危重患者血小板減少的診治課件

1、危重患者血小板減少(jinsho)的診治四川省腫瘤醫(yī)院ICU劉真君2017.4第一頁，共五十二頁。危重患者血小板減少的診治1.概述血小板減少(jinsho)的定義、機(jī)制、診斷思路、常用的檢查方法2.危重患者中血小板減少的診斷和治療3.總結(jié)4.病例討論第二頁，共五十二頁。危重患者血小板減少的診治 血小板減少（thrombocytopenia） 定義為各種遺傳或獲得性因素導(dǎo)致的血小板減少，血小板計(jì)數(shù)7.9 fl could predict hyperdestructive sensitivity of 82.3% (95% CI: 70.5-90.8), specificity of 92.5%

2、(95% CI: 79.6-98.4), positive predictive value of 94.4% (95% CI: 84.6-98.8), negative predictive value of 77.1% (95% CI: 62.7-88.0) A prospective evaluation of normal mean platelet volume in discriminating hyperdestructive thrombocytopenia from hypoproductive 0thrombocytopenia.International journal

3、of laboratory hematology,2008 Oct;30(5):408-14.第十八頁，共五十二頁。危重患者血小板減少的診治 血小板指數(shù) （platelet indices），包括MPV, 血小板體積變異(biny)寬度（platelet size deviation width ，PDW) 和大血小板比率（ platelet-to-large-cell ratio ，P-LCR) The study group was divided into two categories: hypoproliferative and destructive thrombocytopenia

4、 All the three platelet indices were significantly higher in destructive group as compared to the hypoproliferative category第十九頁，共五十二頁。危重患者血小板減少的診治 134 thrombocytopenic patients (69 men, 65 women) who were divided into two groups group I (n = 63) included ITP patients group II (n = 71) included pati

5、ents with HT due to myelosuppression secondary to chemotherapy Concerning MPV and PDW indices, sensitivity, specificity, positive prognostic value, negative prognostic value, efficiency and Youden index were 100% for the diagnosis of ITP. On the contrary, the values for P-LCR were significantly lowe

6、r。第二十頁，共五十二頁。危重患者血小板減少的診治 血小板指數(shù)的局限性在于血小板嚴(yán)重(ynzhng)下降的患者（10 x 10(9)/L ）結(jié)果有較大的偏差，輸血等治療措施影響對(duì)結(jié)果的判斷。 在ICU的應(yīng)用價(jià)值需要再評(píng)估。 Role of platelet volume indices in the differential diagnosis of thrombocytopenia: a simple and inexpensive method.Hematology (Amsterdam, Netherlands) ,2009 Jun;14(3):182-6. Increased valu

7、es of mean platelet volume and platelet size deviation width may provide a safe positive diagnosis of idiopathic thrombocytopenic purpura.Acta Haematol. 2008;119(3):173-7. 第二十一頁，共五十二頁。危重患者血小板減少的診治未成熟血小板比例(bl)和網(wǎng)織血小板比例(bl) Group 1. Central thrombocytopenia IPF 8.67% (6.49-10.46%) RP 4.08% (2.86- 5.30%

8、) Group 2. Thrombocytopenia as a result of enhanced peripheral platelet destruction6.80% (12.20-21.39%) ，16.14%). (P 0.01). Group 3. Peripheral non-immune thrombocytopenia by abnormal distribution 9.04% (6.95-11.14%) ，5.23% (3.41-7.05%). Correlation between immature platelet fraction and reticulated

9、 platelets. Usefulness in the etiology diagnosis of thrombocytopenia.Eur J Haematol. 2010 Aug;85(2):158-63.第二十二頁，共五十二頁。危重患者血小板減少的診治 促血小板生成素（Thrombopoietin ，TPO)在生成障礙患者，特別是再障患者明顯升高，但在鑒別診斷中的價(jià)值有限。 血小板相關(guān)抗體在免疫性血小板減少中有一定的價(jià)值，但檢測方法的標(biāo)準(zhǔn)化和特異性需要(xyo)再評(píng)估。 Is the thrombopoietin assay useful for differential diagn

10、osis of thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia and defined platelet life span.Clin Chem. 2001 Sep;47(9):1660-5. Attempt to improve the diagnosis of immune thrombocytopenia by combined use of two different platelet autoantibodies assays (PAIgG and MACE).Haematolo

