Post-thrombotic syndrome in children: a single center experience.

BACKGROUND: Development of post-thrombotic syndrome (PTS) is increasingly being recognized as a complication of deep venous thrombosis (DVT) in children. OBJECTIVE: To determine the prevalence, clinical characteristics, and predictors of moderate to severe PTS in children. METHODS: A retrospective chart review was performed on those children who were followed in the coagulation clinic for objectively confirmed DVTs from December 2004 to December 2006. The scoring system used by Kuhle et al was used to grade the severity of PTS as: mild, moderate, and severe. RESULTS: PTS developed in 20% (11/55; 95% confidence interval 9.4-30.1) of children, in which 8/11 were moderate and 3/11 were severe. Median interval between diagnosis of PTS and DVT was 90 days (range, 46 d to 3 y). The majority (72.7%) of patients in the non-PTS group received treatment intervention within 48 hours of diagnosis of DVT. Delay in treatment initiation (>48 h) and recurrence of DVT were associated with the development of PTS (P<0.05). Variables including occlusive thrombus, location and number of vessels involved with DVT, age at diagnosis, underlying thrombophilia, intensity of anticoagulation, and body mass index were not associated with the development of PTS. Other debilitating consequences of DVT requiring intervention included portal hypertension (n=2), chylothorax (n=1), and reflux sympathetic dystrophy (n=1). The small sample size and limited follow up restricted the statistical analysis. CONCLUSIONS: PTS is a significant problem in children with symptomatic DVTs. Early treatment intervention within the first 48 hours of diagnosis of DVT and prevention of thrombosis recurrence may prevent development of PTS. Although PTS refers to consequences of intravenous hypertension owing to extremity DVTs, sequlae of nonextremity DVTs require special consideration in pediatric PTS classification.

Effectiveness of mesoglycan in patients with previous deep venous thrombosis and chronic venous insufficiency.

AIM: Retrospective analysis of mesoglycan therapeutic activity in venous disorders. The clinical data have been selected from the outpatient database of the Chair of Angiology of the University of Catania (from 1988 to 1997) through a cross survey between the prescription commercial name of mesoglycan and the key words varicose veins, deep venous thrombosis (DVT), chronic venous insufficiency (CVI), post-thrombotic syndrome (PTS), venous thrombosis, venous ulcer. METHODS: Patients have been selected on the basis of definite data relative to principal diagnosis, clinical history, clinical and instrumental objective phlebological picture, posology and duration of treatment, follow-up visits in the first three years following the first observation. Group 1: 56 patients with first episode DVT; Group 2: 27 patients with recurrent DVT; Group 3: 182 patients with CVI (107 with primitive CVI and 75 with secondary CVI). The selected patients data have been included in new databases. DVT patients were evaluated for recurrence prevalence during the follow-up period (6, 12, 18, 24, 30 and 36 months). In Group 2 the recurrence prevalence in the normal follow-up period was evaluated and, in addition, the clinical chronology of the recurrence previous to observation was drawn, in order to find out the recurrence prevalence of the thrombotic episode preceding our observation. The two prevalence trends ( mesoglycan treatment and episode preceding our observation) have been compared with the Student t test. CVI patients (Group 3) were classified according to CEAP classification criteria. The effectiveness of treatment was assessed according to the changes in the scores of venous dysfunction of CEAP classification (disability score; pain; oedema; skin color change; cutaneous ulcer). The mean and standard deviation of the considered scores have been evaluated with the Student t test comparing each series with the immediately previous series and with the T0 series. The mean dose of mesoglycan was 50 mg twice per day. RESULTS: Group 1 (1(st) episode DVT): the recurrence prevalence was 3.5% at 6 months, 9% at 12 months, 12.5% at 18 months, 14.28% at 24, 30 and 36 months. At the end of the 3 follow-up years the PTS diagnosis could be performed in 10 patients (17.85%). Group 2 (recurrent DVT): the recurrence prevalence was 3.7% at 6 months, 11.11% at 12 months, 14.81% at 24 months, 18.51% at 36 months during mesoglycan treatment. In the preceding period the prevalence was 11.11% at 6 months from the preceding episode, 16.66% at 12 months, 33.33% at 24 months and 37.03% at 36 months. In the remaining 62.96% the recurrence occurred at 36 and 48 months. The comparison between the two series showed a significant difference with P < 0.0004. PTS prevalence at the end of the 3 follow-up years was 17.85% in patients with a first episode of DVT and 81.41% in patients with recurrent DVT. Group 3 (CVI): all the venous dysfunction scores showed a significant improvement during the follow-up period, both in comparison with the beginning of treatment and with the immediately preceding control visit. CONCLUSION: The results obtained in groups 1 and 2 show that mesoglycan is effective in preventing thrombotic recurrence in patients with previous DVT. The recurrence prevalence in patients with DVT at 1(st) episode was lower than the prevalence reported by the literature data (17.5% within 2 years and 24.6% within 5 years). The positive trend was also confirmed in the recurrent DVT group, although with a major prevalence (18.51%) due to a higher thrombotic risk. However, the prevalence in the treatment period is significantly lower than the previous thrombotic episode. Mesoglycan was also effective in CVI patients, with a progressive and significant improvement of disability, pain and edema, which are the pathophysiologic elements responsible for the impairment of quality of life. At the various follow-up points the mean score value significantly reduced compared to T0 and to the values of the preceding control. In conclusion mesoglycan is a useful and effective medication in the treatment of venous disorders, both in the subacute phase of DVT and in the long-term therapy for CVI, and is worth more extensive documentation, in accordance with the criteria of evidence-based medicine.

