Cancer-Associated Venous Thromboembolic Disease Version 1.2016

癌症相关静脉血栓栓塞症2016年第1版山东省肿瘤医院呼吸肿瘤内科张品良

Updates in Version 1.2016 of the NCCN Guidelines for Cancer-Associated Venous Thromboembolic Disease from Version 1.2015 include:
2016年第1版的NCCN癌症相关静脉血栓栓塞症指南自2015年第1版的更新包括：

General 总体

* “pomalidomide” was added to “thalidomide/lenalidomide” as appropriate throughout the guidelines.
*将“泊马度胺”添加到“沙利度胺/来那度胺”贯穿整个指南是合适的。

Venous Thromboembolism 静脉血栓栓塞

VTE-1

* At-Risk Population *高危人群

▶ 3rd bullet: Revised “Providers are encouraged to discuss VTE risk factors, risks and benefits of VTE prevention, and the importance of patient adherence to care programs.” (Also for VTE-2)
▶第3项核心：修改为“鼓励医生探讨静脉血栓栓塞危险因素、风险和VTE预防的收益以及患者遵守医疗计划的重要性。”(同样适用于VTE-2)

* Footnote “c” was revised: “Discuss prevention and risks/benefits of VTE prophylactic anticoagulation by pharmacologic intervention. Discuss VTE prevention and the risks/benefits of pharmacologic and mechanical VTE prophylaxis. A systematic approach to patient risk assessment is recommended. Institutions are strongly encouraged to implement best practice programs to monitor provider and patient adherence to VTE prophylaxis.”
*修订了脚注“c”：“探讨通过药物干预静脉血栓栓塞预防性抗凝治疗的预防与风险/收益。探讨VTE预防以及药物和机械预防VTE的风险/效益。建议的一个系统评估患者风险的方法。学会强烈鼓励实施最佳实践方案来监控医生和病人对VTE预防的依从性。”

VTE-2

* At-Risk Population *高危人群

▶ Recommendations for “Surgical oncology patient” were revised to: “Out-of-hospital primary VTE prophylaxis is recommended for up to four weeks post-operation (particularly for high-risk abdominal or pelvic cancer surgery patients.)”
▶对“肿瘤外科患者”的建议修订为：“院外初级VTE预防推荐手术后最多4周(特别是对于高危腹或盆腔癌症手术患者)”

▶ For “Medical oncology patient” treated in “Other outpatient settings”, footnote was removed: “Consider patient conversation about risks and benefits of VTE prophylaxis in patients with a Khorana score ≥3. (See Khorana Predictive Model [VTE-A 3 of 3]).”
▶对于“其他情况的门诊患者”中的“内科肿瘤患者”，删除了脚注：“在Khorana评分≥3的患者中考虑与患者交谈有关静脉血栓栓塞预防的风险与收益。（见Khorana预测模型VTE-A 3/3）。”

Acute Deep Vein Thrombosis (DVT) and Acute Superficial Vein Thrombosis (SVT)
急性深静脉血栓形成（DVT）与急性浅静脉血栓形成（SVT）

* Deep or Superficial Vein Thrombosis (DVT/SVT) was divided into two new pages.
*深或浅静脉血栓形成（DVT/SVT）分到两个新页。

SVT-1

* “Acute Superficial Vein Thrombosis (SVT)” was extensively revised.
*广泛修订了“急性浅静脉血栓形成（SVT）”。

DVT-1

* “Acute Deep Vein Thrombosis (DVT)” was extensively revised.
*广泛修订了“急性深静脉血栓形成（DVT）”。

DVT-3

* Treatment *治疗

▶ DTV, no contraindication, 1st bullet was revised: “Anticoagulation for at least 3 months or as long as catheter CVAD is in place if catheter removed, total duration of therapy is at least 3 months”
▶DTV，无禁忌症，第一项核心修订：“抗凝至少3个月或只要导管CVAD存在就要抗凝；如果导管拔除，总的治疗持续时间是至少3个月”

▶ No DVT, bullet was revised from “Consider further imaging/testing with another modality if clinical suspicion is high and initial imaging failed to show” to “Consider further diagnostic imaging/testing if initial testing is unrevealing and clinical suspicion remains high”
▶无DVT，“如果临床高度怀疑而初步的影像未显示，则考虑用另外的方式进一步影像/检测”核心修订为“如果初步检测未发现而临床仍高度怀疑，则考虑进一步影像/检测”

▶ Footnote “k” is new: “Consider longer duration anticoagulation in patients with poor flow, persistent symptoms, or unresolved thrombus.”
▶脚注“K”是新的：“在血流不畅、症状持续或血栓未解决的患者中，考虑更长时间的抗凝治疗。”

