and evolving treatment approaches. Vasc Health Risk Manag2011; 7: 569–575. Review.
88.
Beyer-WestendorfJSchellongSMGerlachH, et al.Prevention of thromboembolic complications in patients with superficial-vein thrombosis given rivaroxaban or fondaparinux: the open-label, randomised, non-inferiority SURPRISE phase 3b trial. The Lancet Haematol2017; 4: e105–e113.
89.
BaggenVJChungKKooleK, et al.Association of varicosities and concomitant deep venous thrombosis in patients with superficial venous thrombosis, a systematic review. Eur J General Practice2015; 21: 70–76.
90.
ScovellSDErgulEAConradMF. Medical management of acute superficial vein thrombosis of the saphenous vein. J Vasc Surg Venous Lymphat Disord2018; 6: 109–117.
91.
VerlatoFZucchettaPPrandoniP, et al.An unexpectedly high rate of pulmonary embolism in patients with superficial thrombophlebitis of the thigh. J Vasc Surg1999; 30: 1113–1115.
92.
FarberA. Chronic limb-threatening ischemia. N Engl J Med2018; 379: 171–180.
93.
MostiGIabichellaMLPartschH. Compression therapy in mixed ulcers increases venous output and arterial perfusion. J Vasc Surg2012; 55: 122–128.
94.
MostiGCavezziAMassimettiG, et al.Recalcitrant venous leg ulcers may heal by outpatient treatment of venous disease even in the presence of concomitant arterial occlusive disease. Eur J Vasc Endovasc Surg2016; 52: 385–391.
PompELenselinkARosendaalF, et al.Pregnancy, the postpartum period and prothrombotic defects: risk of venous thrombosis in the MEGA study. J Thromb Haemost2008; 6: 632–637.
100.
McCollMRamsayJTaitR, et al.Superficial vein thrombosis: incidence in association with pregnancy and prevalence of thrombophilic defects. J Thromb Haemost1998; 80: 741–742.
101.
Reich-SchupkeSLeisteAMoritzR, et al.Sclerotherapy in an undetected pregnancy - a catastrophe?Vasa2012; 41: 243–247. Case Reports Review.
102.
DoddHWrightHP. Vulval varicose veins in pregnancy. Br Med J1959; 1: 831–832.
103.
Van CleefJ-F. Treatment of vulvar and perineal varicose veins. Phlebolymphology2011; 18: 38–43.
104.
HamiltonHGPittamRFHigginsRS. Active therapy of varicose veins in pregnancy. South Med J1949; 42: 608–612.
105.
CohenHArachchillageDMiddeldorpS, et al.Management of direct oral anticoagulants in women of childbearing potential: guidance from the SSC of the ISTH. J Thromb Haemost2016; 14: 1673–1676.
106.
KamelHNaviBBSriramN, et al.Risk of a thrombotic event after the 6-week postpartum period. New Engl J Med2014; 370: 1307–1315.
107.
BatesSMGreerIAPabingerI, et al.Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians evidence-based clinical practice guidelines. Chest2008; 133: 844S–886S.
LeungMLeungLFungD, et al.Management of the low-flow head and neck vascular malformations in children: the sclerotherapy protocol. Eur J Pediatric Surg2014; 24: 97–101.
110.
LonnerdalBForsumEHambraeusL. A longitudinal study of the protein, nitrogen, and lactose contents of human milk from Swedish well-nourished mothers. Am J Clin Nutr1976; 29: 1127–1133.
111.
Australasian College of Phlebology Standards Committee. Ultrasound guided sclerotherapy standards document, 2016, http://www.phlebology.com.au/standards
112.
ConradPMaloufGMStaceyMC. The Australian polidocanol (aethoxysklerol) study. Results at 2 years. Dermatol Surg1995; 21: 334–336.
113.
MyersKAJolleyD. Factors affecting the risk of deep venous occlusion after ultrasound-guided sclerotherapy for varicose veins. Eur J Vasc Endovasc Surg2008; 36: 602–605.
