危重患者血小板減少的診治

1、危重患者血小板減少的診治,.,1,概述血小板減少的定義、機制、診斷思路、常用的檢查方法 危重患者中血小板減少的診斷和治療 總結 病例討論,.,2,血小板減少（thrombocytopenia）定義為各種遺傳或獲得性因素導致的血小板減少，血小板計數150.0 x 10(9)/L，通常小于100.0 x 10(9)/L. 其主要機制為破壞增加（hyperdestructive ）、生成減少（ hypoproductive ）和分布異常（altered distribution,常見于充血性脾大或低體溫）。,.,3,.,Hospital-acquired thrombocytopenia. Hosp

2、 Pract , 2014 Oct;42(4):142-52.,4,.,5,.,6,血小板減少的病因多樣，涉及多個學科，常規(guī)檢查特異性和敏感性不高，特異性檢查受到技術條件和標準化的制約難以開展，導致診斷及鑒別診斷困難。 同一病因導致血小板減少的時間、程度個體差異大，發(fā)生嚴重出血受到患者年齡、基礎疾?。ㄐ?、肝、腎等）和有創(chuàng)操作等的影響，及時評估、干預非常重要。,.,7,相關病史（基礎疾病、藥物史、 出血事件） 查體（出血傾向、 肝脾淋巴結、免疫相關疾病、 皮膚鞏膜黃染）,.,8,外周血涂片,.,EDTA抗凝劑導致的血 小板 聚集（clumping），自動血細胞計數儀中血小板計數下降，稱為假性血小

3、板減少（pseudothrombocytopenia） 人工計數或枸櫞酸抗凝可以識別,9,.,裂紅細胞（破碎紅細胞）,10,.,球形紅細胞,11,骨髓涂片/活檢,.,了解巨核細胞系（巨核細胞數量及產板情況），還可發(fā)現粒系/紅系異常,12,.,破壞增多骨髓檢查巨核細胞數量正?；蛟黾?。部分 ITP可見巨核細胞成熟障礙，產板少。,13,.,生成減少骨髓涂片巨核細胞減少。 再障患者活檢增生極度低下，造血組織少。,14,抗人球蛋白試驗,即Coombs直接試驗:將洗滌過的紅細胞2%混懸液加入Coombs試劑，混和后離心一分鐘促進凝集。如果肉眼或顯微鏡下能見到紅細胞凝集，即為陽性，說明紅細胞表面有抗體或補體

4、。 Coombs間接試驗:先將受試的血清加入等量5%適當的正常紅細胞(Rh陽性的O型紅細胞)，在37溫育3060分鐘，以促使血清中的半抗體結合于紅細胞上(致敏)，將紅細胞充分洗滌，以后同直接試驗。,.,15,.,血小板減少診斷簡易流程,16,以下的實驗室方法能幫助我們進一步明確診斷,.,17,平均血小板容積（MPV，meanplateletvolume ） One hundred two patients were completely evaluated. When compared with the BM examination, the MPV of 7.9 fl could predi

5、ct hyperdestructive sensitivity of 82.3% (95% CI: 70.5-90.8), specificity of 92.5% (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 hyperdestru

6、ctive thrombocytopenia from hypoproductive 0thrombocytopenia.International journal of laboratory hematology,2008 Oct;30(5):408-14.,.,18,血小板指數（platelet indices），包括MPV, 血小板體積變異寬度（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 cate

7、gories: hypoproliferative and destructive thrombocytopenia All the threeplateletindiceswere significantly higher in destructive group as compared to the hypoproliferative category,.,19,134 thrombocytopenic patients (69 men, 65 women) who were divided into two groups group I (n = 63) included ITP pat

8、ients group II (n = 71) included patients 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 thediagnosisof ITP. On the contrary, the value

9、s for P-LCR were significantly lower。,.,20,血小板指數的局限性在于血小板嚴重下降的患者（10 x 10(9)/L ）結果有較大的偏差，輸血等治療措施影響對結果的判斷。 在ICU的應用價值需要再評估。 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. Incre

10、ased values 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.,.,21,未成熟血小板比例和網織血小板比例 Group 1. Centralthrombocytopenia IPF 8.67% (6.49-10.46%) RP 4.08% (2.86- 5.30%) Group 2. Thromboc

11、ytopenia as a result of enhanced peripheralplateletdestruction 6.80% (12.20-21.39%) ，16.14% (9.89-22.40%). (P 0.01). Group 3. Peripheral non-immune thrombocytopenia by abnormaldistribution 9.04% (6.95-11.14%) ，5.23% (3.41-7.05%). Correlation between immature platelet fraction and reticulated platele