11、gica. 2002 Oct;87(10):1046-52. Quantification of platelet-associated IgG for differential diagnosis of patients with thrombocytopenia.Thromb Haemost. 2000Nov;84(5):779-83.第二十三頁，共五十二頁。危重患者血小板減少的診治 以上是簡易流程(lichng)，最常見的幾種疾病。針對(duì)住院特別是ICU患者情況可能更復(fù)雜，更多的是基礎(chǔ)疾病和治療性因素導(dǎo)致的血小板減少，醫(yī)院獲得性血小板減少（Hospital-acquired thrombo

12、cytopenia）。 Hospital-acquired thrombocytopenia.Hosp Pract (1995). 2014 Oct;42(4):142-52. Thrombocytopenia in the intensive care unit patient.Hematology Am Soc Hematol Educ Program. 2010;2010:135-43. 第二十四頁，共五十二頁。危重患者血小板減少的診治 Infection is a common cause of thrombocytopenia. Viral infections associated

13、 with thrombocytopenia include the human immunodeficiency virus, hepatitis C virus, and Epstein-Barr virus，cytomegalovirus Thrombocytopenia is also frequent in patients with bacterial infections and sepsis or severe sepsis. Mechanisms of infection-induced thrombocytopenia are multiple and may includ

14、e bone marrow suppression, peripheral immune destruction, and activation and consumption. The fall in platelet count associated with sepsis is typically gradual, occurring over 5 to 7 days, and the thrombocytopenia is characteristically mild. Management consists of treatment of the underlying infect

15、ion and supportive care. 1.感染(gnrn)第二十五頁，共五十二頁。危重患者血小板減少的診治 2 primary mechanisms ：decreased platelet production secondary to bone marrow suppression (eg, chemotherapeutic agents) and increased platelet destruction caused by drug-induced immune thrombocytopenia (DITP) 后者更難以(nny)識(shí)別。2.藥物(yow)誘導(dǎo)免疫性血小板減少

16、第二十六頁，共五十二頁。危重患者血小板減少的診治 Drug-induced immune thrombocytopenia typically presents in a delayed fashion, 5 to 10 days after initiation of the offending drug. There are 2 exceptions to this rule: (1) patients previously exposed to a drug （2）patients may develop thrombocytopenia immediately after initia

17、tion of a glycoprotein IIb/IIIa inhibitor (eg, eptifibatide, tirofiban, and abciximab) 第二十七頁，共五十二頁。危重患者血小板減少的診治 The following clinical criteria have been proposed to estimate the likelihood that a given drug is the cause of DITP: (1) thrombocytopenia occurs after exposure to the drug and improves af

18、ter the drug is stopped; (2) the candidate drug is the only drug used before the onset of thrombocytopenia, or other drugs are continued or reintroduced without affecting the platelet count; (3) other causes of thrombocytopenia are excluded; (4) thrombocytopenia recurs if the drug is restarted 但在ICU

19、的環(huán)境下，多種藥物(yow)使用，合并多種疾病，可能難以判斷。 第二十八頁，共五十二頁。危重患者血小板減少的診治萬古霉素青霉素哌拉西林頭孢曲松甲氧芐氨嘧啶(m dn)/磺胺甲惡唑利福平卡馬西平苯妥英丙戊酸阿昔單抗替羅非班依替巴肽奎寧對(duì)乙酰氨基酚布洛芬米氮平 雷尼替丁第二十九頁，共五十二頁。危重患者血小板減少的診治 Suspected DITP is treated by discontinuing the potentially offending drug. The platelet count typically begins to improve within 1 to 2 days a

20、fter the drug is stopped .The median time to recovery of platelet count is 7 days. Patients with severe thrombocytopenia and bleeding may be treated with platelet transfusion. In particularly severe cases, corticosteroids, intravenous immunoglobulin, and plasma exchange have been used, although ther

21、e is limited evidence of efficacy with these第三十頁，共五十二頁。危重患者血小板減少的診治 Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that occurs after exposure to unfractionated heparin or low molecular weight heparin. Unlike most other forms of DITP, HIT is generally prothrombotic rather than