114.
ParsiKPanozzoBBullA, et al.Deep vein sclerosis following sclerotherapy: ultrasonic criteria and the role of D-Dimer. Phlebology2019; 35: 325–336. in press.
115.
TessariLIzzoMCavezziA, et al.Timing and modality of the sclerosing agents binding to the human proteins: laboratory analysis and clinical evidences. Veins Lymphatics2014; 3: 3275.
116.
ConnorDJosephJExnerT, et al.Infusion of foam sclerosants results in a distance-dependent procoagulant activity, haemoconcentration and elevation of D-dimer levels. Phlebology2014; 29: 677–687.
117.
Hamel-DesnosCDesnosPFerreB, et al.In vivo biological effects of foam sclerotherapy. Eur J Vasc Endovasc Surg2011; 42: 238–245.
118.
Raymond-MartimbeauP. Activation of blood coagulation after injection sclerotherapy of tthe lower extremity. J Dermatol Surg1991; 17: 88–89.
119.
ParsiKConnorDEPilotelleA, et al.Low concentration detergent sclerosants induce platelet activation but inhibit aggregation due to suppression of GPIIb/IIIa activation in vitro. Thromb Res2012; 130: 472–478. Research Support Non-U.S. Gov’t.
120.
ChangS-LHuangY-LLeeM-C, et al.Association of varicose veins with incident venous thromboembolism and peripheral artery disease. JAMA2018; 319: 807–817.
121.
GolemiISalazar AdumJPTafurA, et al.Venous thromboembolism prophylaxis using the Caprini score. Dis Mon2019; 65: 249–298.
122.
GouldMKGarciaDAWrenSM, et al.Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest2012; 141: e227S–e277S.
123.
LobastovKVorontsovaABargandzhiyaA, et al.The frequency and clinical significance of nontarget superficial and deep vein occlusion after physician compounded foam sclerotherapy of varicose tributaries. Phlebology2020; 35: 430–439. Epub ahead of print 12 Jan 2020. DOI: 10.1177/0268355519898595
124.
MyersKAJolleyD. Factors affecting the risk of deep venous occlusion after ultrasound-guided sclerotherapy for varicose veins. Eur J Vasc Endovasc Surg2008; 36: 602–605.
125.
FeiedCF. Deep vein thrombosis: the risks of sclerotherapy in hypercoagulable states. Semin Dermatol1993; 12: 135–149. Review.
126.
LabropoulosNJenJJenH, et al.Recurrent deep vein thrombosis: long-term incidence and natural history. Ann Surg2010; 251: 749–753. Research Support, Non-U.S. Gov’t.
127.
FahrniJHusmannMGretenerSB, et al.Assessing the risk of recurrent venous thromboembolism--a practical approach. Vasc Health Risk Manag2015; 11: 451–459.
128.
ZollerBOhlssonHSundquistJ, et al.Familial risk of venous thromboembolism in first-second- and third-degree relatives: a nationwide family study in Sweden. Thromb Haemost2013; 109: 458–463.
129.
Sindet-PedersenCOestergaardLBGundlundA, et al.Familial clustering of venous thromboembolism - A Danish nationwide cohort study. PLoS One2016; 11: e0169055.
130.
CouturaudFLeroyerCTromeurC, et al.Factors that predict thrombosis in relatives of patients with venous thromboembolism. Blood2014; 124: 2124–2130.
131.
BezemerIDvan der MeerFJEikenboomJC, et al.The value of family history as a risk indicator for venous thrombosis. Arch Intern Med2009; 169: 610–615.
132.
Hamel-DesnosCMGilletJLDesnosPR, et al.Sclerotherapy of varicose veins in patients with documented thrombophilia: a prospective controlled randomized study of 105 cases. Phlebology2009; 24: 176–182. Multicenter Study Randomized Controlled Trial.
133.
