Pathogenesis and Coagulopathy

Related to COVID-19

PRASENOHADI
Perhimpunan Dokter Paru Indonesia
Departemen Pulmonologi dan Kedokteran Respirasi FKUI – RSUP Persahabatan
JAKARTA
COVID-19 Disease Burden
• The Coronavirus Disease (COVID-19) outbreak is still evolving globally and
remains a Public Health Emergency of International Concern (PHEIC)
• As cases of COVID-19 continue to climb, public concern in Indonesia
regarding the severity of the disease and population vulnerability is also
growing.
• Around 1 in every 5 people with COVID-19 develop difficulty in breathing
and require hospital care.
• People > 60 years, and people who have underlying medical conditions
(diabetes, heart disease, respiratory disease or hypertension) are among
those who are at greater risk of developing severe or critical illness if
infected with the virus.

WHO Indonesia information on COVID-19: www.who.int/indonesia/news/novel-coronavirus

COVID-19 Disease Burden
COVID-19 Disease Burden
Classification of COVID-19 Disease States

J Heart Lung Transplant. 2020;39(5):405-7.

Pathogenesis, Immune Response and
Coagulopathy of COVID-19
 Aberrant immune host response occurring during COVID-19 infection

Cytokine storm (CS) is a critical life-

threating condition requiring intensive
care admission and having a quite high
mortality. CS is characterized by a clinical
presentation of overwhelming systemic
inflammation, hyperferritinemia,
hemodynamic instability, and multi-organ
failure, and if left untreated, it leads to
CXCL10, CCL2, TNF𝛼, IL-1, IFN-𝛾, IP-10,
death.
monocyte chemoattractant protein 1 (MCP-1

Front. Immunol. 11:1446. doi: 10.3389/fimmu.2020.01446; Front. Immunol. 11:2132. doi: 10.3389/fimmu.2020.02132
 The molecular link between key genes in coagulation during COVID-19 infection

Front. Pharmacol. 11:587451. doi: 10.3389/fphar.2020.587451

The potential pathophysiological evolutions underlying SARS-CoV-2 infection, linking pulmonary
inflammation, multiple organ failure, and thrombosis and coagulopathy

Front. Cardiovasc. Med. 7:599334.

doi: 10.3389/fcvm.2020.599334
Schematic mechanisms for the dynamic D-dimer level in COVID-19 patients
(Clinicopathological mechanisms for elevated plasma D-dimer in COVID-19 patient)

Front. Immunol. 12:691249. doi: 10.3389/fimmu.2021.691249

Pulmonary intravascular
coagulopathy in COVID-19
pneumonia

Lancet Rheumatol. Published online May 7, 2020.

Microthrombi in the Lymphocytic Inflammation
Interalveolar Septa. The gross appearance of a lung from a patient who died from
The interalveolar septum of this coronavirus disease 2019 (Covid-19) is shown in Panel A
patient shows The histopathological examination, shown in Panel B,
slightly expanded alveolar walls revealed interstitial and perivascular predominantly
with multiple fibrinous lymphocytic pneumonia with multifocal endothelialitis.
microthrombi (arrowheads) in
the alveolar capillaries.
Extravasated erythrocytes and a
loose network of fibrin
can be seen in the intraalveolar
space.
Case study of CAC non-survivor patient
from Persahabatan Hospital
Severity COVID-19 RSUP PERSAHABATAN
(Maret 2020 – April 2021)
No. Kategori Kasus (%) Kematian CFR (%)
1. Kritis 1246 (37,4) 572 45,9
2. Berat 949 (28,5) 65 6,8
3. Sedang 571 (17,2) 16 2,8
4. Ringan 562 (16,9) 0 0
3328 (100) 653 19,6
KOAGULOPATI COVID-19
(RSUP Persahabatan, Maret 2020 – April 2021)

Ada Tidak Rerata (d-Dimer)

Hiperkoagulasi pada COVID-19 2077 (84,9) 370 (15,1%) 3871 ± 9172,6

DERAJAT
Ringan Sedang Berat Kritis
COVID + Koagulopati 331 (15,9) 256 (12,3) 579 (27,9) 911 (43,8)
• Meninggal 0 9 (3,5) 47 (8,1) 445 (48,8)
• Hidup 331 (100) 247 (96,5) 532 (91,8) 466 (51,2)
COVID tanpa Koagulopati 50 (13,5) 103 (27,8) 128 (34,6) 89 (24,1)
• Meninggal 0 3 (2,9) 3 (2,3) 22 (24,7)
• Hidup 50 (100) 100 (97,1) 125 (97,6) 67 (75,3)
Penggunaan Antikoagulan pada Pasien COVID-19
(RSUP Persahabatan, Maret 2020 – April 2021)

