INTERN WEBINAR : Covid Series, 11th July 2020

COAGULOPATHY in PATIENT with COVID19

from Cardiologist Perspectives : a case sharing

Devie Caroline, dr, Sp.JP

BACKGROUND
• Since December 2019, the coronavirus disease 2019 (COVID-19) has spread
globally.

• Infecting more than 3 million people and causing more than 213,273 deaths
in over 200 countries.

• Tang et al reported that among 1099 hospitalized patients with COVID-19,

46.4% presented with an increased D-Dimer level above 0.5 mg/L.

• A higher D-Dimer level was documented among severe compared to non-

severe COVID-19 patients (59.6% vs. 43.2%, respectively).

Tang, N.; Li, D.; Wang, X.; Sun, Z. Abnormal coagulation parameters are associated with poor prognosis in
patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020, 18, 844–847
CASE SHARING

• This presentation reports 2 patients COVID19 with

coagulopathy (marked with high level of D-Dimer) and
compare the clinical manifestation between those 2
cases.
CASE I

Present Illness History

• Mr.A, 49 years old male, complained of fatique since 8 days prior
to the admission.
• He was also suffered from watery diarrhea about 3 days, cough
but no fever.
• A day before admission he felt shortness of breath, especially
during walk or light activity.

Past Medical History

DM,HT denied. The patient was obese (Height 170 cm,W 100 kg)
Examination Thorax :
• Gen.app : weak • Rh -/-, Whz -/-
• Vital Sign : • Cor : within normal limit
– BP 140/80 ECG :
– HR 107 bpm
– RR 22 x/m
– t : 36,8 °C
– SpO2 90%
CXR

Laboratory result :
• Hb 17,6 g/dL
• WBC 9330 /UL
• PLT 227.000/UL
• Seg 86%, Limf 6%
• Na 130, K 4,4
• Rapid test : non reactive
• Others within normal limit
Management

01.06.2020 PCR Covid : Positive

• O2 FM 5 lpm
• Levofloxacin 1 x 750 mg,iv
• NAC 1x1600 mg/day, iv
• Isoprinosin 3 x 500 mg tab
• Multivitamin
Additional treatment :
• Oseltamivir 2 x 75 mg tab
• Hyloquin 2 x 400 mg tab
--> 2 x 200 tab (7 days)
Progress of the disease 08.06.2020
shortness of breath worsened

09.06.2020 D-Dimer 7595 ng/mL

Treatment : ???

01.06.2020 04.06.2020 08.06.2020

Oral NOAC ?
Injection LMWH ?
Injection Fondaparinux ?
Injection UFH ?
Inj. Enoxaparin 2 x 0,4 cc sc
Shortness of breath >>
MP 3 x 125 mg iv
Furosemid 1-1-0 inj iv 14.06.2020 20.06.2020
Tocilizumab (Actemra®) 1 x 400 mg iv D-Dimer : 2791 ng/mL D-Dimer: 918 ng/mL

Antibiotic : Levofloxacin 1 x 750 mg iv--> Meropenem 3 x 1 g iv

10.06.2020 19.06.2020 22.06.2020

Continue LMWH? Oral Rivaroxaban 1 x 20 mg tab

switch to NOAC ?
 25.06.2020 28.06.2020 02.07.2020

26.06.2020
switch to LMWH again D-Dimer 563 Oral NOAC Rivaroxaban
D-Dimer 1152 ng/L
ng/mL
CASE 2
• Present Medical Illness • Examination
Male, 55 yo, complaint of fatique • Gen app : dyspneu
since 2 weeks prior to admission. • BP 150/80
He also felt fever and shortness • HR 112 bpm
of breath 1 week prior to
• RR 43 x/m
admission
• t 37,1 C
Past Medical History
• DM (+) • SpO2 87%
• HT (+) Thorax :
• Rh+/+, basal
• whz -/-
• CXR Laboratorium
• Rapid test : reactive
• Hb 14,7/WBC 10770/PLT
211000
• Na 132/K 4,5
• BS 373/Ur 71/Cr 1,1
• D-Dimer 1073 ng/L
• BGA : pH 7,47/pCO2 32/pO2 69/HCO3
23/BE 0,5/AaDO2 272
• ECG
Cardiologist treatment :
Inj Enoxaparin 2 x 0,4 cc sc
Inj Furosemid 1-1-0 Amp iv
Losartan 50 mg 1 x 1 tab
Amlodipin 5 mg 1-0-0 tab
15.06.2020
• O2 FM 8 lpm
• Levofloxacin 1 x 750 mg,iv
• NAC 1x1600 mg/day, iv
• Isoprinosin 3 x 500 mg tab
• Oseltamivir 2 x 75 mg tab
• Hyloquin 2 x 400 mg --> 2 x
200 mg tab
• Novorapid inj
• Multivitamin
 Progress of the disease
shortness of breath >>,
Treatment :
+ NIV with PEEP 20.06.2020
PCR Hb 12,6
COVID : + Meropenem 3 x 1 g iv
WBC 13.550 25.06.2020
positive + Hydrocortison 1 x 100 mg iv (3d)
PLT 239.000 D-Dimer 1935 ng/L
+ Tocilzumab 1 x 400 mg iv

