Venous thromboembolism in COVID-19: A meta-summary of cases

Naif Saad ALGhasab; Leen A. Altamimi; Mohammed Salem Alharbi; Sulaman S. ALMesned; Aditya K. Khetan

doi:10.15537/smj.2022.43.9.20220316

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- Flow chart of study selection.

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Table 1

- Characteristics of published cases of coronavirus associated venous thromboembolism (N=48).

Variable	Valid= (n/48)	n (%)	Confirmed PE (n=38)	Confirmed DVT (n=10)	P-value
Age (years)**	48	56±17.17	56±16.90	58.00±19.07	0.796
Male	48	34 (70.8)	26 (68.4)	8 (80.0)	0.745
Presenting symptoms of COVID-19	45
Fever		29 (60.4)	24 (63.2)	5 (50.0)	0.694
Chills		3 (6.2)	2 (5.3)	1 (10.0)	1.000
Cough		29 (60.4)	26 (68.4)	3 (30.0)	0.065
SOB, dyspnoea		24 (50.0)	22 (57.9)	2 (20.0)	0.076
Fatigue, malaise		9 (18.8)	7 (18.4)	2 (20.0)	1.000
Myalgia		9 (18.8)	6 (15.8)	3 (30.0)	0.569
Headache		6 (12.5)	5 (13.2)	1 (10.0)	1.000
New loss of taste or smell (anosmia)		1 (2.1)	1 (2.6)	0 (0.0)	1.000
Nausea or vomiting		2 (4.2)	2 (5.3)	0 (0.0)	1.000
Diarrhea		6 (12.5)	5 (13.2)	1 (10.0)	1.000
Chest pain (pleuritic pain)		5 (10.4)	4 (10.5)	1 (10.0)	1.000
Presenting symptoms/signs of PE	38
Chest pain		9 (18.8)	8 (21.1)	1 (10.0)	0.733
Tachycardia		2 (4.2)	1 (2.6)	1 (10.0)	0.882
Shortness of breath (dyspnea)		30 (62.5)	27 (71.1)	3 (30.0)	0.044
Hypoxia (O2 saturation <90%)		9 (18.8)	9 (23.7)	0 (0.0)	0.211
Presenting symptoms of DVT	9
Unilateral erythematous swelling of the lower extremity		4 (8.3)	1 (2.6)	3 (30.0)	0.032
Leg pain or tenderness of the thigh or calf		3 (6.2)	0 (0.0)	3 (30.0)	0.006
Comorbidities	34
Diabetes mellitus		13 (27.1)	10 (26.3)	3 (30.0)	1.000
Hypertension		19 (39.6)	14 (36.8)	5 (50.0)	0.694
Dyslipidemia		11 (22.9)	8 (21.1)	3 (30.0)	0.86
Asthma		6 (12.5)	6 (15.8)	0 (0.0)	0.42
Atrial fibrillation		5 (10.4)	3 (7.9)	2 (20.0)	0.594
Coronary artery disease		4 (8.3)	1 (2.6)	3 (30.0)	0.032
Congestive heart failure		4 (8.3)	2 (5.3)	2 (20.0)	0.391
Hypothyroidism		4 (8.3)	2 (5.3)	2 (20.0)	0.391
Obstructive sleep apnea		2 (4.2)	2 (5.3)	0 (0.0)	1.000
Risk factors for VTE	41
Overweight/ obese		6 (12.5)	6 (15.8)	0 (0.0)	0.42
Immobility		1 (2.1)	1 (2.6)	0 (0.0)	1.000
Prior VTE		3 (6.2)	1 (2.6)	2 (20.0)	0.199
Advanced age (>40 years)		38 (79.2)	30 (78.9)	8 (80.0)	1.000
Hospitalization, surgery		2 (4.2)	1 (2.6)	1 (10.0)	0.882
Family history of VTE, stroke		2 (4.2)	1 (2.6)	1 (10.0)	0.882
Recent or recurrent cancer		1 (2.1)	0 (0.0)	1 (10.0)	0.468
Serology	48
D-dimer >500ng/ml		38 (79.2)	30 (78.9)	9 (90.0)	0.403
Lactate (mml/L) **		4.93±4.40	5.74±4.39	0.90	N/A
LDH (units/L) **		454.89 ±222.34	454.89±222.34	0 (0.0)	N/A
Ferritin >1000 ng/ml		8 (16.7)	8 (21.1)	0 (0)	N/A
EKG	4	4 (8.3)	4 (10.5)	0 (0.0)	0.668
Normal sinus rhythm		3 (6.3)	3 (7.9)	0 (0.0)
Sinus tachycardia		1 (2.1)	1 (2.6)	0 (0.0)
Echocardiogram	11
Right ventricular dysfunction		6 (12.5)	6 (15.8)	0 (0.0)	0.42

