Tatalaksana Thrombosis pada pasien COVID-19

dengan Kelainan Kardiovaskular

Dr. dr. Dafsah Arifa Juzar, SpJP
Kardiovaskular Intensivist & intervensi
PJN Harapan Kita, Jakarta
Dept. Kardiologi & Kedokteran Vaskualr, FKUI
P. Kardiovaskular
&
COVID 19

Thrombosis arteri
1. Acute limb Iskemia
2. Acute Ischemic stroke

Thrombo embolism Vena

1. Deep Vein Thrombosis
2. Acute Pulmonary edema
Nishiga M, et.al. Nat Rev Cardiol. 2020;17(9):543-58.
 Manifestasi P. kardiovaskular & COVID-19
komplikasi atau koinsidens
Manifestasi COVID
Sedang
OTG Ringan berat
Kritis
Preexisting
P.
Kardiovaskular
Penyakit
Ringan
Kardiovaskular
Sedang –
berat-
kritis

Rawat
Komplikasi Jantung Pada
COVID-19
Trombosis – Gangguan Koagulasi
Tipe antikoagulan:
LMWH dosis standar 1 x 0,4 cc subkutan atau
unfractionated heparin (UFH) dosis 2 x 5000 unit sehari secara
subkutan1

Dosis profilaksis intermediate2

enoxaparin 2 x 0,4 cc, low-intensity heparin infusion
dapat dipertimbangkan pada pasien kritis (critically-ill)

Fondaparinux dosis standar juga dapat dipertimbangkan

pada pasien COVID-19 yang dirawat, tapi pada kondisi pasien
COVID-19
yang kritis tidak menjadi pilihan utama karena pada kondisi pasien
yang tidak stabil sering didapatkan gangguan ginjal.

1. UCSD H. UFH and LMWH

Dose: https://health.ucsd.edu/specialties/anticoagulation/providers/perioperative/procedure-
checklist/Pages/dose.aspx
2. MSHS. MSHS COVID ANTICOAGULATION PROTOCOL.New York: Mount Sinai Health System; 2020. Available
From: https://www.mountsinai.org/files/MSHealth/Assets/HS/About/Coronavirus/COVID-19-Anticoagulation-
Algorithm.pdf.
VTE prophylaxis
risk stratification for VTE prevention
Risk VTE – Modified PADUA SCORE Bleeding Risk – IMPROVE SCORE

nilai ≥ 4 (untuk TEV) menunjukan risiko tinggi, nilai <4 menunjukkan risiko rendah
Algoritme Prophylaxis VTE

Konsensus tatalaksana TEV pada penyakit kritis 2019 PERDICI-PTHI-PERKI-IKKI-PETRI

The Diagnostic approach to
Venous Thromboembolism : DVT & APE
Deep Vein Thrombosis (TVD) Acute Pulmonary Embolism (APE)
Sign & Symptom Sign & Symptom
• Pain deep in the calf or thigh • Pleuritic pain
• Unilateral swelling • Dyspnoea
• Increased temperature of the leg • Syncope
• Tenderness • Haemoptysis
• Redness • Palpitations

Risk Stratification Risk Stratification

• Geneva score, simplified PE
• Well’s score, simplified DVT • Well’s score, simplified PE
Clinical examination and Laboratory
Deep Vein Thrombosis
1. Contrast Venography (gold standard).
2. Impedence Plethysmography.
3. Comperssion Ultrasound (CUS) with
Venous Imaging.
4. Magnetic resonance Imaging.
5. D-dimmer.
Bold most feasible
Acute Pulmonary Embolism
1. Electrocardiography.
2. Arterial Blood Gas Analysis.
3. Chest Radiography.
4. D-Dimer.
5. The Ventilation-Perfusion Scan.
6. Pulmonary Angiography.
7. Spiral (Helical) Computed
Tomography.
8. Magnetic Resonance Imaging.
9. Echocardiography
 DUPLEX ULTRA SOUND OF LOWER EXTREMITY

Popliteal Vein
*
Popliteal Artery

RIGHT LEG

Thrombus was seen in right popliteal vein, CUS (+)

 DUPLEX ULTRA
SOUND OF LOWER
EXTREMITY

Popliteal Vein

Thrombus was seen in Popliteal Artey

right popliteal vein,
CUS (+)
 Prophylaxis TVD
Trombosis – Gangguan Koagulasi (Trombofilaksis DVT)
• LMWH
• Fondaparinux
• UFH
• pada kondisi khusus
seperti gangguan ginjal,
obesitas, kehamilan,
diperlukan monitoring
dengan pemeriksaan anti-
Xa.