19.06.2020 22.06.2020 25.06.2020

Progress of the disease

28.06.2020
• Hb 14,2/WBC 20630/PLT
130.000
• D-Dimer 7198 mg/mL
• Na 142/K3,1/Alb 2,8

Increase dose of LMWH : Inj. Enoxaparin 2 x 0,6 cc sc

• 30.06.2020 : patient got worse, Rh +/+, then bradycardia

• --> asystole --> passed away
DISCUSSION
Coagulopathy
Carmo Junior et al reported : elevated D-Dimer, a product of fibrin
degradation --> associated with a higher mortality rate
• Expert opinion : systemic inflammatory response in patients
with infection --> endothelial damage --> increase in thrombin
generation, reduction in endogenous fibrinolysis.

• This prothrombotic state is called sepsis-induced

coagulopathy (SIC) and precedes DIC.

• Evicendence has shwon : bidirectional relationship between

inflammation and coagulation
Arq Bras Cardiol. 2020; 114(5):829-833
Pathophysiology of COVID19-Induced Coagulopathy (CIC)
• Inflammation : cytokines and inflammatory mediators
(IL-6, IL-7, IL-22, etc.) can lead to activating pro-coagulant
pathways and further drive a pro-thrombotic state
• Endothelial activation : endothelial cell activation/damage
due to the virus binding to the ACE2 receptor promoting
acute inflammatory and hypercoagulable
• Severe Hypoxemia

Severe lung inflammation and impaired pulmonary gas exchange

in COVID-19 can stimulate thrombosis through a hypoxia-
inducible transcription factor-dependent signaling pathway.

“Silent hypoxemia ” : patient with COVID19 were

hypoxemic,SpO2 80% room air, but clinically looked
comfortable, and not dyspneic or tachypneic

Gupta, N.; Zhao, Y.-Y.; Evans, C.E. The stimulation of thrombosis by hypoxia.
Thromb. Res. 2019, 181, 77–83
MANAGEMENT ??

Rannuci et al. recently showed that the use of an increased dose of

LMWH :
– Reduce the downstream thrombotic effects of the marked
inflammatory response to COVID-19
– decrease the contribution of microvascular thrombosis in
severely hypoxemic COVID patients.

• Ranucci, M.; Ballotta, A.; Di Dedda, U.; Bayshnikova, E.; Dei Poli, M.; Resta, M.; Falco, M.; Albano, M.; Albano, G.; Menicanti, L. The
procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J. Thromb. Haemost. 2020
Regarding antithrombotic options, the ISTH consensus
statement recommended :
– prophylactic dose LMWH in all patients (including non-critically
ill) who required hospital admission for COVID-19 infection
– in the absence of any contraindications (active bleeding and/or
platelet count less than 25.109/L)
• Thachil, J

Thachil, J.; Tang, N.; Gando, S.; Falanga, A.; Cattaneo, M.; Levi, M.; Clark, C.; Iba, T. ISTH
interim guidance on recognition and management of coagulopathy in COVID-19. J. Thromb. Haemost. 2020, 18,
1023–1026.
 If deciding to
use anticoagulation, LMWH should be
chosen for stable
patients with normal creatinine
clearance (dose of 1 mg/
kg, 12/12h, subcutaneous).

In case of shock or creatinine

clearance below 50 mL/min/m²,
intravenous heparin (18
IU/kg/h) should be used, aiming at
an activated partial
thromboplastin time between 1.5
and 1.8.

However, there
is no evidence to support the wide
use of the therapeutic
dose of heparin in COVID-19

Arq Bras Cardiol. 2020; 114(5):829-833

Yale New Haven Health System
Covid Treatment Algorithm, 2020
CONCLUSION
• In conclusion, the pathophysiology of COVID-19 involves
activation of the inflammatory response and induction of the
thrombotic system.

• Currently, the expert consensus suggests anticoagulant treatment

for patients with the pro-coagulant phenotype (high D-dimer,
prolongation of prothrombin time and increased plasma levels of
fibrin fragments).

• Further studies are required to confirm the real role of

anticoagulation to prevent COVID-19 complications.
 THANK YOU
STAY SAFE,STAY HEALTHY