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I. Hematologic issues in the high-risk infant

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  1. Catheter-related venous thromboembolism

    1. Definition

      1. Catheter-related deep venous thromboembolism (VTE) is the most common etiology of DVT in infants.

      2. It may occur in association with catheters in the upper extremities and lower extremities as well as umbilical venous catheters.

    2. Incidence

      1. The incidence of symptomatic thromboembolism in infants is estimated at 0.51 per 10,000.

      2. Over 80% to 90% of VTEs in neonates are secondary to central venous catheters.

      3. The incidence of VTE is increasing due to increasing complexity of care.

    3. Pathophysiology

      VTE results from obstruction of blood flow, damage to the endothelium, and prothrombotic factors in the blood.

    4. Risk factors

      1. The primary risk factor is the catheter itself due to obstruction of blood flow and damage of the endothelium by the catheter.

      2. Additional risk factors include dehydration, polycythemia, infection, and inherited thrombophilias. Inherited thrombophilias include protein C deficiency, protein S deficiency, antithrombin deficiency, factor V Leiden mutation(s), prothrombin gene mutation(s), elevated lipoprotein (a), and hyperhomocysteinemia.

      3. Maternally transferred antiphospholipid antibodies may also increase risk of thrombosis.

    5. Clinical presentation

      1. Signs and symptoms

        • This condition may be asymptomatic and detected as an incidental finding.

        • Symptoms include dysfunctional catheter and/or swelling, pain, and redness of the affected extremity.

        • Recurrent central line infection may be a sign of VTE.

        • UE VTE may be associated with superior vena cava (SVC) syndrome if there is occlusive thrombus in the SVC. SVC syndrome presents with plethora and hemodynamic instability.

      2. Condition variability: The condition ranges from asymptomatic to life threatening with SVC syndrome.

    6. Diagnosis

      1. Clinical history: Review clinical history for VTE risk factors. Review family history for history of thrombosis.

      2. Imaging: Diagnosis is made with imaging of the affected vessel(s); most often using Doppler ultrasonography (U/S). U/S depends on compression of the affected vessel. In some cases, magnetic resonance venography (MRV) may be required for diagnosis, especially in the UE. Echocardiogram may be useful to detect extension into the right atrium.

      3. Laboratory evaluation

        • Baseline studies prior to anticoagulation: complete blood count, PT, PTT, fibrinogen, D-dimer, creatinine, and antithrombin activity.

        • Thrombophilia evaluation: Factor VIII activity, lupus anticoagulant panel, anticardiolipin antibody, anti-β2 glycoprotein 1, homocysteine, factor V Leiden, and prothrombin gene mutation.

    7. Management

      1. Medical: Anticoagulation with unfractionated heparin (UFH) or low molecular weight heparin (LMWH). The clinician should consider the risks and benefits of anticoagulation in each neonate. Table 18-1 shows contraindications to anticoagulation. Table 18-2 shows dosing and monitoring recommendations for UFH and LMWH.

        • Observation: If anticoagulation is contraindicated, monitor with physical examination and imaging to detect thrombus extension. Reconsider anticoagulation if extension occurs.

        • UFH

          • Advantages: Rapid onset of action, short half-life, clearance independent of renal function, antidote available.

          • Disadvantages: Unpredictable dose response requires frequent monitoring, requires dedicated IV line, mechanism of action is dependent on antithrombin, which is deficient in neonates.

          • Side effects: Bleeding, heparin-induced thrombocytopenia (HIT), and osteoporosis with long-term use.

          • Duration of anticoagulation depends on extent of thrombosis, resolution of thrombosis, and ongoing risk factors (Table 18-3).

        • LMWH...

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