DarvallKASamRCAdamDJ, et al.Higher prevalence of thrombophilia in patients with varicose veins and venous ulcers than controls. J Vasc Surg2009; 49: 1235–1241.
134.
MakrisM.Thrombophilia: grading the risk. Blood2009; 113: 5038–5039. Comment.
135.
PruthiRK. Optimal utilization of thrombophilia testing. Int J Laborat Hematol2017; 39: 104–110.
136.
StevensSMWollerSCBauerKA, et al.Guidance for the evaluation and treatment of hereditary and acquired thrombophilia. J Thromb Thromb2016; 41: 154–164.
137.
ChristiansenSCCannegieterSCKosterT, et al.Thrombophilia, clinical factors, and recurrent venous thrombotic events. JAMA2005; 293: 2352–2361.
WillisRPierangeliSS. Pathophysiology of the antiphospholipid antibody syndrome. Autoimmun High2011; 2: 35–52.
140.
LucchiGBilanciniSTucciS, et al.Superficial vein thrombosis in non-varicose veins of the lower limbs and thrombophilia. Phlebology2018; 33: 278–281.
141.
MilioGSiragusaSMinàC, et al.Superficial venous thrombosis: prevalence of common genetic risk factors and their role on spreading to deep veins. Thromb Res2008; 123: 194–199.
142.
National Institute for Health and Care Excellence (NICE). Venous thromboembolic diseases: diagnosis, management and thrombophilia testing, 2012, https://www.nice.org.uk/guidance/cg144 (accessed 31 May 2020).
143.
TranHAGibbsHMerrimanE, et al.New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism. Med J Aust2019; 210: 227–235.
KhoranaAAFrancisCWCulakovaE, et al.Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost2007; 5: 632–634.
146.
KyrlePA. Predicting recurrent venous thromboembolism in cancer: is it possible?Thromb Res2014; 133: S17–S22.
147.
VersoMDi NisioM. Management of venous thromboembolism in cancer patients: Considerations about the clinical practice guideline update of the American society of clinical oncology. Eur J Intern Med2020; 71: 4–7.
148.
SadickNSUrmacherC. Estrogen and progesterone receptors: their role in postsclerotherapy angiogenesis Telangiectatic Matting (TM). Dermatol Surg1999; 25: 539–543.
149.
PrandoniPLensingAWPiccioliA, et al.Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood2002; 100: 3484–3488.
150.
SorigueMSarrateEMiljkovicMD. Interactions between direct anticoagulants and chemotherapy. Ann Oncol2019; 30: 1170.
151.
ZhangSZhaiZYangY, et al.Long-term treatment with low-molecular-weight heparin prolonged the survival time for acute pulmonary embolism patients concurrent with malignancy: an observational analysis from a long-term follow-up study. Thromb Res2015; 135: 582–587.
152.
MulderFICandeloroMKamphuisenPW, et al.The Khorana score for prediction of venous thromboembolism in cancer patients: a systematic review and meta-analysis. Haematologica2019; 104: 1277–1287.
153.
ChindamoMCMarquesMA. Role of ambulation to prevent venous thromboembolism in medical patients: where do we stand?J Vasc Bras2019; 18: e20180107.
154.
KahnSRLimWDunnAS, et al.Prevention of VTE in nonsurgical patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest2012; 141: e195S–e226S.
155.
StreiffMBAgnelliGConnorsJM, et al.Guidance for the treatment of deep vein thrombosis and pulmonary embolism. J Thromb Thrombol2016; 41: 32–67.
156.
ArfvidssonBEklofBKistnerRL, et al.A prospective evaluation of the risk for venous leg thrombosis associated with prolonged air travel: a pilot study. Cardiovasc Surgevaluation Stud2001; 9: 455–457.
157.
CannegieterSCDoggenCJvan HouwelingenHC, et al.Travel-related venous thrombosis: results from a large population-based case control study (MEGA study). PLoS Med2006; 3: e307.
