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PREVENTION OF VENOUS
THROMBOEMBOLISM IN
MEDICALLY ILL PATIENTS
Pembimbing: dr. Kartika Widayati, SpPD-KHOM
Presentan: dr. Levina Prima Rosalia
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Venous
Thromboembolism
(VTE)
PulmonaryEmbolism
(PE)
Deep VeinThrombosis
(DVT)
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Strong risk factor
(odds ratio >10)
Fraktur
(panggul/kaki)
Penggantian sendi
panggul/lutut
Operasi mayor
Trauma mayor
Cedera spinal cord
Moderate risk factor
(odds ratio 2-10)
Arthroscopic knee surgery
Kateter vena sentral
Kemoterapi
CHF
Gagal nafas
Terapi pengganti hormon
Keganasan
Terapi kontraseptif oral
Stroke paralitik
Kehamilan/post-partum
Riwayat VTE
Trombofilia
Weak risk factor
(odds ratio
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VTE pada Pasien Medically ill
Pasien yang dirawat di RSresiko VTE lebih tinggi 100X
Tanpa tromboprofilaksis, insidensi DVT pada pasien RS :
16-55% dan pasien bedah ortopedi mayor: 50-60%. PE5-10% kematian di RS150-200 ribu kematian
per tahun di AS
Sebagian besar (78%) pasien memiliki 1 faktor resiko
VTEmenetap sampai beberapa minggu setelah pulang
Profilaksis VTE keselamatan pasien
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VTE pada Pasien Critically ill (ICU)
Perubahan koagulasi darah, inflamasi, & respons imun
Imobilisasi, ventilator, sedasigejalanya terkaburkan
silent VTE
Insidensi VTE tanpa profilaksis : 15-60%:
DVT: 28-32%, bisa sampai 60% pada pasien trauma &
70% pada stroke iskemik akut
PE fatal: pada hemiplegi: 1-2% 40-50% pasien DVT simtomatikdidapatkan PE
asimtomatik saat skrining
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Pasien rawat inap dengan sakit akut & peningkatan resiko
trombosis tromboprofilaksis antikoagulan: LMWH, UFH
dosis kecil 2-3x/hari, atau fondaparinux (Grade 1B)
Pasien rawat inap dengan sakit akut & resiko trombosis
rendah profilaksis tidak direkomendasikan (Grade 1B)
Pasien rawat inap dengan sakit akut & perdarahan/resiko
perdarahan tinggi tromboprofilaksis antikoagulan tidak
direkomendasikan (Grade 1B)
ACCP Guideline (2012)
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Pasien rawat inap dengan sakit akut & resiko trombosis
& perdarahan/resiko tinggi tromboprofilaksis mekanik:
graduated compression stocking(Grade 2C)/
intermittent pneumatic compression (IPC) (Grade 2C).
Bila resiko perdarahan & resiko VTE menetap gantidengan obat (Grade 2B)
Pasien rawat inap dengan sakit akut yang diberitromboprofilaksis direkomendasikan diberikan sampai
imobilisasi selesai/sampai saat pulang (Grade 2B)
ACCP Guideline (2012)
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Pasien sakit kritis tidak direkomendasikan skrining DVT
rutin dengan USG Dopler (Grade 2C)
Pasien sakit kritis direkomendasikan pemberian LMWH
/UFH low dose dibandingkan tanpa profilaksis (Grade 2C)
Pasien sakit kritis dengan perdarahan/resiko tinggi
tromboprofilaksis mekanik dengan GCS/IPC (Grade 2C)
sampai resiko perdarahan ganti obat (Grade 2C)
ACCP Guideline (2012)
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1
Nilai faktor resiko VTE dasar pasien
2
Nilai faktor resiko VTE tambahan pada pasien alasan
hospitalisasi, operasi, trauma, penyakit
3 Nilai resiko perdarahan & kontraindikasi profilaksis VTE
4 Formulasikan keseluruhan penilaian (risk-benefit)
5 Tentukan cara dan jenis profilaksis VTE
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CAPRINI SCORE
Total Score Incident of DVT Risk Level
0-1
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Penilaian Resiko Perdarahan
Perdarahan mayor (butuh transfusi 2 unit produk darah
dalam 24 jam)
Perdarahan kronis yang signifikan >48 jam
Bleeding disorder (misal: hemofilia) Lesi intrakranial/spinal
Perdarahan sistem saraf pusat
Koagulasi darah abnormal
Trombositopenia (AT < 50,000/l)
Disfungsi trombosit berat (uremia, obat-obatan, MDS)
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Penilaian Resiko Perdarahan
Penyakit gastrointestinal ulseratif/ulkus peptikum aktif
Obstructive jaundice/kolestasis
Prosedur operasi mayor dengan resiko perdarahan tinggi
Penggunaan obat-obatan yang mempengaruhi proses
pembekuan darah (antikoagulan, antiplatelet, NSAID,
agen trombolitik)
Anestesi aksial regional atau pungsi lumbal Resiko jatuh yang tinggi
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The IMPROVE VTE Risk Modelprobabilitas VTE akut sejak
