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Pulmonary Embolism, Infarction, and Hemorrhage
Pulmonary Embolus and Infarction
Keywords
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pulmonary hemorrhage
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pulmonary embolism
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deep venous thrombosis
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air embolism
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thrombophilia
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partial thromboplastin time
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hemosiderin
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bronchoalveolar lavage
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acute idiopathic pulmonary hemorrhage of infancy (AIPHI)
Venous thromboembolic disease (VTE) has become an increasingly recognized critical problem in children and adolescents with chronic disease, as well as in patients without identifiable risk factors ( Table 436.1 ). Improvements in survival with chronic illness have likely contributed to the larger number of children presenting with these thromboembolic events; they are a significant source of morbidity and mortality and may only be recognized on postmortem examination. A high level of clinical suspicion and appropriate identification of at-risk individuals is therefore recommended.
Table 436.1
Risk Factors for Pulmonary Embolism
Modified from Goldhaber SZ: Pulmonary embolism, Lancet 363:1295–1305, 2004.
| ENVIRONMENTAL |
|
| WOMEN'S HEALTH |
|
| MEDICAL ILLNESS |
|
| SURGICAL |
|
| THROMBOPHILIA |
|
| NONTHROMBOTIC |
|
Etiology
A number of risk factors may be identified in children and adolescents; the presence of immobility, malignancy, pregnancy, infection, indwelling central venous catheters, and a number of inherited and acquired thrombophilic conditions have all been identified as placing an individual at risk. In children, a significantly greater percentage of VTEs are risk associated as compared with their adult counterparts. Children with deep venous thrombosis (DVT) and pulmonary embolism (PE) are much more likely to have one or more identifiable conditions or circumstances placing them at risk. In contrast to adults, idiopathic thrombosis is a rare occurrence in the pediatric population. In a retrospective cohort of patients with VTE in U.S. children's hospitals from 2001 to 2007, the majority (63%) of affected children were found to have one or more chronic medical comorbidities. In a large Canadian registry, 96% of pediatric patients were found to have one risk factor and 90% had two or more risk factors. In contrast, approximately 60% of adults with this disorder have an identifiable risk factor (see Table 436.1 ). The most common identified risk factors in children include infection, congenital heart disease, and the presence of an indwelling central venous catheter.
Embolic disease in children is varied in its origin. An embolus can contain thrombus, air, amniotic fluid, septic material, or metastatic neoplastic tissue. Thromboemboli are the type most commonly encountered. A commonly encountered risk factor for DVT and PE in the pediatric population is the presence of a central venous catheter. More than 50% of DVTs in children and more than 80% in newborns are found in patients with indwelling central venous lines. The presence of a catheter in a vessel lumen, as well as instilled medications, can induce endothelial damage and favor thrombus formation.
Children with malignancies are also at considerable risk. Although PE has been described in children with leukemia, the risk of PE is more significant in children with solid rather than hematologic malignancies. A child with malignancy may have numerous risk factors related to the primary disease process and the therapeutic interventions. Infection from chronic immunosuppression may interact with hypercoagulability of malignancy and chemotherapeutic effects on the endothelium. In a retrospective cohort of patients with VTE from 2001 to 2007, pediatric malignancy was the medical condition most strongly associated with recurrent VTE.
In the neonatal period, thromboembolic disease and PE may be related to indwelling catheters used for parenteral nutrition and medication delivery. Pulmonary thromboemboli in neonates generally occurs as a complication of underlying disease; the most common associated diagnosis is congenital heart disease, but sepsis and birth asphyxia are also notable associated conditions. Other risk factors include a relative immaturity of newborn infants’ coagulation; plasma concentrations of vitamin K-dependent coagulation factors (II, VII, IX, X); factors XII, XI, and prekallikrein and high molecular weight kininogen are only approximately half of adult levels (see Chapter 502 ). PE in neonates may occasionally reflect maternal risk factors, such as diabetes and toxemia of pregnancy. Infants with congenitally acquired homozygous deficiencies of antithrombin, protein C, and protein S are also more likely to present with thromboembolic disease in the neonatal period (see Chapter 505 ).