Acute Pulmonary Embolism (PE) 急性肺栓塞（PE）

PE-1

* Diagnosis and Evaluation ＊诊断与评估

▶ Under “Diagnosis”, a bullet was removed: “Incidental PE”
▶在“诊断”下面，删除了：“偶发性PE”

▶ “Unsuspected PE” pathway is new, with the evaluation: “If not already performed: Comprehensive medical history, and physical examination; CBC with platelet count; PT, aPTT; Liver and kidney function tests; EKG,” then referred to: “See PE Treatment (PE-2)”
▶“不受怀疑的PE”路径是新的，增加了评价：“如果尚未完成：全面的病史和体格检查；CBC加血小板计数；PT，aPTT；肝肾功能检测；EKG，”则参考：“见PE治疗（PE-2）”

▶ Clinical suspicion of PE, Imaging, 3rd bullet was revised: “... (if patient has renal insufficiency or uncorrectable allergy to contrast allergy refractory to anaphylaxis prophylaxis)”
▶临床、影像学怀疑PE，修订了第三项核心：“... （如果病人有肾功能不全或对造影剂过敏无法纠正过敏预防措施抵抗）”

▶ Footnote “c” was revised: “Repeat imaging and diagnostic studies are is not routinely needed in patients with incidental PE. Consider outpatient management for these patients.”
*修订了脚注“c”：“在偶发PE患者中不常规要求重复影像和诊断性研究。对于这些患者考虑门诊管理。"

PE-2

* Treatment *治疗

▶ Footnote was removed from risk stratification procedures: “The Pulmonary Embolism Severity Index (PESI) clinical prediction rule can also be considered, but should not be substituted for the risk stratification procedures indicated above. (Donze J, Le Gal G, Fine MJ, et al. Prospective validation of the Pulmonary Embolism Severity Scale. Throm Haemost 2008;100:943-948). Consideration can also be given to the RIETE Cancer Score (den Exter P, Gómez V, Jiménez D, et al. A clinical prognostic model for the identification of low-risk patients with acute symptomatic pulmonary embolism and active cancer. Chest 2013;143:138-145.)”
▶从危险分层方法中删除了脚注：“也可以考虑肺栓塞严重指数(PESI)临床预测规则，但是不应该取代上面所述的危险分层方法。（Donze J, Le Gal G, Fine MJ,等。肺栓塞严重程度量表的前瞻性证实。Throm Haemost 2008;100:943-948）。也可考虑给予RIETE癌症评分（den Exter P, Gómez V, Jiménez D, 等。用于识别低危急性症状性肺栓塞与癌症活跃患者的一个临床预后模型。Chest 2013;143:138-145。）”

Heparin-Induced Thrombocytopenia (HIT) 肝素诱导的血小板减少症(HIT)

HIT-1

* Diagnosis and Treatment of HIT ＊HIT的诊断与治疗

▶ “Low” pathway: Fourth bullet removed: “Consider HIT antibody test (enzyme-linked immunosorbent assay [ELISA]) for select patients (See HIT antibody test results HIT-2)”
▶“低”路径：删除了第4项核心：“对于选择性的患者考虑HIT抗体检测(酶联免疫吸附测定[ELISA])(见HIT抗体检测结果HIT-2)”

▶ “Moderate/High” pathway: ▶“中/高”路径

♢ 1st bullet was revised from “Eliminate unfractionated and LMWH exposure from all sources, including treatment, prophylaxis, flush doses, and coated catheters” to “Eliminate UFH/LMWH exposure from all sources (treatment, prophylaxis, line flushes, coated catheters)”
第1项核心“消除来自所有来源的普通与低分子肝素暴露，包括治疗、预防、冲管用药以及涂层导管”修订为“消除暴露于UFH/LMWH的各种来源（治疗、预防、冲管、涂层导管）”

♢ 2nd bullet was revised from “For patients receiving warfarin, discontinue it and reverse with vitamin K” to “Discontinue and reverse warfarin (and other vitamin K antagonists) with vitamin K”
♢第2项核心“对于正在接受华法林的患者，停止华法林并用维生素K对抗”修订为“停止并用维生素K对抗华法林（以及其他维生素K拮抗剂）”