admisi sampai dengan pulang
The IMPROVE Bleeding Risk Modelprobabilitasperdarahan mayor sejak admisi sampai 14 hari kemudian
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Profilaksis VTE
Primary prophylaxisobat/metode fisik yang
efektif mencegah VTE
Secondary preventiondeteksi dini dengan
skrining dan terapi VTE subklinismahaljarang
dilakukan
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Profilaksis VTE - Farmakoterapi
Unfractionated heparin (UFH) atau low molecular weight
heparin(LMWH) subkutan
Fondaparinux subkutaninhibitor activated Factor X (Xa) Rivaroxaban oralinhibitor langsung faktor Xa
Dabigatran etexilate oralinhibitor trombin
Warfarin oral
antagonis vitamin K
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Profilaksis VTE - Mekanik
aliran darah vena dengan kompresi eksternal
stasis vena dan stagnasi darah
Intermittent pneumatic compression devices (IPCs)
Kontraindikasi: iskemi kaki karena PAD Segera dimulai secepat mungkin
Resiko perdarahan kombinasi atau ganti dengan
farmakoterapi
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Profilaksis VTE - Mekanik
Graduated compression stockings
(GCS)
Meta-analysistidak efektif
dalam prevensi VTE pada pasien
stroke iskemik
resiko ulkus kulit dan nekrose
Venous foot pumps (VFP)
Data tentang efikasi terbatas
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PenelitianPenelitian HASIL
Tapson et
al, 2005
Tromboprofilaksis masih underused di RS di Amerika
3778 rekam medis pasien dipilih secara random di 38 RS
Pasien AF dengan resiko tinggi stroke: 54.7% dapat warfarin, 20%
tidak mendapat aspirin/warfarin
Operasi ortopeditromboprofilaksis 85%
Bergmann et al,
2010
ENDORSE global surveyn = 37,356 pasien di 32 negara
Resiko VTE bervariasi tergantung diagnosis medis (global rate 41.5%)
Profilaksis VTE diberikan pada hanya 39.5% pasien beresiko
Samama et al,
1999
MEDENOX studyn = 1102
Pasien >40 tahun, hospitalisasi 6 hari, imobilisasi sebelumnya 3 hari
Enoxaparin 20 mg atau 40 mg/hari vs placebo, 1-14 hari
Skrining DVT dengan venografi/USG pada hari 6-14
DVT: Enoxaparin 20 mg 15%, 40 mg 5.5%, placebo 014.9%, RR 463% (p
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Cohen AT et
al,2006
ARTEMIS studyn = 849
Pasien rawat inap >60 thn dengan CHF, PPOK eksaserbasi
akut, infeksi akut, kemungkinan akan immobile 4 hari
Fondaparinux 2,5 mg/hari vs placebo, 6-14 hari
Skrining DVT dengan venografi pada hari 6-15
DVT: Fondaparinux 5,6%, placebo 0, 5%, RR 46,7% (p = 0.029)
Perdarahan mayor masing-masing kelompok: 1 orang
Penelitian HASIL
Leizorovicz et
al, 2004
PREVENT studyn = 3706
Pasien rawat inap >40 thn dengan penyakit akut, membutuhkan
rawat inap 4 hari, imobilisasi sebelumnya 3 hari
Dalteparin 5000 IU/hari vs placebo, 14 hari
Skrining DVT dengan USG pada hari 21
DVT: Dalteparin 2,77%, placebo 4.96%, RR 45% (p = 0.0015) Perdarahan mayor: Dalteparin 0.49%, placebo 0.16%
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Glynn RJ et
al, 2007
39,876 perempuanaspirin dosis rendah 100 mg setiap 48 jam
vs placebo selama 10 tahun
Insidensi VTE pada kelompok aspirin 1.18 vs 1.25 per 1000
orang tahun pada kelompok placebo
Aspirin meningkatkan resiko perdarahan
Penelitian HASIL
Li Wang et al,
2011
11,135 rekam medis pasien
Kejadian VTE lebih rendah pada pasien yang mendapat
profilaksis dibanding yang tidak (1,3% vs 2.99%, HR 0.37)
Penggunaan profilaksis berhubungan dengan biaya healthcare
lebih rendah
PRINCE
study, 2003
Enoxaparin (40 mg/hari) vs UFH (5000 IU 3x/hari) selama 10 hari
pada 665 pasien kardiopulmoner beratsama efektifnya
PRIME study,
2006
RCT double blind Enoxaparin (40 mg/hari) vs UFH (5000 IU
3x/hari) pada 959 pasien resiko tinggi VTE seimbang, namun
efek samping Enoxaparin lebih sedikit
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Alex C Spyropoulos, Charles Mahan. 2009. Venous Thromboembolysm Prophylaxis in The Medical
Patients: Controversies and Perspectives. The American Journal of Medicines. Amir Qaseem, Roger Chou, Linda L. Humphrey,Melissa Starkey, Paul Shekelle.2011.Venous
Thromboembolism Prophylaxis in Hospitalized Patients: A Clinical Practice Guideline From the
American College of Physicians.American College of Physicians
Caprini, J A.2005.Update on Risk Factors for Venous Thromboembolism.Elsevier
Chee M. Chan, Andrew F. Shorr. 2010. Venous Thromboembolic Disease in the Intensive Care Unit.