Smythe MA et al. Journal of thrombosis and thrombolysis, 41(1), 165–186.

https://doi.org/10.1007/s11239-015-1315-2
 Komplikasi Jantung Pada COVID-19
Trombosis – Gangguan Koagulasi (Trombofilaksis DVT)
• LMWH
• Fondaparinux
• UFH
• pada kondisi khusus
seperti gangguan ginjal,
obesitas, kehamilan,
diperlukan monitoring
dengan pemeriksaan anti-
Xa.

Smythe MA et al. Journal of thrombosis and thrombolysis, 41(1), 165–186.

https://doi.org/10.1007/s11239-015-1315-2
 VTE Treatment

Aim of the initial anticoagulant treatment

To prevent thrombus extention.

To prevent PE.
To prevent early & late recurrence of VTE.

Initial treament
Long term treatment
Extended treatment

≥ 5 days At least three months indefinite

Kearon clive et al. Antithrombotic therapy for venous thromboembolic Disease.

Chest 2008; 133:454s-545s.
 VTE Treatment

Aim of the long-term anticoagulant treatment

To complete of the acute episode of VTE.

To prevent of new episode VTE.

Initial treament
Long term treatment
Extended treatment

≥ 5 days At least three months indefinite

Kearon clive et al. Antithrombotic therapy for venous thromboembolic Disease.

Chest 2012; 133:454s-545s.
 VTE Treatment
UFH (i.v., s.q., s.q. fixed dose)
LMWH
Fondaparinux
NOAC
Thrombolysis

Vitamin K antagonists

Initial treament INR 2.0-3.0 INR 2.0-3.0 or:

Long term treatment INR 1.5-1.9
Extended treatment

≥ 5 days At least three months indefinite

Kearon clive et al. Antithrombotic therapy for venous thromboembolic Disease.

Chest 2012; 133:454s-545s.
The Spyral of haemodynamic collapse acute PE

2019 ESC Guidelines Acute pulmonary embolism

 Revise Geneva clinical prediction to rule PE
Original Simplified
Variables
version version
Original Simplified
Previous PE / DVT 3 1 Clinical probabilities
version version
Heart rate 75-94 bpm 3 1 Three level score
Heart rate > 95 bpm 5 2 Low 0-3 0-1
Surgery fracture w/in 1 month 2 1 intermediate 4-10 2-4
Haemoptysis 2 1 High >11 >5
Active cancer 2 1
Unilateral lower limb pain 3 1 Two level score
Pain on lower limb deep PE unlikely 0-5 0-2
venous palpation and unilateral 4 1
PE likely >6 >3
oedema
Age > 65 yo 1 1
2019 ESC Guidelines Acute pulmonary embolism
Pencitraan Emboli pulmonal Akut

4 Chamber
Apical LAX

RV
LV

RA

RV right ventricle, RA right Atrium ; LV left ventricle

CTPA Echo Cardiogram

Transthoracal echo parameters for Pressure
overload

2019 ESC Guidelines Acute pulmonary embolism

Pulmonary Embolism Severity Index - PESI
Original & Simplified
Original Simplified Risk Strata - Original version
Parameter
version version
Class I: < 65 points very low 30 day mortality risk (01.- 6%)
1 point (if age
Age Age in years
>80 years) Class II 66 - 85 points
Male sex +10 points - low mortality risk (1.7 -3.5%)

Cancer +30 points 1 point Class III: 86 - 105 points

moderate mortality risk (3.2 - 7.1%)
Chronic heart failure +10 points
1 point Class IV: 106 - 125 points
Chronic pulmonary disease +10 points high mortality risk (4.0 - 11.4%)
Pulse rate > 110 +20 points 1 point Class V: >125 points
very high mortality risk (10.0-24.5%)
Systolic BP < 100 mmhg +30 points 1 point
Respiratory rate > 30
+20 points - Risk Strata – simplified version
breath/minute
Temperature < 360 C +20 points - 0 points 30 day mortality risk 1.0% (95% CI 0.0 2.1%)
Altered mental status +60 points - > 1 points 66 - 85 points
Arterial oxyhaemoglobin sat
+20 points 1 point
low mortality risk (1.7 -3.5%)
< 90%
Classification of PE Based on mortality risk

2019 ESC Guidelines Acute pulmonary embolism

Definition haemodynamic instability
Cardiac arrest Obstructive shock
Need for cardiopulmonary Systolic BP < 90,mhg, or
resuscitation vasopressors required to achieve a
BP > 90 mmhg despite adequate
filling status
AND
Persistent Hypotension
Systolic BP < or systolic BP drop >
40 mmhg, either lasting more than
15 minutes and not caused by new
onset arryhtmnia, hypovolemia &
sepsis

