Kurosh Parsi

The Lytic Effects of Detergent Sclerosants on Erythrocytes, Platelets, Endothelial Cells and Microparticles are Attenuated by Albumin and other Plasma Components in Vitro

OBJECTIVE To investigate the lytic effects of sodium tetradecyl sulphate (STS) and polidocanol (POL) on erythrocytes, platelets, endothelial cells and platelet-derived microparticle (PDMP) formation in vitro and the potential protective effects of serum albumin and agents such as procaine. MATERIALS AND METHODS The effects of sclerosants were studied in blood samples obtained from normal individuals. Absorbance densitometry was used to assess the lytic effects of sclerosants on blood cells and cultured human microvascular endothelial cells (HMEC) in plasma and in saline. PDMP were quantified by flow cytometry. RESULTS Haemolysis occurred in whole blood at sclerosant concentrations greater than 0.25% for STS and above 0.45% for POL. Similar concentrations of both agents caused platelet and endothelial cell lysis. Both sclerosants released PDMP at low concentrations but destroyed PDMP at higher concentrations. Albumin significantly reduced the lytic effect of both sclerosants on all cells but had a greater inhibitory effect on POL. Protamine at 0.01% had a neutralising effect on STS, whereas procaine and lignocaine showed no such activity. CONCLUSIONS Sclerosants at therapeutic concentrations lyse blood cells and endothelial cells in vitro. This effect is strongly reduced by serum albumin possibly contributing towards the low incidence of thromboembolic complications of sclerotherapy.

Paradoxical embolism, stroke and sclerotherapy

Sclerotherapy has been associated with 13 published cases of stroke since 1994. Four earlier reports implicated liquid sclerosants while nine recent cases have followed foam sclerotherapy. This adverse event represents a very rare complication of a very popular procedure. Ten of the 13 reported patients recovered completely with no long-term sequelae. A right-to-left shunt and in particular a patent foramen ovale (PFO) was the most consistent risk factor. Paradoxical gas emboli were observed in the brain-supplying or the intra-cranial arteries of five patients with an immediate onset of stroke after foam sclerotherapy. Paradoxical clot embolism was suspected in three patients with a delayed onset of stroke and concurrent venous thrombosis. In the remaining five cases, which included two cases with an immediate onset after liquid sclerotherapy, no specific cause was identified. Patients with a past history of cryptogenic stroke or a long life history of recurrent classic migraine attacks (with aura) have a higher risk of neurological adverse events and may benefit from preoperative screening and percutaneous closure of PFO.

Catheter-directed sclerotherapy

Background Catheter directed sclerotherapy (CDS) involves the use of a long catheter to deliver a sclerosing agent into a target vessel (saphenous trunks or venous malformations) under ultrasound guidance. Aims and Methods This article reviews the history, current techniques and devices and the evidence as it relates to these procedures. Results CDS was developed to increase the safety and efficacy of ultrasound-guided sclerotherapy (UGS). With the advent of foam sclerosants and tumescent anaesthesia, the procedure has enjoyed a higher primary success rate. CDS has a better safety profile when compared with UGS with virtually no risk of intra-arterial injection or sclerosant extravasation. Compared with endovenous laser (EVLA) and radiofrequency ablation (RFA), CDS is a quicker procedure with less associated pain. Some balloon catheters, however, have been found to force the sclerosant down the perforators causing femoral vein occlusion. Based on the current level of evidence, no firm conclusion regarding the efficacy of CDS techniques can be drawn in comparison with EVLA or RFA, but the primary success rate is probably higher than the standard UGS. Conclusion CDS ensures a safe intraluminal delivery of the sclerosing agent into the trunk of the saphenous veins using a single access point. This procedure preceded EVLA and RFA, and remains a safe alternative for the treatment of saphenous incompetence and venous malformations.

Three cases of stroke following peripheral venous interventions

We report three cases of stroke in association with peripheral venous interventions that each included foam ultrasound-guided sclerotherapy (UGS). All three female patients experienced a right middle cerebral artery (MCA) stroke causing dysphasia and left hemiparesis. A patent foramen ovale was found in each patient. The first incident occurred two days after foam UGS to treat small tributaries of a great saphenous vein (GSV). Paradoxical clot embolism was presumed in this case where concurrent deep vein thrombosis with non-occlusive thrombus in a medial gastrocnemius vein extending to the popliteal vein was detected on ultrasound. The second case occurred immediately at the completion of foam UGS and ambulatory phlebectomy to treat GSV tributaries. Paradoxical gas embolism was demonstrated in this patient confirmed by visualization of bubbles in the right MCA on CT angiography. The third case occurred one day after endovenous laser ablation (1470 nm) and foam UGS to treat both great and small saphenous veins. No specific cause could be confirmed in this patient. Sodium tetradecyl sulphate foam was used in all three cases (3%, 16 mL; 1.5%, 4 mL and 3%, 25 mL, respectively). All three patients recovered completely within a few days.

Venous gas embolism during foam sclerotherapy of saphenous veins despite recommended treatment modifications.