Seminars in Respiratory and Critical Care Medicine
Deborah J. Cook, James Douketis, Donald Arnolda, Mark A. Crowther. 2009. Bleeding and venous
thromboembolism in the critically ill with emphasis on patients with renal insufficiency. Current Opinion
in Pulmonary Medicine
Frederick A. Anderson, Frederick A. Spencer.2003.Risk Factors for Venous
Thromboembolism.Circulation.American Heart Association
Deborah Cook , Maureen Meade, Gordon Guyatt, Stephen D. Walter, Diane Heels-Ansdell, William
Geerts, Theodore E. W, D. Jamie Cooper, Nicole Zytaruk, Shirley Vallance, Otavio Berwanger, Marcelo
Rocha, Ismael Qushmaqi, Mark Crowther. 2011. Prophylaxis for Thromboembolism in Critical Care
Trial Protocol and Analysis Plan.Journal of Critical Care 26, 223.e1223.e9.
Graham F P Lawrence LK Leung, Jess Mandel, Stephen A L. 2011. Prevention of venous
thromboembolic disease in medical patients.UpToDate.
Referensi
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Li Wang, Nishan Sengupta, Onur Baser.2011.Risk of venous thromboembolism and benefits of
prophylaxis use in hospitalized medically ill US patients up to 180 days post-hospital discharge.
Thrombosis Journal
Jean-Francois Bergmann, Alexander T. Cohen, Victor F. Tapson, Samuel Z. Goldhaber, Ajay K.Kakkar, Bruno Deslandes, Wei Huang, Frederick A. Anderson. 2010. Venous thromboembolism risk
and prophylaxis in hospitalised medically ill patients: The ENDORSE Global Survey. Blood
Coagulation, Fibrinolysis and Cellular Haemostasis
National Health and Medical Research Council. 2009. Clinical practice guideline for the prevention of
venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to
Australian hospitals. Melbourne: National Health and Medical Research Council
Sarah M Adriance, Claire V Murphy.2013.Prophylaxis and treatment of venous thromboembolism in the
critically ill.International Journal of Critical Illness and Injury Science
Susan R. Kahn, Wendy Lim, Andrew S. Dunn, Mary Cushman, Francesco Dentali, Elie A. Akl ,
Deborah J. Cook, Alex A. Balekian , Russell C. Klein, Hoang Le , Sam Schulman, M. Hassan Murad.
2012. Prevention of VTE in Nonsurgical Patients Antithrombotic Therapy and Prevention ofThrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines. Antithrombotic Therapy and Prevention of Thrombosis, 9th Edition: ACCP Guidelines
Scott M Stevens, James D Douketis. 2010. Deep Vein Thrombosis Prophylaxis in Hospitalized Medical
Patients: Current Recommendations, General Rates of Implementation, and Initiatives for
Improvement.Chestmed.
