76 Članek prispel / Received 27. 9. 2021 Članek sprejet / Accepted 19. 5. 2022 Ključne besede: globoka venska tromboza; lokalna usmerjena tromboliza; perkutano interventno zdravljenje; phlegmasia cerulea dolens Key words: catheter-directed thrombolysis; deep vein thrombosis; percutaneous interventional treatment; phlegmasia cerulea dolens Lokalna katetrska tromboliza kot terapija za globoko vensko trombozo – poročilo o primeru Catheter-directed thrombolytic therapy for lower- extremity deep vein thrombosis: a case report Avtor / Author Aja Pajnik Snoj, MD1, Andrej Markota, MD, PhD2 Ustanova / Institute 1Urgentni center, Univerzitetni Klinični Center Maribor, Maribor, Slovenija; 2Oddelek za intenzivno interno medicino, Univerzitetni Klinični Center Maribor, Maribor, Slovenija; 1Emergency Department, University Medical Centre Maribor, Maribor, Slovenia; 2Medical Intensive Care Unit, University Medical Centre Maribor, Maribor, Slovenia; Abstract Patients with lower-extremity deep vein thrombosis commonly present to emergency departments. However, the propagation of deep vein thrombosis to phlegmasia cerulea dolens is rarely seen. Catheter-directed thrombolytic therapy is widely accepted as an appropriate treatment for severe forms of lower-limb deep vein thrombosis such as phlegma- sia cerulea dolens. It is usually available only in a few selective hospitals. This study aimed to present a case of the first such procedure performed in the Univer- sity Medical Centre Maribor. Izvleček Globoka venska tromboza spodnjih okončin je pogost razlog za obravnavo bolnika v urgentni ambulanti. Kljub temu so napredovale oblike globoke venske tromboze redke (npr. phlegmasia cerulea dolens). Lokalna katetrska trom- boliza velja za terapijo izbora pri zdra- vljenju napredovalih oblik globoke ven- ske tromboze, kot je phlegmasia cerulea dolens. V članku bomo predstavili prvi primer tovrstnega zdravljenja v Uni- verzitetnem kliničnem centru Maribor (UKC Maribor). Naslov za dopisovanje / Correspondence Aja Pajnik Snoj, Emergency Department, University Medical Centre Maribor, Maribor, Slovenia E-pošta: aja.pajnik.snoj@gmail.com Poročilo o primeru / Case report ACTA MEDICO-BIOTECHNICA 2022; 15 (1): 76–80 https://doi.org/10.18690/actabiomed.235, CC BY 4.0 © 2022 University of Maribor, University Press 77 Poročilo o primeru / Case report ACTA MEDICO-BIOTECHNICA 2022; 15 (1): 76–80 INTRODUCTION Deep venous thrombosis (DVT) is a common dis- ease with an annual incidence of around 1–5 per 1000 people/year or an 11% absolute lifetime risk for an individual (1). It usually manifests with leg swelling, pain, warmth, and erythema, and is usu- ally diagnosed with ultrasound. A majority of pa- tients are treated with anticoagulation therapy (2). Infrequently, DVT progresses to phlegmasia cerulea dolens (PCD), which can manifest in venous gan- grene. The symptoms result from the obstruction of venous drainage from the extremity and include se- vere pain, swelling, cyanosis, and edema. The result- ing compartment syndrome impairs arterial supply, such that circulatory collapse and shock frequently occur. A delay in treatment may result in death or loss of the patient's limb (3). PCD is usually managed with catheter-directed thrombolysis or thrombectomy using mechanical techniques (4,5,6). We presented a case of a 56-year- old man suffering from PCD. Catheter-directed thrombolytic therapy and mechanical thrombecto- my were required to prevent further complications. CASE REPORT A 56-year-old Caucasian male patient presented to the emergency department complaining of pain, swelling, and discoloration of his lower left extrem- ity. The symptoms started on the morning of the day he presented to the emergency department. He was otherwise healthy with no regular medication and unremarkable medical history. The examination revealed that his entire left lower extremity was swollen with purple discoloration and was very painful to palpate (figure 1). The arterial pulses distally were present but weak. He was hypo- tensive, tachycardic, and normopnoeic. A bedside ultrasound revealed DVT of the femoral and pop- liteal veins. Computed tomography angiography re- vealed a filling defect in the inferior vena cava, ex- tending from the branching of the right renal vein caudally through the iliac veins and the entire left lower extremity. The patient also had signs of DVT in the right leg. The laboratory results revealed leukocytosis (44 x 109/L), acute renal failure [creatinine 275 µmol/L, urea 9.8 mmol/L, calculated glomerular filtration rate 21 mL/(min · 1.73 m2)], and hyperkalemia (7.3 mmol/L). The levels of inflammatory markers (C- reactive protein 231 mg/L, procalcitonin 1.6 µg/L) and myoglobin (9855 µg/L) were also elevated. The arterial blood gas analysis revealed metabolic acido- sis (pH 7.3) with low bicarbonate (12 mmol/L) and high lactate levels (4.6 mmol/L). He was admitted to the medical intensive care unit. At admission to the intensive care unit, he was un- responsive to fluids. He required 0.3 µg/(kg · min) of noradrenaline and vasopressin (0.035 IU/min) to maintain mean arterial pressure around 75 mm Hg. Bicarbonate was continuously infused for urine alkalinization. Hyperkalemia was treated with insu- lin and glucose. Anticoagulation