This patient is a 32-year-old male who presented with intermittent right chest stabbing pain since November 29th. He had a history of COVID-19 infection in September 2021. Imaging showed signs suggestive of chronic pulmonary embolism including Hampton's hump on CXR and enlargement of the right pulmonary artery on CT scan. Echocardiogram also supported chronic thromboembolic pulmonary hypertension. He was treated with 5 days of enoxaparin and then switched to dabigatran. Further workup was suggested to investigate possible causes of thrombophilia. The duration of anticoagulation in chronic thromboembolic pulmonary hypertension is indefinite to prevent recurrent pulmonary embolism.

1. Chest pain after COVID-19
infection, merely bad luck or the last straw?
許琬宜 廖優美 林佩瑾 邱世欣
高雄醫學大學附設中和紀念醫院 小兒科部 小兒血液腫瘤科
Apr/28/2023
一一二年度高雄地區兒科聯合病例討論會

2. Patient profile
• Gender: male
• Age: 32 year-old
• BW: 59.9 kg
• BH: 170 cm
• Admission date: 2022/Dec/05
• Chief complaint:
• Intermittent right chest stabbing pain
during 11/29-12/01
• Underlying disease
• HbH disease, without regular blood
transfusion, with splenectomy in 2006
• IgA Nephritis with persisted hematuria
and protienuria, CKD stage II
• Cholinergic allergic disease
• Cholecystitis with cholelithiasis, post
cholecystectomy in 2005
• Personal history
• Cigarette smoking, 1 pack per week for
1 year during collage
• Family history
• Grandfather and grandmother: HTN
• Mother: cervical cancer

3. Current Medicine
● Valsartan (Diovan 160mg/Tab), 0.5 Tab PO QD AMPC
● Dipyridamole (Dipyridamole 25mg/Tab), 1 Tab PO BID PC
● Benzbromarone (Nogout 100mg/Tab), 0.5 Tab PO QD HS
● Calcitriol (U-Ca 0.25 mcg/Cap), 1 Cap PO QOD AM
● Zinc gluconate (Zinga 78mg/Tab (Elemental Zn: 10mg)), 1 Tab PO QOD AM
● Buclizine (Buclizine 25mg/Tab), 1 Tab PO BID PC
● Ketotifen (Zatizen 1mg/Tab), 1 Tab PO BID PC
● Methylephedrine (DL-Methylephedrine 30mg/Tab), 1 Tab PO BID PC

4. Brief history
09/21
11/29
COVID-19 infection
Intermittent right chest stabbing pain
→ 他院ER: CXR, 3-day antibiotics for pneumonia
12/02 → 他院Chest OPD : mild right pleural effusion
→ 他院CV OPD : arrange EKG and MRI on 12/07
12/05 KMUH PED HEMA OPD : arrange admission

5. Brief history
09/21
11/29
Exacerbation: position (-), movement(-), breathing (-)
Relief: taking deep breathe gradually without any analgesics
Associated S/S: fever (-), dyspnea (-), orthopnea (-), radiation
pain / numbness (-), edema (-), bodyweight increased/loss (-),
poor appetite (-), fatigue (-), strain injury (-), trauma (-)
COVID-19 infection
Intermittent right chest stabbing pain
→ 他院ER: CXR, 3-day antibiotics for pneumonia
12/02 → 他院Chest OPD : mild right pleural effusion
→ 他院CV OPD : arrange EKG and MRI on 12/07
12/05 KMUH PED HEMA OPD : arrange admission

6. Physical Examination
SpO2:98.0 % BT:36.7 ℃ PR:98.0 bpm RR:20.0 cpm
BP:113/78 mmHg
Consciousness: alert
Conjunctiva: not pale
Sclera/Conjunctiva: anicteric
Neck: supple。
Chest: symmetric movement with respiration
Breath sound:
Right side: clear。 Left side: clear
Other site: not applicable
Heart sound:
Rhythm: regular
S1 and S2: normal S3: absent S4: absent
Murmur: absent Other extra sound: absent
Abdomen:
Inspection: normal
Bowel sound: normoactive
Palpation:
general: soft flat
tenderness: absent
rebound pain: absent
Percussion: normal
Flank knocking pain: absent
General appearance: grossly normal
Edema: absent