Wheeler A.2005.Venous thromboembolism in medically ill patients: identifying risk and strategies for
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FAKTOR RESIKO
STASIS HIPERKOAGULABILITAS CEDERA ENDOTELUsia >40 tahun
Imobilitas
CHF
StrokeParalisis
Cedera spinal cord
Hiperviskositas
Polisitemia
PPOK berat
Anestesi
Obesitas
Vena varikosa
Kanker
Kadar estrogen tinggi
Inflammatory Bowel
DiseaseSindrom Nefrotik
Sepsis
Merokok
Kehamilan
Trombofilia
Operasi
Riwayat VTE
Kateter vena
sentralTrauma
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Inherited thrombophilia:
Factor V Leiden mutation
Prothrombin gene mutation
Protein S deficiency
Protein C deficiency
Antithrombin (AT) deficiency
Rare disorders: Dysfibrinogenemia
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1. Assess level of mobility, VTE and bleeding risk for every adult patient
admitted to SUHT, including ambulatory patients: (1) Complete national risk
assessment tool, and (2) document assessment in the relevant section on
the patients drug chart. Medical patients who are NOT expected to have
significantly reduced mobility relative to normal state are not regarded atincreased VTE risk and do not need to be risk assessed further
2. Balance risks of VTE and bleeding
If any VTE risk factors identified, offer VTE prophylaxis, ensuring that there
are no contraindications. Do not offer pharmacological prophylaxis if bleeding
risk outweighs risk of VTE.3. Reassess VTE & bleeding risk within 24 hours of admission and whenever the
clinical situation changes. If the VTE or bleeding risk changes during the
admission the VTE prophylaxis must be reviewed and adjusted as
appropriate
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Guideline ACP
Recommendation 1: ACP recommends assessment of the risk forthromboembolism and bleeding in medical (including stroke)
patients prior to initiation of prophylaxis of venous
thromboembolism (Grade: strong recommendation,
moderatequality evidence). Risk factors for bleeding with anticoagulant therapy include older
age; female sex; diabetes; hypertension; presence of cancer;
acute or chronic alcoholism; liver disease; severe chronic kidney
disease; peptic ulcer disease; anemia; poor treatment adherence;
prior stroke or intracerebral hemorrhage; presence of bleeding
lesions; bleeding disorder; and concomitant use of aspirin,
nonsteroidal anti-inflammatory drugs, antiplatelet agents,
antibiotics, statins, fibrates, and steroids.
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Guideline ACP
Recommendation 2: ACP recommends pharmacologicprophylaxis with heparin or a related drug for venous
thromboembolism in medical (including stroke) patients
unless the assessed risk for bleeding outweighs the likely
benefits (Grade:strong recommendation, moderate-qualityevidence).
Recommendation 3: ACP recommends against the use of
mechanical prophylaxis with graduated compression
stockings for prevention of venous thromboembolism (Grade:strong recommendation, moderate-quality evidence).
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Guideline Australia
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Guideline Australia
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Guideline Australia
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Guideline Australia
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Penilaian Resiko Perdarahan
Pasien critically ill di ICUresiko perdarahan
Sebuah penelitian RCT di ICU223 pasien on
ventilatorperdarahan mayor pada kelompok terapi
nadroparin 6.5% vs placebo 2.7%
Penelitian prospektif 100 pasien di ICU90% pasien
mengalami perdarahan (70% minor, 20% mayor)
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ACCP Guideline
In outpatients with cancer who have no additional risk
factors for VTE, we suggest against routine prophylaxis with
LMWH or LDUH (Grade 2B) and recommend against the
prophylactic use of vitamin K antagonists (Grade 1B).
Remarks: Additional risk factors for VTE in cancer outpatientsinclude previous VTE, immobilization, hormonal therapy,
angiogenesis inhibitors, thalidomide, & lenalidomide.
In outpatients with cancer and indwelling central venous
catheters, we suggest against routine prophylaxis withLMWH or LDUH (Grade 2B) and suggest against the
prophylactic use of vitamin K antagonists (Grade 2C).
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ACCP Guideline
In outpatients with solid tumors who have additional risk
factors for VTE and who are at low risk of bleeding, we
suggest prophylactic dose LMWH or LDUH over no
prophylaxis (Grade 2B).
In chronically immobilized persons residing at home or at a
nursing home, we suggest against the routine use of
thromboprophylaxis (Grade 2C)
For long-distance travelers, we suggest against the use ofaspirin or anticoagulants to prevent VTE (Grade 2C).
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ACCP Guideline For long-distance travelers at increased risk of VTE (including
previous VTE, recent surgery or trauma, active malignancy,
pregnancy, estrogen use, advanced age, limited mobility, severe
obesity, or known thrombophilic disorder), we suggest frequent
ambulation, calf muscle exercise, or sitting in an aisle seat if
feasible(Grade 2C). For long-distance travelers at increased risk of VTE (including
previous VTE, recent surgery or trauma, active malignancy,
pregnancy, estrogen use, advanced age, limited mobility, severe
obesity, or known thrombophilic disorder), we suggest use of
properly fitted, below-knee GCS providing 15 to 30 mmHg ofpressure at the ankle during travel (Grade 2C). For all other long-
distance travelers, we suggest against the use of GCS(Grade 2C).
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Vitamin K Antagonist
Warfarin, coumarin, tecarfarin
Inhibition of the vitamin K-dependent gamma-carboxylation
of coagulation factors II, VII, IX, and X
Efeknya delayed sampai faktor pembekuan normal
(protrombin) hilang dari sirkulasi36-72 jam setelah
pemberian
Parenteral anticoagulants and warfarin should OVERLAP by
four to five days when warfarin is initiated in patients with
acute thrombotic disease
Use of the INR The INR is the PT ratio obtained by testing a
given sample using the WHO reference thromboplastin.
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