Sclerotherapy and thrombophilia: How to do it? Saturday 29 March 2014 Pascal Giordana Nice, France.

expression of interest: No conflict

Thrombophilia is the term now used to describe predisposition to increase risk of venous and occasionally arterial thromboembolism due to hematological abnormalities. Thrombophilia and venous thromboembolism; international concensus (Int Angiol 2005; 24: 1-26) Cancer is associated with 4.1 fold increased the risk for VTE witch increases to 6.5 with treatment by chemotherapy. 72% of individuals with travel-related DVT have associated coagulation defects. Lebanon exhibits one of the highest general population frequencies for factor V Leiden mutation in the eastern Mediterranean region (7.4% in general population and 39.7% in patients with VTE).

Thrombophilia and venous thromboembolism; international concensus (Int Angiol 2005; 24: 1-26) 4.1 to 16.2 increase risk of VTE

1025 patients treated with foam sclerotherapy (818 GSV and 207 SSV) Persons with personal history of VTE or previous identified thrombophilia were excluded 11 thrombo embolics events occured: 10 DVT o 5 symptomatics (all distal) o 5 no symptomatic (not completly occlisive) 1 PE DVT were more frequent for SSV (2.42%) vs GSV (0.61%) Foam doesn’t lead to more VTE than other methods of treatment Surgery = 5.3% Radiofrequency = 0 to 16% Laser = 0 to 8% J.L. Gillet et Al: phlebology. 2009; 24:

European guidelines for sclerotherapy in chronic venous disorders (Rabe et al: Phlebology 2013) Thromboembolic events are very rare and uncommon.

Effects of detergent sclerosants on anticoagulation…

In vitro effects of detergent sclerosants on coagulation, platelets and microparticles (K. Parsi et al: Eur J Vasc Endovasc Surg 34, 731_740) STS at high concentration (> 0.3 %): destroyed platelets, microparticles and the clotting factors V, VII and X. It prolongs all clotting test [prothrombin time (PT), activated partial thromboplastine time (APTT), non-activated partial prothromboplastin time (NAPTT), Thrombin time (TT), factor Xa clotting time (XACT)and surface activated clotting time (SACT)]. Higher concentration of POL were required to achieve some anticoagulant activity when compared with STS. POL never achieved the same degree of prolongation when compared with STS. STS has more anticoagulant activity than POL in high concentration.

In vitro effects of detergent sclerosants on coagulation, platelets and microparticles (K. Parsi et al: Eur J Vasc Endovasc Surg 34, 731_740) Low concentrations sclerosant demonstrate pro-activity.

In vitro effects of detergent sclerosants on antithrombotic mechanisms (K. Parsi et al: Eur J vasc Endovasc surg 2009, 38; ) Effect on protein C:  STS caused a moderate reduction in protein C level at a concentration of 0.3%. It reduce the PC level down to 10% with higher concentration.  POL only caused a mild reduction in PC level.

In vitro effects of detergent sclerosants on antithrombotic mechanisms (K. Parsi et al: Eur J vasc Endovasc surg 2009, 38; ) Effect on protein S:  STS at concentration of 0.6% and more completely destroyed free PS  POL reduced PS levels by 60%

In vitro effects of detergent sclerosants on antithrombotic mechanisms (K. Parsi et al: Eur J vasc Endovasc surg 2009, 38; ) Effect on AT:  STS significantly destroyed AT at concentration above 0.3%  POL reduced AT level down to 60%

In vitro effects of detergent sclerosants on antithrombotic mechanisms (K. Parsi et al: Eur J vasc Endovasc surg 2009, 38; ) Effect on APC and APCR:  STS prolonged APTT potentiating the anticoagulant activity of APC.  POL had the opposite effect increasing APCR.

The lytic effects of detergent sclerosants on Erythrocytes, platelets, endothelials cells and micro_particles are attenuated by albumin and other plasma components in vitro (K. Parsi et al: Eur J Vasc Endovasc Surg (2008) 36, ) Sclerosant at therapeutic concentrations lyse blood cells and endothelial cells in vitro. The effect is strongly reduced by serum albumin possibly contributing toward the low incidence of thromboembolic complications of sclerotherapy. The plasma components appeared to neutralize the lytic effects of sclerosants. STS was 50 fold and POL was 163 fold less hemolytic in blood than in saline. The displacement of blood from the vessel lumen decreased the exposure of the sclerosant to the plasma components and increases the exposure of the endothelial lining of the vessel lumen to the active agent.

An Investigation of coagulation cascade activation and induction for fibrinolysis using foam sclerotherapy of reticular veins (S. Guillen Fabi et al: Dermatol Surg 2012; 38: ) The objective was to evaluate the effect of foam bubbles on coagulation and fibrinolysis after foam sclerotherapy with STS. Patients were treated with up to 30 ml of foam STS. Blood was drawn immediately and 15 min after the procedure. There was no significant difference in coagulation or fibrinolysis, as measured according to platelet count and concentrations of clotting factor and fibrinogen after sclerotherapy with STS.

In practice…

Sclérothérapie chez le patient thrombophile connu. Etude prospective randomisée contrôlée de 105 cas (Hamel Desnos C. et al : phlébologie 2010,63, 1p ) 105 thrombophilics patients in combination with thromboprophylaxis in two randomized arms using low molecular weight heparin (LMWH) or warfarin. 75 with factor V Leiden mutation 18 with prothrombin A mutation 7 high level of factor VIII 5 combinations of these After randomization: 51 received Warfarin (1 mg once a days during 4 weeks after the last treatment) 54 received LMWH (nadroparin 4000 UI one injection at the same time with the sclerotherapy). A control (clinical examination and ultrasound screening) was realized after 3 or 4 weeks

Sclerotherapy of varicose veins in patients with documented thrombophilia: a prospective controlled randomized study of 105 cases (Hamel Desnos C. et al: Phlebology 2009; 24: )

Results: No episodes of symptomatic deep vein thrombosis or PE occurred No instances of DVT were revealed by ultrasound monitoring Conclusion: sclerotherapy, in combination with thromboprophylaxis, can performed safely in these tree most common thrombophilia. Prophylaxis by LHWM is easier to use than Warfarin Antithrombotic prophylaxis do not change the efficacy of the treatment. Sclérothérapie chez le patient thrombophile connu. Etude prospective randomisée contrôlée de 105 cas (Hamel Desnos C. et al : phlébologie 2010,63, 1p )

Conclusion: European guidelines for sclerotherapy in chronic venous disorders (Rabe et al: Phlebology 2013) Recommendation 2: we recommend to consider the following absolute and relative contraindications (Grade 1c):  Absolute contraindication: acute DVT or PE, long lasting immobility and confinement to bed.  Relative contraindication: High thromboembolic risk (history of thromboembolic events, known severe thrombophilia, hyper coagulate state and active cancer).

European guidelines for sclerotherapy in chronic venous disorders (Rabe et al: Phlebology 2013) Recommendation 9: in patients with a high risk of thromboembolism such as those with history of spontaneous DVT or known severe thrombophilia we recommend:  Use of pharmacological thromboprophylaxis in line with current guidelines recommendations (Grade 1c)  Implement physical prophylaxis (compression, movement) (Grade 1c)  Avoid the injection of large volumes of foam (Grade 1c)  Decide on a case-by-case basis (perform a benefit-risk assessment based on the particular indication) (Grade 1c)