动脉导管未闭介入封堵术后血小板急剧减少三例.doc

动脉导管未闭介入封堵术后血小板急剧减少三例 Three Cases Report about Platelet Decreased Sharply after the Interventional Closure of Patent Ductus Arteriosus 例1 患者男性，9岁，因劳力性气促9年入院。经超声心动图及X线胸片等检查诊断为动脉导管未闭（Patent ductus arteriosus，PDA）。Case 1 A nine-year-old male patient was hospitalized because of exertional polypnea for nine years. he was diagnosed patent ductus arteriosus(PDA）by echocardiography and X-ray chest radiography examination .入院后查血常规示：血小板为136.00109/L，红细胞为4.601012/L，嗜酸性粒细胞计数为0.30109/L。术中测肺动脉收缩压为90 mm Hg（1 mm Hg=0.133 kPa），舒张压为49 mm Hg，平均压为62 mm Hg。 After admission , checking routine blood showed: thrombocyte 136.00109/L，erythrocyte 4.601012/L,eosinophilic granulocyte 0.30109/L。during operation, the systolic pulmonary artery pressure was 90 mm Hg（1 mm Hg=0.133 kPa）diastolic blood pressure was 49 mm Hg, average pressure was 62 mm Hg.造影示：巨大PDA（呈管状，最窄处直经为26 mm），主动脉弓降部直径为32 mm。因无相应大小的PDA封堵器，遂用32 mm房间隔封堵器试行封堵。封堵即刻，测肺动脉收缩压为52 mm Hg，舒张压为21 mm Hg，平均压力为31 mm Hg，但试封堵后数分钟，封堵伞即自行脱位，遂取出封堵器，终止手术。 在。的当时 Pulmonary and aorta angiography showed: giant PDA (tubular shape , diameter of the narrowest place is 26 mm) , the aortic arch descending segment diameter was 32 mm. Because there was no suitable size of PDA occluder , we tried to use interatrial septum defect occluder to closure the duct occluder. At the time of plugging , systolic pulmonary artery pressure was 52 mm Hg, diastolic blood pressure was 21 mmHg， the average pressure was 31 mm Hg， but a few minutes after the plugging, the duct occluder immediately fall off automatically. Then, we took the occluder out, and terminated the operation.7 d后采用特制的32 mm PDA封堵伞（上海形状记忆合金材料公司）再次封堵成功，但术后即刻造影示：封堵器内可见明显的滤过血流。Seven days later , we closured the PDA successfully by using specially made 32 mm duct occluder(Shanghai shape memory alloy materials company), but it could be seen that filtration blood flow ran through the duct occluder obviously by immediately postoperative angiograph. 术后即刻测肺动脉收缩压为55 mm Hg，舒张压为25 mm Hg，平均压为34 mm Hg。患者有气促症状，术后48 h复查血常规示：血小板为30.00109/L，红细胞为4.09109/L，嗜酸性粒细胞计数为0.30109/L。Immediately after the operation,wemeasured systolic pulmonary artery pressure was 55mmHg, diastolic blood pressure was 25 mmHg, the mean blood pressure was 34 mmHg. The patient had tachypnea symptoms. Forty-eight hours after the opreation, we rechecked the blood routine, it showed, platelet was 30.00 x 109 / L, erythrocyte was 4.09109/L,eosinophilic granulocyte was 0.30109/L.患者无出血倾向，无皮肤瘀斑及血尿，予泼尼松10 mg（每天1次），并碱化尿液。术后第8天复查血常规示：血小板为61.00109/L。出院1个月后复查血常规示：血小板为186.00109/L，患者无不适，复查超声心动图显示，肺动脉收缩压为35 mm Hg，舒张压16 mm Hg，平均压为29 mm Hg。 Patient without bleeding tendency, skin petechia， and cruenturesis .Transfusing prednisone 10mg per day, and alkalize urine, eight days after the opreation, we rechecked the blood routine , it showed that platelet was 186.00 x 109 / L, one month after the operation, we checked the blood routine again, it showed that platelet was 186.00x109,Patients without any discomfort, reviewed of echocardiography display: systolic pulmonary artery pressure was 35mmHg,diastolic blood pressure was 16 mmHg, the average pressure was 29 mmHg.例2 患者女性，22岁，因发现心脏杂音20年入院。经超声心动图及X线胸片等检查诊断为PDA。入院查血常规示：血小板为125.00109/L，红细胞4.20109/L，嗜酸性粒细胞计数为0.06109/L。Case 2 A 22-year-old female patient was hospitalized because of heart murmurs for 20 years. The diagnosis was PDA by echocardiography and X-ray chest radiography examination. Blood routine examination showed that platelet was 125.00 x 109 / L, erythrocyte was 4.20109/L,eosinophilic granulocyte was 0.06109/L. 术中测肺动脉收缩压为67 mm Hg，舒张压为40 mm Hg，平均压为51 mm Hg。