was performed by continuous infusion of unfractionated heparin. The catheter-directed thrombolysis was initiated via a catheter inserted through the left popliteal vein after other options were exhausted approximately 16 h following admission to the hospital (figure 3). Over the following 24 h, our patient received a con- tinuous infusion of tissue plasminogen activator at 2 mg/h. Control venography showed a significantly improved flow through the venous system. At the same time, clinical and laboratory improvement was observed (figure 2). The infusion of noradrenaline was discontinued on day 3, along with the reduc- tion of the fraction of inspired oxygen to 22% and normalization of urine output at around 80 mL/h. He was discharged from the intensive care unit on day 4 and discharged from the hospital on day 12. DISCUSSION We rapidly obtained the diagnosis of PCD with evidence of cardiocirculatory instability and 78 Figure 3. Filling defect of the patient's left iliac veins seen on a venogram. Figure 4. Venogram of the left iliac veins after stent placement. Figure 1. Patient's legs upon the first examination. Figure 2. Patient's legs after successful reperfusion. Poročilo o primeru / Case report ACTA MEDICO-BIOTECHNICA 2022; 15 (1): 76–80 79 Poročilo o primeru / Case report ACTA MEDICO-BIOTECHNICA 2022; 15 (1): 76–80 multiorgan failure, which demonstrated the need for more immediate and aggressive therapy. Catheter-directed rather than systemic thrombolytic therapy is now the most common method of administering thrombolytic agents in patients with PCD. Patients should receive systemic anticoagulation, usually with an infusion of unfractionated heparin. A number of studies have shown that thrombolytic therapy results in a more rapid and complete lysis of clots, compared with anticoagulant therapy alone, but it has no impact on recurrent thromboembolism or mortality (2,4,5,6). Also, it does not reduce the incidence of post- thrombotic syndrome (2,4,5). Catheter-directed approaches have the additional advantage of combining thrombolysis with mechanical thrombus removal, which results in faster restoration of limb perfusion (5,6). Usually, the catheter is placed deep into the thrombus by an interventional radiologist with the help of a guidewire using the Seldinger technique (3,5). During the procedure, sometimes an inferior vena cava (IVC) filter is placed to trap thrombus fragments and prevent pulmonary embolism. Pulmonary embolism, which causes significant morbidity and mortality, has been reported to occur in as many as 4.5% of patients who undergo catheter-directed procedures for DVT. The absolute indication for this procedure is in patients who have DVT despite adequate anticoagulation therapy or those who cannot take anticoagulation therapy (7). The morbidity associated with additional interventional procedures of insertion and retrieval of the filter should also be considered. Furthermore, IVC filters that are not removed on time have been reported to be associated with an increased risk of complications such as IVC thrombosis, recurrent DVT, thrombophlebitis, and venous stasis disease (8). In our case, the aforementioned procedure was not performed, since the thrombus extended to the level of renal veins. The most commonly used drug for thrombolysis is tissue plasminogen activator, with the usual dose 0.5–1 mg/h. As for our patient, a venogram is usually performed 12–24 h after the start of the infusion (5). The manual extraction of the thrombus was continued in the present case using aspiration. The venogram uncovered an underlying stenotic lesion at the level of external iliac veins, and the interventional radiologist postponed venous graft placement (figure 4). While the catheter is in place, it is imperative to check the patient frequently for adverse effects, such as bleeding. Sometimes, reperfusion results in further swelling and ischemia. Possible local complications are catheter displacement, perforation, infection, and hematoma (5). If catheter-directed thrombolysis is not successful, alternative approaches include mechanical extraction using aspiration; angioplasty; rotational, rheolytic, or ultrasound devices; and surgical thrombectomy (4). Furthermore, establishing the cause of DVT is important. PCD is most commonly caused by malignancy, but it may also be because of procoagulant states, genetic disorders, or May–Thurner syndrome (3). Our patient tested negative for coagulopathies. However, we discovered a stenotic segment of the common iliac vein. Therefore, the most likely cause of the disease in the present case was May–Thurner syndrome. CONCLUSIONS Our case demonstrated that prompt treatment of the life-threatening forms of DVT, such as PCD, with catheter-directed thrombolysis and mechanical aspiration of the thrombus can result in a rapid clinical, laboratory, and radiological improvement. This treatment strategy should be made available 24/7 in tertiary-level hospitals. DISCLAIMER The images were taken with explicit permission from the patient to be used for educational purposes. 80 REFERENCES 1. Lijfering WM, Rosendaal FR, Cannegieter SC. 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Poročilo o primeru / Case report ACTA MEDICO-BIOTECHNICA 2022; 15 (1): 76–80