▶ Footnote “c” was revised: “A “low” pre-test probability score combined with a negative antibody test is useful in ruling out a diagnosis of HIT; a positive test increases the suspicion for HIT. Sending for the HIT antibody test should be individualized and based on clinical judgment. Patients with 4T scores<4 are very unlikely to have HIT, so routine HIT antibody testing in these patients is probably not advisable. In non-cancer patients with 4T scores of 1–3, the risk of HIT is small but not zero, but this has not been validated in cancer patients. Based on clinical judgment HIT antibody testing may be warranted in select patients of concern.”
*修订了脚注“c”：修订为：“验前概率评分“低”结合抗体检测阴性在排除HIT诊断方面是有用的；测试阳性增加了对HIT的怀疑。应该个体化送肝素诱导的血小板减少症抗体检测并以临床判断为基础。4T评分<4的患者不太可能是HIT，因此在这些患者中常规HIT抗体检测可能是不明智的。在4T评分1–3的非癌症患者 中，HIT风险很小但并不是没有，不过这未在癌症患者中验证。根据临床判断，在选择性的担心的患者中，HIT抗体检测可能是必要的。”

▶ Footnote “e” is new: “Data supporting use of fondaparinux is limited; however, among experienced clinicians it is commonly used for outpatient management in low-risk patients.”
▶脚注“e”是新的：“支持使用磺达肝素的数据是有限的；不过，在有经验的临床医生中，它通常用于低危患者的门诊管理。”

Therapeutic Options for HIT
HIT的治疗方案

HIT-B 1 of 2

* Direct Thrombin Inhibitors (Preferred); Argatroban: *直接凝血酶抑制剂（首选）；阿加曲班：

▶ 1st sub-bullet was revised: “Normal liver function, non-ICU patient: 1 2 mcg/kg/min adjusted to aPTT ratio (first check in 4 hours)”
▶修订了第1项次核心：“肝功能正常，非ICU患者：1 2μg/kg/min根据aPTT比调整（首次复查在4小时内）”

▶ 2nd sub-bullet was revised: “Abnormal liver function (total bilirubin 1.8–3.6 mg/dL; aspartate transaminase/alanine transaminase [AST/ALT] 150–600 IU/L) or ICU, heart, or multi-organ failure patient: 0.25 0.5 mcg/kg/min”
▶修订了第2项次核心：“肝功能异常（总胆红素1.8 - 3.6mg/dL；天冬氨酸转氨酶/丙氨酸转氨酶[AST/ALT]150-600IU/L)或ICU、心脏或多器官衰竭患者：0.25 0.5μg/kg/min”

* Footnote “3” is new: “Prescribing information: Argatroban injection, for intravenous infusion only. 2016.”
*脚注“3”是新的：“处方信息：阿加曲班注射液，只能用于静脉输液。2016.”

HIT-B 2 of 2

* Indirect Factor Xa Inhibitor, fondaparinux, 1st sub-bullet was revised: “For patients with CCr 30–50 mL/min (clearance reduced by ≥40%): Use caution Consider using a DTI”
*Ⅹa因子间接抑制剂，磺达肝癸，修订了第1项次核心：“对于Ccr 30–50ml/min（清除率降低≥40%）的患者：慎重使用考虑使用DTI”

* Footnote “6” was added: “Prescribing information: Fondaparinux sodium, solution for subcutaneous injection. 2009”
*添加了脚注“6”：“处方信息：磺达肝素钠，溶液用于皮下注射。2009”

Splanchnic Vein Thrombosis (SPVT) 内脏静脉血栓(SPVT)

SPVT-1

* Footnote “a”, Risk factors relevant to cancer population for SPVT; 8th sub-bullet was revised: “Myeloproliferative disorder (polycythemia vera, essential thrombocythemia) neoplasms associated with the JAK2 V617F mutation (most common) or CALR mutation (rare)”
*脚注“a”，与癌症人群SPVT有关的危险因素；修订了第8项核心：“骨髓增殖异常（真性红细胞增多症、原发性血小板增多症）肿瘤与JAK2 V617F突变（最常见）或CALR突变（罕见）相关”

SPVT-2

* Footnote “d” was revised: “Duration of anticoagulation should be at least 6 months for triggered events (eg, postsurgical) and indefinite if active cancer, thrombophilic state, or idiopathic thrombosis persistent thrombophilic state or unprovoked thrombotic event.”
*修订了脚注“d”：“对于触发事件（如术后）且不确定是否癌症活跃、易栓状态或特发性血栓持续易栓状态或无缘无故的血栓事件，抗凝持续时间应该至少6个月。”

VTE Risk Factors In Cancer Patients 癌症患者VTE危险因素

VTE-A 1 of 3

* High-risk outpatients on chemotherapy, based on combinations of the following risk factors; 5th bullet was revised: “Use of erythropoietic erythropoiesis-stimulating agents”
*高危门诊化疗患者，具有下列危险因素；修订了第5项核心：“红细胞生成的红细胞生成刺激药物的使用”