造影示：PDA呈漏斗状，最窄处直经为12 mm。选用16 mm PDA封堵器(深圳先健科技公司)封堵成功。术后即刻造影示：封堵器内可见明显的滤过血流。During the operation, measuring systolic pulmonary artery pressure was 67mmHg, diastolic blood pressure was 40mmHg, the mean blood pressure was 51mmHg. Pulmonary angiography showed that PDA was funnel-shaped, the diameter of the narrowest place was 12mm, we selected 16 mm occluder (Shenzhen Xianjian Technology Company) to closure PDA successfully. Immediately after the procedure, angiography showed, blood flow filtrated through the occluder.术后即刻测肺动脉收缩压为45 mm Hg，舒张压为22 mm Hg，平均压为32 mm Hg。术后48 h血小板下降至38.00109/L。术后第5天血小板进行性下降至17.00109/L，红细胞为3.64109/L，嗜酸性粒细胞计数为0.12109/L。无血尿，但患者有鼻出血，予局部填塞处理，并予地塞米松及升血小板胶囊口服治疗，效果不佳。先后输注血小板10 U，鼻出血停止，复查血常规示血小板为123.00109/L，患者症状消失并出院。 Immediately after the operation, measuring systolic pulmonary artery pressure was 45mmHg, diastolic blood pressure was 22 mmHg, the mean blood pressure was 32 mmHg. Forty-eight hours after the operation, we rechecked the blood routine , it showed that platelet declined sharply to 17 109 / L, erythrocyte was 3.64109/L,eosinophilic granulocyte was 0.12109/L,without hematuria, but patient had nasal bleeding, dealing with tamping in the nose. using dexamethasone and rising platelets drugs, but its ineffective, we transfused thrombocyte 10U successively ,then, nasal bleeding stopped. rechecking the blood routine showed platelet was 123.00 x 109 / L .The patient discharged from hospitals after his symptoms disappeared.例3 患者女性，19岁，因发现心脏杂音11年入院。经超声心动图诊断为PDA。入院查血常规示：血小板为145.00109/L，红细胞为4.30109/L，嗜酸性粒细胞计数为0.12109/L。Case 3 A 19-year-old female patient was hospitalized because of heart murmurs for11 years. diagnosis is PDA by echocardiographic checking. blood rutine examination showed that platelet was 145.00 x 109/ L, erythrocyte was 4.30109/L,eosinophilic granulocyte was 0.12109/L. 术中测肺动脉收缩压为59 mm Hg，舒张压为28 mm Hg，平均压为38 mm Hg。造影示：PDA呈漏斗状，最窄处直经为16 mm。选用20 mm PDA封堵器(上海形状记忆合金材料公司)，封堵成功。术后即刻造影示：封堵器内可见明显的滤过血流。During the operation, measuring systolic pulmonary artery pressure was 59mmHg, diastolic blood pressure was 28mmHg, the mean blood pressure was 38 mmHg. Pulmonary angiography showed that PDA was funnel-shaped, the diameter of the narrowest place was 16 mm, we selected 20mm occlude(Shanghai Shape Memory Alloy Materials Company)to closure the PDA successfully. Immediately after the procedure, angiography showed that blood flow filtrated through the occlude obviously.术后复测肺动脉收缩压为43 mm Hg，舒张压为21 mm Hg，平均压为31 mm Hg。术后24 h血小板下降至36.00109/L，无血尿症状。术后第4天血小板进行性的下降至29.00109/L，红细胞为3.68109/L，嗜酸性粒细胞计数为0.13109/L。患者有鼻出血，予局部填塞处理，并输注血小板4 U，鼻出血停止，复查血常规示血小板为126.00109/L，患者无不适反应而出院。 After the operation, we measured systolic pulmonary artery pressure was 45mmHg, diastolic blood pressure was 22 mmHg, the mean blood pressure was 32 mmHg. Four days after the operation, we checked the blood routine again, it showed platelet gradual declined to 29 x 109 / L, erythrocyte was 3.68109/L,eosinophilic granulocyte was 0.13109/L.Patients with nasal bleeding. We used carbasus to tampe in the nose,transfused thrombocyte 4 U, then,nasal bleeding stopped. rechecking the blood routine , it showed platelet was 126.00 x 109 / L , patient had no adverse reaction, and discharged from hospital.讨论 Pastmann于1967年成功开创PDA介入封堵术后，介入封堵已经成为动脉导管未闭治疗的首选方法。该术式具有创伤小、痛苦少、恢复快，操作简便、疗效可靠等优点。但少数患者也可能发生封堵器脱落、残余分流、机械溶血等并发症。Discussion After Pastmann successfully inaugurate the operation of PDA transcatheter interventional closure In 1967, this procedure has become the preferred method . This method has little trauma, less pain, recovery quickly, easy to operation, reliable curative effect, etc. A few patients may also occur complications, such as occluder falls off, residual shunt, mechanical hemolytic.