Meninggal (%)
Antikoagulan 237 (47,3)
Tanpa antikoagulan 264 (52,7)
TOTAL 501

Meninggal Hidup Total

UFH 184 (43,1) 255 (58,1) 439
Enoxaparin 49 (28,0) 126 (72,0) 175
Fondaparinux 4 (21,1) 15 (78,9) 19
5-3-2021 10-3-2021 15-3-2021

Tn. HS/44 tahun

Fondaparinux 1x2,5mg 05/03/21 10/03/21 15/03/21
d-Dimer 490 8620 15930
Fibrinogen 787,8 697,3
PT 10,2 (10,3) 11,4 (10,3)
APTT 38,3 (34,8) 34,1 (34,8) 46,3 (34,8)
 11-3-2021
Ny. SH/39 tahun
Heparin 10.000-12.000u/24jam 11/03/21 11/03/21 13/03/21 14/03/21
d-Dimer 1610 910 590
Fibrinogen 513,6 681,4
PT 9,7 ( 10,3) 11 (10,3)
APTT 50,5 (34,8) 45,9 (34,8) 36,4 (34,8)
 10-3-2021 15-3-2021
Ny. SR/51 tahun
Enoxaparin 2x0,6 sc 10/03/21 12/03/201 15/03/21
d-Dimer 840 2840 1650
Fibrinogen
PT 11 (10,3)
APTT 34,5 (34,8) 38,1 (34,8)
Important coagulation parameter to define therapeutic
strategy for COVID-19-associated coagulopathy
Hematologic and Coagulation biomarkers abnormalities
in COVID-19 patients with severe systemic disease

• WBC count
Increased
• Neutrophil count
• Lymphocyte count
Hematologic • Platelet count
biomarkers • Eosinophil count
Decreased
• T cell count
• B cell count
• NK cell count
Coagulation • PT (prothrombin time)
Increased
biomarkers • D-dimer
Crit Rev Clin Lab Sci. 2020;57(6):389–99.
Correlation of D-dimer elevations and aberrant fibrin deposition with
organ dysfunction

Front. Immunol. 12:691249. doi: 10.3389/fimmu.2021.691249

Correlation of D-dimer elevations and aberrant fibrin deposition with
organ dysfunction
(Outcomes correlate with D-dimer levels)

Front. Immunol. 12:691249. doi: 10.3389/fimmu.2021.691249

Correlation between D-dimer and C-reactive protein Correlation between peak D-dimer and peak C-
at admission in patients with Covid-19 and reactive protein during hospital stay in patients with
suspected pulmonary embolism (rs = 0.146; p = Covid-19 and suspected pulmonary embolism
0.208). (rs = 0.279; p = 0.015).

Front. Med. 7:557. doi: 10.3389/fmed.2020.00557

Correlation between peak D-dimer and worst Correlation between highest C-reactive protein
PaO2:FiO2 during hospital stay in patients with and worst PaO2:FiO2 during hospital stay in
COVID-19 and suspected pulmonary embolism patients with COVID-19 and suspected
(rs = −0.471; p < 0.001). pulmonary embolism (rs = −0.473; p < 0.001).

Front. Med. 7:557. doi: 10.3389/fmed.2020.00557

Meta-regressions of plasma D-dimer level on admission with some clinical variables
(Dashed vertical red lines indicate the normal range)

Front. Immunol. 12:691249. doi: 10.3389/fimmu.2021.691249

D-dimer correlates with CT imaging of COVID-19 patients

Correlation of representative
CT imaging with D-dimer
and Neutophil to Lymphocyte
Ratio (NLR) in mild (A),
moderate (B), and severe (C)
groups of COVID-19 patients

Front. Med. 7:572989. doi: 10.3389/fmed.2020.572989

The days of the prediction between the detection of inflammatory factors and the time
occurring coagulation disorders, or Viral Sepsis Caused by SARS-CoV-2 (VSCS-2)

Front. Cell. Infect. Microbiol. 10:586054. doi: 10.3389/fcimb.2020.586054

Anticoagulant Doses for COVID-19-Associated Coagulopathies
(CACs) Prophylaxis and Treatment

Bali Med J. 2020; 9(2):482–8.

 CONCLUSION

• The role of coagulopathy in COVID-19 remains to be

clarified.
• Abnormal coagulation results, are associated with poor
prognosis.
• Anticoagulant is usefull for patients with COVID-19-
associated coagulopathies as a prophylaxis and treatment.
• Important for physician, especially pulmonologist to check
serum coagulation patients at the admission time.
Thank You