靜脈栓塞及肺栓塞 Venous Thromboembolism Including Pulmonary Embolism

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Introduction

    • Pulmonary embolism(PE): 指blood clot進入肺部血管。大部分PE形成原因是從Deep vein thrombosis(DVT)來的。

    • Venous thromboembolism(VTE) 包含PE and DVT。

    • 依照病因分為provoked, unprovoked

      • Provoked: surgery, trauma, limb immobility, cancer, infection, chronic disease, estrogen use, pregnancy

      • Unprovoked(Idiopathic): 大部分在急診診斷的VTE皆是此類。

    • 至少1/3 DVT的病人伴有PE(不一定有症狀); 但在急診被診斷出PE的非臥床病人中只有40%的人同時有DVT。

    • VTE的危險因子

      • Immobility: whole-body immobility or neurologic immobility(特別是關節) and with travel >8 hours

      • Post-surgery: 通常發生在手術後10天以上。其中，手術時間長、Open surgery等也會增加VTE發生的風險。
        最常發生VTE的手術有：abdominal surgery to remove cancer, joint replacement surgery, and surgery on the brain or spinal cord in the setting of neurologic deficits

      • Cancer: 分化越差的癌細胞以及tumor burden越大 (如：遠端轉移、癌症接受化療期間)，越容易發生VTE。

  • Pulmonary embolism

    • 症狀

      • Dyspnea: 最常見的症狀，無法從PE、EKG、CXR解釋的喘。

      • Chest pain: 第二常見的症狀，常見疼痛位置between clavicles and the costal margin，呼吸或咳嗽會加重。在一些basal lung infarction的病人可能會有referred pain to shoulder，或是mimic biliary pain

      • 其他症狀: syncope, new onset seizure, stroke-like symptoms(paradoxical embolism syndrome)

    • Physical examination(不一定會在PE病人身上出現)

      • Vital signs: Tachycardia, Tachypnea, Desaturation

      • Unilateral limb swelling 

      • Wheezing

    • 其他檢查

      • CXR: 大部分nonspecific
        Westermark’s sign (N Engl J Med 2012; 366:e16)

      • Westermark Sign in Pulmonary Embolism | NEJM

Hampton’s hump (N Engl J Med 2021; 385:1796)
Hampton's Hump | NEJM

  • EKG: V1-V4 TWI, incomplete/complete RBBB, S1-Q3-T3 pattern

  • 診斷

    • 當病人有無法解釋的喘、胸痛時，就應該要懷疑

    • 懷疑病人有PE: 計算Wells’ score評估風險

    • 排除：PREC rule (需要9項都符合)

    • 當臨床沒有很像PE，但也無法排除時：D-dimer

      • D-dimer< 500(or age*10) nanograms/mL: 排除

      • D-dimer> 500(or age*10) nanograms/mL: 要懷疑PE

      • 注意D-dimer false positive or false negative


一張含有 桌 的圖片 自動產生的描述

  • 高度懷疑PE: CTA, 用於診斷PE最常見的檢查，在PE當中可以看到filling defect


＊PE診斷流程表




＊Wells’ score: 用於懷疑有PE的病人計算PE風險


一張含有 桌 的圖片 自動產生的描述


＊PERC rule: 用來排除PE(需要9項都符合)



  • 治療：依照嚴重程度有不同治療方法


1. Massive: hemodynamically unstable (cardiac arrest, SBP < 90, SBP < 100 in HTN, SBP↓40%, desaturation)
＊suggest thrombolysis/embolectomy


2. Sub-massive: hemodynamically stable with evidence of RV dysfunction (Trop, BNP, CT, SpO2 <= 90%, Echo hypokinesia)
＊strongly consider thrombolysis/embolectomy but need to balance risk of bleeding


3. Less severe: hemodynamically stable with normal RV function
＊anticoagulation, inpatient or OPD treatment


以下分述不同的治療方法

  • Systemic fibrinolysis

    • 適用於無contraindication且屬於massive or sub-massive PE者

    • Contraindication: 

  • intracranial disease

  • uncontrolled hypertension at presentation

  • recent major surgery or trauma (past 3 weeks)

  • metastatic cancer

  • 藥物: Alteplase(t-PA), 100 milligrams IV over 2 hours

  • Catheter directed thrombolysis

    • 適用於年紀> 65歲或bleeding risk 較高者

    • less tPA dose needed(可降低bleeding risk): 約10mg tPA in total

  • Surgical embolectomy

    • 適用於young patients with large, proximal PE accompanied by hypotension

    • Mortality rate: 30%

  • Anticoagulation

    • LMWH (ex. Enoxaparin): 最常用, dose 1mg/kg BID

    • UFH: 用於AKI /CKD, extreme obesity, hemodynamically unstable, 用法80 units/kg bolus, then 18 units/kg/h infusion

  • OPD anticoagulation

    • 適用於low risk patient, 可用the Simplified PE Severity Index criteria or modified Hestia criteria來篩選低風險病人

    • 做法: first dose of LMWH (ex. Enoxaparin) or DOAC (ex. Apixaban/Rivaroxaban), 急診觀察24小時後狀況若穩定則回家繼續服藥

    • 一張含有 桌 的圖片 自動產生的描述

    • Enoxaparin: 1mg/kg BID SC

    • Rivaroxaban: 15mg BID for 21 days then 20mg QD with food

    • Apixaban: 10mg BID for 7 days then 5mg BID


  • Special population: pregnancy

    • Scores are not validated in pregnancy 

    • D-dimer: always high

    • No best diagnostic method: CTA(媽媽輻射多) or V/Q scan(小孩輻射多). MRI -> sensitivity too low

    • Treatment: Fibrinolysis if unstable. Preferred LMWH, UFH if overweight or AKI, CKD. 