End Organ hypoperfusion (altered

mental status; cold clammy skin;
oliguria; anuria; increase serum
lactate

2019 ESC Guidelines Acute pulmonary embolism

Diagnostic algorhytm for highly suspected PE

2019 ESC Guidelines Acute pulmonary embolism

Diagnostic algorhtym for highly suspected PE

2019 ESC Guidelines Acute pulmonary embolism

Suspected PE in
Patient with
haemodynamic
instability

2019 ESC Guidelines Acute pulmonary embolism

Treatment of right ventricular failure in
acute high-risk pulmonary embolism
strategy Property & use Caveats

Volume Optimization

Cautious volume loading, saline, or Ringer’s Consider in patients with normal - low central Volume loading can over-distend the RV, wor-
<_500 mL over 15 - 30 min venous pressure (due, for example, to con- sen ventricular interdependence, and reduce
comitant hypovolaemia) CO
Vassopressor and inotropes

Norepinephrine, 0.2 - 1.0 mg/kg/mina Increases RV inotropy and systemic BP, pro- Excessive vasoconstriction may worsen tissue
restores coronary perfusion gradient perfusion

Dobutamine, 2 - 20 mg/kg/min Increases RV inotropy, lowers filling pressures May aggravate arterial hypotension if used
alone, without a vasopressor; may trigger or
aggravate arrhythmias
Mechanical circulatory support

Veno arterial ECMO/extracorporeal life Rapid short-term support combined with Complications with use over longer periods
support oxygenator (>5 10 days), including bleeding and infec-
tions; no clinical benefit unless combined
with surgical embolectomy; requires an
experienced team
2019 ESC Guidelines Acute pulmonary embolism
Recommendations for acute-phase treatment
of high risk PE

2019 ESC Guidelines Acute pulmonary embolism

Thrombolytic regimens, doses, and
contraindications
Molecule Regimen Contraindication to fibrinolysis
rTPA 100 mg over 2 h Absolute
History of haemorrhagic stroke or stroke of
0.6 mg/kg over 15 min (maximum unknown origin Ischaemic stroke in previous
dose 50 mg)a 6 months
Central nervous system neoplasm
Streptokinase 250 000 IU as a loading dose over Major trauma, surgery, or head injury in
30 min, followed by 100 000 IU/h previous 3 weeks Bleeding diathesis
Active bleeding
over 12 - 24 h Relative
Accelerated regimen: 1.5 million IU Transient ischaemic attack in previous 6
months Oral anticoagulation
over 2 h Pregnancy or first post-partum week Non-
compressible puncture sites
Traumatic resuscitation
Refractory hypertension (systolic BP >180
mmHg) Advanced liver disease
Infective endocarditis
Active peptic ulcer
Recommendations for acute-phase treatment
of intermediate or low risk PE
Acute Limb Ischemia
• Sudden decrease in limb perfusion 5-6 P’s
causing potential threat to limb 1. Pain
viability 2. Pulselessness
3. Pallor
4. Paresthesia
• Any sudden decrease in or 5. Paralysis
worsening of limb perfusion
causing a threat to extremity 6. Perishing cold
mobility and viability that has been
present for less than 14 days
• 30 Day mortality: 15%, Amputation
rate 10-30%

Creager MA, N Eng J Med 366: 23- 2012

Causes Patient at risk
• Thromboemboli (90% cardiac origins) 1. CHF, low Ejection Fraction, LV
• In-situ thrombosis Thrombus
• Arterial trauma 2. Atrial Fibrillation
• Arterial aneurysm 3. Aortic aneurysm/dissection with
Thrombus
• Phlegmasia Cerula Dolens 4. Post Arterial puncture
• Aortic Dissection
• External Compression
• Arteritis
• Post-puncture Atrial Fibrilation
Diagnostic – Acute limb ischemia
History :
• Duration, location of pain
• Risk Factors, possible source of Duplex sonography
Emboli Contra-indication to 1. Confirm the presence of
fibrinolysis
Examination : occlusion
• Cardiovascular Status, 2. Stadium
• arterial pulse and
• Rhythm 3. Description of lession:
Imaging : a. Location
• Doppler/Dupplex Sonography b. Thrombus/calcification/stenosis
• CTA c. Collateral
• Angiography
Laboratory : d. Strategy for intervention: access
• Coagulation Parameter, Renal
Function
Management
• Prevention: • Early Management:
§ Recognize patients at risk § Anticoagulation
§ Treat Underlying Diseases § Immediate Referral
§ Anticoagulation § Referral to specific specialist:
Cardiologist, vascular surgeon,
• Diagnosis: Interventional Radiologist:
§ Recognize 6 Ps § Catheter Directed Thrombolysis
§ Send for Correct diagnostic test: § Thrombosuction
Dupplex Ultrasound, CT Angio, § Surgical Embolectomy
Arteriography
Stages of Acute Limb Ischemia