[Disorders of rheologic properties of blood and their correction in postthrombophlebitic syndrome]. / Narushenie reologicheskikh svoistv krovi i ikh korrektsiia pri posttromboflebiticheskom sindrome.

Pathogenetic mechanisms of disorders of rheologic properties of blood in postthrombophlebitic syndrome (PTPS) are analyzed. Thirty-six patients were examined and divided into 2 groups. In combined therapy of the study group (18 patients) pentoxyfillin tablets were included. In the control group derivatives of xantin were used. Good clinical effect of pentoxyfillin based on positive influence on rheologic properties of blood was demonstrated. In the study group significant reduction of edema was in 72,2% patients, of pains - in 83,3%. In the control group positive results were achieved only in 55,6% patients.

El aloe en el tratamiento tópico de las úlceras postrombóticas / Aloe in topical treatment of post-thrombotic ulcers

Se escogieron 30 pacientes tratados en el Servicio de Flebolinfología del INACV en el período de enero de 1997 a mayo de 1999, aquejados de úlceras postrombóticas en los miembros inferiores, divididos en 3 grupos de 10 pacientes cada uno y seleccionados al azar. Se les aplicó tópicamente las cremas de aloe 50(por ciento), sulfadiacina de plata 1(por ciento) y su combinación, indistintamente en un período de 6 semanas. Se les realizó semanalmente mediciones de las lesiones ulcerosas y examen clínico. Se constató reducción del porcentaje de los síntomas subjetivos (dolor, secreción, inflamación y fetidez) con todas las cremas, en primer lugar la sulfadiacina de plata 1(por ciento), luego la de aloe 50(por ciento) y por último la combinación de ambas. En cuanto a los criterios de remisión la sulfadiacina de plata al 1(por ciento) tuvo un 60(por ciento) de remisión total, la de aloe 50(por ciento) un 50(por,ciento) y la combinación de ambas sustancias un 40(por ciento)(AU)

[Role of plasminogen activators in the treatment of deep venous thrombosis]. / Place des activateurs du plasminogène dans le traitement de la thrombose veineuse profonde.

In deep vein thrombosis, thrombolytic agents can improve vein patency more rapidly than conventional anticoagulant therapy. The clinical benefit of thrombolytic use would be a reduction in the incidence and severity of the postthrombotic syndrome and limb salvage in "phlegmatia caerulea". A literature review suggests that streptokinase and rt-PA do better than heparin regarding vein patency. A clinical benefit on postthrombotic syndrome can only be suggested by available evidence. The risk of major bleeding is increased by thrombolytic agents as compared with heparin. Mortality for cerebral bleeding is about 0.5%. Currently, thrombolytic therapy is only recommended for limb salvage in phlegmatia caerulea.

