Made Putra Sedana

Division of Hematology - Medical Oncology

Department of Internal Medicine
Faculty of Medicine Airlangga University-
Dr.Soetomo Hospitall Surabaya
Venous Thromboembolism (VTE) =
1. Deep vein thrombosis (DVT)
2. Pulmonary embolism (PE)

Risk factors

Small DVT Big DVT PE Death

DVT is the formation of a blood clot in one of

the deep veins of the body, usually in the leg
 Epidemiology and Etiology
Annual incidence of venous thromboembolism
(VTE) is 1/1000
DVT accounts for one half of VTE
Carefully evaluated, up to 80% of patients with
VTE have one or more risk factors
Majority of lower extremity DVT arise from calf
veins but ~20% begin in proximal veins
About 20% of calf-limited DVTs will propagate
proximally
 VTE Risk Factors
Malignancy Presence of venous
Surgery catheter
Trauma Congestive failure
Pregnancy Antiphospholipid
Oral contraceptives or antibody syndrome
hormonal therapy Hyperviscosity
Immobilization Nephrotic syndrome
Inherited thrombophillia Inflammatory bowel
disease
 PATHOPHYSIOLOGY
Vessel trauma stimulates the clotting cascade.
Platelets aggregate at the site particularly when venous stasis
present
Platelets and fibrin form the initial clot
RBC are trapped in the fibrin meshwork
The thrombus propagates in the direction of the blood flow.
Inflammation is triggered, causing tenderness, swelling, and
erythema.
Pieces of thrombus may break loose and travel through
circulation- emboli.
Fibroblasts eventually invade the thrombus, scarring vein wall
and destroying valves. Patency may be restored valve damage is
permanent, affecting directional flow.
Deep vein thrombosis (DVT)
Thrombus in one or more deep veins
- legs >>> arms
- portal, mesenteric, splenic, cerebral, renal
Proximal DVT - Popliteal iliac veins
- Lead to >90% of PE

Distal or calf DVT - Distal to popliteal

- Posterior tibial, peroneal veins
- Most calf DVT asymptomatic
- Rarely lead to PE

Superficial thrombosis - Not DVT; dont lead to PE

 Clinical Presentation
Calf pain or tenderness, or both
Swelling with pitting oedema
Increased skin temperature and fever
Superficial venous dilatation
Cyanosis can occur with severe obstruction
 Clinical Presentation
Less frequent manifestations of venous thrombosis
include : Phlegmasia alba dolens
Phlegmasia cerulea dolens
Venous gangrene.
These are clinical spectrum of the same disorder.

Wells developed and tested a clinical prediction

model for DVT
 Clinical Examination
Palpate distal pulses and evaluate capillary refill to assess
limb perfusion.
Move and palpate all joints to detect acute arthritis or
other joint pathology.
Neurologic evaluation may detect nerve root irritation;
sensory, motor, and reflex deficits should be noted
Homans sign: pain in the posterior calf or knee with
forced dorsiflexion of the foot.
WELLS CLINICAL PREDICTION GUIDE

It pre-testprobabilityscore

Helps in early risk stratification and appropriate

use of laboratory tests and imaging modalities.

Wells criteria is an additional tool to diagnosis

rather than being a stand-alone test.
Interpretation

High probability: 3
(Prevalence of DVT 53%)

Moderate probability: 1-2

(Prevalence of DVT - 17%)

Low probability: 0
(Prevalence of DVT - 5%)
 D-dimer
Formed by effect of plasmin on fibrin
plasmin
Increased in VTE Fibrin FDPs (incl D-dimer)

Also increased:
after surgery liver disease
trauma uncomplicated pregnancy
cancer healthy elderly
acute infection etc
inflammatory disease
Generally useless; may be misleading
NEVER done on inpatients or patients at high
risk of having a positive result
Virtually no role in surgical patients
Investigation of Suspected DVT
Doppler ultrasonography (Duplex
scan) = very accurate for proximal DVT
Less accurate for pelvic, calf DVT
Algorithm of Patient Suspected DVT
 MANAGEMENT OF DVT
*Aim of Management:
Initially : to prevent propagation of thrombus
Chronic anticoagulation to allow fibrinolysis and
recanalization.

*Heparin immediately and for at least 5 days

*VKA started on the 1st day
* Failure to achieve optimum treatment early on
leads to recurrence rates of 20 %
 MANAGEMENT OF DVT

1. Anticoagulation
2. Thrombolytic therapy for DVT
3. Surgery for DVT
4. Filters for DVT
5. Compression stockings
 1. ANTICOAGULANT
The optimal regimen is anticoagulation with
heparin or an LMWH followed by full
anticoagulation with oral warfarin for 3-6 months

Warfarin therapy is overlapped with heparin for 4-

5 days until the INR is therapeutically elevated to
between 2-3.
 Advantages LMWH vs UFH

Superior bioavailability
Superior or equivalent safety and efficacy
Subcutaneous once- or twice-daily dosing
No laboratory monitoring*
Less phlebotomy
(no monitoring/no intravenous line)
Less thrombocytopenia
Earlier/facilitated
 UFH
Initial bolus of 80 U/kg
Maintenance infusion of 18 U/kg.
The aPTT is checked 6 hours after the bolus
and adjusted accordingly. .
The aPTT is repeated every 6 hours until 2
successive aPTTs are therapeutic. Thereafter,
the aPTT is monitored every 24 hours as well
as the hematocrit and platelet count.
Comparison of Three LMWH
 Warfarin