    • Do not use warfarin in pregnancy because it crosses the placenta


  • Deep vein thrombosis

    • 症狀

      • extremity pain, swelling or cramping (表現可能會像cellulitis)

      • 若是淺層靜脈塞住，可能會導致thrombophlebitis(血栓靜脈炎)，造成紅腫熱痛等症狀

    • Physical examination

      • 兩腿腿圍差超過2 cm (測量處: tibial tubercle下面10 cm)

      • Homan’s sign: calf vein thrombosis, calf pain occurs with passive foot dorsiflexion (診斷價值不高)

      • Phlegmasia alba dolens: 嚴重proximal DVT, swollen, painful, and pale or white limb, need aggressive treatment

      • Phlegmasia cerulea dolens: 嚴重proximal DVT, dusky or blue color limb, need aggressive treatment

    • 診斷

      • Wells’ criteria



Clinical Feature

Points*

Active cancer (treatment within 6 mo, or palliation)

1

Paralysis, paresis, or immobilization of lower extremity

1

Bedridden for >3 d because of surgery (within 12 wk)

1

Localized tenderness along distribution of deep veins

1

Entire leg swollen

1

Unilateral calf swelling of >3 cm (10 cm below tibial tuberosity)

1

Unilateral pitting edema

1

Collateral superficial veins

1

Alternative diagnosis as likely as or more likely than DVT

–2

#Prior history of DVT or pulmonary embolism

1


＊Original Wells DVT model (不包括最後一項)
≥3 points high risk (75%)

1 or 2 points = moderate risk (17%)
<1 point = low risk (3%)
＊Modified Wells DVT model (包括最後一項#)

≤1 point = DVT unlikely; >1 point = DVT likely


  • 治療

    • 治療原則

      • Treat upper extremity DVT the same as lower extremity DVT

      • consider removing any indwelling catheters associated with clot

      • Do not delay unfractionated heparin for thrombophilia testing

    • Anticoagulation

      • LMWH (ex. Enoxaparin): dose 1mg/kg BID

      • UFH: 用於腎功能差且acute DVT病人, dose 80 units/kg bolus, then 18 units/kg/h infusion

      • Rivaroxaban: 15mg BID for 21 days then 20mg QD with food

      • Apixaban: 10mg BID for 7 days then 5mg BID

    • 特殊情況：Iliofemoral DVT that causes phlegmasia cerulea dolens

      • catheter-directed thrombolysis

      • if not available in 6 hours, consider tPA 50-100mg for 4 hours

    • 需要住院的病人

      • social determinants

      • comorbid conditions

      • the presence of iliofemoral DVT with signs of phlegmasia


PE and DVT 治療藥物總表


Therapy

Dosage

Comments

Unfractionated heparin

80 units/kg bolus, then 18 units/kg/h infusion

Recommended if outpatient therapy not appropriate or in cases of severe renal failure

LMWH

Outpatient treatment with LMWH preferred

Dalteparin

100 IU/kg SC every 12 h or 200 IU/kg SC every day


Enoxaparin

1 milligram/kg SC every 12 h or 1.5 milligrams/kg SC every day


Tinzaparin

175 IU/kg SC every day


Factor Xa inhibitors

Fondaparinux

<50 kg, 5 milligrams SC every day; 50–100 kg, 7.5 milligrams SC every day; >100 kg, 10 milligrams SC every day

Do not use in renal failure

Target-specific anticoagulants

Rivaroxaban (Xarelto®)

15 milligrams BID for 21 d, then 20 milligrams every day with food

No heparin requirement; good choice for outpatient treatment

Apixaban (Eliquis®)

10 milligrams BID for 7 days, then 5 mg BID

No heparin requirement; good choice for outpatient treatment

Dabigatran (Pradaxa®)

150 milligrams BID

Requires run-in of heparin for 5–10 d; renal excretion

Thrombolytic therapy

Tissue plasminogen activator or alteplase (Activase®), 10-milligram IV bolus followed by 90 milligrams infused over 2 h

For PE with hemodynamic compromise; after infusion, begin unfractionated heparin or LMWH





  • 歷屆考題回顧

















Edited by Yu-Hsuan, Huang

Reference: Tintinalli's Emergency Medicine Chapter 56, Venous Thromboembolism Including Pulmonary Embolism

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