PhilbrickJTShumateRSiadatyMS, et al.Air travel and venous thromboembolism: a systematic review. J Gen Intern Med2007; 22: 107–114.
160.
ChandraDParisiniEMozaffarianD. Meta-analysis: travel and risk for venous thromboembolism. Ann Intern Med2009; 151: 180–190.
161.
JacobsonBFMunsterMSmithA, et al.The BEST study--a prospective study to compare business class versus economy class air travel as a cause of thrombosis. S Afr Med J2003; 93: 522–528.
162.
ScurrJH. Travellers’ thrombosis. J R Soc Promot Health2002; 122: 11–13.
163.
ScurrJRAhmadNThavarajanD, et al.Traveller’s thrombosis: airlines still not giving passengers the WRIGHT advice. Phlebology2010; 25: 257–260.
164.
RayhillMBurchR. PFO and Migraine: is there a role for closure?Curr Neurol Neurosci Rep2017; 17: 20.
165.
JiaXMowattGBurrJM, et al.Systematic review of foam sclerotherapy for varicose veins. Br J Surg2007; 94: 925–936. Research Support, Non-U.S. Gov’t Review.
166.
Raymond-MartimbeauP. Transient adverse events positively associated with patent foramen ovale after ultrasound-guided foam sclerotherapy. Phlebology2009; 24: 114–119.
167.
DaviesHOWatkinsMOliverR, et al.Adverse neurological events after sodium tetradecyl sulfate foam sclerotherapy - A prospective, observational study of 8056 treatments. Phlebology2022; 37: 97–104.
168.
HommaSSaccoRL. Patent foramen ovale and stroke. Circulation2005; 112: 1063–1072. Review.
169.
WrightDDGibsonKDBarclayJ, et al.High prevalence of right-to-left shunt in patients with symptomatic great saphenous incompetence and varicose veins. J Vasc Surg2010; 51: 104–107.
170.
SukernikMRMetsBBennett-GuerreroE. Patent foramen ovale and its significance in the perioperative period. Anesth Analg2001; 93: 1137–1146. Review.
171.
KerutEKNorfleetWTPlotnickGD, et al.Patent foramen ovale: a review of associated conditions and the impact of physiological size. J Am Coll Cardiol2001; 38: 613–623.
172.
LandzbergMJKhairyP. Indications for the closure of patent foramen ovale. Heart2004; 90: 219–224.
173.
ColladoFMSPoulinMFMurphyJJ, et al.Patent foramen ovale closure for stroke prevention and other disorders. J Am Heart Assoc2018; 7: e007146.
174.
PintoFJ. When and how to diagnose patent foramen ovale. Heart2005; 91: 438–440.
175.
Di TullioMSaccoRLVenketasubramanianN, et al.Comparison of diagnostic techniques for the detection of a patent foramen ovale in stroke patients. Stroke1993; 24: 1020–1024.
176.
Raymond-MartimbeauP. Pretreatment testing for right-to-left shunt warranted?Phlebolymphology2014; 21.
177.
LeePHSongJKKimJS, et al.Cryptogenic stroke and high-risk patent foramen ovale: the DEFENSE-PFO trial. J Am Coll Cardiol2018; 71: 2335–2342.
178.
DesaiAJFullerCJJesurumJT, et al.Patent foramen ovale and cerebrovascular diseases. Nat Clin Pract Cardiovasc Med2006; 3: 446–455.
179.
KuhlHPHoffmannRMerxMW, et al.Transthoracic echocardiography using second harmonic imaging: diagnostic alternative to transesophageal echocardiography for the detection of atrial right to left shunt in patients with cerebral embolic events. J Am Coll Cardiol1999; 34: 1823–1830.
180.
WillenbergTSmithPCShepherdA, et al.Visual disturbance following sclerotherapy for varicose veins, reticular veins and telangiectasias: a systematic literature review. Phlebology2013; 28: 123–131. Review.
181.