Interferes with hepatic synthesis of vitamin K-

dependent coagulation factors
Dose must be individualized and adjusted to
maintain INR between 2-3
2-10 mg/d PO
Caution in active tuberculosis or diabetes;
patients with protein C or S deficiency are at
risk of developing skin necrosis
Advantages of New Anticoagulant Oral
Limitations of New Anticoagulant Oral
 Comparison of new oral anticoagulant
Dabigatran Rivaroxaban Apixaban
Target Factor IIa Factor Xa Factor Xa

FDA Indications Nonvalvular AF Nonvalvular AF Nonvalvular AF

Ortho VTE Proph
Acute Treatment VTE
Prodrug Yes No No

Dosing Twice daily Daily, with food Twice daily

Onset 1-2 hrs 2-4 hrs 3-4 hrs

Half-life (h) 1417 711 814

Renal Adjustment 15-29ml/min Avoid < 30 ml/min Avoid < 15 ml/min

Avoid < 15 ml/min
Drug Interactions P-gp CYP3A4/P-gp CYP3A4/P-gp
LMWH in Renal Impairment
LMWH used in Renal Impairment
Algorithm of Anticoagulant for DVT Patient
 2. Thrombolytic therapy for DVT
Advantages include
prompt resolution of symptoms,
prevention of pulmonary embolism,
restoration of normal venous circulation,
preservation of venous valvular function,
prevention of postphlebitic syndrome.

Doesnt prevent
clot propagation,
rethrombosis, or
subsequent embolization.
 3. Surgery for DVT
Indications
when anticoagulant therapy is ineffective
unsafe,
contraindicated.
The major surgical procedures for DVT are clot
removal and partial interruption of the inferior
vena cava to prevent pulmonary embolism.
 4. Filters for DVT
Indications for insertion of an inferior vena cava filter
PE with contraindication to anticoagulation
Recurrent PE despite adequate anticoagulation

Controversial indications:
DVT with contraindication to anticoagulation
DVT in patients with pre-existing pulmonary
hypertension
Free floating thrombus in proximal vein
Failure of existing filter device
Post pulmonary embolectomy
 Kasus
Workshop PIN PAPDI 2017

Made Putra Sedana

Divisi Hematologi Onkologi Medik

Departemen Ilmu Penyakit Dalam FK UNAIR- RSUD DR.Soetomo Surabaya
 Case 1 : Wanita, usia 57 Tahun
Keluhan Utama
Bengkak kaki kanan, nyeri, dan kemerahan
Riwayat Penyakit Sekarang

- Bengkak kaki kanan, nyeri, dan kemerahan

secara mendadak 3 hari SMRS
- Badan terasa lemah, pusing, dan mual
- Panas badan naik-turun (sumer2) 2 bulan
SMRS
- Riw Trauma (-) pada kaki kanan
Riwayat Penyakit Dahulu
- Riw MRS 2 minggu yg lalu karena badan lemah dan di
transfusi 4 kantong PRC
 PEMERIKSAAN FISIK
GCS 456
Keadaan Umum:
Tidak anemis Lemah
PKGB colli (-)

Vital Signs:
Sesak (-)
BP 110/60 mmHg
Suara nafas P 96x/min
normal RR 20x/min
Tax 37.20C

hepato/splenomegali (-)

- Kaki kanan : pitting edema,

kemerahan, nyeri spontan dan saat
ditekan, hangat, a.femoralis,
a.poplitea, a tibialis post, a dorsalis
pedis pulsasi masih kuat
- Kaki kiri : normal
a. Assesmen Awal??

a. Pemeriksaan Penunjang ??
 HASIL LABORATORIUM
Hb 12.1 g/dl Plt 188000/uL SGOT 31 U/L
Hct 33.2 % BUN 18 mg/dl SGPT 26 U/L
MCV 85.9 fl SK 1 mg/dl Albumin 3.2 g/dl
MCH 29.6 pg Na 138 mmol/l RBG 143 mg/dl
MCHC 34.4 g/dl K 3.8 mmol/l
WBC 6400/uL Cl 105 mmol/l
D-dimer 10.7 mg/L

Foto Thorax AP :
Normal
 Thrombus
Trombus

USG Doppler: FCVS Thrombus

thrombus ditemukan
Thrombus
di sistem V. Poplitea,
V. Saphena Magna

PPVA
Thrombus
c. Diagnosis??

d. Pilihan Terapi ??

e. Monitoring ??
 Case 2 : Laki-laki, usia 72 Tahun
Keluhan Utama
Bengkak kaki kanan, nyeri, dan kemerahan
Riwayat Penyakit Sekarang

- Bengkak kaki kanan, nyeri, dan kemerahan secara

mendadak 3 hari SMRS
- Pasien cenderung berbaring saja dalam 1 bulan ini karena
merasa lemas
- Riw Trauma (-) pada kaki kanan

Riwayat Penyakit Dahulu

- Riw DM (+) 10 th
a. Assesmen Awal??

a. Pemeriksaan Penunjang ??
 HASIL LABORATORIUM
Hb 12.1 g/dl Plt 188000/uL SGOT 31 U/L
Hct 33.2 % BUN 60 mg/dl SGPT 26 U/L
MCV 85.9 fl SK 3.25 mg/dl Albumin 3.2 g/dl
MCH 29.6 pg Na 138 mmol/l RBG 143 mg/dl
MCHC 34.4 g/dl K 3.8 mmol/l PPT 10, 6 ; C 11,9
WBC 6400/uL Cl 105 mmol/l APTT 27,6; C 24,9
D-dimer 12.7 mg/L

Foto Thorax AP :
Normal
 Thrombus
Trombus

USG Doppler:
thrombus ditemukan
di sistem Vena FCVS Thrombus
Femoralis communis,
Thrombus
profunda, superficial,
Vena poplitea, Vena
Tibialis
anterior/posterior

PPVA
Thrombus
c. Diagnosis??

d. Pilihan Terapi ??

e. Monitoring ??