据文献报道，PDA介入封堵术后血小板减少患者的血常规中，嗜酸性粒细胞计数呈持续上升趋势1，故考虑患者对封堵器的涤纶成分，聚脂纤维过敏，从而导致过敏性血小板减少。但本文资料显示，血小板显著减少者嗜酸性粒细胞计数并无明显升高，且房间隔、室间隔缺损封堵器与PDA封堵器的材质相同，在行房间隔、室间隔缺损封堵术后却几乎无一例患者有显著的血小板减少，故我们认为：过敏反应并非PDA介入封堵术后血小板减少的主要原因。过敏的 Literatures reported , when checking blood routine they found that eosinophil counting showed a trend of rising in those patients with thrombocytopenia after PDA interventinal closure, so they considered patients were allergic to occluders polyester composition which leaded to anaphylactic thrombocytopenia. But our data showed that eosinophil count had no obvious rising in those patient with thrombocyte significantly declined. Moreover, the occluder of interatrial septum and ventricular septal defect were the same material as PDA occluder. There had almost no one case appeared significantly thrombocytopenia after transcatheter closure interatrial or ventricular septal defect , so we thought that allergic reactions was not the main reason which caused thrombocytopenia after the PDA closure.有学者认为，PDA介入封堵术后血小板减少是术中应用肝素所致 2。肝素相关性的血小板减少（heparin-induced thrombocytopenia ，HLT）通常分为两型：（1）型HLT较为常见，血小板极少显著降低，且可自行恢复，一般无明显临床症状。本文3例患者的血小板均为短期内大幅度急剧下降，故不支持型HLT的诊断。Some scholars thought that thrombocytopenia after PDA clusure was caused by intraoperative application of heparin（heparin-induced thrombocytopenia ，HLT）usually divided into two type:(1) type HLT was common in clinical. Fewer patients platelets decreased significantly, thrombocytopenia could restore to normal level ,automatically.Those patients usually have no obvious clinical symptoms . In our study, three patients of platelets declined sharply within a short period of time, therefore, it did not support the diagnosis of type HLT.II型为免疫介导反应，其诊断要点为：除外其他原因导致的血小板减少；使用肝素510 d后血小板下降50%, 或计数低于50.00109 (如发生于5 d以内一般不考虑为型HLT)；合并血栓栓塞。本文患者术前血小板计数均正常，术后也可排除其他疾病所致血小板减少，血小板减少均发生于手术后1248 h以内，而无一例发生血栓栓塞，故也不符合型HLT的诊断。Type II is immune-mediated reaction, the main diagnosis points are:(1) Excluding all other reasons which caused thrombocytopenia .(2) Platelet count drop more than fifty percent in five to ten days after the use of heparin . the number of platelet is below 50.00 x 109 (if it is occurred less than five days that is not generally considered as HLT); (3) Existing thromboembolism. in our study, platelet count in all patients were normal before operation, we can also exclude other diseases caused thrombocytopenia. In our data ,thrombocytopenia occurred within 12 to 48 hours after the operation, and no one case occurred thromboembolism, so it also did not correspond to the diagnosis of type HLT.有研究表明，PDA术后有残余分流者发生血小板减少的几率较高4，这与本文资料相符。无残余分流时，血小板可很快黏附在封堵器金属网眼及其内的涤纶片聚脂网眼中，启动外源性凝血途径，形成相对固定血栓，血小板损失的数量也较少，且血小板的再生周期为714 d，每天能更新总量的10%，只要无持续性的血小板损耗，则血小板的丢失与再生形成动态平衡，故临床上多数患者未表现出血小板的急剧下降。当患者的封堵器较大，分流量也较大，分流持续时间较长时，血小板黏附、变形、损伤后在高速血流冲刷下会形成碎片并被冲刷掉，新的血小板又黏附到封堵器上，部分血小板仍然再次被冲刷掉，如此反复，大量的血小板被持续不断地消耗，大大超过了血小板的再生能力时，临床就表现为进行性血小板减少，个别病例经大量的输注血小板也不能阻止血小板的持续下降，而需要开胸取出封堵器。 