GilletJLDonnetALauseckerM, et al.Pathophysiology of visual disturbances occurring after foam sclerotherapy. Phlebology2010; 25: 261–266.
182.
SarvananthanTShepherdACWillenbergT, et al.Neurological complications of sclerotherapy for varicose veins. J Vasc Surg2012; 55: 243–251. Review.
GilletJ. Complications and side effects: European guidelines for sclerotherapy in chronic venous disorders. Phlebology2014; 29: 34–38.
185.
MorrisonNNeuhardtDL. Foam sclerotherapy: cardiac and cerebral monitoring. Phlebology2009; 24: 252–259.
186.
ParsiK. Venous gas embolism during foam sclerotherapy of saphenous veins despite recommended treatment modifications. Phlebology2011; 26: 140–147.
187.
CeulenRPSommerAVernooyK. Microembolism during foam sclerotherapy of varicose veins. N Engl J Med2008; 358: 1525–1526.
188.
FrulliniABarsottiMCSantoniT, et al.Significant endothelin release in patients treated with foam sclerotherapy. Dermatol Surg2012; 38: 741–747.
189.
RabeEBreuFXCavezziA, et al.European guidelines for sclerotherapy in chronic venous disorders. Phlebology2014; 29: 338–354. Practice Guideline.
190.
HillDHamiltonRFungT. Assessment of techniques to reduce sclerosant foam migration during ultrasound-guided sclerotherapy of the great saphenous vein. J Vasc Surg2008; 48: 934–939.
191.
GuexJJAllaertFAGilletJL, et al.Immediate and midterm complications of sclerotherapy: report of a prospective multicenter registry of 12,173 sclerotherapy sessions. Dermatol Surg2005; 31: 123–128. Multicenter Study Research Support. Non-U.S. Gov't.
192.
GuexJJSchliephakeDEOttoJ, et al.The French polidocanol study on long-term side effects: a survey covering 3, 357 patient years. Dermatol Surg2010; 36(Suppl 2): 993–1003.
193.
FrulliniAFeliceFBurchielliS, et al.High production of endothelin after foam sclerotherapy: a new pathogenetic hypothesis for neurological and visual disturbances after sclerotherapy. Phlebology2011; 26: 203–208.
194.
YamakiTNozakiMSakuraiH, et al.Multiple small-dose injections can reduce the passage of sclerosant foam into deep veins during foam sclerotherapy for varicose veins. Eur J Vasc Endovasc Surg2009; 37: 343–348.
195.
CameronEChenTConnorDE, et al.Sclerosant foam structure and stability is strongly influenced by liquid air fraction. Eur J Vasc Endovasc Surg2013; 46: 488–494.
196.
LaiSWGoldmanMP. Does the relative silicone content of different syringes affect the stability of foam in sclerotherapy?J Drugs Dermatol2008; 7: 399–400.
197.
SylvozNVillierCBlaiseS, et al.Polidocanol induced cardiotoxicity: a case report and review of the literature. J Mal Vasc2008; 33: 234–238.
198.
Marrocco-TrischittaMMGuerriniPAbeniD, et al.Reversible cardiac arrest after polidocanol sclerotherapy of peripheral venous malformation. Dermatol Surg2002; 28: 153–155.
199.
WattanakitKCushmanMStehman-BreenC, et al.Chronic kidney disease increases risk for venous thromboembolism. J Am Soc Nephrol2008; 19: 135–140.
200.
TveitDPHypoliteIOHshiehP, et al.Chronic dialysis patients have high risk for pulmonary embolism. Am J Kidney Dis2002; 39: 1011–1017.
201.
SteinPDHenryJW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest1995; 108: 978–981.
202.
LutzJJurkKSchinzelH. Direct oral anticoagulants in patients with chronic kidney disease: patient selection and special considerations. Int J Nephrol Renovasc Dis2017; 10: 135–143.
203.
OcakGVerduijnMVossenCY, et al.Chronic kidney disease stages 1-3 increase the risk of venous thrombosis. J Thromb Haemost2010; 8: 2428–2435.