Objective To investigate the effectiveness of methods proposed to prevent venous gas embolism during foam sclerotherapy. Methods Transthoracic echocardiography was performed concurrent with ultrasound-guided sclerotherapy (UGS) of great or small saphenous veins. A volume of 2.5 mL of 3% sodium tetradecyl sulphate foam was prepared following the Tessari method and injected slowly 5–10 cm away from saphenous junctions. The procedure was repeated with modifications including using a 5 µm filter to generate microfoam, carbon dioxide as the foaming gas, leg elevation before or after the injection and immobility post-treatment. Results Bubbles entered the right heart in less than 60 seconds and continued for up to 50 minutes despite all treatment modifications. None of the patients had a patent foramen ovale and none developed any neurological or cardiac symptoms. Conclusion Bubble emboli entered the heart during foam UGS of saphenous veins despite all treatment modifications and low volumes of foam used.

Multiple hereditary glomangiomas: Successful treatment with sclerotherapy

Glomangiomas are characterized by cavernous vascular channels surrounded by glomus cells. Multiple glomangiomas, although usually painless, can be a few centimetres in size and appear as blue phlebectatic lesions. Surgical excision of multiple glomangiomas can lead to scarring and recurrences. Laser treatment using vascular lasers and CO2 lasers has been useful in small, superficial lesions. We present the successful sclerotherapy treatment of multiple glomangiomas using sodium tetradecyl sulphate in a 59‐year‐old man who presented with postoperative recurrence of multiple lesions.

Warfarin‐induced skin necrosis associated with acquired protein C deficiency

A 36‐year‐old woman developed skin necrosis of the inner thighs following the re‐introduction of warfarin after a laparoscopic cholecystectomy. She had a history of liver disease and cardiomyopathy and was on warfarin for 10 years. Warfarin‐induced skin necrosis secondary to protein C deficiency was diagnosed. Although warfarin was ceased immediately, the prothrombin time measurements remained prolonged and warfarin levels remained therapeutic. Our patient, who had attached great significance to warfarin therapy, had continued the ingestion of warfarin despite our advice. She required three surgical debridements. Protein C levels, as measured 1 year later, were within normal limits, confirming the transient nature of the acquired deficiency during the acute event. This is the second reported case of warfarin necrosis associated with acquired protein C deficiency.

Thermosensitive lichen amyloidosis

Background  A 26‐year‐old male presented with a 3‐year history of lichen amyloidosis. On examination, there was a pigmented papular eruption with a ripple pattern affecting the limbs and trunk but sparing the axillae, antecubital and popliteal fossae, central chest, neck and face. There was also prominent sparing of the skin overlying the superficial veins of the limbs. The sparing of the superficial veins of the limbs by lichen amyloidosis raised the possible role of cutaneous temperature in governing the distribution of amyloid deposits in our patient.

In vitro Effects of Detergent Sclerosants on Antithrombotic Mechanisms

OBJECTIVES To investigate the in vitro effects of detergent sclerosants on antithrombotic pathways. MATERIALS AND METHODS Proteins C, S and antithrombin (AT) were assayed in normal plasma treated with increasing concentrations of sodium tetradecyl sulphate (STS) and polidocanol (POL). Activated protein C (APC) was investigated by mixing normal plasmas with sclerosants and testing with the activated partial thromboplastin time (APTT) and dilute Russells viper venom time in the presence and absence of APC. The effect on factor Xa (FXa), heparin and enoxaparin was investigated using chromogenic anti-FXa and APTT methods. RESULTS High concentration (>0.6%) STS significantly destroyed proteins C, S and AT whereas POL only caused a mild reduction in PC and AT and a moderate (60%) reduction in PS levels. STS potentiated the anticoagulant effect of APC while POL increased APC resistance. STS mimicked AT and demonstrated significant anti-Xa and anti-IIa activity. STS demonstrated a similar anticoagulant profile to heparin but was 1000x weaker. It also significantly potentiated the anticoagulant effect of heparin while POL had less effect. CONCLUSION STS and POL demonstrated quite distinct and sometimes opposite effects on the antithrombotic mechanisms assayed. These effects were concentration-dependent and in general, STS had the greatest effect on antithrombotic proteins.

In Vitro Effects of Detergent Sclerosants on Clot Formation and Fibrinolysis

OBJECTIVE To investigate the in vitro effects of detergent sclerosants sodium tetradecyl sulphate (STS) and polidocanol (POL) on clot formation and lysis. MATERIALS AND METHODS clot kinetics were assessed in whole blood by thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®). Fibrinogen was measured by the Clauss method in plasma and factor XIII (FXIII) by enzyme-linked immunosorbent assay (ELISA). Turbidity measurements were used to assess clot lysis in plasma, and fibrinolysis in non-cross-linked and cross-linked fibrin. D-dimer was measured by VIDAS®, STA®Liatest® and AxSYM® assays. RESULTS Strong clots were formed at low sclerosant concentrations (0.075-0.1%). At midrange concentrations (0.15% STS, 0.15-0.3% POL), both agents inhibited the contribution of platelets to clot firmness and formed weak clots prone to lysis. At higher concentrations (STS ≥ 0.3% and POL ≥ 0.6%), clot formation was inhibited. STS destroyed FXIII at ≥ 0.15% and fibrinogen at ≥ 0.6%. Neither sclerosant had a significant effect on cross-linked fibrin, but STS had a lytic effect on non-cross-linked fibrin. STS caused an artefactual elevation of D-dimer in the VIDAS® assay when fibrinogen was present. CONCLUSION Detergent sclerosants demonstrated a trimodal effect on clot formation, initiating strong clots at low concentrations, weak clots at midrange concentrations and preventing clot formation at higher concentrations. Neither agent had fibrinolytic activity.