22、prohemorrhagic. Thrombotic complications, include deep venous thrombosis, pulmonary embolism, peripheral arterial thrombosis, ischemic stroke, and myocardial infarction.肝素(n s)誘導(dǎo)的血小板減少第三十一頁，共五十二頁。危重患者血小板減少的診治第三十二頁，共五十二頁。危重患者血小板減少的診治 an intermediate or high probability of HIT, heparin should be disco

23、ntinued the patient should be treated with a nonheparin anticoagulant（argatroban, danaparoid ，bivalirudin fondaparinux） Once the platelet count has recovered, patients may be transitioned to warfarin. 第三十三頁，共五十二頁。危重患者血小板減少的診治 Disseminated intravascular coagulation (DIC) occurs not in isolation but s

24、econdary to an underlying disorder These conditions may generate procoagulant substances, leading to widespread activation of coagulation and deposition of fibrin in the microvasculature. The end result is thrombosis of small vessels and end-organ ischemic injury. Accelerated consumption of coagulat

25、ion factors and platelets may also produce a concomitant bleeding tendency3.彌散(msn)性血管內(nèi)凝血第三十四頁，共五十二頁。危重患者血小板減少的診治DIC的病理(bngl)生理機(jī)制第三十五頁，共五十二頁。危重患者血小板減少的診治第三十六頁，共五十二頁。危重患者血小板減少的診治第三十七頁，共五十二頁。危重患者血小板減少的診治 The cornerstone of therapy for DIC is treatment of the underlying condition. Transfusion is indica

26、ted in patients who are bleeding or otherwise at high risk for bleeding. Therapeutic heparin should be considered in patients with DIC complicated by overt thrombosis. Antifibrinolytic treatments are generally contraindicated in patients with DIC due to an increased risk of thrombosis.第三十八頁，共五十二頁。危重

27、患者血小板減少的診治 Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy It is characterized by thrombocytopenia and microangiopathic hemolytic anemia and may also include neurologic symptoms, fevers, and renal impairment TTP is caused by a deficiency of ADAMTS13, a protease that cleaves

28、 von Willebrand factor. In the absence of ADAMTS13, ultralarge von Willebrand factor multimers promote formation of platelet aggregates in the microvasculature, causing shear stress and mechanical fragmentation of erythrocytes in areas of high flow.4.血栓性血小板減少(jinsho)性紫癜第三十九頁，共五十二頁。危重患者血小板減少的診治第四十頁，共

29、五十二頁。危重患者血小板減少的診治TTP患者(hunzh)肺栓塞病理TTP患者(hunzh)腎小球病變第四十一頁，共五十二頁。危重患者血小板減少的診治 Diagnosis of TTP is based on a combination of clinical signs and symptoms and laboratory values. The median platelet count at presentation is 10 to 30 109/L. The median hemoglobin is 8 to 10 g/dL and is accompanied by marker

30、s of intravascular hemolysis. Schistocytes, and often nucleated red cells, are found in the peripheral blood smear. The PT and aPTT are typically normal, and the direct Coombs test is negative. Patients may have acute kidney injury or proteinuria.第四十二頁，共五十二頁。危重患者血小板減少的診治 Thrombotic thrombocytopenic

31、purpura is a medical emergency, and treatment of suspected TTP must be commenced immediately. daily plasma exchange (PEX) decreases mortality rates from 80%90% to under 20%. plasma infusion while awaiting exchange therapy. Plasma exchange is continued until platelet count recovery. high-dose cortico

32、steroids, which have been shown in some studies to improve outcomes. Rituximab, a monoclonal antibody that targets CD20 on B lymphocytes, is widely used in patients with refractory or relapsed disease. platelet transfusion is relatively contraindicated unless serious bleeding is present.第四十三頁，共五十二頁。

33、危重患者血小板減少的診治 Posttransfusion purpura (PTP) is a rare complication of blood transfusion that causes acute, severe thrombocytopenia with a median nadir platelet count , 10 109/L. occurs 5 to 10 days after transfusion caused by alloantibodies against a platelet antigen， alloantibodies induce clearance of donor platelets and recipients own platelets, resulting in severe thrombocytopenia and a pronounced bleeding diathesis5. 輸血(sh xu)后紫癜第四十四頁，共五十二頁。危重患者血小板減少的診治 Posttransfusion purpura may be treated with intravenous immunoglo