204.
MolnarAOBotaSEGargAX, et al.The risk of major hemorrhage with CKD. J Am Soc Nephrol2016; 27: 2825–2832.
205.
AggarwalAPuriKLiangpunsakulS. Deep vein thrombosis and pulmonary embolism in cirrhotic patients: systematic review. World J Gastroenterol2014; 20: 5737–5745.
206.
KucukEVTahraABindayiA, et al.Long-term functional results of aspiration and sclerotherapy with ethanol in patients with autosomal dominant polycystic kidney disease: a non-randomized pilot clinical study. Int Urol Nephrol2016; 48: 457–463.
207.
ValerioMMeuwlyJYTawadrosC, et al.Percutaneous drainage and sclerotherapy as definitive treatment of renal lymphangiomatosis. Can Urol Assoc J2012; 6: E3–E7.
208.
ZenerRIliutaIShiB, et al.Safety and efficacy of 3% sodium tetradecyl sulfate foam sclerotherapy in the treatment of renal cysts in autosomal dominant polycystic kidney disease. J Vasc Interv Radiol2017; 28: S141.
209.
RomanoGAgrusaAAmatoG, et al.Endoscopic sclerotherapy for hemostasis of acute esophageal variceal bleeding. G Chir2014; 35: 61–64.
210.
CroffieJSomogyiLChuttaniR, et al.Sclerosing agents for use in GI endoscopy. Gastrointest Endosc2007; 66: 1–6.
211.
DaviesHOPopplewellMSinghalR, et al.Obesity and lower limb venous disease - The epidemic of phlebesity. Phlebology2017; 32: 227–233.
212.
KabrhelCVarrasoRGoldhaberSZ, et al.Prospective study of BMI and the risk of pulmonary embolism in women. Obesity (Silver Spring)2009; 17: 2040–2046.
213.
AbdollahiMCushmanMRosendaalFR. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use. Thromb Haemost2003; 89: 493–498.
214.
KucherNLeizoroviczAVaitkusPT, et al.Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch Intern Med2005; 165: 341–345.
215.
KadamPLimJPaverI, et al.Telangiectatic matting is associated with hypersensitivity and a bleeding tendency. Eur J Vasc Endovasc Surg2018; 55: 554–559.
216.
ParsiKExnerTLowJ, et al.In vitro effects of detergent sclerosants on clot formation and fibrinolysis. Eur J Vasc Endovasc Surg2011; 41: 267–277.
217.
ParsiKKangMAbbottL. Livedo vasculopathy: ablation of the affected vessels to prevent recurrent ulcerations. Phlebology2019; 34: 582–597.
218.
YangAHannafordPKangM, et al.Skin necrosis following sclerotherapy: classification of pathogenic mechanisms and review of management strategies. To be submitted.
RameletAA. Sclerotherapy in tumescent anesthesia of reticular veins and telangiectasias. Dermatol Surg2012; 38: 748–751.
221.
CavezziAMostiGDi PaoloS, et al.Re: ‘catheter-directed foam sclerotherapy of great saphenous veins in combination with pre-treatment reduction of the diameter employing the principals of perivenous tumescent local anesthesia. Eur J Vasc Endovasc Surg2014; 48: 597.
222.
MiyakeRK. Cryo-laser and cryo-sclerotherapy guided by augmented reality. Phlebologie2018; 43: 257–261.
223.
PhamJNgKThooS, et al.Pigment composition of cultaneous vascular conditions of lower limbs: contribution of haemosiderin and Melanin. Phlebology2019; 64: 456-460.
224.
ThibaultPKWlodarczykJ. Correlation of serum ferritin levels and postsclerotherapy pigmentation. A prospective study. J Dermatol Surg Oncol1994; 20: 684–686.
225.
