2022年危重患者血小板减少的诊治

1、危重患者血小板减少(jinsho)的诊治四川省肿瘤医院ICU刘真君2017.4第一页，共五十二页。1.概述血小板减少(jinsho)的定义、机制、诊断思路、常用的检查方法2.危重患者中血小板减少的诊断和治疗3.总结4.病例讨论第二页，共五十二页。 血小板减少（thrombocytopenia） 定义为各种遗传或获得性因素导致的血小板减少，血小板计数7.9 fl could predict hyperdestructive sensitivity of 82.3% (95% CI: 70.5-90.8), specificity of 92.5% (95% CI: 79.6-98.4), pos

2、itive 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 of laboratory hematology

3、,2008 Oct;30(5):408-14.第十八页，共五十二页。 血小板指数 （platelet indices），包括MPV, 血小板体积变异(biny)宽度（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 All the three platelet indices were

4、 significantly higher in destructive group as compared to the hypoproliferative category第十九页，共五十二页。 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 patients with HT due to myelosuppression secondary t

5、o 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 lower。第二十页，共五十二页。 血小板指数的局限性在于血小板严重(ynzhng)下降的患者（10 x

6、 10(9)/L ）结果有较大的偏差，输血等治疗措施影响对结果的判断。 在ICU的应用价值需要再评估。 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 values of mean platelet volume and platelet size deviation width

7、 may provide a safe positive diagnosis of idiopathic thrombocytopenic purpura.Acta Haematol. 2008;119(3):173-7. 第二十一页，共五十二页。未成熟血小板比例(bl)和网织血小板比例(bl) Group 1. Central thrombocytopenia IPF 8.67% (6.49-10.46%) RP 4.08% (2.86- 5.30%) Group 2. Thrombocytopenia as a result of enhanced peripheral platelet

8、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 platelets. Usefulness in the etiology diagnosis of thrombocytopenia.Eur

9、 J Haematol. 2010 Aug;85(2):158-63.第二十二页，共五十二页。 促血小板生成素（Thrombopoietin ，TPO)在生成障碍患者，特别是再障患者明显升高，但在鉴别诊断中的价值有限。 血小板相关抗体在免疫性血小板减少中有一定的价值，但检测方法的标准化和特异性需要(xyo)再评估。 Is the thrombopoietin assay useful for differential diagnosis of thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia

10、 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. Quantification of platelet-associated IgG for differe

11、ntial diagnosis of patients with thrombocytopenia.Thromb Haemost. 2000Nov;84(5):779-83.第二十三页，共五十二页。 以上是简易流程(lichng)，最常见的几种疾病。针对住院特别是ICU患者情况可能更复杂，更多的是基础疾病和治疗性因素导致的血小板减少，医院获得性血小板减少（Hospital-acquired thrombocytopenia）。 Hospital-acquired thrombocytopenia.Hosp Pract (1995). 2014 Oct;42(4):142-52. Thrombo

12、cytopenia in the intensive care unit patient.Hematology Am Soc Hematol Educ Program. 2010;2010:135-43. 第二十四页，共五十二页。 Infection is a common cause of thrombocytopenia. Viral infections associated with thrombocytopenia include the human immunodeficiency virus, hepatitis C virus, and Epstein-Barr virus，c

13、ytomegalovirus 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 and consumption. The fall in platel

14、et 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. 1.感染(gnrn)第二十五页，共五十二页。 2 primary mechanisms ：decreased platelet production secondar

15、y to bone marrow suppression (eg, chemotherapeutic agents) and increased platelet destruction caused by drug-induced immune thrombocytopenia (DITP) 后者更难以(nny)识别。2.药物(yow)诱导免疫性血小板减少第二十六页，共五十二页。 Drug-induced immune thrombocytopenia typically presents in a delayed fashion, 5 to 10 days after initiation

16、 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) 第二十七页，共五十二页。 The following clinical criteria

17、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 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 rein

18、troduced without affecting the platelet count; (3) other causes of thrombocytopenia are excluded; (4) thrombocytopenia recurs if the drug is restarted 但在ICU的环境下，多种药物(yow)使用，合并多种疾病，可能难以判断。 第二十八页，共五十二页。万古霉素青霉素哌拉西林头孢曲松甲氧苄氨嘧啶(m dn)/磺胺甲恶唑利福平卡马西平苯妥英丙戊酸阿昔单抗替罗非班依替巴肽奎宁对乙酰氨基酚布洛芬米氮平 雷尼替丁第二十九页，共五十二页。 Suspected

19、DITP is treated by 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 trans

20、fusion. In particularly severe cases, corticosteroids, intravenous immunoglobulin, and plasma exchange have been used, although there is limited evidence of efficacy with these第三十页，共五十二页。 Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder that occurs after exposure to unfractionat

21、ed heparin or 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.肝素(n s)诱导的血

22、小板减少第三十一页，共五十二页。第三十二页，共五十二页。 an intermediate 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. 第三十

23、三页，共五十二页。 Disseminated intravascular coagulation (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

24、 of small vessels and end-organ ischemic injury. Accelerated consumption of coagulation factors and platelets may also produce a concomitant bleeding tendency3.弥散(msn)性血管内凝血第三十四页，共五十二页。DIC的病理(bngl)生理机制第三十五页，共五十二页。第三十六页，共五十二页。第三十七页，共五十二页。 The cornerstone of therapy for DIC is treatment of the underly

25、ing condition. Transfusion is indicated 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 increas

26、ed risk of thrombosis.第三十八页，共五十二页。 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,

27、 a protease that cleaves 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.血栓性血小板减少(jinsho)性紫癜第三十九页，

28、共五十二页。第四十页，共五十二页。TTP患者(hunzh)肺栓塞病理TTP患者(hunzh)肾小球病变第四十一页，共五十二页。 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 markers of intrava

29、scular 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.第四十二页，共五十二页。 Thrombotic thrombocytopenic purpura is a medical eme

30、rgency, 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 corticosteroids, which have bee

31、n 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.第四十三页，共五十二页。 Posttransfusion purpura

32、 (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. 输血(sh xu)后紫癜第四十四页，共五十二页。 Posttransfusio