Challenges in Management of VTE in Children With Cancer: Risk Factors and Treatment Options.

Venous thromboembolism (VTE) occurs in 2.1 to up to 50% of children with cancer and contributes to long term morbidity as well as early mortality in this population. Pediatric patients with malignancy are predisposed to VTE due to the prothrombotic nature of cancer and its associated coagulopathies as well as chemotherapeutic agents, use of central venous catheters, surgery, radiotherapy, and concomitant thrombophilia. Management of thrombosis in this population is challenging due to concomitant thrombocytopenia, associated bleeding risks, concurrent co-morbidities, and toxicities of therapy. The aim of this paper is to highlight clinically relevant issues and management dilemmas using clinical vignettes. We review the clinical significance of asymptomatic and symptomatic thrombosis, examine the various options for asparaginase-associated thrombosis, address the role and controversies of direct oral anticoagulants, and describe our approach to managing anticoagulation therapy in the context of chemotherapy-induced thrombocytopenia.

Successful Use of Thrombolysis in an Extremely Low Birth Weight, Premature Infant With Aortic Thrombosis.

BACKGROUND: Severe neonatal aortic thrombosis is rare but can lead to significant morbidity or death if inadequately treated. Thrombolytic therapy is indicated for thrombi which are life-threatening, organ-threatening, or limb-threatening, but dosing consensus has not been established. OBSERVATION: We report a case of a 700 g preterm neonate with spontaneous intestinal perforation who developed an occlusive aortic thrombus with signs of limb ischemia. He was treated successfully with tissue plasminogen activator without hemorrhagic complications. He was started at a dose of 0.06 mg/kg/h and received a maximum dose of 0.3 mg/kg/h. Long-term follow-up at 3 years and 3 months showed no negative sequelae. CONCLUSION: Alteplase may be considered in premature, extremely low-birth weight infants with careful assessment of risk and benefits, along with frequent surveillance and supportive care.

Risk factors for neonatal thrombosis: A retrospective study conducted in a single Canadian intensive care unit.

Among children, neonates have the highest incidence of thrombosis. We conducted a retrospective review of neonatal thrombosis, in a single intensive care unit (ICU) over 4.5 years. Among 4860 ICU admissions to our center, identified through the Canadian Neonatal Network database, 186 were associated with arterial and venous thrombosis involving 195 thrombotic sites. The neonatal thrombosis incidence was 38 per 1000 neonatal ICU admissions. We assessed patient characteristics and compared the association between risk factors and thrombosis. In the multivariate analysis, central venous catheters, sepsis, and respiratory distress syndrome were significant predictors of neonatal thrombosis.

Epidemiology, diagnosis and management of neonatal thrombosis: a single-center cohort study.

The incidence of neonatal venous and arterial thrombosis ranges from 6.9 to 15/1000 neonatal ICU (NICU) admissions, and is likely an underestimate based on population demographics, frequency of surveillance and vascular catheterization. This retrospective study involving 234 infants reviewed the epidemiology, diagnosis, and management of neonatal thrombosis in a single, tertiary care institution over more than 10 years. The incidence of thrombosis was 25/1000 NICU admissions, with a preterm to term infant ratio of 1.5 : 1 and a slightly higher proportion of male sex (55.1%). The mean (range) gestational age and birth weight was 33.8 weeks (23-41.6) and 2360 g (512-5890). The median age (IQR) of thrombus diagnosis was 7 (3-17) days. Portal vein thrombosis was most prevalent (59.4%) compared with other sites of thrombosis. Almost three-quarter (171/234; 73.1%) of the thrombotic episodes were line-related, while infection and surgery were associated with 19.7% (46/234) and 10.7% (25/234), respectively. Twenty patients (8.3%) were screened for thrombophilia and 3 were positive; 2 for antithrombin deficiency, 1 for factor V Leiden gene mutation. Subjects were followed with imaging for 3 months with a treatment duration, mean (IQR) of 33.5 (10.8-42.5) days. Complete clot resolution was significantly higher in the anticoagulation group (48%; 17%; P = 0.03) compared with untreated patients. No group difference was noted for partial thrombus resolution (33.3%; 12.4%; P = 0.313). Anticoagulation halted thrombus progression (2.6 versus 12.4%; P = 0.025) and fewer treated patients failed to attend follow-up visits (6.5 versus 18.6%; P = 0.022). Well designed, multicenter prospective studies with larger sample sizes are required to confirm these findings.

Management of Anticoagulation Therapy in Patients With Thromboembolism in the Context of Renal Dysfunction: Challenging Cases and Practical Algorithms.

BACKGROUND: Low-molecular-weight heparin is cleared through the kidneys and is commonly used for anticoagulation in the pediatric population. OBSERVATION: We present 3 challenging cases of children requiring anticoagulation in the context of acute kidney injury, nephrotic syndrome, and hemodialysis. CONCLUSIONS: A significant change in anti-factor Xa (anti-Xa) levels-used for drug monitoring-should prompt an assessment of renal function. In nephrotic syndrome, anti-Xa levels should be closely monitored when there is a change in the status of nephrotic disease activity. In hemodialysis patients, enoxaparin at once daily reduced dosing should be considered with trough and peak anti-Xa levels monitoring.

