肿瘤性骨软化症并发肺栓塞临床特点及诊治:2例报道并文献复习

Tumor induced osteomalacia complicated with deep vein thrombosis and pulmonary embolism:report of two cases and literature review

目的通过复习肿瘤性骨软化症(tumor induced osteomalacia,TIO)并发深静脉血栓形成(deep vein thrombosis,DVT)、肺栓塞(pulmonary embolism,PE)病例,以提高对该罕见病及其严重并发症的认识。方法分析2例TIO并发下肢DVT、PE患者的临床特点、诊治经过及结局,并进行文献复习及总结。结果患者1,男性,46岁;患者2,女性,52岁。病程均为2年余。临床表现为全身骨痛、乏力、活动困难,血液生物化学检查示低磷血症、碱性磷酸酶升高、磷廓清指数降低,影像学检查发现骨密度减低及致病肿瘤,2例患者确诊TIO;2例患者均有D-二聚体升高,临床评分提示PE可能,经深静脉彩超、CT肺动脉显影明确诊断并发DVT、PE。予抗凝治疗,植入下腔静脉滤器后行肿瘤切除术,患者TIO治愈,随访无再发血栓。结合文献检索到的1例维生素D缺乏性骨软化症并发DVT、致死性PE的老年患者分析,3例静脉血栓栓塞症共同危险因素为制动、骨折、年龄>40岁;肺栓塞症状轻重程度不一,隐匿者可无症状或仅有轻度胸闷、气短,严重者可发生急性呼吸循环骤停。结论 TIO并发DVT、PE为临床疑难重症,可能危及患者生命,临床评分联合D-二聚体筛查有重要参考价值,深静脉彩超、CT肺动脉显影可明确诊断,早期识别、及时治疗和多科协作是改善患者临床结局的关键。

Objective Clinial analysis of tumor induced osteomalacia （TIO） complicated with deep vein thrombosis （DYT） and pulmonary embolism （PE） cases in China to improve the clinicians＇ recognition of this rare disease and its severe complications. Methods Two cases of TIO complicated with DVT and PE were reviewed and summarized. Results The two patients （ one male and one female） , middle-aged onset, suffered from TIO more than 2 years. Clinical manifestations included diffuse bone pain, muscle weakness, difficulty in walking. They demonstrated hypophosphatemia, elevated serum alkaline phosphatase and reduced tubular maximum for phosphorus/glomerular filtration rate. Low hone density and the responsible tumors were discovered by imaging examinations. The diagnosis of TIO was clear. Both patients had elevated D-dimer levels and the possibility of PE revealed by the Wells score. They were confirmed with DVT and PE by ultrasonography and CT pulmonary artery angiography （CTPA）. They received anticoagulant therapy, preoperative placement of inferior vena cava filter and resection of the responsible tumor. TIO was cured and there was no recurrent thrombosis during the follow up. One patient with vitamin D deficiency osteomalacia complicated with DVT and fatal PE had been reported. Analysis of the three patients indicated that the risk factors for venous thromboembolism were immobilization, fractures and age over 40 years. The severity of PE varied widely. Some might be asymptomatic or just have slight chest tightness and shortness of breath, while others could present as acute respiratory and circulatory arrest. Conclusion TIO concomitant with DVT and PE constitutes a complicated, severe and potentially fatal clinical situation. The combination of clinical probability scores and D-dimer testing are helpful to in the diagnosis of VTE screening, while ultrasonography and CTPA can confirm the diagnosis VTE. Early recognition, appropriate treatment and multidisciplinary collaboration are essential to improve the patients＇ outcome.