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• W2005751388 abstract "While anticoagulation remains standard therapy for deep vein thrombosis (DVT), catheter-directed thrombolysis (CDT) in adults results in more rapid and complete clot lysis and decreased frequency of post-thrombotic syndrome (PTS) (Mewissen et al, 1999; Enden et al, 2012). CDT delivers thrombolytic agents directly into the thrombus, potentially reducing systemic exposure and bleeding risk. Opinion and practice regarding CDT use in children vary considerably and published results are limited. Current guidelines suggest reserving thrombolytic therapy for life, limb or organ-threatening thrombosis in the absence of contraindications (Monagle et al, 2012). However, in a survey of paediatric haematologists, CDT was the preferred treatment for occlusive ilieo-femoral thrombus in an adolescent (Yee et al, 2009). Several small case series of CDT in children have reported efficacy and safety with a variety of dosing regimens (Wang et al, 2003; Goldenberg et al, 2007, 2011). In this report we describe the largest single-centre paediatric experience with CDT for DVT. The study was approved by the Institutional Review Board of Johns Hopkins University. We reviewed medical records of patients age 21 years or younger who underwent CDT for DVT at the Johns Hopkins Hospital between 1998 and 2009. Patients were identified using Current Procedural Technology billing codes (88·60, 88·62, 88·66, 88·67 and 99·10). Clinical characteristics, details of the procedure, complications and outcomes following CDT were recorded. We used the International Society on Thrombosis and Haemostasis definition of major bleeding in children (Mitchell et al, 2011). Patients were considered for CDT if they presented with acute (within 2 weeks) symptomatic proximal (iliofemoral or axillosubclavian) DVT with a large clot burden and no increased bleeding risk (no surgery within 2 weeks, ongoing coagulopathy, active bleeding). For the CDT procedure, a 5-F vascular sheath was inserted proximal to the ipsilateral thrombosed vein segment under real time ultrasonographic guidance. The thrombolytic agent was slowly infused throughout the clot segment through a multiple–side-hole catheter. Adjuvant mechanical thrombectomy was performed based on individual operator preference using a rheolytic Angiojet Expedior catheter system (Possis, Warrendale, PA, USA) to further macerate and remove residual thrombus. The catheter was removed and infusion discontinued when maximum clot resolution was judged to have been achieved. Self-expandable metallic stents were used to treat stenotic lesions. Inferior vena cava (IVC) filters were placed before initiation of infusions in some patients, at the discretion of the interventional radiologist. A standardized nomogram was used to titrate the thrombolytic dose when the fibrinogen dropped below the normal range (1·5 g/l). Heparin was not routinely administered with CDT either at systemic treatment or prophylactic doses. Treatment success was assessed by venography independently reviewed by two radiologists using a previously published thrombus scoring system (Mewissen et al, 1999). For the lower extremity, seven vessels were assessed (inferior vena cava, common iliac, external iliac, common femoral, proximal superficial femoral vein, distal superficial femoral vein and popliteal vein). A score of 0–2 was given for each vascular segment (0 patent; 1 partially occluded; 2 completely occluded) and a total thrombus score was assigned from 0 to 14 before and after CDT. The percent lysis was calculated by the difference of pre- and post-CDT thrombus scores divided by the pre-lysis score. Lysis <50% was defined as grade I, lysis 50–99% was grade II, and lysis of 100% was grade III (Mewissen et al, 1999). A total of 44 CDT procedures were performed in 34 patients. Baseline characteristics are shown in Table 1. The median age was 17 years and 59% were female. Fifty-two percent had vascular obstruction; the majority underwent procedures to relieve compression (venous stent placement for May-Thurner syndrome and cervical rib resection for thoracic outlet syndrome). Many patients (47%) underwent subsequent mechanical thrombectomy for residual thrombus after thrombolytic infusion. Tissue plasminogen activator (tPA) was used in 27 and urokinase in seven patients. The median infusion rate of tPA was 0·5 mg/h with a median duration of 25 h. The median infusion rate was 0·007 mg/kg/h, which is lower than reported in ‘low-dose’ systemic thrombolysis (0·03–0·06 mg/kg/h) (Wang et al, 2003; Goldenberg et al, 2007). Cryoprecipitate 9% (3/34) PRBC 6% (2/34) Major haemorrhage 3% (1/34) (GI bleed and transfusion) Minor haemorrhage 6% (2/34) (Oozing from venepuncture, haematoma) In 23 evaluable infusions in 19 patients with lower extremity DVT, radiographic clot lysis >50% was achieved in 69% of procedures (Table 1). The average total thrombus score was 8·8 (out of 14 maximum) pre-procedure and 3·5 post-procedure. No pulmonary emboli occurred during the treatment period. Two patients (9%) had a drop in haemoglobin of at least 20 g/l and underwent transfusion of packed red blood cells. One patient who had developed heparin-induced thrombocytopenia suffered gastrointestinal bleeding during concomitant treatment with lepirudin and CDT. The bleeding episode was not associated with hypofibrinogenaemia. The other previously reported patient was an infant who received high systemic doses of tPA (0·1 mg/kg/h for 13 h) (Khan et al, 2008) but did not have clinical evidence of bleeding. In the present study, hypofibrinogenaemia was common (fibrinogen <1·5 and 1·0 g/l in 42% and 31%, respectively). The median pre-CDT fibrinogen was 4·1 g/l and the median nadir fibrinogen was 1·51 g/l (Fig 1). The median time to fibrinogen nadir was 33 h (interquartile range 28–49 h). Three patients (6%) received cryoprecipitate when their fibrinogen was <0·7 g/l. Major bleeding was noted in one patient (3%) and minor bleeding noted in two patients (6%). We found no correlation between the dose or duration of thrombolytic infusion and either degree of clot lysis or hypofibrinogenaemia. In conclusion, we report the largest case series of CDT in paediatric patients. We found that CDT was effective in reducing clot burden in the majority of patients. Major haemorrhage was infrequent. While the infusion rate of thrombolytic agents was less than that used for systemic thrombolysis, hypofibrinogenaemia was still common. Some outcomes, such as the development of PTS, could not be determined in this study due to its retrospective observational design. These results suggest that CDT is safe and effective in children, but fibrinogen activity should be monitored closely. Future studies are warranted to prospectively compare CDT with standard anticoagulation in paediatric patients with VTE. DSD, FA, KD, JK, JS, MBS, KH and CMT performed the research. FA, JS, MBS, KH and CMT designed the research study. DSD, DD, FA, KD, JK, JS, MBS, KH and CMT analysed the data. DSD, JS, MBS, KH and CMT wrote the paper. All authors reviewed and approved the manuscript." @default.
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• W2005751388 date "2012-08-31" @default.
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• W2005751388 title "Safety and efficacy of catheter directed thrombolysis in children with deep venous thrombosis" @default.
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• W2005751388 doi "https://doi.org/10.1111/bjh.12025" @default.
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