VTE-A 2 of 3

* Risk Factors, Myeloma Therapy: *危险因素，骨髓瘤治疗：

▶ 1st bullet was revised: “Thalidomide or lenalidomide IMiD in combination with:”
▶修订了第1项核心：“沙利度胺或来那度胺IMiD联合：”

▶ Footnote “2” is new: “Immunomodulator drugs (IMiDs), including thalidomide, lenalidomide, and pomalidomide.”
▶脚注“2”是新的：“免疫调节药物（IMiDs），包括沙利度胺、来那度胺和 泊马度胺。”

* Footnote “1” was revised: “Reproduced Adapted with permission from Nature Publishing Group. Palumbo A, Rajkumar SV, Dimopolous MA et al, Prevention of thalidomide-and lenalidomide-associated thrombosis in myeloma. Leukemia 2008;22:414-423. Copyright 2008. http://www.nature.com/leu/journal/v22/n2/full/2405062a.htm” *修订了脚注“1”：“自然出版集团允许转载改编。Palumbo A, Rajkumar SV, Dimopolous MA等，多发性骨髓瘤中沙利度胺和来那度胺相关的血栓形成的预防。Leukemia 2008;22:414-423.版权所有2008。
http://www.nature.com/leu/journal/v22/n2/full/2405062a.htm ”

VTE-A 3 of 3

* Title was revised: “VTE Risk Factors in Cancer Outpatients.”
*修订了标题：“门诊癌症患者VTE的危险因素。”

VTE-B

* Contraindications To Prophylactic or Therapeutic Anticoagulation Treatment *预防性或治疗性抗凝治疗禁忌症。

▶ 8th bullet under “Relative” was added: “Interventional spine and pain procedures”
▶在“相对”下面增加了第8项核心：“脊柱介入和痛苦的操作”

▶ Footnote “1” was revised: “Refer to institutional-specific anesthesia practice guidelines, if available. Twice daily prophylactic dose UFH (5000 units every 12 hours) and once daily LMWH (eg, enoxaparin 40 mg once daily) may be used with neuraxial anesthesia. Twice daily prophylactic dose LMWH (eg, enoxaparin 30 mg every 12 h), prophylactic dose fondaparinux (2.5 mg daily), and therapeutic dose anticoagulation should be used with extreme caution with neuraxial anesthesia. The safety of thrice daily prophylactic dose UFH in conjunction with neuraxial anesthesia has not been established. (Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine Evidence-Based Guidelines (Third Edition). Reg Anesth Pain Med 2010;35:64-101.)
*修订了脚注“1”：“如果可得到的话，参考学会具体的麻醉实践指南。预防剂量的UFH bid（5000u q12h）和LMWH qd（如依诺肝素40mg qd）可以与硬膜外麻醉一起使用。预防剂量的LMWH bid（如依诺肝素30mg q12h）、预防剂量的磺达肝素（2.5mg qd）以及治疗剂量的抗凝与硬膜外麻醉一起使用应该格外谨慎。预防剂量的UFH每日3次与硬膜外麻醉一起使用的安全性尚未确定。（Horlocker TT, Wedel DJ, Rowlingson JC, et al.正在接受抗凝或溶栓治疗患者的局部麻醉：美国局部麻醉与疼痛医学协会循证指南（第三版）。Reg Anesth Pain Med 2010;35:64-101.)

Therapeutic Anticoagulation for Venous Thromboembolism 静脉血栓栓塞症的治疗性抗凝

VTE-D 1 of 2

* Footnote “2” was revised: “Follow institutional standard operating procedures (SOPs) for dosing schedules. If no SOPs then use the American College of Chest Physicians (ACCP) recommendations. (Kearon C, Kahn SR, Agnelli G, Goldhaber S, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008;133[suppl]:454S-545S. [www.chestjournal.org]) Garcia DA , Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S-43S.”
*修订了脚注“2”：“关于给药计划遵循学会的标准操作规程（SOPs）。如果没有标准操作规程则使用美国胸内科医师学会（ACCP）的推荐。(Kearon C, Kahn SR, Agnelli G, Goldhaber S, et al.静脉血栓栓塞性疾病的抗血栓治疗：美国医师学会循证临床指南(第8版)。Chest 2008;133[suppl]:454S-545S.[www.chestjournal.org]) Garcia DA , Baglin TP, Weitz JI, Samama MM.肠道外抗凝剂：抗栓治疗和血栓形成预防，第九版：美国胸内科医师协会循证临床指南。Chest 2012;141:e24S-43S.”