Feasibility and safety of delivering full-dose anticoagulation therapy in children treated according to Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium therapy protocols.

BACKGROUND: The literature is void of an evidence-based anticoagulation therapy (ACT) management strategy in the context of thrombocytopenia. We examined the impact of thrombocytopenia on low-molecular-weight heparin (LMWH) dosing and incidence of bleeding in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL) who developed thromboembolism (TE) during therapy according to DFCI ALL protocols. PROCEDURE: Patient records from our tertiary care center were reviewed for demographics, details of diagnoses and therapy of ALL/LL and TE diagnoses, platelet counts during ACT, LMWH dosing, and bleeding episodes. RESULTS: Thirty-nine TEs were diagnosed in 33 patients [mean age 9 years (range, 2.5-18); 16 males and 31 with ALL] during the study period. A majority (85%) of patients were diagnosed with TE in the consolidation phase with mean time to TE 5.75 months from ALL/LL diagnosis. All patients received LMWH, and the median duration of ACT was 5.9 months (range, 1-11 months). Platelets were measured weekly. On 29 occasions, platelet nadir was <50 × 109 /L, and twice it was < 20 × 109 /L. One (3%) patient had major bleeding episode while on ACT. Platelet count at the time of bleeding was 222 × 109 /L. Ninety-two procedures [83 lumbar punctures (LPs), 9 central venous line (CVL) insertion/revision] were completed without bleeding complications. Asparaginase was held temporarily with TE diagnosis in 48% of patients; most (88%) patients completed all scheduled doses as per protocol. CONCLUSIONS: Ability to administer full-dose LMWH, expected bleeding rate, and completion of asparaginase doses while on ACT suggest full-dose ACT is feasible and safe in children with ALL/LL who develop TE during DFCI ALL consortium therapy protocols.

Outcomes following neonatal portal vein thrombosis: A descriptive, single-center study and review of anticoagulant therapy.

BACKGROUND: Neonatal portal vein thrombosis (PVT) is uncommon with potentially serious complications that may manifest in infancy and childhood. OBJECTIVE: The primary aim of our study was to describe the short-term and long-term outcomes of neonatal PVT. METHODS: A retrospective chart review was conducted from 2008 to 2016 of neonates diagnosed with PVT. A systematic review was also performed from 2000 to 2018 to evaluate anticoagulant therapy (ACT) in neonatal PVT. RESULTS: Forty-four premature and 30 term infants (mean gestational age 30.7 vs 39.1 weeks, respectively) had PVT. Sixty-eight involved the left portal vein, one involved only the main portal vein, and 5 involved ≥1 vein. PVT was catheter associated in 46 (62%); none of the 7 neonates tested had thrombophilia. Of 74 neonates, 19 (26%) received ACT and 55 (74%) were untreated. The mean follow-up duration was 16.6 months (SD = 17.62; range, 0-89.6); 59.5% were followed for ≥6 months. On last ultrasound examination, thrombus resolution was documented in treated (ACT; n = 19) and nontreated (n = 55) neonates: 12 (63%) versus 32 (58%) with complete resolution, 1 (5%) versus 6 (11%) partial, 0 versus 1 (2%) extension, and 6 (32%) versus 16 (29%) had nonprogressive lesions, respectively. Seventy-one (96%) had no complications. Seventy-one articles met inclusion criteria for the systematic review and 19 were retained for analysis after assessment. CONCLUSIONS: PVT resolution rate was similar to previous reports. Although a low complication rate was detected, longer follow-up is necessary to determine the need for early treatment and the precise incidence of outcomes such as portal hypertension.

Fanconi Syndrome Secondary to Deferasirox in Diamond-Blackfan Anemia: Case Series and Recommendations for Early Diagnosis.

Deferasirox is an oral iron chelator used to treat patients with transfusion-related iron overload. We report, from two institutions, two children with Diamond-Blackfan anemia who developed Fanconi syndrome secondary to deferasirox administration, along with a review of the literature. The current recommendation for the laboratory monitoring of patients receiving deferasirox does not include serum electrolytes or urine analysis. Thus, despite routine clinic visits and bloodwork, these two patients presented with life-threatening electrolyte abnormalities requiring hospitalization. Hence, we propose the inclusion of serum electrolytes and urine analysis as part of routine monitoring to facilitate the early diagnosis of Fanconi syndrome in the context of high doses of deferasirox therapy.

Vaginal Yolk Sac Tumor in an Infant: A Case Report and Literature Review of the Last 30 Years.

Vaginal yolk sac tumor is a rare malignant germ-cell tumor occurring most commonly in young girls. The treatment has evolved over the last 3 decades from radical surgery to conservative surgery with chemotherapy to chemotherapy alone. Here we present a case of a 6-month-old girl successfully treated with upfront surgery followed by chemotherapy. We include a literature review of studies on vaginal yolk sac tumor published in the last 30 years. We discuss the role of upfront surgery where possible followed by chemotherapy as a safe alternative to chemotherapy alone for the treatment of this rare malignancy.