วันพฤหัสบดีที่ 14 พฤษภาคม พ.ศ. 2569

Catheter-Directed Thrombolysis (CDT) in Lower Extremity DVT

Catheter-Directed Thrombolysis (CDT) in Lower Extremity DVT

Overview

Thrombolytic agents:

  • activate plasminogen → plasmin
  • accelerate clot lysis

ปัจจุบันนิยม:

  • catheter-directed thrombolysis (CDT)
    มากกว่า systemic thrombolysis

Goals of thrombolysis

ใน selected severe DVT:

  • rapidly dissolve thrombus
  • relieve severe symptoms
  • restore venous outflow
  • prevent venous gangrene
  • reduce severity of post-thrombotic syndrome (PTS)

Important principle

Most DVT patients ไม่ต้อง thrombolysis

Standard treatment ส่วนใหญ่:

  • anticoagulation alone

เพราะ thrombolysis:

  • bleeding risk สูงขึ้น
  • ไม่ลด mortality/recurrent VTE ชัดเจน

Patients suitable for thrombolysis

Main indications

Extensive proximal/iliofemoral DVT ร่วมกับ:

  • severe symptomatic swelling
    หรือ
  • limb-threatening ischemia

โดยเฉพาะ:

  • phlegmasia cerulea dolens (PCD)

Additional practical criteria

มักเลือกผู้ป่วยที่:

  • symptoms <14 days
  • good functional status
  • life expectancy >1 year
  • low bleeding risk

Possible candidates

  • extensive iliofemoral DVT
  • severe refractory symptoms despite anticoagulation
  • threatened limb
  • venous gangrene risk

NOT routinely indicated

Uncomplicated DVT

เพราะ:

  • bleeding ↑
  • no clear mortality benefit
  • no clear recurrent VTE reduction

Contraindications

ใช้หลักคล้าย PE thrombolysis

Important contraindications:

  • active bleeding
  • recent intracranial hemorrhage
  • recent major surgery
  • severe uncontrolled HT
  • intracranial neoplasm
  • severe thrombocytopenia

Initial management before CDT

Start anticoagulation immediately

Preferred:

  • IV UFH
    หรือ
  • LMWH

พร้อม:

  • bed rest
  • limb elevation

Preferred thrombolysis method

Catheter-directed thrombolysis (CDT)

Preferred over systemic thrombolysis เพราะ:

  • lower total drug dose
  • less bleeding
  • more targeted clot lysis

Systemic thrombolysis

ปัจจุบัน:

  • rarely used

ใช้เฉพาะ:

  • CDT unavailable
  • cannot transfer
  • concurrent massive PE

CDT technique

Catheter ใส่เข้า thrombus โดยตรงผ่าน:

  • popliteal vein
  • common femoral vein
  • internal jugular vein
  • posterior tibial vein

Imaging during procedure

ใช้:

  • venography
  • ± intravascular ultrasound (IVUS)

เพื่อ:

  • define clot burden
  • detect May-Thurner syndrome
  • identify stenosis

Thrombolytic agents

Most commonly:

tPA (alteplase)

Typical infusion rate:

tPA approx 0.5-1 mg/hr

Mechanical thrombectomy (MT)

สามารถใช้ร่วมกับ CDT:

  • aspiration
  • rotational
  • rheolytic
  • ultrasound-assisted devices

Advantages:

  • faster reperfusion
  • less thrombolytic exposure

Anticoagulation during CDT

Usually continue UFH

แต่ใช้ lower intensity

Example:

  • reduced UFH infusion
  • omit bolus

หลัง CDT:

  • return to therapeutic anticoagulation

Monitoring during CDT

ต้อง monitor:

  • symptom improvement
  • swelling
  • pulses/Doppler signals
  • neurologic status
  • signs of PE
  • bleeding

Laboratory monitoring

ทุก ~6 hr:

  • fibrinogen
  • anti-Xa/aPTT

Daily:

  • CBC

Important fibrinogen threshold

บาง center หยุด infusion หาก:

Fibrinogen <100 mg/dL

Repeat venography

มักทำ:

  • 12–24 hr หลังเริ่ม infusion

ประเมิน:

  • continue vs stop infusion
  • thrombectomy need
  • underlying stenosis

Typical duration

ส่วนใหญ่:

  • 24–48 hr

rarely >48 hr

Follow-up anticoagulation

หลัง CDT:

  • therapeutic anticoagulation ต่อทันที

มักเริ่มภายใน:
12-24 hr after CDT completion

นิยม:

  • apixaban
  • rivaroxaban

Complications

Bleeding

Most common complication

Major bleeding

Major bleeding <2%

Intracranial hemorrhage

ICH <1%

Other complications

  • PE from clot fragmentation
  • catheter hematoma
  • infection
  • vessel perforation
  • reperfusion swelling
  • compartment syndrome

Evidence summary

Benefits

Compared with anticoagulation alone:

  • faster clot lysis
  • improved venous patency
  • may reduce severity of PTS
  • symptom relief better

Limitations

No clear reduction in:

  • mortality
  • recurrent VTE

ATTRACT trial pearls

Pharmacomechanical CDT:

  • no overall PTS reduction
  • no mortality benefit
  • bleeding increased

แต่ severe iliofemoral DVT:

  • moderate/severe PTS อาจลดลง

Mechanical thrombectomy alone

Useful in:

  • high bleeding risk
  • failed thrombolysis
  • thrombolysis contraindication

Surgical thrombectomy

ใช้เมื่อ:

  • endovascular unavailable
  • failed CDT/MT
  • severe threatened limb

IVC filter

พิจารณาใน:

  • contraindication to anticoagulation
  • high embolic risk
  • thrombectomy/high clot burden

Patients unsuitable for thrombolysis

  • uncomplicated DVT
  • high bleeding risk
  • poor functional status
  • limited life expectancy
  • chronic clot >14 days

Clinical pearls

  • CDT preferred over systemic thrombolysis
  • thrombolysis reserved for severe/extensive iliofemoral DVT
  • phlegmasia cerulea dolens = emergency indication
  • UFH usually continued during CDT
  • monitor fibrinogen and bleeding closely
  • mechanical thrombectomy increasingly favored
  • thrombolysis improves clot lysis but not mortality
  • bleeding risk remains major limitation
  • uncomplicated DVT → anticoagulation alone remains standard

 

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Venous Thromboembolism (VTE): Causes and Risk Factors

Venous Thromboembolism (VTE): Causes and Risk Factors

Overview

VTE ประกอบด้วย:

  • Deep vein thrombosis (DVT)
  • Pulmonary embolism (PE)

สาเหตุของ VTE มักเป็น:

  • multifactorial
  • acquired + inherited risk factors ร่วมกัน

พบ risk factor ได้ >80% ของผู้ป่วย

Virchow Triad

Pathophysiology หลักของ thrombosis:

Virchow triad = stasis + endothelial injury + hypercoagulability

1. Venous stasis

เช่น:

  • immobilization
  • hospitalization
  • HF
  • prolonged travel
  • paralysis

2. Endothelial injury

เช่น:

  • surgery
  • trauma
  • central venous catheter
  • vascular injury

3. Hypercoagulability

เช่น:

  • cancer
  • pregnancy
  • APS
  • inherited thrombophilia
  • estrogen therapy

Major acquired risk factors

Previous VTE

Major risk factor for recurrence

Pattern:

  • previous PE → recurrent PE more likely
  • previous DVT → recurrent DVT more likely

Active malignancy

หนึ่งใน strongest acquired risk factors

VTE พบประมาณ:
Cancer-associated VTE approx 15%

High-risk cancers:

  • pancreatic
  • metastatic disease
  • MPNs (myeloproliferative neoplasms)

Additional risks:

  • chemotherapy
  • surgery
  • hospitalization
  • central lines/PICC

Surgery

High-risk surgery:

  • orthopedic
  • vascular
  • pelvic
  • neurosurgery
  • cancer surgery

Trauma

Especially:

  • spinal cord injury
  • major trauma
  • prolonged immobilization

Immobilization / hospitalization

Examples:

  • ICU admission
  • stroke
  • MI
  • HF
  • leg injury

Long travel ("economy class syndrome")

Risk increase:

  • prolonged immobility
  • dehydration
  • venous stasis

Older age

Risk increases markedly after age 65

Incidence rises exponentially with age

Pregnancy

Risk approximately:

Pregnancy VTE risk approx 4 times

เพิ่มมากขึ้นหากมี inherited thrombophilia

Cardiovascular conditions

Heart failure

Particularly:

  • right HF
  • hospitalized HF

Mechanisms:

  • stasis
  • inflammation
  • hypercoagulability

Atherosclerotic disease

MI/stroke เพิ่ม risk VTE โดยเฉพาะช่วงแรก

Obesity

Risk increase:
Obesity-associated VTE risk approx 2-3 times

เพิ่มมากขึ้นหากร่วมกับ:

  • factor V Leiden
  • estrogen
  • prolonged travel

Smoking

Relative risk:
~1.3–3.3×

Dose-dependent relationship

Hormonal therapy

Estrogen-containing contraceptives

Riskสูงสุด:

  • first 6–12 months

Hormone replacement therapy

Oral estrogen:

  • increases VTE risk

Transdermal estrogen:

  • lower risk

Tamoxifen

เพิ่ม VTE risk โดยเฉพาะเมื่อ:

  • cancer
  • surgery
  • fracture

Antiphospholipid syndrome (APS)

ทำให้:

  • venous thrombosis
  • arterial thrombosis
  • recurrent pregnancy loss

Kidney disease

High-risk conditions:

  • nephrotic syndrome
  • ESRD
  • CKD
  • kidney transplant

Hematologic disorders

HIT

Major cause of venous + arterial thrombosis

Myeloproliferative neoplasms (MPNs)

Examples:

  • polycythemia vera
  • essential thrombocythemia

Associated thrombosis:

  • DVT
  • PE
  • Budd-Chiari syndrome
  • arterial thrombosis

Hyperviscosity syndromes

Examples:

  • Waldenström macroglobulinemia
  • multiple myeloma

PNH

Thrombosis often:

  • intraabdominal veins
  • cerebral veins

Other associated conditions

  • inflammatory bowel disease
  • chronic liver disease
  • COVID-19
  • rheumatoid arthritis
  • tuberculosis
  • sepsis
  • obstructive sleep apnea
  • psoriasis
  • asthma
  • IV drug use
  • VEXAS syndrome

Inherited thrombophilia

Most common

Factor V Leiden

Risk:
Factor V Leiden risk approx 4-5 times

Prothrombin G20210A mutation

Risk:
Prothrombin mutation risk approx 3-4 times

High-risk inherited defects

Antithrombin deficiency

Risk:
Antithrombin deficiency risk approx 16 times

Protein C deficiency

~7×

Protein S deficiency

~5×

Important principle

Inherited thrombophilia มักต้องมี acquired trigger ร่วมด้วย

Anatomic risk factors

May-Thurner syndrome

Compression:

  • left common iliac vein
    โดย
  • right common iliac artery

สัมพันธ์กับ:

  • left iliofemoral DVT

Inferior vena cava abnormalities

Examples:

  • IVC agenesis
  • hypoplasia
  • malformations

Clues:

  • young patient
  • bilateral/recurrent iliofemoral DVT

Varicose veins

สัมพันธ์กับ:

  • increased DVT risk
  • increased PE risk

Upper extremity thrombosis

Major risk:

  • central venous catheter/PICC

Spontaneous cases:

  • thoracic outlet compression
    (Paget-Schroetter syndrome)

Laboratory-associated thrombotic factors

Associated with increased VTE risk:

  • elevated factor VIII
  • elevated factor IX/XI
  • elevated fibrinogen
  • elevated VWF
  • reduced fibrinolysis

Non-O blood group

Blood group:

  • A/B/AB

Higher VTE risk than O blood group

Clinical pearls

  • VTE มักเกิดจากหลาย risk factors ร่วมกัน
  • Virchow triad เป็น core mechanism
  • malignancy เป็น acquired risk factor สำคัญ
  • previous VTE = strongest predictor of recurrence
  • immobilization + illness dramatically increase risk
  • obesity + smoking + estrogen synergistically increase risk
  • inherited thrombophilia alone มักไม่พอ ต้องมี trigger ร่วม
  • left iliofemoral DVT → think May-Thurner syndrome
  • young recurrent bilateral DVT → think IVC anomaly/thrombophilia
  • APS และ cancer มี recurrence risk สูง