Rutherford B, J Vasc Surg 26: 317- 1997

Management

Creager MA, N Eng J Med 366: 23- 2012

Modes of Revascularization
• Endovascular Catheter directed thrombolysis
• Catheter-directed /Intra-arterial
thrombolysys
• Thrombus Aspiration • Streptokinase : 5.000-10.000 U/h
• Percutaneous Mechanical • Urokinase : 50.000-120.000 U/h
Thrombectomy • R-TPA : 0.5 mg/h
Concomitant Heparin 200-300 U/h
• Surgical
• Embolectomy
• Bypass Graft
Cidera Miokardium Pada COVID-19
Algoritme

Definisi
• Kenaikan troponin batas atas 99th
persentil

Bila meningkat, perlu evaluasi klinis/

serial enzim
(a) Cedera miokard kronik –
(b) Cedera miokard non iskemik –
(c) Infark miokard akut (IMA) –
Shi S, et.al. JAMA Cardiol 2020;Mar 25
Guo T, et.al.. JAMA Cardiol 2020;Mar 27
Sandoval Y, et.al. J Am Coll Cardiol 2020;Jul 3
 Cidera Miokardium Pada COVID-19
Deteksi Dini

Cedera miokard kronik Cedera miokard non Infark miokard akut (IMA)
– iskemik • kenaikan dan penurunan
• Pada pemeriksaan • kenaikan dan troponin tanpa lesi
penurunan troponin obstruktif di arteri
serial kadarnya sama
tanpa lesi obstruktif di koroner
arteri koroner
• Kenaikan danpenurunan
bermakna perubahan
lebih 20%

Shi S, et.al. JAMA Cardiol 2020;Mar 25

Guo T, et.al.. JAMA Cardiol 2020;Mar 27
Sandoval Y, et.al. J Am Coll Cardiol 2020;Jul 3
 Cidera Miokardium Pada COVID-19
Algoritme
Pasien Terkonfirmasi COVID-19

Memenuhi salah satu atau lebih kriteria:

Usia 56-74 tahun (terutama di sekitar 66 tahun)
Komorbid:1
-. Hipertensi
-. Diabetes mellitus
Waspada kemungkinan besar -. Penyakit jantung
keterlibatan
cedera miokardium

1. Giustino G et al. J Am Coll Cardiol. 2020 Nov 3;76(18):2043–55.

2. Saus PS et al. Indonesian Journal of Cardiology. 2020 May 29;41(2):49–53.
 Cidera Miokardium Pada COVID-19
Algoritme
Pasien Terkonfirmasi COVID-19

Memenuhi salah satu atau lebih kriteria:

Usia 56-74 tahun (terutama di sekitar 66 tahun)
Komorbid:1
-. Hipertensi
-. Diabetes mellitus
Waspada kemungkinan besar -. Penyakit jantung Kemungkinan kecil
keterlibatan keterlibatan
cedera miokardium cedera miokardium

CEK EKG à Apakah terdapat abnormalitas:1,2

-. ST Elevasi/depresi regional maupun difus
-. Perubahan segmen ST-T dinamik
-. Gangguan konduksi
-. Gambaran voltase rendah (low voltage)

Tidak
1. Giustino G et al. J Am Coll Cardiol. 2020 Nov 3;76(18):2043–55. Pemeriksaan EKG per hari
2. Saus PS et al. Indonesian Journal of Cardiology. 2020 May 29;41(2):49–53. Ya
EKG saat masuk RS
- usia >56 tahun DAN
- komorbid Hipertensi, Diabetes mellitus, Penyakit jantung

1. ST Elevasiregional maupun difus

2. ST depresi
3. Perubahan segmen ST-T dinamik
4. -. Gangguan konduksi
5. -. Gambaran voltase rendah
(low voltage)
Cidera Miokardium Pada COVID-19
Algoritme
Pemeriksaan laboratorium, bila:
Troponin I (ng/ml) above upper limit
ATAU Troponin T (ng/ml) above upper limit
ATAU High sensitive Troponin T (hs-Trop T) - (ng/ml) above upper limit
ATAU CKMB (ng/ml) above upper limit

DAN

Brain natriuretic peptide (BNP) - (pg/ml) above upper limit

Dipertimbangkan:
COVID 19 + Manifestasi Cedera Antivirus, Ace-I,
Miokardium tatalaksana cytokine
storm,

Disfungsi sistolik/diastolik:
Pemeriksaan Ekokardiografi untuk menilai fungsi jantung
Tatalaksana anti-failure

Giustino G et al. J Am Coll Cardiol. 2020 Nov 3;76(18):2043–55.

