1、動脈導管未閉介入封堵術后血小板急劇減少三例Three Cases Report about Platelet Decreased Sharply after the Interventional Closure of Patent Ductus Arteriosus例1患者男性，9歲，因勞力性氣促9年入院。經超聲心動圖及 X線胸片 等檢查診斷為動脈導管未閉(Patent ductus arteriosus , PDA。Case 1 A nine-year-old male patient was hospitalized because of exertional polypnea for n

2、ine years. he was diagnosed patent ductus arteriosus( PDA by echocardiography and X-ray chest radiography examination .入院后查血常規示：血小板為136.00 X 109/L ,紅細胞為4.60X1012/L,嗜酸 性粒細胞計數為0.30 X 109/L。術中測肺動脈收縮壓為 90 mmHg (1 mmHg=0.133 kPa),舒張壓為49 mm Hg平均壓為62 mm HgAfter admission , checking routine blood showed: th

3、rombocyte136.00 x 109/L , erythrocyte 4.60x 1012/L,eosinophilic granulocyte 0.30x9,10/L o during operation, the systolic pulmonary artery pressure was90mnHg (1 mmHg=0.133 kPa) diastolic blood pressure was 49 mmHg, average pressure was 62 mm Hg.造影示：巨大PDA(呈管狀，最窄處直經為26 mrm,主動脈弓降部直徑為32 mm因無相應大小的PDAM堵器，遂

4、用32 mmf間隔封堵器試行封堵。封堵即刻， 測肺動脈收縮壓為52 mm Hg舒張壓為21 mm Hg平均壓力為31 mm Hg但試 封堵后數分鐘，封堵傘即自行脫位，遂取出封堵器，終止手術。在。的當時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

5、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 mnHg, diastolicblood pressure was 21 mmHg the average pressure was 31 mm Hg , but a few minutes after the plugging, the duct occluder

6、 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寸堵傘（上海形狀記憶合金材料公司）再次封 堵成功，但術后即刻造影示：封堵器內可見明顯的濾過血流。Seven days later , we closured the PDAsuccessfully by using specially made 32 mm duct occluder（Shanghai shape memory alloy materials com

7、pany）, but it could be seen that filtration blood flow ran through the duct occluder o bviously by i mmediately postoperative angiograph.術后即刻測肺動脈收縮壓為 55 mm Hg舒張壓為25 mm Hg平均壓為34 mm Hg?；颊哂袣獯侔Y狀，術后 48 h復查血常規示：血小板為 30.00 X 109/L,紅細 胞為4.09 X 109/L ,嗜酸性粒細胞計數為 0.30 X 109/L。Immediately after the operation,we

8、 measured systolic pulmonary artery pressure was 55mmHgdiastolic blood pressure was25 mmHgthe mean blood pressure was 34 mmHg. The patient had tachypnea symptoms. Forty-eight hours after the opreation, we rechecked theblood routine, it showed,platelet was 30.00 x 109 / L, erythrocyte was 4.09x 109/L

9、,eosinophilic9, granulocyte was 0.30 x 10/L.患者無出血傾向，無皮膚瘀斑及血尿，予潑尼松 10 mg（每天1次），并堿化 尿液。術后第8天復查血常規示：血小板為61.00 X 109/L。出院1個月后復查血 常規示：血小板為186.00 X 109/L,患者無不適，復查超聲心動圖顯示，肺動脈 收縮壓為35 mm Hg舒弓K壓16 mm Hg平均壓為29 mm HgPatient without bleeding tendency, skin petechia, and cruenturesis .Transfusing prednisone 10mg

10、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,Patientswithout any discomfort, reviewed of echocardio

11、graphy display:systolicpulmonary artery pressure was 35mmHg,diastolic blood pressure was 16 mmHg, the average pressure was 29 mmHg.例2患者女性，22歲，因發現心臟雜音20年入院。經超聲心動圖及 X線 胸片等檢查診斷為PDA入院查血常規示：血小板為125.00 X 109/L,紅細胞4.20 X 109/L ,嗜酸性粒細胞計數為 0.06 X 109/L。Case 2 A 22-year-old female patient was hospitalized bec