 

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May-Thurner Syndrome (MTS)

May-Thurner Syndrome (MTS)

Overview

May-Thurner syndrome (MTS) =
iliac vein compression syndrome

เกิดจาก:

  • extrinsic venous compression
    ใน iliocaval territory

Classic lesion:

  • left common iliac vein
    ถูกกดโดย
  • right common iliac artery
    against lumbar vertebra

Clinical importance

สัมพันธ์กับ:

  • left iliofemoral DVT
  • chronic venous hypertension
  • post-thrombotic syndrome (PTS)

ควรคิดถึงเสมอเมื่อ:

  • young female
  • unilateral left leg swelling
  • extensive proximal DVT

Pathophysiology

Chronic pulsatile arterial compression →

  • endothelial injury
  • venous spur formation
  • venous stenosis
  • venous stasis
  • thrombosis

Classic anatomy

Left common iliac vein compression by right common iliac artery

Epidemiology

  • many patients asymptomatic
  • significant iliac stenosis (>50%) พบได้ ~25% ในบาง imaging studies
  • symptomatic MTS ประมาณ 1–5% ของ venous disorders

Risk factors

  • female sex
  • postpartum/multiparity
  • oral contraceptives
  • dehydration
  • hypercoagulable state
  • scoliosis
  • radiation exposure

Clinical presentations

1. Acute DVT presentation

Typical:

  • acute unilateral left leg swelling
  • pain
  • extensive iliofemoral DVT

2. Chronic venous hypertension

  • chronic edema
  • heaviness
  • venous claudication
  • skin discoloration
  • venous ulcer

3. Pelvic congestion syndrome

โดยเฉพาะใน female patients

Venous claudication

Definition:

  • thigh/leg pain and tightness with exercise
  • improves with rest/elevation

พบได้ถึง:
Venous claudication prevalence 85%

Important clinical clues

ควรสงสัย MTS หากมี:

  • left-sided proximal DVT
  • whole-leg swelling
  • recurrent ipsilateral DVT
  • persistent symptoms despite anticoagulation
  • post-thrombotic syndrome
  • visible abdominal/groin collaterals

Diagnosis

Initial approach

ประเมิน DVT ก่อน:

  • Wells score
  • D-dimer
  • duplex ultrasound

Duplex ultrasound

Useful for:

  • proximal DVT
  • iliocaval obstruction clues

Suggestive findings:

  • absent respiratory variation
  • narrowed iliac vein
  • sluggish flow
  • poor augmentation

Peak vein velocity (PVV)

Significant stenosis if:

PVV gradient >2.0

CT/MR venography

Sensitivity/specificity:

95%

Useful for:

  • anatomy
  • collaterals
  • alternative causes of compression

Gold standard

Intravascular ultrasound (IVUS)

Sensitivity/specificity:

98%

Advantages:

  • defines spur morphology
  • accurate stenosis severity
  • guides stenting
  • evaluates stent expansion

Hemodynamic confirmation

Iliac vein pressure gradient significant if:

Pressure gradient > 2 mmHg

Differential diagnosis

  • uncomplicated DVT
  • chronic venous insufficiency
  • lymphedema
  • pelvic mass
  • retroperitoneal fibrosis
  • uterine enlargement
  • aneurysm
  • osteophyte compression

Treatment overview

Depends on:

  • presence of DVT
  • severity of symptoms

Nonthrombotic MTS

Mild symptoms (CEAP 1–3)

Conservative:

  • compression stockings

Moderate/severe symptoms (CEAP 4–6)

Preferred:

  • angioplasty + stenting

Important:

  • angioplasty alone insufficient
  • recurrence high without stent

Thrombotic MTS

Initial treatment

  • full anticoagulation

then:

  • catheter-directed thrombolysis (CDT)
    หรือ
  • pharmacomechanical thrombectomy

Key principle

หลัง thrombus removal:
ต้องค้นหา underlying stenosis ด้วย IVUS

ถ้ามี stenosis:
→ angioplasty + stenting

Outcomes with treatment

Successful treatment:
PTS <10%

Without treatment:
PTS ประมาณ

Untreated PTS risk approx 80-90%

Contraindication to thrombolysis

ใช้:

  • mechanical thrombectomy

Options:

  • rheolytic thrombectomy
  • rotational thrombectomy
  • suction thrombectomy

Surgery

Reserved for:

  • failed endovascular therapy
  • unsuitable anatomy
  • severe chronic occlusion

Examples:

  • Palma-Dale bypass
  • venous reconstruction

Post-procedure management

Compression stockings

Recommended:

  • 30–40 mmHg

Anticoagulation

Follow standard VTE guidelines

After stenting

reasonable to add:

  • antiplatelet therapy
    หาก bleeding risk ต่ำ

Complications of intervention

  • stent migration
  • restenosis
  • iliac vein rupture
  • contralateral iliac vein thrombosis
  • arterial erosion

Evidence summary

CDT + stenting

Benefits:

  • improved venous patency
  • reduced PTS
  • better symptom relief
  • improved quality of life

ATTRACT trial pearl

Routine CDT for all proximal DVT:

  • not beneficial overall

แต่ subgroup:

  • iliofemoral DVT
    อาจ benefit มากกว่า

Patency rates after stenting

Primary patency:
~61–92% at 1 year

Secondary patency:
up to 98%

Clinical pearls

  • think MTS in young female with left iliofemoral DVT
  • whole-leg swelling + proximal DVT strongly suggestive
  • IVUS = current diagnostic standard
  • angioplasty alone inadequate → stenting usually required
  • anticoagulation alone often suboptimal in thrombotic MTS
  • untreated MTS → very high PTS risk
  • successful stenting markedly improves symptoms/patency
  • persistent unilateral symptoms after DVT treatment → reassess for MTS
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Phlegmasia Cerulea Dolens / Phlegmasia Alba Dolens

Phlegmasia Cerulea Dolens / Phlegmasia Alba Dolens

Overview

Phlegmasia เป็น severe form ของ DVT
เป็นภาวะ:

  • limb-threatening
  • life-threatening

เกิดจาก massive venous thrombosis โดยเฉพาะ:

  • iliocaval thrombosis

พบที่ lower extremity มากกว่า upper extremity

Pathophysiology

Massive venous obstruction →

  • severe venous hypertension
  • fluid sequestration
  • massive edema
  • impaired microcirculation
  • tissue ischemia

progression:
DVT → phlegmasia alba dolens → phlegmasia cerulea dolens → venous gangrene

Types

1. Phlegmasia alba dolens

Collateral veins ยังพอ drainage ได้

Clinical triad:

  • pain
  • swelling
  • pale/blanched skin

ผิวยัง blanch ได้

2. Phlegmasia cerulea dolens

Collateral thrombosis ร่วมด้วย →
severe venous congestion

Clinical triad:

  • severe pain
  • massive swelling
  • blue/cyanotic nonblanching skin

3. Venous gangrene

microcirculatory collapse →
capillary thrombosis →
arterial compromise

นำไปสู่:

  • tissue necrosis
  • compartment syndrome
  • limb loss

Risk factors

Most common:

  • malignancy (~≥1/3)

Other associated conditions

  • HIT
  • antiphospholipid syndrome
  • trauma
  • surgery
  • pregnancy
  • COVID-19
  • femoral venous catheter
  • IVC filter
  • May-Thurner syndrome
  • congenital venous anomalies
  • hypercoagulable states

Epidemiology pearls

  • lower extremity > upper extremity
  • female predominance (~5:1)
  • left leg more common
    (สัมพันธ์กับ May-Thurner syndrome)

Clinical presentation

Symptoms

Classic:

  • sudden unilateral pain
  • severe swelling

Pain:

  • severe
  • constant
  • out of proportion

Progression

เริ่ม proximal →
ลามทั้ง extremity

อาจ progress:

  • hours → days

Severe manifestations

  • cyanosis
  • sensory loss
  • weakness
  • compartment syndrome
  • hypovolemic shock

fluid sequestration อาจมากถึง:
Fluid sequestration approx 10 L

Physical examination

Early (alba)