Reversal of Anticoagulation in the Event of Life-Threatening Bleeding or Emergent Surgery 如果发生致命性出血或紧急手术抗凝逆转

VTE-E 1 of 9

* Statement was revised: “In the event of bleeding or the need for urgent/emergent invasive procedures, anticoagulant effect must be reversed promptly. It is incumbent on the provider to keep in stock the recommended reversal agents for all anticoagulants included in this table. This includes: protamine; vitamin K oral (phytonadione), and IV solution; fresh frozen plasma (FFP); 4-factor prothrombin complex concentrate (4-factor PCC), 3-factor PCC, rhFVIIa, activated prothrombin complex concentrates (aPCC) (anti-inhibitor coagulant complex, vapor heated), desmopressin (DDAVP), idarucizumab, and oral charcoal.”
*修订了声明：“如果出血或需要紧急/突发的侵袭性操作，抗凝剂作用必须被及时逆转。本表中推荐的所有逆转抗凝剂保持库存是医生义不容辞的。这包括：鱼精蛋白；口服的维生素K（植物甲萘醌）和静脉注射液；新鲜冰冻血浆（FFP）；4-因子凝血酶原复合浓缩物（4-因子PCC）、3-因子PCC、rhFVIIa、活化凝血酶原浓缩物（aPCC）（蒸汽加热的抗-凝血复合物抑制剂）、去氨加压素（DDAVP）、 idarucizumab（达比加群酯的特异性拮抗剂）以及口服木炭。”

* Low-molecular-weight heparin (LMWH) (Half-life 3–7 hours); 4th bullet was revised: “Administer protamine by slow IV infusion (≤ 5 mg/min) (no faster than 5 mg per min)”
*低分子肝素（LMWH）（半衰期3–7小时）；修订了第4项核心：“鱼精蛋白缓慢静脉滴注（≤5mg/min）（不超过5mg/min）

VTE-E 6 of 9

* Reversal of Anticoagulation for “Dabigatran” *“达比加群”的抗凝逆转

▶ 2nd bullet is new: “Administer idarucizumab, 5 g IV”
▶第2项核心是新的：“给予idarucizumab，5g IV”

▶ 3rd bullet was revised: “No specific antidote exists, but beneficial effects have been ascribed to the following For special situations with slow or incomplete clearance (eg, renal dysfunction or failure), consider adding to idarucizumab:”
▶修订了第3项核心：“目前没有特异性解毒药，但下列是有益的作用对于清除缓慢或不完全（如肾功能异常或衰竭）的特殊情况，考虑加idarucizumab：”

▶ Statement was removed: “May be helpful based on in vitro or animal models aPCC (anti-inhibitor coagulant complex, vapor heated 25–50 units/kg IV) rhFVIIa 90 mcg/kg IV”
▶删除了声明：“基于体外或动物模型，aPCC（蒸汽加热的抗-凝血复合物抑制剂，25–50u/kg IV）rhFVIIa 90μg/kg IV也许会有帮助”

* Precautions/Additional Considerations for “Dabigatran”
*“达比加群”的注意事项/其他需要考虑的事项

▶ 3rd bullet revised: “In patients with renal failure/severe renal insufficiency, dialysis may be the most helpful in addition to idarucizumab.”
▶第3项核心修订：”在肾衰竭/严重肾功能不全患者中，除了idarucizumab之外，透析可能是最有用的。

VTE-E 8 of 9

* This is a new page with recommendations for reversal of edoxaban anticoagulation in the event of life-threatening bleeding or emergent surgery.
*万一发生致命性出血或紧急手术，对于依度沙班抗凝逆转的建议这是新的一页。

VTE-J

* A new box was added listing indications for thrombolysis:
*新包装增加了溶栓适应症列表：

▶ “Limb-threatening/life-threatening acute proximal DVT
▶“威胁肢体/危及生命的急性近端DVT

▶ Symptomatic ileal femoral thrombosis
▶有症状的回肠股动脉血栓

▶ Massive/life-threatening PE
▶巨大/致命性PE

▶ Intestinal SPVT with high risk of ischemia”
▶肠SPVT与高危缺血”

Perioperative Management of Anticoagulation and Antithrombotic Therapy 围手术期抗凝的管理与抗血栓形成治疗

PMA-A 1 of 2

* Types of Surgery or Procedures＊手术或措施的类型

▶ 8th bullet for high bleeding risk was added: “Head and neck surgery” ▶对于出血高危增加了第8项核心：“头颈外科”