GreenD.Persistent post-sclerotherapy pigmentation due to minocycline. Three cases and a review of post-sclerotherapy pigmentation. J Cosmet Dermatol2002; 1: 173–182. Case Reports.
226.
LeffellDJ. Minocycline hydrochloride hyperpigmentation complicating treatment of venous ectasia of the extremities. J Am Acad Dermatol1991; 24: 501–502. Case Reports.
227.
MooreMMishraVFriedmannDP, et al.Minocycline-induced postsclerotherapy pigmentation successfully treated with a picosecond alexandrite laser. Dermatol Surg2016; 42: 133–134.
228.
StarPChoyCParsiK. Black veins: a case of minocycline-induced pigmentation post-sclerotherapy and a review of literature. J Cutan Pathol2017; 44: 83–92.
229.
JallouliMFrancesCPietteJC, et al.Hydroxychloroquine-induced pigmentation in patients with systemic lupus erythematosus: a case-control study. JAMA Dermatol2013; 149: 935–940.
230.
Cooley-AndradeOJothidasAGohWX, et al.Low-concentration detergent sclerosants stimulate white blood cells and release proinflammatory and proangiogenic cytokines in vitro. J Vasc Surg Venous Lymphat Disord2014; 2: 433–440.
231.
Cooley-AndradeOCheungKChewAN, et al.Detergent sclerosants at sub-lytic concentrations induce endothelial cell apoptosis through a caspase dependent pathway. Apoptosis2016; 21: 836–845.
232.
Cooley-AndradeOConnorDEMaDD, et al.Morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants. Phlebology2016; 31: 177–191.
233.
BushRBushP. Evaluation of sodium tetradecyl sulfate and polidocanol as sclerosants for leg telangiectasia based on histological evaluation with clinical correlation. Phlebology2017; 32: 496–500.
234.
ThibaultP. Perivenous tumescent compression to enhance sclerotherapy results and reduce adverse effects. In: XVIth World Meeting of the Union Internationale de Phlebologie Monaco. September, 2009, pp. 38–39. Int. Angiol.
235.
TchaikovskiSNRosingJ. Mechanisms of estrogen-induced venous thromboembolism. Thromb Res2010; 126: 5–11.
236.
MiddeldorpSMeijersJCvan den EndeAE, et al.Effects on coagulation of levonorgestrel- and desogestrel-containing low dose oral contraceptives: a cross-over study. Thromb Haemost2000; 84: 4–8.
237.
MeijersJCMiddeldorpSTekelenburgW, et al.Increased fibrinolytic activity during use of oral contraceptives is counteracted by an enhanced factor XI-independent down regulation of fibrinolysis: a randomized cross-over study of two low-dose oral contraceptives. Thromb Haemost2000; 84: 9–14.
238.
TansGCurversJMiddeldorpS, et al.A randomized cross-over study on the effects of levonorgestrel- and desogestrel-containing oral contraceptives on the anticoagulant pathways. Thromb Haemost2000; 84: 15–21.
239.
LidegaardONielsenLHSkovlundCW, et al.Venous thrombosis in users of non-oral hormonal contraception: follow-up study, Denmark 2001-10. BMJ2012; 344: e2990.
240.
ColeJANormanHDohertyM, et al.Venous thromboembolism, myocardial infarction, and stroke among transdermal contraceptive system users. Obstet Gynecol2007; 109: 339–346.
ScarabinPYOgerEPlu-BureauG, et al.Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet2003; 362: 428–432.
243.
GomesMPDeitcherSR. Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review. Arch Intern Med2004; 164: 1965–1976.
244.
CanonicoMOgerEPlu-BureauG, et al.Hormone therapy and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration and progestogens: the ESTHER study. Circulation2007; 115: 840–845.
245.
ScarabinPYAlhenc-GelasMPlu-BureauG, et al.Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial. Arterioscler Thromb Vasc Biol1997; 17: 3071–3078.
246.