Pulmonary air embolism is a defined entity in the newborn or young infant and is attributed to the conventional ventilation of critically ill (and generally premature) infants with severe pulmonary disease. In the majority of instances, the pulmonary air embolism is preceded by an air-leak syndrome. Infants may become symptomatic and critically compromised by as little as 0.4 mL/kg of intravascular air; these physiologic derangements are thought to be secondary to the effects of nitrogen.
Prothrombotic disease can also manifest in older infants and children. Disease can be congenital or acquired. Inherited thrombophilic conditions include deficiencies of antithrombin, protein C, and protein S, as well as mutations of factor V Leiden (G1691A) (see Chapter 505 ) and prothrombin (factor II 20210A mutation) (see Chapter 505 ), and elevated values of lipoprotein A. In addition, multiple acquired thrombophilic conditions exist; these include the presence of lupus anticoagulant (may be present without the diagnosis of systemic lupus erythematosus), anticardiolipin antibody, and anti–β 2 -glycoprotein 1 antibody. Finally, conditions such as hyperhomocysteinemia (see Chapter 104 ) may have both inheritable and dietary determinants. All have all been linked to thromboembolic disease. DVT/PE may be the initial presentation.
Children with sickle cell disease are also at high risk for pulmonary embolus and infarction. Acquired prothrombotic disease is seen in conditions such as nephrotic syndrome (see Chapter 545 ) and antiphospholipid antibody syndrome. From one-quarter to one-half of children with systemic lupus erythematosus (see Chapter 183 ) have thromboembolic disease. There is a significant association with VTE onset in children for each inherited thrombophilic trait evaluated, thereby illuminating the importance of screening for thrombophilic conditions for those at risk for VTE. Septic emboli are rare in children but may be caused by osteomyelitis, jugular vein or umbilical thrombophlebitis, cellulitis, urinary tract infection, and right-sided endocarditis.
Other risk factors include infection, cardiac disease, recent surgery, and trauma. Surgical risk is thought to be more significant when immobility will be a prominent feature of the recovery. Use of oral contraceptives confers additional risk, although the level of risk in patients taking these medications appears to be decreasing, perhaps because of the lower amounts of estrogen in current formulations. In a previously healthy adolescent patient, the risk factors are often unknown or are similar to adults (see Tables 436.1 and 436.2 ).
Table 436.2
Clinical Decision Rules for Deep Vein Thrombosis and Pulmonary Embolism
From Di Nisio M, van Es N, Büller HR: Deep vein thrombosis and pulmonary embolism, Lancet 388:3060–3069, 2016 (Table 1, p. 3062).
| WELLS' SCORE FOR DEEP VEIN THROMBOSIS * | ||
| Active cancer | +1 | NA |
| Paralysis, paresis, or recent plaster cast on lower extremities | +1 | NA |
| Recent immobilization >3 days or major surgery within the past 4 wk | +1 | NA |
| Localized tenderness of deep venous system | +1 | NA |
| Swelling of entire leg | +1 | NA |
| Calf swelling >3 cm compared to asymptomatic side | +1 | NA |
| Unilateral pitting edema | +1 | NA |
| Collateral superficial veins | +1 | NA |
| Previously documented deep vein thrombosis | +1 | NA |
| Alternative diagnosis at least as likely as deep vein thrombosis | −2 | NA |
| WELLS' SCORE FOR PULMONARY EMBOLISM † , ‡ | ||
| Alternative diagnosis less likely than pulmonary embolism | +3 | +1 |
| Clinical signs and symptoms of deep vein thrombosis | +3 | +1 |
| Heart rate >100 beats/min | +1⋅5 | +1 |
| Previous deep vein thrombosis or pulmonary embolism | +1⋅5 | +1 |
| Immobilization or surgery within the past 4 wk | +1⋅5 | +1 |
| Active cancer | +1 | +1 |
| Hemoptysis | +1 | +1 |
| REVISED GENEVA SCORE FOR PULMONARY EMBOLISM § , || | ||
| Heart rate ≥95 beats/min | +5 | +2 |
| Heart rate 75–94 beats/min | +3 | +1 |
| Pain on lower-limb deep venous palpation and unilateral edema | +4 | +1 |
| Unilateral lower-limb pain | +3 | +1 |
| Previous deep vein thrombosis or pulmonary embolism | +3 | +1 |
| Active cancer | +2 | +1 |
| Hemoptysis | +2 | +1 |
| Surgery or fracture within the past 4 wk | +2 | +1 |
| Age >65 yr | +1 | +1 |
* Classification for original Wells' score for deep vein thrombosis: deep vein thrombosis unlikely if score ≤2; deep vein thrombosis likely if score >2.