  • swollen
  • tender
  • pale/blanching skin

Late (cerulea)

  • tense edema
  • cyanotic skin
  • nonblanching
  • absent venous flow

Important vascular findings

ใช้ handheld Doppler ประเมิน:

  • arterial signals
  • venous signals

Progression pattern

Venous gangrene:

  • venous signals disappear first
  • then arterial signals lost

ต่างจาก arterial occlusion:

  • venous signals preserved initially

Shock findings

  • tachycardia
  • hypotension
  • oliguria

Diagnosis

Clinical + duplex ultrasound

Supportive findings:

  • massive swelling
  • severe pain
  • cyanosis
  • venous gangrene

Duplex ultrasound findings

  • extensive DVT
  • noncompressible veins
  • absent/reduced venous flow

ควรประเมิน:

  • superficial veins
  • deep veins
  • arterial flow

Iliocaval obstruction clues

Common femoral venous waveform:

  • absent respiratory variation

suggests proximal obstruction

Cross-sectional imaging

CT/MR:

  • usually not necessary before treatment

หาก clinical + duplex ชัดเจน

Differential diagnosis

Limb swelling

  • cellulitis
  • lymphedema
  • compartment syndrome
  • uncomplicated DVT

Acute limb ischemia

Arterial occlusion:

  • pale limb
  • minimal swelling
  • delayed venous filling

Phlegmasia:

  • swollen cyanotic limb

Treatment principles

Goals:

  • stop thrombus propagation
  • restore venous outflow
  • reduce venous hypertension
  • preserve limb
  • prevent shock

Supportive management

  • absolute bed rest
  • aggressive limb elevation (>30°)
  • analgesia
  • fluid resuscitation
  • monitor rhabdomyolysis
  • monitor compartment syndrome

Anticoagulation

Start immediately

แม้ยังรอ ultrasound หาก suspicion สูง

Preferred anticoagulant

IV UFH

เพราะ:

  • rapid titration
  • short half-life
  • reversible
  • suitable for intervention

Duration

หลัง stabilize:
อย่างน้อย

Minimum anticoagulation duration = 3 months

Severity classification

Early phlegmasia

(Rutherford I; viable limb)

ยังมี arterial Doppler signal

Late phlegmasia

(Rutherford II; threatened limb)

ไม่มี arterial Doppler signal

Early phlegmasia treatment

เริ่ม:

  • UFH
  • limb elevation

observe response ~12 hr

หากไม่ดีขึ้น:
→ venous intervention

Late phlegmasia treatment

ต้อง urgent intervention

เพราะ delay เพิ่ม:

  • amputation
  • mortality

Endovascular options

1. Mechanical thrombectomy (MT)

Preferred first approach

Advantages:

  • rapid clot removal
  • faster reperfusion
  • shorter ICU/hospital stay

2. Catheter-directed thrombolysis

ใช้:

  • tPA
  • urokinase
  • streptokinase

often adjunct to MT

3. Surgical thrombectomy

ใช้เมื่อ:

  • MT unavailable
  • failed MT
  • thrombolysis contraindicated

After thrombectomy

หากมี venous stenosis:

  • angioplasty/stenting

ถ้า stent:

  • add antiplatelet therapy

Fasciotomy

พิจารณาเมื่อ:

  • compartment syndrome
  • reperfusion injury
  • venous gangrene

Nonviable limb

→ amputation required

Complications

  • pulmonary embolism
  • shock
  • compartment syndrome
  • rhabdomyolysis
  • venous gangrene
  • post-thrombotic syndrome
  • chronic venous insufficiency
  • limb loss

Mortality & amputation

Mortality: 20%-66%

Amputation among survivors

Amputation rate 12%-50%

Major amputation:

  • up to 25%

Clinical pearls

  • Phlegmasia = severe iliocaval DVT with limb ischemia
  • cyanotic swollen painful limb = classic clue
  • absent arterial Doppler = threatened limb
  • start IV UFH immediately
  • mechanical thrombectomy preferred when available
  • early intervention improves limb salvage
  • compartment syndrome/reperfusion injury common
  • mortality และ amputation สูงมากหาก delayed treatment
  • malignancy เป็น risk factor สำคัญที่สุด
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