Cicatrización de úlceras venosas con difenilhidantoinato de sodio / Cicatrization of venous ulcers with dyphenilhydantoin sodium

Introducción. Las úlceras venosas de extremidades inferiores muestran una incidencia de 2.5 millones de casos anuales en los Estados Unidos y una prevalencia de 22 por cada 100 personas. Además son recurrentes, incapacitantes y repercuten en forma severa para la deambulacion. Un medicamento utilizado en casos de epilepsia, el Difenilhidantoinato de sodio (DFH-Na), puede favorecer la cicatrización de las úlceras venosas.Material y métodos. Seleccionamos 20 pacientes que presentaron ulceración de la pierna con diagnostico de secuela postflebitica, a 10 de esos pacientes se les aplico diariamente DFH-Na, por vía tópica y por espacio de 2 a 3 meses en las úlceras, previo aseo con agua y jabón. Los diez pacientes restantes correspondieron al grupo testigo que recibió tratamiento convencional (agua y jabón. Se evaluaron parámetros generales en los 20 pacientes (sexo, edad, ocupación, antecedentes sobre anticonceptivos, patologías asociadas, tiempo de aparición de la úlcera, recidivas), así como tomas de biopsias, fotografías y mediciones planimétricas al inicio y final del tratamiento.Resultados. Al final del tratamiento observamos que el 40 por ciento de los pacientes respondió al DFH-Na como inductor de la cicatrización y ninguno al tratamiento ordinario. En el primer grupo se desarrolló tejido de granulación y desplazamiento epitelial hacia las soluciones de continuidad de la piel.Conclusiones. La aplicación tópica del DFH-Na, como recurso farmacológico para la cicatrización de úlceras venosas resulta favorecedor por disminuir el tiempo de curación y disminución en el costo del tratamiento.

Daño arterial y uso de fleboesclerosantes / Arterial damage and use of fleboesclerosing agents

Aunque el tratamiento con agentes fleboesclerosantes constituye una alternativa para las várices, éste no está exento de complicaciones, las que pueden ser de tipo general y local. De estas últimas, la inyección intraarterial accidental es la más temida y devastadora, ya que puede llevar a la pérdida de la extremidad. Presentamos un caso clínico de esta complicación que fue tratado en forma algo tardía con un resultado aceptable, a través de una infusión sistémica con estreptoquinasa. Se concluye que si bien este tratamiento es una buena alternativa para tratar las várices, éste debe ser restringido a casos muy seleccionados, evitando los sitios de riesgo de punción arterial y hecho por profesionales entrenados en la materia

[Questionable effectiveness of autologous platelet growth factors (PDWHF) in treatment of venous ulcers of the leg]. / Fragliche Wirksamkeit autologer thrombozytärer Wachstumsfaktoren (PDWHF) in der Behandlung venöser Beinulzera.

Chronic venous insufficiency (CVI) can cause ulcers of the lower limb having the character of a full thickness wound involving the subcutaneous tissues and fat. Healing requires wound contraction, connective tissue formation and finally reepithelialization. To induce wound healing, on an underlying disturbed environment due to longterm effects of CVI, artificial stimuli may be needed. In a placebo controlled study we tried topical application of autologous PDWHF (platelet derived wound healing factors), to achieve ulcer healing and improve the microangiopathy surrounding of the ulcer area, as there are decreased number of skin capillaries and reduction in cutaneous vascular reserve. Alterations of cutaneous circulation during the course of the study were documented by capillaroscopy, transcutaneous oxygen pressure and laser Doppler flux (LDF) measurements. We were able to recruit 15 patients a I suffering from chronic nonhealing venous stasis ulcers. Eleven of the 15 patients agreed to participate in a placebo-controlled double blind study, whereas 4 patients agreed to participate only if they would be treated with PDWHF. The median age and duration of ulceration of the 6 patients (3 male/3 female) treated with placebo were 71 years and 1089 days. The median age and duration of ulceration of the 9 patients (1 male/8 females) treated with PDWHF were 66 years and 732 days. Duration of therapy for the PDWHF group was 91 days, as compared to 154 days for the placebo group. Despite 2 completely healed ulcers, the expensive treatment did not reveal any significant clinical advantage. In den PDWHF group an ulcer area of 26.9 cm2 was measured at the beginning, of 26.2 cm2 at the end; in the placebo group, 34.7 cm2 and 35.5 cm2. The nonsignificant increase of the capillary density at the ulcer border in the active group as well as the increase in the tcPO2, in contrast to little change in both parameters in the placebo group, suggests neoangiogenic abilities to PDWHF, secondarily leading to a better blood distribution with higher oxygen tension.