7. Differential Diagnosis
● Pleural effusion
● Pleuritis
● Pulmonary embolism
● Pneumonia
● Malignacy

8. Clinical Course
12/5
(D1)
CXR
EKG
Lab 1

9. CXR
Palla sign
(right descending
pulmonary artery
enlargement)
Hampton's hump
(a wedge shaped,
pleural based
consolidation
associated with
pulmonary infarction)

10. EKG

11. Laboratory Data 1
Infection: CBC,DC,CRP, Gas
Heart: proBNP, troponinI, CPK, CKMB
Liver: GOT,GPT, Bil (D/T), ASMA
Kidney: BUN, Cr, E+, Albumin, C3, C4, Lipid profile, IgA, U/R. U-Cr, U-TP
Thrombosis: PT,PT, Fibrinogen, D-dimer
Malignancy: CEA, SCC, CA19-9
Thalasemia: Folic acid, Ferritin

13. Clinical Course
12/5
(D1)
CXR
EKG
Lab 1
CXR: Hampton hump and palla sign
EKG: mild tachycardia
Lab: D-dimer increased
=> Highly suspect pulmonary embolism
12/6
(D2)
Chest
CT
Chest
man

14. Chest CT

15. Chest CT

16. Clinical Course
12/5
(D1)
CXR
EKG
Lab 1
12/6
(D2)
Chest
CT
Chest
man
12/7
(D3)
Heart
echo
Lab 2
CV
man

17. Laboratory data 2: possible cause of thrombophilia
• Thrombophilia:
COVID19 hypercoagulability (D-DIMER, Fibrinogen, Factor 8 )
APS (aPsPt-G&M, LAC, aCLIgG/M, B2GP1-M)
Inherited disease (PC, PS, Anti-thrombin III)
Homocysteine
JAK2
Factor 7,9,11
Thrombin time
• Survey the possible bleeding site :
U/R, S/R

19. Cardiac echo

20. Clinical Course
12/5
(D1)
CXR
EKG
Lab 1
12/6
(D2)
Chest
CT
Chest
man
12/7
(D3)
Heart
echo
Lab 2
CV
man
12/8
(D4)
5-day LMWH:
Enoxaparin 1mg/kg/dose Q12H

21. Clinical Course
12/5
(D1)
CXR
EKG
Lab 1
12/6
(D2)
Chest
CT
Chest
man
12/7
(D3)
Heart
echo
Lab 2
CV
man
12/8
(D4)
5-day LMWH:
Enoxaparin 1mg/kg/dose Q12H
12/13
(D9)
Dabigatran 150mg BID →
DVT
echo
•Suspected resolved thrombosis
in the left popliteal vein
•Chronic venous insufficiency in
the right popliteal vein
→ Discharge with OPD f/u

22. Final Diagnosis
• Pulmonary embolism
• Inactive disease
• Pulmonary hypertension
• suspect chronic thromboembolic pulmonary hypertension
• HbH disease
• without regular blood transfusion
• with splenectomy when 16 y/o
• Thrombocytosis
• IgA Nephritis with persisted hematuria and protienuria, CKD stage II
• Chronic venous insufficiency in the right popliteal vein
• Resolved event
• COVID-19 infection
• Suspected resolved thrombosis in the left popliteal vein

23. COVID-19 infection & thrombosis

24. Incidence of venous thromboembolism (VTE) in COVID-19 patients
• 3% in non-ICU hospitalized patients
• 13% in ICU patients
• did not increase in non-hospitalized patients in the subsequent 30 days
Blood Adv. 2020 Nov 10;4(21):5373-5377.
JAMA. 2020 Aug 25;324(8):799-801.
J Emerg Med. 2022 Jun;62(6):716-724