丢失与再生保持动态平衡Studies have shown that the patients with postoperative residual shunt have increased the chance of thrombocytopenia. This is conrrespondence with our opinions. Without residual shunt，platelets can be quickly adhesion in occluders metal mesh and polyester mesh, initiate the extrinsic coagulation pathway, format relatively fixed thrombosis, thus,less platelet will be damaged. Moreover, platelet regeneration cycle is about seven to fourteen days, 10% of the total platelet can update every day, damage keep dynamic balance with regeneration as long as no persistent platelet losing.Therefore, most of the patients showed without platelet declined sharply. While patients occluder is bigger, residual shunt amount is bigger also, Long time duration of shunt cause platelet adhesion, deformation and damage under high speed blood flow scouring which can form fragmentation and wash the platelet away. New platelets adhere to the occluder still be washed off again. Such situation happened repeatedly,thus, large number of platelets are constantly consumed which greatly exceed the regeneration ability of platelets, then, clinical symptom manifest of the progressive thrombocytopenia. Few cases by transfusion a large number of platelet can not stop the falling of platelets,which need to open the chest to take out of occluder.本文资料中，发生显著血小板减少者封堵器均较大，但如果单纯用封堵器的大小来衡量发生血小板减少的可能性似乎有些片面。部分房间隔缺损封堵器直径可达4056 mm却也未引起明显的血小板减少。In our study, occluder is larger in those patients with significantly thrombocytopenia. It seems to be some one-sided if we simple use the size of the occluder to estimate the possibility of thrombocytopenia. A part of atrial septal defects occluder ,which diameter was up to 40- 56 mm, did not cause obvious thrombocytopenia.究其原因，左右房间隔之间的压力差较小，血小板吸附在伞内形成血栓后，无进一步的冲刷性的损伤，因而无血小板的持续下降。不过室间隔缺损患者的左右室间的压力差也较大，故室间隔缺损封堵术后往往存在残余分流或滤过血流，但患者血小板却无明显减少，考虑与室间隔缺损封堵器较小，吸附血小板的能力有限，在血小板未明显减少时就已经在封堵器腰部形成血栓而封堵了整个分流通道，无分流就无血小板的进一步下降。Exploring its reason is that the pressure differential between the left and right atrial septum is lesser, platelets adhere to the occluder, then form fixed thrombus in the umbrella, no further erosion damage, thus no platelets continued to decline. The pressure between the two chamber in patients with ventricular septal defect is bigger too, it tend to has postoperative residual shunt or filter blood flow after the ventricular septal defect closure , but the patient has no obvious platelet decrease , we consider its related to the relative smaller size of ventricular septal defect occluder ,its adherency ability to platelet is limited ，the thrombosis formed at the waist of the occluder and blocked the distributary channel, without shunt,there is no platelet further declined . 而PDA的形状为柱状，其内的涤纶成分明显较多，吸附的能力血小板的能力也随之增加，特别是封堵器较大，中间存在速度较快的滤过血流时，在分流束的冲刷下，血栓难以形成，血小板持续损伤，临床表现为短时间内血小板大幅度下降。the shape of the PDA occluder is columnar,it has more polyester composition,the adsorption ability of platelet increase accordingly, especially when occluder is bigger, has remnant fast filtration blood flow, under the scour of shunt beam, platelet be damaged sustained. Clinical performance as platelets declined sharply within a short period of time.Anil 等4报道，PDA直径越大，用弹簧圈封堵后有残余分流者发生溶血、血尿的几率也越大，与红细胞反复高速通过弹簧圈封堵后的残余分流通道所致的切割损伤有关。Anil, etc. 4 reported, The greater the diameter of the PDA,the rate of hemolysis, blood in urine are much higher ,when there are residual shunt exist after the operation of spring coil blocking. Erythrocytes flow through the spring coil by high speed which caused cutting injury repeatedly .而近年来换用Amplatze或国产伞形封堵器后引起血小板减少的病例可见陆续报道，考虑与PDA封堵器内增加的涤纶成分、聚酯纤维对血小板有一定的吸附作用有关，而分流束的冲刷对血小板形成持续的损伤也是血小板急剧减少的重要原因。In recent years , amplatze or domestic producting occluder caused thrombocytopenia were reported successively. PDA occluder has more polyester,terylene fibre which has certain adsorption effect to the platelet. moreover, scour of shunt beam on platelet which cause platelet decreased shapely, too.PDA介入封堵术后血小板减少尚不能除外遗传、个体差异、免疫等因素所致，但目前缺少证据，需要进一步研究。PDA interventional closure related thrombocytopenia can not exclude ot