[Heparan sulfate in the therapy of postphlebitic syndrome. Evaluation of the efficacy and tolerability as compared to mesoglycan]. / Eparansolfato nella terapia a medio termine della sindrome postflebitica. Valutazione dell'efficacia e della tollerabilità nei confronti del mesoglicano.

BACKGROUND: Antithrombotics and profibrinolytics are indicated in several clinical thrombophilic conditions such as postphlebitic syndrome. Heparansulphate, a glycosaminoglycan, shows an antithrombotic activity with low anticoagulant effect. The aim of the study was to evaluate the efficacy and the safety of heparansulphate (100 mg b.i.d.) versus mesoglycan (50 mg b.i.d.), both administered for three months in patients with postphlebitic syndrome. METHODS: The trial was performed in an open-label, controlled, with parallel and randomized groups, design. Thirty patients, with chronic venous insufficiency and a history of venous thrombosis were enrolled. Coagulative and fibrinolytic parameters (PT, aPTT, euglobulin lysis time, fibrinogen, D-dimer, t-PA, PAI-1) and signs and symptoms (cramps, paresthesia, itch, edema, local pain, skin trophism) were assessed at enrollment, 15 days later after the pharmacological washout period and after 1, 2, 3 months of treatment. Safety was evaluated by monitoring any adverse event during the study and performing clinical laboratory tests at the beginning and at the end of treatment. RESULTS: The two drugs showed a superimposable efficacy and very good tolerability. Coagulative and fibrinolytic parameters were positively affected by both treatments and the clinical benefit was particularly evident in the heparansulphate group with a significant decrease "between times" of local pain, edema, paresthesia and itching. CONCLUSIONS: These data support the use of heparansulphate, and in general of glycosaminoglycans, in the postflebitic syndrome.

Treatment of deep vein thrombosis: is thrombosis regression a desirable endpoint?

Recent studies on the treatment of acute deep vein thrombosis (DVT) with low-molecular-weight heparins have demonstrated that a certain degree of early recanalization of thrombosed veins can be obtained which is higher than that observed under standard heparin treatment. Thrombolytic treatment of DVT is mainly advocated because a reduction of late sequelae of DVT is expected from early thrombolysis. It has been made likely by several small long-term studies that this expectation is true, but conclusive evidence is still missing. There are also large differences in the reported incidence of late postthrombotic syndrome after acute DVT. It seems likely that there is a minimal reopening rate which is required to be of possible clinical value to the individual patient. A 30% or higher reduction of the Marder score is at present used in several clinical trials as a sign of individual response to the treatment and may prove to be a useful clinical endpoint in these and in future studies. Validated methods to predict the late sequelae of acute DVT, mainly severe postthrombotic syndrome, do not yet exist. Foot plethysmography, air plethysmography, duplex sonography (peak velocity of venous reflux, valve competence), and venous pressure reduction under exercise are possible candidates to be used in future prospective trials. From the existing evidence it is very likely that a marked or total reduction of thrombi will reduce the incidence of postthrombotic syndromes. Clinical studies aiming at a high rate of venous recanalization by prolonged treatment with low-molecular-weight heparins are ongoing.

Postphlebitic syndrome: clinical activity and tolerability of desmin, new LMW dermatan sulfate.

One hundred patients suffering from postphlebitic syndrome of the lower limbs were enrolled in an open, randomized, and multicenter (six centers) trial for a period of eighteen months. Patients were randomly assigned to three treatment groups to receive (for ninety consecutive days) Desmin, a new low-molecular-weight dermatan sulfate, at the dose, respectively, of 100 mg once daily by subcutaneous (SC) route (36 patients), 100 mg twice a day by SC route (33 patients), and 200 mg once daily by intramuscular (IM) route (31 patients). The general and local tolerability and the clinical efficacy of the drug were evaluated by means of clinical, instrumental, and laboratory parameters. Desmin is effective in the decompensation stage of postphlebitic syndrome; this was demonstrated by a significant reduction in the severity of a number of typical symptoms as well as by the drug's positive effect on venous tone as confirmed by phlebotensiometric examination. The daily dose of 200 mg (either SC or IM) was more effective than the 100 mg dose. The results obtained at the end of the trial (ninety days) were statistically better than those obtained after thirty days of treatment. This trial demonstrated that both the systemic and the local (at the site of injection) tolerability of the drug, administered for three months, were good and without significant variations in the laboratory parameters monitored.