12、ause of heart murmurs for 20 years. The diagnosis was PDAby echocardiography and X-ray chest radiography examination. Blood routine examination showed that platelet was 125.00 x 109 / L, erythrocyte was 4.20 x 109/L,eosinophilic,c9，granulocyte was 0.06 x 10/L.術中測肺動月收縮壓為 67 mm Hg舒張壓為40 mm Hg平均壓為51 mm

13、 Hg 造影?。?PDAg漏斗狀，最窄處直經為12 mm選用16 mmPDA寸堵器(深圳先健 科技公司)封堵成功。術后即刻造影示：封堵器內可見明顯的濾過血流。During the operation, measuring systolic pulmonary artery pressure was 67mmHgdiastolicblood pressure was 40mmHgthe mean bloodpressure was 51mmHg. Pulmonary angiography showed that PDA was funnel-shaped, the diameter of th

14、e 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.術后即刻測肺動脈收縮壓為 45 mmHg,舒張壓為22 mmHg,平均壓為32 mm Hg。術后48 h血小板下降至38.00 X 109/L。術后第5天血小板進行性

15、下降至17.00 X109/L,紅細胞為3.64 X 109/L ,嗜酸性粒細胞計數為 0.12X109/L。無血尿， 但患者有鼻出血，予局部填塞處理，并予地塞米松及升血小板膠囊口服治療，效果不佳。先后輸注血小板10 U,鼻出血停止，復查血常規示血小板為123.00 X109/L,患者癥狀消失并出院。Immediately after the operation,measuring systolic pulmonaryartery pressure was 45mmHg,diastolic blood pressure was 22 mmHg, the mean blood pressure

16、was 32 mmHg. Forty-eight hours after the operation, we rechecked the blood routine , it showed that platelet declined sharply to 17X 10 9 / L, erythrocyte was 3.64 x 109/L,eosinophilicgranulocyte was0.12 x 109/L,without hematuria, but patient had nasal bleeding, dealing with tamping in the nose. usi

17、ng dexamethasone and rising platelets drugs, but it ' s ineffective, we transfused thrombocyte 10U successively ,then, nasal bleeding stopped. rechecking the blood routine showed platelet was 123.00 x 10 9 / L .The patient discharged from hospitals after his symptoms disappeared.例3患者女性，19歲，因發現心臟

18、雜音11年入院。經超聲心動圖診斷為 PDA入院查血常規示：血小板為145.00 X 109/L,紅細胞為4.30 X 109/L ,嗜酸性粒細胞計數為0.12X109/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,erythrocy

19、te was 4.30 x 109/L,eosinophilic granulocyte was 0.12x 109/L.術中測肺動脈收縮壓為 59 mmHg,舒張壓為28 mmHg,平均壓為38 mmHg= 造影小： PDAg漏斗狀，最窄處直經為16 mm選用20 mmPDAM堵器(上海形狀 記憶合金材料公司)，封堵成功。術后即刻造影示：封堵器內可見明顯的濾過血 流。During the operation, measuring systolic pulmonary artery pressure was 59mmHgdiastolic blood pressure was 28mmHgth

20、e 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 MemoryAlloy Materials Company)to closure the PDAangiography showed thatsuccessfully. Immediately after the procedure, bloo

21、d flow filtrated through the occlude obviously.術后復測肺動脈收縮壓為43 mnHg,舒張壓為21 mnHg,平均壓為31 mnHg= 術后24 h血小板下降至36.00 X 109/L,無血尿癥狀。術后第4天血小板進行性 的下降至29.00 X 109/L,紅細胞為3.68 X 109/L ,嗜酸性粒細胞計數為 0.13 X 109/L?；颊哂斜浅鲅杈植刻钊幚?，并輸注血小板 4 U,鼻出血停止，復查 血常規示血小板為126.00 X 109/L,患者無不適反應而出院。After the operation, we measured syst