Values are presented as number and percentages (%). **Median, N/A- not available, COVID-19: coronavirus disease 2019, PE: pulmonary embolism, DVT: deep vein thrombosis, VTE: venous thromboembolism, EKG: electrocardiogram, ICU: intensive care unit, LDH: lactic acid dehydrogenase, O2: Oxygen, SOB: shortness of breath

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Table 1

- Characteristics of published cases of coronavirus associated venous thromboembolism (continuation).

Variable	Valid= (n/48)	Total cases (n=48)	Confirmed PE (n=38)	Confirmed DVT (n=10)	P-value
Covid management	25
Hydroxychloroquine		15 (31.2)	15 (39.5)	0 (0.0)	0.044
Azithromycin		6 (12.5)	6 (15.8)	0 (0.0)	0.42
Amoxicillin clavulanate		4 (8.3)	4 (10.5)	0 (0.0)	0.668
Dexamethasone		5 (10.4)	3 (7.9)	2 (20.0)	0.594
Cefepime		5 (10.4)	3 (7.9)	2 (20.0)	0.594
Linezolid		3 (6.2)	2 (5.3)	1 (10.0)	1.000
Outcome	48
Recovery or discharge		37 (80.4)	30 (81.1)	7 (77.8)	1.000
Death		9 (19.6)	7 (18.9)	2 (22.2)	1.000
Undetermined		2 (4.1)	1 (2.6)	1 (0.10)	0.882
Severity of Covid infection	28
ICU admissions		10 (20.8)	9 (23.7)	1 (10.0)	0.663
Average length of ICU admission (days)		3.31 (±8.25)	1.84 (±3.54)	40.00 (1 patient)	N/A
Average length of hospital admission		4.90 (±4.45)	4.83 (±4.67)	5.50 (±2.12)	0.847
Complication during admission		13 (27.1)	10 (26.3)	3 (30.0)	1.000
Time of dx till VTE discovery**		10.30 (±7.92)	10.82 (±8.28)	8.11 (±6.11)	0.363
Duration of COVID symptoms**	43	7.91 (±7.03)	7.97 (±7.45)	7.57 (±4.65)	0.892

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Table 2

- Imaging characteristics of confirmed cases of coronavirus associated venous thromboembolism.