[Prevention and treatment of thrombosis in pregnancy]. / Zur Prophylaxe und Behandlung der Thrombose in der Schwangerschaft.

Pregnancy and especially delivery and the puerperium are associated with an increased risk of thromboembolic disease. Intravenous high dose heparin is the therapy of choice for manifest thromboembolic disease in pregnancy. However, high-dose heparin fails to prevent postthrombotic chronic venous insufficiency in more than one-third of the cases. Low-dose heparin may be used for antithrombotic prophylaxis during pregnancy. However, low-dose heparin may induce a substantial loss of bone density in up to 30% of cases and may be complicated by heparin-associated thrombopenia in up to 2%. This review discusses strategies to reduce these considerable risks. Prospective studies suggest that the risk of recurrence after prior deep vein thrombosis may be somewhat overestimated. These data suggest new therapeutic options in women with no risk factors other than a personal history of thrombosis. Improved diagnostic techniques may contribute to a better evaluation of the individual risk by assessing possible underlying problems such as resistance to activated protein C or deficiencies of coagulation inhibitors. Also, duration of prophylactic anticoagulation may be reduced by targeting treatment to periods of increased risk such as immobilisation, dehydration, surgery, delivery and the puerperium. Recently, evidence has been provided indicating that the use of low molecular weight heparins may be associated with reduced loss of bone density and a significantly attenuated risk of heparin-associated thrombopenia.

Pathogenesis and pathophysiology of the post-thrombotic syndrome: clinical implications.

Anticoagulant therapy can successfully prevent pulmonary embolism and rethrombosis in most cases, but cannot affect either early morbidity or the late post-thrombotic sequelae. In carefully selected cases, early clot removal by thrombolysis or thrombectomy may be justified by improved outcome because of the significant role early and late outflow obstruction plays in determining the ultimate severity of post-thrombotic sequelae. Nevertheless, it is recognized that anticoagulant therapy will continue to be used in the majority of patients because of serious intercurrent disease, sedentary lifestyle, limited extent of thrombosis, lack of tissue loss and, unfortunately, delay in referral for treatment.

Deep vein thrombosis: recovery or recurrence?

As many as two thirds of patients with new symptoms after documented DVT have postphlebitic syndrome, not DVT. Noninvasive imaging is central to the differentiation so that unnecessary anticoagulation therapy can be avoided. Recent changes in heparin and warfarin protocols for DVT are also outlined.

[Ambulatory treatment of postphlebitic ulcers of lower limbs. Physiopathological bases and clinical results]. / Il trattamento ambulatoriale delle ulcere postflebitiche degli arti inferiori. Basi fisiopatologiche e risultati clinici.

Venous ulceration is a troublesome and disabling complication, representing one of the most difficult problems to be treated by the vascular surgeon. Venous insufficiency is a widespread condition, the prevalence of venous ulceration being 0.5 - 1 per cent in European populations. Although all venous ulcers will heal if the limb is elevated above heart level for an extended period of time, patients need a safe, effective, not disabling and quick therapy. Hence, the competent vascular surgeon must be familiar with venous pathophysiology and possess a thorough understanding of the treatment options available for a discouraged patient in need of an acceptable and effective approach. The aim of the present study was to assess the efficacy and the speed of healing of venous ulcer using an outpatient ambulatory treatment protocol. This protocol consisted of elastic compression bandage allowing deambulation, local dressing using lyophilized heterologous collagen (Condress, Gentili) and systemic profibrinolytic drugs. Exclusion criteria were coexisting arterial insufficiency, ulcer area greater than 25 cm2, coexisting disabling diseases (congestive cardiac failure, hepatic insufficiency, malignancy). From December 1990 to June 1993, 37 patients affected by venous ulcer were treated, according to the aforementioned protocol, at the Surgical Department of Montecchio Maggiore Hospital (VI). There were 16 male and 21 female patients, mean age was 66 years (range 59-91). Results show the complete healing of the venous ulcer in 94.5% of patients; mean time for ulcer healing was 128 days (range 45-91). The Authors conclude that the outpatient ambulatory treatment protocol is safe, quick, and effective for the therapy of chronic venous ulcer; once obtained the healing of the ulcer, elastic compressive bandage with elastic stockings is mandatory to prevent recurrences.