22、olic 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, erythrocytewas 3.68 x 109/L,eosinophilic granulocyte was 0.13x

23、 109/L.Patients withnasal 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.討論 Pastmann于1967年成功開創PDg入封堵術后，介入封

24、堵已經成為 動脈導管未閉治療的首選方法。該術式具有創傷小、痛苦少、恢復快，操作簡便、 療效可靠等優點。但少數患者也可能發生封堵器脫落、殘余分流、機械溶血等并 發癥。Discussion After Pastmann successfully inaugurate the operation of PDAtranscatheter interventional closure In 1967, this procedure has become the preferred method . This method has little trauma, less pain, recovery qu

25、ickly, easy to operation, reliable curative effect, etc. A few patients may also occur complications, such as occluder falls off, residual shunt, mechanical hemolytic.據文獻報道，PD協入封堵術后血小板減少患者的血常規中，嗜酸性粒細胞 計數呈持續上升趨勢1,故考慮患者對封堵器的滌綸成分，聚脂纖維過敏，從而 導致過敏性血小板減少。但本文資料顯示，血小板顯著減少者嗜酸性粒細胞計數 并無明顯升高，且房間隔、室間隔缺損封堵器與PDA寸堵器

26、的材質相同，在行房 間隔、室間隔缺損封堵術后卻幾乎無一例患者有顯著的血小板減少，故我們認為：過敏反應并非PDA介入封堵術后血小板減少的主要原因。過敏的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 allergi

27、c to occluder ' s 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 sam

28、e material as PDA occluder. There had almost no one case appeared significantly thrombocytopenia after transcatheter closure interatrial or ventricular septal defect ,so wethought that al lergic reactions was not the main reason which caused thrombocytopenia after the PDA closure.有學者認為，PDA介入封堵術后血小板減

29、少是術中應用肝素所致2。肝素相關性的血小板減少(heparin-induced thrombocytopenia , HL1)通常分為兩 型：(1) I型HLT較為常見，血小板極少顯著降低，且可自行恢復，一般無明顯 臨床癥狀。本文3例患者的血小板均為短期內大幅度急劇下降，故不支持I型 HLT的診斷。(heparin-inducedSome scholars thought that thrombocytopenia after PDA clusurewas caused by intraoperative application of heparinthrombocytopenia,HLT)

30、usuallydivided into two type: (1) type I HLT wascommonn clinical.Fewer patient's platelets decreased significantly,thrombocytopeniacould restoreto normal level ,automatically.Thosepatients usuallyhave no obviousclinical symptoms . In our study, threepatients of platelets declined sharply within

31、a short period of time, therefore, it did not support the diagnosis of typeI HLT.II型為免疫介導反應，其診斷要點為：除外其他原因導致的血小板減少； 使用肝素510 d后血小板下降50%,或計數低于50.00 X 109 (如發生于5 d 以內一般不考慮為II型 HLT);合并血栓栓塞。本文患者術前血小板計數均正 常，術后也可排除其他疾病所致血小板減少，血小板減少均發生于手術后1248 h以內，而無一例發生血栓栓塞，故也不符合II型HLT的診斷。Type II is immune-mediated reaction

32、, 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 consi

33、dered as HLTH ); (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 thromboembol

34、ism, so it also did not correspond to the diagnosis of type H HLT.有研究表明，PDA術后有殘余分流者發生血小板減少的幾率較高4,這與本 文資料相符。無殘余分流時，血小板可很快黏附在封堵器金屬網眼及其內的滌綸 片聚脂網眼中，啟動外源性凝血途徑，形成相對固定血栓，血小板損失的數量也 較少，且血小板的再生周期為 714 d,每天能更新總量的10%只要無持續性 的血小板損耗，則血小板的丟失與再生形成動態平衡， 故臨床上多數患者未表現 出血小板的急劇下降。當患者的封堵器較大，分流量也較大，分流持續時間較長 時，血小板黏附、變形、損傷后在高

