1、危重患者血小板减少的诊治.1.概述血小板减少的定义、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 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), positive predictive value of 94.4% (95% CI: 84.6-98.8), n
2、egative 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,2008 Oct;30(5):408-14. 血小板指数 （platelet indices），包括MPV
3、, 血小板体积变异宽度（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 significantly higher in destructive group as compared to the hypoproli
4、ferative category 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 to chemotherapy Concerning MPV and PDW indices, sensitivity, specificity, positive
5、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。 血小板指数的局限性在于血小板严重下降的患者（10 x 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 differenti
6、al 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 may provide a safe positive diagnosis of idiopathic thrombocytopenic purpura.Acta Haematol. 2008;119
7、(3):173-7. 未成熟血小板比例和网织血小板比例 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 destruction6.80% (12.20-21.39%) ，16.14% (9.89-22.40%). (P 0.01). Group 3. Peripheral non-immune thrombocytopenia by abnor
8、mal 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 J Haematol. 2010 Aug;85(2):158-63. 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
9、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再评估。 Is the thrombopoietin assay useful for differential diagnosis 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
10、 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 differential diagnosis of patients with thrombocytopenia.Thromb Haemost. 2000Nov;84(5):779-83. 以上是简易流程，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，
11、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. Thrombocytopenia in the intensive care unit patient.Hematology Am Soc Hematol Educ Program. 2010;2010:135-43. Infection is a common cause of thrombocyto
12、penia. Viral infections associated 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 thrombocyt
13、openia are multiple and may include 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
14、treatment of the underlying infection and supportive care. 1.感染 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) 后者更难以识别。2.药物诱导免疫性血小板减少 Drug-
15、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 initiation of a glycoprotein IIb/III
16、a inhibitor (eg, eptifibatide, tirofiban, and abciximab) 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 after the drug is stopped; (2) the candidate drug is the
17、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的环境下，多种药物使用，合并多种疾病，可能难以判断。 万古霉素青霉素哌拉西林头孢曲松甲氧苄氨嘧啶/磺胺甲恶唑利
18、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 Suspected 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 thrombocyt
19、openia and bleeding may be treated with platelet transfusion. In particularly severe cases, corticosteroids, intravenous immunoglobulin, and plasma exchange have been used, although there is limited evidence of efficacy with these Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder
20、 that occurs after exposure to unfractionated 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 st
21、roke, and myocardial infarction.肝素诱导的血小板减少 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
22、 warfarin. 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 thrombosi
23、s of small vessels and end-organ ischemic injury. Accelerated consumption of coagulation factors and platelets may also produce a concomitant bleeding tendency3.弥散性血管内凝血DIC的病理生理机制 The cornerstone of therapy for DIC is treatment of the underlying condition. Transfusion is indicated in patients who ar
24、e 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. Thrombotic thrombocytopenic purpura
25、 (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 von Willebrand factor. In the absence of ADAM
26、TS13, 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.血栓性血小板减少性紫癜TTP患者肺栓塞病理TTP患者肾小球病变 Diagnosis of TTP is based on a combination of clinical signs an
27、d 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 intravascular hemolysis. Schistocytes, and often nucleated red cells, are found in the peripheral blood smear. The PT and aPTT are typ
28、ically normal, and the direct Coombs test is negative. Patients may have acute kidney injury or proteinuria. 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
29、under 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 patient
30、s with refractory or relapsed disease. platelet transfusion is relatively contraindicated unless serious bleeding is present. 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 t
31、o 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. 输血后紫癜 Posttransfusion purpura may be treated with intravenous i
32、mmunoglobulin, which often increases platelet counts to 100 109/L within several days. The disorder is self-limited and platelet counts typically recover within 3 weeks. Extracorporeal Circuits and Intra-Arterial De vices，such as extracorporeal membrane oxygenation(ECMO), Intra-aortic balloon pumps
33、(IABPs). platelet activation and consumption Major Surgery. platelet consumption and hemodilution6.其它1.重视血涂片在诊断中的价值2.综合考虑临床环境（普通ICU、儿童、产科差异性），血小板下降的时间和严重程度，血栓和（或）出血表现3.治疗基于及时、正确的诊断4.HIT和TTP是输血小板的禁忌症summary 患者，男，68岁，因“ 便血1月，腹痛20天”入院。查体贫血貌，右上腹扪及2*3cm包块，有压痛，余无阳性发现。肠镜及病检提示结肠肝曲腺癌。术前检查未发现肺、肝等转移，于2009年11月行根治性右半结肠切除术，术后病理检查示低分化腺癌侵及结肠全层，淋巴结转移。术后1月出现意识淡漠，昏睡与清醒交替出现，体温38.5度，双下肢散在瘀斑，神经系统检查颅神经及周围神经感觉运动正常，肌张力正常，病理征阴性。 血常规白细胞9.8*109/L，中性粒细胞86%，HGB74g/L，HCT21%，PLT38*109/L病例讨论 还需要重点查体的地方？血小板减少的原因？安排哪些检查？治疗手段？