25. Heart. 2022 Dec 22;109(2):119-126

26. Heart. 2022 Dec 22;109(2):119-126

27. Heart. 2022 Dec 22;109(2):119-126

28. SN Compr Clin Med. 2022;4(1):190.

29. COVID-19-associated coagulopathy

30. COVID-19-associated coagulopathy
Nat Rev Immunol. 2022 Oct;22(10):639-649
• Micro/Macro-vascular thrombosis
• Arterial/Venous thrombosis

31. COVID-19-associated coagulopathy
Anaesthesia 2020; 75 : 1432-6.
• Micro/Macro-vascular thrombosis
• Arterial/Venous thrombosis
• Elevated D-dimer & Fibrinogen; normal PLT, PT/aPTT

32. COVID-19-associated coagulopathy
Innate immune response
Vasculopathy
Blood. 2020 Jul 23; 136(4): 381–383

33. COVID-19-associated coagulopathy
Treatment suggestion
CHEST 2022; 162(1):213-225

34. In the absence of confirmed or suspected VTE
• All hospitalized adults with COVID-19 should at a minimum receive
pharmacologic thromboprophylaxis, unless the risk of bleeding even on
prophylactic dosing outweighs the risk of thrombosis
• LMWH is preferred over unfractionated heparin (UFH)
• In patients for whom anticoagulants are contraindicated or unavailable,
mechanical thromboprophylaxis (e.g., pneumatic compression devices) can be
used
• ICU patients: standard prophylactic doses of anticoagulants
• Non-ICU patients: therapeutic-intensity anticoagulation
COVID-19-associated coagulopathy
Treatment suggestion

35. Nat Rev Immunol. 2022 Oct;22(10):639-649
COVID-19-associated coagulopathy

36. Back to our case……
Q1: Old or new pulmonary embolism?

38. Pulmonary embolism diagnosis
• Lab finding
• Unexplained hypoxemia in the
setting of a normal chest
radiograph
• D-dimer
• Negative (<5ng/dL) predictive
value in patients with a low or
intermediate probability of PE

40. 2014/5/31
Admission

41. Back to our case……
Q1: Old or new pulmonary embolism?

42. Back to our case……
Q1: Old or new pulmonary embolism?
• Chest stabbing pain
• Fluctuated SpO2
• No elevated D-dimer
• CXR: Palla sign (right descending pulmonary artery enlargement)
• Cardiac echo:
• suspect chronic thromboembolic pulmonary hypertension (CTPH)

43. Back to our case……
Q1: Old or new pulmonary embolism?
• Chest stabbing pain
• Fluctuated SpO2
• No elevated D-dimer
• CXR: Palla sign (right descending pulmonary artery enlargement)
• Cardiac echo:
• suspect chronic thromboembolic pulmonary hypertension (CTPH)

44. Back to our case……
Q1: Old or new pulmonary embolism?
• Chest stabbing pain
• Fluctuated SpO2
• No elevated D-dimer
• CXR: Palla sign (right descending pulmonary artery enlargement)
• Cardiac echo:
• suspect chronic thromboembolic pulmonary hypertension (CTPH)
Hemostasis and Thrombosis Basic
Principles and Clinical Practice 6/E 2012

45. Diagnosis of chronic thromboembolic pulmonary hypertension

46. Back to our case……
Q1: Old or new pulmonary embolism?
• Chest stabbing pain
• Fluctuated SpO2
• No elevated D-dimer
• CXR: Palla sign (right descending pulmonary artery enlargement)
• Cardiac echo:
• suspect chronic thromboembolic pulmonary hypertension (CTPH)
Hemostasis and Thrombosis Basic
Principles and Clinical Practice 6/E 2012

47. Back to our case……
Q1: Old or new pulmonary embolism?
Q2: The duration of anti-coagulant ?
Hemostasis and Thrombosis Basic
Principles and Clinical Practice 6/E 2012

48. Back to our case……
Q1: Old or new pulmonary embolism?
Q2: The duration of anti-coagulant ?
Hemostasis and Thrombosis Basic
Principles and Clinical Practice 6/E 2012

49. DOAC(Direct Oral Anti-coagulant)

50. DOAC(Direct Oral Anti-coagulant)

51. Warfarin
• T1/2: 36hrs
• Require 4~5 days to achieve a therapeutic INR

53. Thank You