Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) - a review of a new treatment paradigm.
Local pulmonary administration of factor VIIa (rFVIIa) in diffuse alveolar hemorrhage (DAH) - a review of a new treatment paradigm.
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DOI：
10.2147/btt.s25507
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发表时间：
2012
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影响因子：
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通讯作者：
Nepper-Christensen S
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文献类型：
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作者：
Heslet L;Nielsen JD;Nepper-Christensen S
弥漫性肺泡出血（diffusealveolarhemorrhage，DAH）是一种以呼吸困难、咯血为典型症状的临床综合征. DAH是特定疾病的并发症，在某些情况下伴有急性灾难性咯血，而其他患者则表现为轻度肺泡出血，需要慢性输血，如肺含铁血黄素沉着症。对PubMed数据库和其他来源中的当前文献进行了审查，以评价当前的治疗建议、该治疗的疗效以及最终评价标签外用药rFVIIa治疗DAH后的并发症风险。(i)为了阐明肺泡出血的临床方面，（ii）开发一个简单的诊断算法，以区分DAH从其他重要的肺部疾病具有相似的临床表现和极高的死亡率。这种算法具有重要的治疗效果，因为这些疾病：急性肺损伤（ALI），急性呼吸窘迫综合征（ARDS）和闭塞性细支气管炎机化性肺炎（BOOP）有不同的治疗方法，（iii）评估和讨论局部肺部给药是否可以改善DAH的结局并降低死亡率，以及（iv）建议治疗方案。迄今为止，DAH的诊断和治疗一直基于轶事报告。治疗依赖于不同的非特异性治疗方式，这些治疗方式基于基础疾病的治疗和没有针对性阻止肺泡出血的证据的治疗的混合。然而，最近一些出版物提倡使用肺内rFVIIa。即使在严重出血中，当FVIIa通过空气侧局部给药时，DAH也显示出迅速响应而没有血栓栓塞并发症，因为FVIIa不会穿透肺泡-毛细血管膜到达血液侧。DAH的发病率（在美国和欧洲为100，000 - 150，000，每年有50，000名患者在造血干细胞移植（HSCT）和自身免疫性疾病后有发展DAH的风险。最后，50，000 - 100，000名患者可能被错误地归类为患有急性呼吸窘迫综合征/急性肺损伤（ARDS/ALI），因为DAH和ARDS在临床上无法分开。由于没有其他干预措施能够确保DAH的肺止血，因此提出了DAH的新治疗模式。DAH的诊断很简单，一系列的支气管肺泡灌洗液变得越来越血腥。该试验应在所有肺部阴影患者中进行，以区分ARDS/ALI和DAH。通过肺途径施用的FVIIa是“首选药物”，因为它在危及生命的综合征DAH中停止出血。仅在一至两个小剂量的FVIIa（每剂量50 μg/kg体重）后获得止血，并且在止血后氧转运迅速改善。推荐将rFVIIa肺内给药作为DAH和爆震性肺损伤（BLI）的治疗选择，因为尽管仅记录了一小部分DAH，但该治疗已被证明是成功且不复杂的。
Diffuse alveolar hemorrhage (DAH) is a clinical syndrome with typical symptoms dyspnea and hemoptysis. DAH is a complication of specific diseases, in some cases with acute catastrophic hemoptysis, while other patients present low grade alveolar bleeding with a need of chronic transfusion as in pulmonary hemosiderosis. Current literature in the PubMed database and other sources was reviewed in order to evaluate the current treatment recommendations, efficacy of this treatment, and finally the risk of complications after off-label use of rFVIIa in respect to DAH. (i) To elucidate the clinical aspects of alveolar hemorrhage, (ii) to develop a simple diagnostic algorithm in order to separate DAH from other important pulmonary diseases with similar clinical picture and comparably high mortality. Such an algorithm has important therapeutic consequences because these diseases: acute lung injury (ALI), acute respiratory distress syndrome (ARDS) and bronchiolitis obliterans organizing pneumonia (BOOP) have different therapies, (iii) to evaluate and discuss whether local pulmonary administration may improve outcome and reduce mortality in DAH, and (iv) to suggest a treatment schedule. Hitherto the diagnosis and treatment of DAH has been based on anecdotal reports. The treatment has relied on different unspecific treatment modalities based on a mixture of treatment of the underlying disease and treatment without evidence targeted to stop the alveolar bleeding. However, recently a number of publications have advocated the use of intrapulmonary rFVIIa. Even in severe bleeding DAH has been shown to respond promptly without thromboembolic complication when FVIIa was administered locally via the air side, because the FVIIa does not penetrate the alveolo-capillary membrane to the blood-side. The incidence of DAH (in the US and Europe is 100,000–150,000, and 50,000 patients annually are at risk of developing DAH following hematopoietic stem cell transplant (HSCT) and autoimmune diseases. Finally 50,000–100,000 patients may be falsely categorized as having acute respiratory distress syndrome/acute lung injury (ARDS/ALI) because DAH and ARDS cannot be separated clinically. A new treatment paradigm of DAH is proposed as no other intervention has been able to ensure pulmonary hemostasis in DAH. The diagnosis of DAH is simple, a series of broncho-alveolar washes which become increasingly bloody. This test should be performed in all patients with pulmonary opacities in order to separate ARDS/ALI from DAH. FVIIa administrated via pulmonary route is “drug of choice”, because it stops bleeding in the life-threatening syndrome DAH. Hemostasis is obtained after only one to two small doses of FVIIa (50 μg/kg body weight per dose) and after hemostasis the oxygen transport quickly improves. Intrapulmonary administration of rFVIIa is recommended as the treatment of choice for DAH and blast lung injury (BLI) because the treatment has been shown to be successful and uncomplicated in spite of the fact that only a small series of DAH has been documented.