12、ts. Usefulness in the etiology diagnosis of thrombocytopenia.Eur J Haematol. 2010 Aug;85(2):158-63.,.,22,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值有限。 血小板相關抗體在免疫性血小板減少中有一定的價值，但檢測方法的標準化和特異性需要再評估。 Is the thrombopoietin assay useful for differential diagnosis of thrombocytopenia? Analysi

13、s 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).Haematologica. 2002 Oct;87(10):1046-52. Qu

14、antification of platelet-associated IgG for differential diagnosis of patients with thrombocytopenia.Thromb Haemost. 2000Nov;84(5):779-83.,.,23,以上是簡易流程，最常見的幾種疾病。針對住院特別是ICU患者情況可能更復雜，更多的是基礎疾病和治療性因素導致的血小板減少，醫(yī)院獲得性血小板減少（Hospital-acquired thrombocytopenia）。 Hospital-acquired thrombocytopenia.Hosp Pract (1

15、995). 2014 Oct;42(4):142-52. Thrombocytopenia in the intensive care unit patient.Hematology Am Soc Hematol Educ Program. 2010;2010:135-43.,.,24,1.感染,Infection is a common cause of thrombocytopenia. Viral infections associated with thrombocytopenia include the human immunodeficiency virus, hepatitis

16、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 include bone marrow suppression, peripheral immune destruction, and activation an

17、d 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 infection and supportive care.,.,25,2.藥物誘導免疫性血小板減少,2 primary mechanisms ：decrease

18、d platelet production secondary to bone marrow suppression (eg, chemotherapeutic agents) and increased platelet destruction caused by drug-induced immune thrombocytopenia (DITP) 后者更難以識別。,.,26,Drug-induced immune thrombocytopenia typically presents in a delayed fashion, 5 to 10 days after initiation

19、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 initiation of a glycoprotein IIb/IIIa inhibitor (eg, eptifibatide, tirofiban, and abciximab),.,27,The following clinical criteria have been

20、 proposed to estimate the likelihood that a given drug is the cause of DITP: (1) thrombocytopenia occurs after exposure to the drug and improves after 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

21、without affecting the platelet count; (3) other causes of thrombocytopenia are excluded; (4) thrombocytopenia recurs if the drug is restarted 但在ICU的環(huán)境下，多種藥物使用，合并多種疾病，可能難以判斷。,.,28,.,萬古霉素 青霉素 哌拉西林 頭孢曲松 甲氧芐氨嘧啶/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 對乙酰氨基酚 布洛芬 米氮平 雷尼替丁,29,Suspected DITP is treated by

22、discontinuing the potentially offending drug. The platelet count typically begins to improve within 1 to 2 days after 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 particul

23、arly severe cases, corticosteroids, intravenous immunoglobulin, and plasma exchange have been used, although there is limited evidence of efficacy with these,.,30,肝素誘導的血小板減少,Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that occurs after exposure to unfractionated heparin or

24、low molecular weight heparin. Unlike most other forms of DITP, HIT is generally prothrombotic rather than prohemorrhagic. Thrombotic complications, include deep venous thrombosis, pulmonary embolism, peripheral arterial thrombosis, ischemic stroke, and myocardial infarction.,.,31,.,32,an intermediat

25、e or high probability of HIT, heparin should be discontinued 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.,.,33,3.彌散性血管內凝血,Disseminated intravascular coa

26、gulation (DIC) occurs not in isolation but secondary 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

27、 injury. Accelerated consumption of coagulation factors and platelets may also produce a concomitant bleeding tendency,.,34,.,DIC的病理生理機制,35,.,36,.,37,The cornerstone of therapy for DIC is treatment of the underlying condition. Transfusion is indicated in patients who are bleeding or otherwise at hig

28、h 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.,.,38,4.血栓性血小板減少性紫癜,Thrombotic thrombocytopenic purpura (TTP) is a

29、 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 von Willebrand factor. In the absence of ADAMTS13, ultra

30、large 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.,.,39,.,40,.,TTP患者肺栓塞病理,TTP患者腎小球病變,41,Diagnosis of TTP is based on a combination of clinical signs and sympt

31、oms 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 markers of intravascular hemolysis. Schistocytes, and often nucleated red cells, are found in the peripheral blood smear. The PT and aPTT are typically

32、normal, and the direct Coombs test is negative. Patients may have acute kidney injury or proteinuria.,.,42,Thrombotic thrombocytopenic 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 un

33、der 20%. plasma infusion while awaiting exchange therapy. Plasma exchange is continued until platelet count recovery. high-dose corticosteroids, 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

34、with refractory or relapsed disease. platelet transfusion is relatively contraindicated unless serious bleeding is present.,.,43,5. 輸血后紫癜,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