Sudha Parasuraman

Venous Thromboembolism in Children

Case 1: A 4-year-old boy with acute lymphoblastic leukemia (ALL) and disseminated candidiasis was found to have a right atrial thrombus on a routine imaging study. He had a central venous catheter (CVC) and was receiving chemotherapy that contained asparaginase. Thrombophilia workup was negative. Case 2: A 17-year-old girl presented to the emergency department with a 3-week history of left-sided chest pain and shortness of breath. She had been taking high-dose estrogen therapy for congenital tall stature. D-dimer was positive. Chest CT revealed multiple small pulmonary emboli and infarcts. Lower-extremity venous ultrasound was negative for deep vein thrombosis, and echocardiography showed normal right ventricular function. Thrombophilia workup was negative. Decreased capacity to generate thrombin, increased capacity of α2-macroglobulin to inhibit thrombin, and enhanced antithrombotic potential by the vessel wall appear to contribute to the low incidence of venous thromboembolism (VTE) during childhood. Nevertheless, VTE is being diagnosed more frequently in children. The annual incidence is 0.07 to 0.14 per 10 000 children, or 5.3 per 10 000 hospital admissions of children, and 24 per 10 000 admissions to neonatal intensive care units.1–3 The highest incidence is during the neonatal period, followed by another peak in adolescence. Patients in neonatal and pediatric intensive care units and oncology patients are particularly at high risk. Teenage girls have twice the rate of VTE as do teenage boys. This appears to be due to the use of oral contraceptives and pregnancy.4 ### Risk Factors Idiopathic VTE in the pediatric population is relatively infrequent and is almost always associated with an underlying disease or risk factor. Both congenital and acquired conditions contribute to the development of thrombosis. More than 90% of children with VTE will have ≥2 predisposing factors (Figure). Figure 1. Risk factors for childhood VTE. #### Acquired Conditions The presence of a CVC is the …

Bortezomib, Bendamustine, and Rituximab in Patients With Relapsed or Refractory Follicular Lymphoma: The Phase II VERTICAL Study

PURPOSE The aims of this multicenter study were to evaluate the response rate, progression-free survival, and toxicity of the combination of bortezomib, bendamustine, and rituximab in patients with follicular lymphoma whose disease was relapsed or refractory to prior treatment. PATIENTS AND METHODS Patients received five 35-day cycles of bortezomib, bendamustine, and rituximab: bortezomib administered intravenously (IV) at a dose of 1.6 mg/m(2) on days 1, 8, 15, and 22, cycles one to five; bendamustine 50, 70, or 90 mg/m(2) IV over a 60-minute infusion on days 1 and 2, cycles one to five; and rituximab 375 mg/m(2) on days 1, 8, 15, and 22 of cycle one and day 1 of subsequent cycles. Patients were assessed using the International Workshop Response Criteria, with the primary end point of 60% complete response rate. RESULTS Seventy-three patients were enrolled. During the dose-escalation phase, the maximum-tolerated dose for bendamustine was not reached; the 90 mg/m(2) dose level was expanded for the efficacy assessment, and a total of 63 patients received bendamustine 90 mg/m(2). In these 63 patients, the overall response rate was 88% (including 53% complete response). Median duration of response was 11.7 months (95% CI, 9.2 to 13.3). Median progression-free survival was 14.9 months (95% CI, 11.1 to 23.7). Toxicities were manageable; myelosuppression was the main toxicity (25% and 14% of patients experienced grade 3 to 4 neutropenia and grade 3 to 4 thrombocytopenia, respectively). Transient grade 3 to 4 neuropathy occurred in 11% of patients. CONCLUSION The combination of bortezomib, bendamustine, and rituximab is highly active in patients with follicular lymphoma who have received previous treatment.

