Thrombotic complications of central venous catheterization with peripherally inserted catheters in patients with classical‐Hodgkin lymphoma

Patients with classical-Hodgkin lymphoma (c-HL) require long-term (≥2 months) central venous catheter (CVC), which provides simple and quick access for cytotoxic agent administration (mostly, anthracycline-based regimens, which are strongly phlebizing drugs for acidic pH [<5]), intravenous hydration, blood product transfusions, total parenteral nutrition, and/or venous sampling.1 The selection of the insertion site, either the internal jugular vein (IJV) or subclavian vein, or even the basilic vein and brachial vein of the right or left upper arm, may contribute to the emergence of catheter-related (CR) complications.2, 3 This is an important issue for the treating physicians who usually select the insertion site at their own discretion. In patients with c-HL, there are scarce data on intravascular complications of an upfront approach with a peripherally inserted central catheter (PICC) for long-term use.4 We read with great interest the report by Assanto et al. published in Hemasphere in 2025,5 which focused on risk factors for thrombosis in lymphoma. The retrospective study by Assanto et al. describes a total of 470 c-HL patients (median age at diagnosis: 37 years, range 17–85 years), who received (without thromboprophylaxis) adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD)- or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone (BEACOPP)-based frontline treatments from 2014 to 2022. Forty-eight percent (N = 224) of patients had a PICC inserted. Ultrasonography (US) with Doppler and color imaging was used to diagnose venous thromboembolism (VTE) only in symptomatic patients, and computed tomography angiography was performed in selected cases to detect pulmonary embolism (PE). Clinically significant events (symptomatic thrombosis requiring treatment) were recorded. Among the 470 patients, 57 (12%) experienced a thromboembolic event (TE), which occurred after a median follow-up of 3.3 months (range: 1–52 months) from c-HL diagnosis: 21/470 events were PICC-related (4.5%) and 36/470 (7.66%) were not-PICC-related. Among these, five were arterial thromboses, and four were PEs. Multivariate analysis including ThroLy parameters6 identified PICC presence, bulky disease (>7 cm lymph node), mediastinal involvement, and Eastern Cooperative Oncology Group Performance Status (ECOG PS) 2–4 as independent risk factors for TE events. According to the authors, large prospective cohorts are needed in c-HL to identify patients who would benefit from primary low-molecular-weight heparin (LMWH) prophylaxis and those who could safely avoid it.5 In our tertiary hospital in southern Italy (the Hematology Unit of the Federico II University Medical School of Naples), PICC implantation has been implemented as a routine minimally invasive procedure for patients with hematological diseases. Recently, we carried out a real-life analysis from the registry database of the Unit focusing on the impact of long-term PICC on symptomatic venous thrombosis (s-VT).7 We reviewed clinical charts of patients suffering from chronic hematological diseases with PICC placement intended to be in situ for at least 60 days after catheterization. The period of observation was between January 2014 and December 2023. A total of 1150 PICCs were inserted into 1150 patients through the basilic vein in 86.9% of cases (brachial vein in the remaining cases) at hematologic diagnosis. Overall, there were 600 females and 550 males with a median age of 30 years (range, 16–70 years). Underlying chronic diseases were the following: non-Hodgkin lymphoma (N = 760, 66.1%), Hodgkin lymphoma (HL) (N = 200, 17.4%), multiple myeloma (N = 100, 8.7%), chronic lymphocytic leukemia (N = 50, 4.3%), severe aplastic anemia (N = 15, 1.3%), sickle cell disease (N = 10, 0.9%), thalassemia (N = 10, 0.9%), and hemophilia (N = 5, 0.4%). Prothrombotic risk factors were hypertension in 218 (19%) cases, smoking in 207 (18%), ECOG PS 2–3 in 173 (15%), and diabetes in 81 (7%). The most frequent catheter implanted was a 4-French (Fr) device with a single lumen (open-ended, non-valved power-injectable polyurethane PICC with a flexible tip; ProPic MEDCOMP, Harleysville, USA). Median attempts at venipuncture were 1 (range, 1–2). Tip location was at the lower third of the superior vena cava in 230 (21.8%) cases and at the cavo-atrial junction in 920 (78.2%) cases. Parenteral infusions were anticancer therapy in 1081 (94%) cases and/or supportive care in 69 (6%) cases. About chemotherapy-induced hematological toxicity, neutropenia occurred in 575 (50%) patients and thrombocytopenia in 460 (40%). The median duration of in situ PICC placement was 300 days (range, 120–400 days). Overall, a symptomatic CR-VT was recorded in 30 cases (2.6%) with a rate of 0.13 (95% confidence interval [CI]: 0.04–0.30) per 1000 implantation days. The median interval between PICC insertion and thrombotic episode was 30 days (range, 4–95 days). For patients with HL, the rate of PICC-related s-VT was 4.5%. HL resulted in a numerically higher incidence of CR-symptomatic VT with a rate of 0.15 (95% CI: 0.07–0.29) per 1000 implantation days versus 0.074 (95% CI: 0.047–0.11) per 1000 implantation days for the other chronic hematological diseases (rate ratio = 2.03; 95% CI: 0.93–4.4; P = 0.07, Poisson test) (Figure 1). In our hands, a detailed protocol was followed during PICC implantation.1 First, bilateral US of all veins of the arm and neck was performed before the implantation. The selection of the appropriate vein at the upper-mid arm (the green zone of the zone insertion method) was made according to the vein's diameter in millimeters on US, which had to be at least equal to the catheter in Fr. Second, a clear identification on the US of the median nerve and brachial artery was required before venipuncture, which was performed with US guidance. Third, we strictly performed hand washing, aseptic technique, and maximal barrier protection. Fourth, US of the IJV was also performed during the introduction of the catheter. Finally, we used an intracavitary electrocardiographic method to assess the tip position and secured the PICC with a sutureless device. In addition, a dedicated central venous access team managed all PICCs following standardized procedures from insertion to weekly follow-up. In conclusion, patients with c-HL experienced a high CR-VT rate compared to the other chronic hematological diseases. The stiffened tissue of nodal masses, which is usually located in the cervical-thoracic district, that is, neck, axillary, and/or mediastinum, could more easily lead to vein thrombosis due to vascular compression.8 These findings suggest that instead of alternative vascular accesses such as centrally inserted central catheter (e.g., totally implantable venous access devices, i.e., Port-a-caths), primary prophylaxis with LMWH should be considered in HL cases with in situ PICC placement as underlined by Assanto et al.5 Marco Picardi: Conceptualization; methodology; writing—original draft. Claudia Giordano: Investigation; writing—review and editing; formal analysis; data curation. Annamaria Vincenzi: Investigation; methodology; data curation. Alessia Scarpa: Data curation; methodology. Novella Pugliese: Methodology; formal analysis; data curation; conceptualization. Roberta Della Pepa: Data curation; conceptualization; methodology. Fabrizio Pane: Conceptualization; supervision; validation; visualization. The authors declare no conflicts of interest. This research received no funding. The data that support the findings of this study are available from the corresponding author upon reasonable request.