ST non elevasi IMA (NSTEMI)
ST elevasi inferior dengan reciprocal ST depresi I, aVL

Deviasi 0.1 mV (1 mm)

Pada semua liadin all lead
Inferior ST elevasi IMA (STEMI)
ST elevasi inferior dengan reciprocal ST depresi I, aVL

Deviasi 0.1 mV (1 mm)

Pada semua liadin all lead
 Peri-Miokarditis
ST elevasi di semua leads
Downsloping PR segment depression

Deviasi 0.1 mV (1 mm)

Pada semua liadin all lead

ST elevasi hampir di
semua leads
Komplikasi Jantung Pada COVID-19
Cedera Miokardium – Perbandingan dengan IMA
Infark Miokard Akut (IMA)
Klinis Nyeri dada tipikal Angina
Cardiac enzyme Peningkatan marker kerusakan
miokardium (Troponin, CKMB) di
awal kedatangan ke RS
Natriuretic peptide Meningkat
D - dimer Meningkat
Elektrokardiografi Umumnya ST depresi, ST elevasi,
atau T inversi regional
Echo Regional Wall Motion
Abnormalities
Giustino G et al. J Am Coll Cardiol. 2020 Nov 3;76(18):2043–55.
Miokarditis
Nyeri dada tidak khas atau
asimpomatik
Peningkatan marker
kerusakan miokardium (Troponin,
CKMB) di rata-rata hari ke-5
perawatan RS
Meningkat
ST depresi atau ST elevasi difus
Global Hipokinetik
Cidera Miokardium Pada COVID-19

non – Sindroma koroner akut Sindroma koroner akut

• Terapi antiviral: Remdesivir dapat • ST elevasi – revaskularisasi segera.
dipertimbangkan untuk pasien dengan infeksi • Non ST elevasi – sesuai stratifikasi risiko
COVID-19 yang berat.1

• Ace-inhibitor: Menurunkan angka mortalitas

dan kebutuhan akan ventilasi mekanik pada
pasien non-severe2 acute respiratory
syndrome (SARS).

• Tatalaksana cytokine storm: anti-syok,

simtomatik dan suportif, serta pemberian
steroid. Perlu diperhatikan, pemberian
steroid dosis tinggi dapat berakibat pada
pemanjangan waktu bersihan virus.1
1. Peng W et al. Life Sci. 2020 Dec 1;262:118496.
2. Mortensen EM et al. Eur Respir J. 2008 Mar;31(3):611–7.. https://inaheart.org/guideline/
 STEMI onset < 12 jam / NSTEMI risiko sangat tinggi

Pengisian Formulir
Penyelidikan Epidemiologi

Kontak
NON Suspek COVID +
erat

IKK Primer Ruang katerisasi terdedikasi dengan APD level III

RAPID TEST POSITIF IMA

Selama
Lymphopenia absolut perawatan
Tidak
memenuhi RAWAT
RAWAT memenuhi NLR > 3.13 salah satu ICCU
ICCU seluruh
kriteria Isolasi
kreteria CRP > 10

Infiltrat pada X-Ray

ICCU Intensive cardiovascular care unit; IMA infark miokard akut PPK STEMI COVID -19 Harapan Kita Nov 2021
 Manajemen STEMI dengan HTB
use of thrombus
aspiration devices

Mechanical distal protection

treatments devices

Delayed stent
implantation

antiplatelet
Manajemen HTB
agents

anticoagulant drugs

Drug treatments thrombolytic agents

statins

Hang Ren et al, Int J Clin Exp Med 2019;12(11):13068-13078 vasodilators

Atrial Fibrilation/
Flutter
management
Eur Heart J, ehab697,

https://doi.org/10.1093/eurheartj/ehab697
Rangkuman
Tatalaksana thrombosis Kardiovaskular
Penyakit Kardiovaskular MANAGEMENT
• Komorbid /Koinsidens • Prophylaxis
• Komplikasi • Tambahan Padua score dari algorithm
OP5
• Acute management
Thrombosis • Long term management
• Thromboemboli Vena :
• Deep Vein thrombosis
• Acute pulmonary embolism
• Thromboemboli arteri :
• Acute limb iskemia
• Atrial Fibrilasi à acute ischemic
cerebri