Prevention of Pulmonary Embolism in General Surgery Patients

Case Presentation : A 29-year-old woman presented to the emergency department with complaints of pleuritic chest pain, fever, and left ankle swelling and tenderness. Cardiac examination was normal except for tachycardia. A chest computed tomography scan with contrast demonstrated extensive bilateral pulmonary emboli. Thirteen days previously, an intoxicated driver with multiple prior convictions for driving under the influence of alcohol crashed head-on into her car at a high speed. She was 8 months’ pregnant and suffered the loss of the child. She spent 7 days in the hospital and underwent cesarean section, exploratory laparotomy, and splenectomy. No preoperative pharmacological prophylaxis against venous thromboembolism (VTE) was administered. VTE, which includes deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important and common complication of general surgery. A new era in the postoperative management of surgical patients began in 1975 when the effectiveness of low-dose heparin in preventing postoperative DVT and PE was established by the pivotal International Multicenter Trial.1 The dose was 5000 U subcutaneously every 8 hours, with the first injection administered 2 hours before the skin incision. Compared with control, the incidence of DVT in patients receiving heparin decreased from 24.6% to 7.7%. Similarly, the incidence of autopsy-proven PE was reduced 8-fold. The results of this trial introduced and validated the concept of using low-dose heparin to prevent postoperative VTE. This trial revolutionized surgical practice. By 1994, 90% of North American general surgeons reported the routine use of thromboprophylaxis.2 Most postoperative DVT originates in the deep calf veins, primarily within the valve cusps. Most thrombi remain confined to the calf. Propagation into the proximal veins increases the risk of PE. Symptoms and signs of postoperative VTE such as mild hypoxia or low-grade fever are frequently nonspecific. Moreover, clinical manifestations of postoperative VTE may not occur until …

Gastrointestinal complications after 3 months of dual antiplatelet therapy for drug-eluting stents as assessed by wireless capsule endoscopy.

Little is known about the frequency of symptomatic and asymptomatic gastrointestinal complications of dual antiplatelet therapy. We recruited 30 patients between 18 and 80 years who were started on aspirin and clopidogrel following percutaneous coronary intervention with drug-eluting stents. We hypothesized that the 3 months of dual antiplatelet therapy would be associated with frequent upper gastrointestinal endoscopic abnormalities. Patients were followed with weekly phone calls to inquire about the new gastrointestinal symptoms and after a minimum of 80 days, their upper gastrointestinal mucosa was visualized with PillCam ESO® wireless capsule endoscopy. 18 (90%) of the 20 successful wireless capsule endoscopies revealed at least 1 type of gastrointestinal mucosal lesion. Gastric erosions (n = 14, 70%) were the most common abnormality. We believe this is the first noninvasive endoscopic study of gastrointestinal complications of dual antiplatelet therapy in patients who undergo percutaneous coronary intervention with drug-eluting stents. Future studies should expand on our observations to determine whether prophylaxis with proton pump inhibitors is warranted.

Once daily enoxaparin for outpatient treatment of acute venous thromboembolism: a case-control study.

We studied the efficacy and safety of an investigational enoxaparin regimen, 1.5 mg/kg once daily, as a bridge to warfarin for the outpatient treatment of acute venous thromboembolism. We undertook a case-control design. We enrolled 40 acute venous thromboembolism cases prospectively and matched them by age, gender, and location of venous thromboembolism to 80 previously treated controls. All controls had received enoxaparin 1 mg/kg twice daily. The primary end point was recurrent venous thromboembolism. We followed the cases for 30 days. We discontinued enoxaparin after we achieved the target international normalized ratio between 2.0 and 3.0. One case (2.9%) and three controls (3.8%) had recurrent venous thromboembolic events (P = 1.00). There were no major bleeding complications in the case group, compared to 3 (3.8%) in the control group (P = .55). Once daily enoxaparin, 1.5 mg/kg, as a bridge to warfarin was as effective with a similar safety profile as twice daily enoxaparin, 1mg/kg, for initial treatment of acute venous thromboembolism in the outpatient setting. This case-control study provides the rationale for undertaking a randomized controlled trial comparing enoxaparin 1.5 mg/kg once daily versus enoxaparin 1.0 mg/kg twice daily as a bridge to warfarin in outpatients with acute venous thromboembolism.