35、速血流沖刷下會形成碎片并被沖刷掉，新的 血小板又黏附到封堵器上，部分血小板仍然再次被沖刷掉，如此反復，大量的血 小板被持續不斷地消耗，大大超過了血小板的再生能力時，臨床就表現為進行性 血小板減少，個別病例經大量的輸注血小板也不能阻止血小板的持續下降，而需要開胸取出封堵器。丟失與再生保持動態平衡Studies have shown that the patients with postoperative residual shunthave increased the chance of thrombocytopenia. This is conrrespondencewith our opin

36、ions. Without residual shunt, platelets can be quicklyadhesion in occluder ' s metal mesh and polyester mesh, initiate the extrinsiccoagulationpathway, format relativelyfixed thrombosis,thus,less platelet will be damaged. Moreover, platelet regeneration cycle is about seven to fourteen days, 10%

37、 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 showedwithout platelet declined sharply. While patients occluder is bigger, residual shunt amount is bigger also, Long time duration of

38、shunt cause platelet adhesion, deformation and damage under high speed blood flow scouring which can form fragmentation and wash the platelet away. Newplatelets adhere to the occluder still be washed off again. Such situation happened repeatedly,thus, l arge number of platelets are constantly consum

39、edwhich 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.本文資料中，發生顯著血小板減少者封堵器均較大，但如果

40、單純用封堵器的 大小來衡量發生血小板減少的可能性似乎有些片面。 部分房間隔缺損封堵器直徑 可達4056 mm也未引起明顯的血小板減少。In our study, occluder is larger in those patients with significantly thrombocytopenia. It seemsto be someone-sided if we simple use the size of the occluder to estimate the possibility of thrombocytopenia. A part of atrial septal de

41、fects occluder ,which diameter was up to 40- 56 mm, did not cause obvious thrombocytopenia.究其原因，左右房間隔之間的壓力差較小，血小板吸附在傘內形成血栓后， 無進一步的沖刷性的損傷，因而無血小板的持續下降。不過室間隔缺損患者的左 右室間的壓力差也較大，故室間隔缺損封堵術后往往存在殘余分流或濾過血流，但患者血小板卻無明顯減少，考慮與室間隔缺損封堵器較小，吸附血小板的能力 有限，在血小板未明顯減少時就已經在封堵器腰部形成血栓而封堵了整個分流通 道，無分流就無血小板的進一步下降。Exploring its r

42、eason 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

43、 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 it ' s related to the relative smaller size of ventricular septal defect occluder ,its adher

44、ency ability to platelet is limited,the thrombosis formed at the waist of the occluder and blocked the distributary channel, without shunt,there is no plateletfurtherdeclined .而PDA勺形狀為柱狀，其內的滌綸成分明顯較多，吸附的能力血小板的能力 也隨之增加，特別是封堵器較大，中間存在速度較快的濾過血流時，在分流束的沖刷下，血栓難以形成，血小板持續損傷，臨床表現為短時間內血小板大幅度下 降。the shape of the

45、 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 sh

46、arply within a short period of time.Anil等4報道，PDA直徑越大，用彈簧圈封堵后有殘余分流者發生溶血、血 尿的幾率也越大，與紅細胞反復高速通過彈簧圈封堵后的殘余分流通道所致的切 割損傷有關。Anil, etc. 4 reported, The greater the diameter of the PDA,the rate of hemolysis, blood in urine are muchhigher , when there are residual shunt exist after the operation of spring coil

47、blocking. Erythrocytes flow through the spring coil by high speed which caused cutting injury repeatedly .而近年來換用Amplatze或國產傘形封堵器后引起血小板減少的病例可見陸 續報道，考慮與PDA寸堵器內增加的滌綸成分、聚酯纖維對血小板有一定的吸附 作用有關，而分流束的沖刷對血小板形成持續的損傷也是血小板急劇減少的重要 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 beamon platelet which cause platelet