† Classification for original Wells' score for pulmonary embolism: pulmonary embolism unlikely if score ≤4; pulmonary embolism likely if score >4.
‡ Classification for simplified Wells' score for pulmonary embolism: pulmonary embolism unlikely if score ≤1; pulmonary embolism likely if score >1.
§ Classification for original revised Geneva score for pulmonary embolism: non-high probability of pulmonary embolism if score ≤10; high probability of pulmonary embolism if score >10.
|| Classification for simplified revised Geneva score for pulmonary embolism: non-high probability of pulmonary embolism if score ≤4; high probability of pulmonary embolism if score >4.
Epidemiology
A retrospective cohort study was performed with patients younger than 18 yr of age, discharged from 35 to 40 children's hospitals across the United States from 2001 to 2007. During this time, a dramatic increase was noted in the incidence of VTE; the annual rate of VTE increased by 70% from 34 to 58 cases per 10,000 hospital admissions. Although this increased incidence was noted in all age groups, a bimodal distribution of patient ages was found, consistent with prior studies; infants younger than 1 yr of age and adolescents made up the majority of admissions with VTE, but neonates continue to be at greatest risk. The peak incidence for VTE in childhood appears to occur in the 1st mo of life. It is in this neonatal period that thromboembolic events are more problematic, likely as a result of an imbalance between procoagulant factors and fibrinolysis. The yearly incidence of venous events was estimated at 5.3/10,000 hospital admissions in children and 24/10,000 in the neonatal intensive care.
Pediatric autopsy reviews have estimated the incidence of thromboembolic disease in children as between 1% and 4%, although not all were clinically significant. Thromboembolic pulmonary disease is often unrecognized, and antemortem studies may underestimate the true incidence. Pediatric deaths from isolated pulmonary emboli are rare. Most thromboemboli are related to central venous catheters. The source of the emboli may be lower or upper extremity veins as well as the pelvis and right heart. In adults, the most common location for DVT is the lower leg. However, one of the largest pediatric VTE/PE registries found two-thirds of DVTs occurring in the upper extremity.
Pathophysiology
Favorable conditions for thrombus formation include injury to the vessel endothelium, hemostasis, and hypercoagulability. In the case of PE, a thrombus is dislodged from a vein, travels through the right atrium, and lodges within the pulmonary arteries. In children, emboli that obstruct <50% of the pulmonary circulation are generally clinically silent unless there is significant coexistent cardiopulmonary disease. In severe disease, right ventricular afterload is increased with resultant right ventricular dilation and increases in right ventricular and pulmonary arterial pressures. In severe cases, a reduction of cardiac output and hypotension may result from concomitant decreases in left ventricular filling. In rare instances of death from massive pulmonary embolus, marked increases in pulmonary vascular resistance and heart failure are usually present.
Arterial hypoxemia results from unequal ventilation and perfusion; the occlusion of the involved vessel prevents perfusion of distal alveolar units, thereby creating an increase in dead space and hypoxia with an elevated alveolar–arterial oxygen tension difference (see Chapter 400 ). Most patients are hypocarbic secondary to hyperventilation, which often persists even when oxygenation is optimized. Abnormalities of oxygenation and ventilation are likely to be less significant in the pediatric population, possibly owing to less underlying cardiopulmonary disease and greater reserve. The vascular supply to lung tissue is abundant, and pulmonary infarction is unusual with pulmonary embolus but may result from distal arterial occlusion and alveolar hemorrhage.
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