BergendalAKielerHSundstromA, et al.Risk of venous thromboembolism associated with local and systemic use of hormone therapy in peri- and postmenopausal women and in relation to type and route of administration. Menopause2016; 23: 593–599.
247.
CrandallCJHoveyKMAndrewsCA, et al.Breast cancer, endometrial cancer, and cardiovascular events in participants who used vaginal estrogen in the women’s health initiative observational study. Menopause2018; 25: 11–20.
248.
RottH. Prevention and treatment of venous thromboembolism during HRT: current perspectives. Int J Gen Med2014; 7: 433–440.
249.
World Health Organization. Medical eligibility criteria for contraceptive use. 5th ed.Geneva, Switzerland: Department of Reproductive Health, 2015.
250.
van VlijmenEFWiewel-VerschuerenSMonsterTB, et al.Combined oral contraceptives, thrombophilia and the risk of venous thromboembolism: a systematic review and meta-analysis. J Thromb Haemost2016; 14: 1393–1403.
251.
SadickNSUrmacherC. Estrogen and progesterone receptors: their role in postsclerotherapy angiogenesis telangiectatic matting (TM). Dermatol Surg1999; 25: 539–543.
252.
CiardulloAVPanicoSBellatiC, et al.High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women. J Vasc Surg2000; 32: 544–549.
253.
HernandezRKSorensenHTPedersenL, et al.Tamoxifen treatment and risk of deep venous thrombosis and pulmonary embolism: a Danish population-based cohort study. Cancer2009; 115: 4442–4449.
254.
HussainTKneeshawPJ. Stopping tamoxifen peri-operatively for VTE risk reduction: a proposed management algorithm. Int J Surg2012; 10: 313–316.
255.
FabianCJ. The what, why and how of aromatase inhibitors: hormonal agents for treatment and prevention of breast cancer. Int J Clin Pract2007; 61: 2051–2063.
ShenasaMShenasaH. Hypertension, left ventricular hypertrophy, and sudden cardiac death. Int J Cardiol2017; 237: 60–63.
259.
SchmidMWolfRCFreudenmannRW, et al.Tomophobia, the phobic fear caused by an invasive medical procedure - an emerging anxiety disorder: a case report. J Med Case Rep2009; 3: 131.
260.
ArendtsGStevensMFryM. Topical anaesthesia and intravenous cannulation success in paediatric patients: a randomized double-blind trial. Br J Anaesth2008; 100: 521–524.
261.
BrotzmanEASandovalLFCraneJ. Use of nitrous oxide in dermatology: a systematic review. Dermatol Surg2018; 44: 661–669.
262.
MeierTOJacomellaVClemensRK, et al.Nitrous oxide/oxygen inhalation provides effective analgesia during the administration of tumescent local anaesthesia for endovenous laser ablation. Vasa2015; 44: 473–478.
263.
JephcottCGrummetJNguyenN, et al.A review of the safety and efficacy of inhaled methoxyflurane as an analgesic for outpatient procedures. Br J Anaesth2018; 120: 1040–1048.
264.
PorterKMDayanADDickersonS, et al.The role of inhaled methoxyflurane in acute pain management. Open Access Emerg Med2018; 10: 149–164.
CoteCJWilsonSAmerican Academy Of Pediatrics, et al.Guidelines for monitoring and management of pediatric patients before, during, and after sedation for diagnostic and therapeutic procedures. Pediatrics2019; 143: e20191000.
267.
PhillipsKAWilhelmSKoranLM, et al.Body dysmorphic disorder: some key issues for DSM-V. Depress Anxiety2010; 27: 573–591. Review.
268.
O'MalleyASSwankoskiKPeikesD, et al.Patient dismissal by primary care practices. JAMA Intern Med2017; 177: 1048–1050.
HullSKBroquetK. How to manage difficult patient encounters: these strategies will help you turn problematic encounters into productive ones. Fam Pract Manag2007; 14: 30–34.
271.
Medical Board of Australia. Good medical practice: a code of conduct for doctors in Australia, 2014.