Author name	Age/Gender	D-dimer >500 ng/mL**	Chest x-ray with pneumonia		Echocardiogram	CTPA	Duplex ultrasound / CUS	Other
Davis, Kenyani	34 M	N/A	+		N/A	Right Lower Lobe PE	N/A	N/A
Aoi et al	70 F	+	N/A		Dilated RV and clot in transit	Saddle PE	N/A	N/A
Brüggemann et al	57 M	++	+		N/A	Right pulmonary artery and bilateral sub-segmental PE	N/A	CT Brain showed right frontal lobe infarction
Colombo et al	73 F	N/A	+		N/A	Bilateral PE	Normal	N/A
Delcros et al	31 M	++	N/A		N/A	Bilateral PE	N/A	CT venography showed a femoropopliteal DVT expanding to the subrenal vena cava
Fiorini et al	26 F	+	N/A		Normal	Bilateral sub-segmental PE	Normal	N/A
Haider et al	46 F	+	+		N/A	Bilateral PE (segmental and sub-segmental)	N/A	N/A
Kasinathan et al	20 F	+	+		N/A	Bilateral PE	N/A	N/A
Mene-Afejuku et al	67 M	++	+		N/A	Bilateral PE	N/A	N/A
	58 F	++	+		N/A	Large saddle PE extending to lobar, segmental, and subsegmental pulmonary arteries.	N/A	N/A
	89 F	++	N/A		N/A	Bilateral PE	N/A	N/A
	82 F	++	+		N/A	Bilateral PE	N/A	N/A
Akel et al	28 F	++	N/A		Dilated RV with interventricular septal flattening	Bilateral extensive PE	N/A	N/A
	52 M	++	+		N/A	Bilateral PE	N/A	N/A
	62 M	++	N/A		McConnell’s sign	Bilateral PE	N/A	N/A
	49 M	++	N/A		RV dilatation along with systolic and diastolic flattening of the septum	Right segmental PE	N/A	N/A
	59 F	+	+		N/A	Bilateral PE	N/A	N/A
	69 M	++	N/A		N/A	Large bilateral PE	N/A	N/A
Fortuzi et al	52 M	++	+		N/A	Right PE	N/A	N/A
	74 F	++	N/A		N/A	Bilateral PE	N/A	N/A
	31 M	+	N/A		N/A	Right sub-segmental PE	N/A	N/A
Kanso et la	68 M	++	+		N/A	Right segmental PE	N/A	N/A
Kanso et la	62 M	++	+		N/A	Left segmental PE	N/A	N/A
Lewis et al	77 M	++	N/A		N/A	Bilateral PE	N/A	N/A
	70 M	+	N/A		N/A	N/A	Partial occlusion in popliteal and femoral veins	N/A
	76 M	++	N/A		N/A	Right segmental and sub-segmental PE	N/A	N/A
	80 M	N/A	N/A		N/A	N/A	DVT of femoral vein	N/A
	92 M	+				Care withdrawn
Manek et al	66 M	++	N/A	N/A		Bilateral PE	DVT of the left femoral vein	N/A
Mangala et al	55 M	+	N/A	N/A		Right segmental PE.	N/A	EKG showed normal sinus rhythm
Mangala et al	67 F	N/A	+	N/A		PE in right upper lobe pulmonary artery and segmental branches of right lower lobe pulmonary artery	N/A	EKG showed normal sinus rhythm
Nelson, et al	61 M	+	+	N/A		Right segmental PE	Multiple areas of turbulent flow in lower extremity	N/A
Nelson, et al	54 M	++	+	N/A		Negative for PE	Turbulent blood flow in the right lower extremity and right calf vein thrombosis	N/A
Overstada et al	55 M	++	N/A	N/A		N/A	DVT in the left leg	N/A
	39 M	+	N/A	N/A		Bilateral PE	N/A	N/A
	57 M	+	N/A	N/A		Left segmental PE	N/A	N/A
	55 M	++	+	N/A		Bilateral PE	N/A	N/A
Sakr et al	66 M	++	+	Dilated RV and paradoxical septal motion		Bilateral PE	Right femoral vein thrombosis	N/A
	65 M	N/A	+	Mild dilatation of the RV with preserved LV function		Right segmental PE	Normal	N/A
	56 M	N/A	+	N/A		Right segmental PE	Normal	N/A
	41 M	N/A	+	Acute right heart failure with paradoxical septal motion and large thrombus in the right pulmonary artery		N/A	Thrombosis of the left femoral vein	N/A
	49 M	N/A	+	N/A		Right segmental PE	Normal	N/A
Salam et al	36 M	+	+	McConnell’s sign with septal flattening		Saddle PE with significant clot burden.	Normal	EKG showed sinus tachycardia
Sethi et al	44 M	++	+	EF of 45%, severely dilated and reduced RV systolic function with a flattening of the septum.		N/A	Normal	N/A
Singh et al	69 F	+	N/A	N/A		N/A	N/A	CTA showed thrombotic occlusion in tibial arteries on the right leg, aortic thrombus in the aorta, with evidence of splenic infarct.
	33 M	+	N/A	N/A		N/A	N/A	CTA showed occlusive thrombus at the aortic bifurcation with near-complete occlusion of right common iliac arteryy.
	69 F	+	N/A	EF of 25%-35% and evidence of a large LV thrombus at the apex.		N/A	N/A	N/A
Uppuluri et al	32 M	N/A	+	N/A		Left segmental and subsegmental PE.	N/A	EKG showed normal sinus rhythm

N/A: not available, RV: right ventricle, EF: ejection fraction, LV: left ventricle, PE: pulmonary embolism, Echo: echocardiogram, CT: computed tomography, CTPA: CT pulmonary angiography, CUS: compression ultrasonography, CTA: computed tomography angiography, EKG: electrocardiogram, F: female, M: male, **(+) means >500 ng/mL, (++) means >5000 ng/mL.

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Table 3

- Anti-coagulation type used to treat confirmed cases of coronavirus associated venous thromboembolism.

Author name	Age/Gender	Type of anticoagulant			Outcome	Complications
Author name	Age/Gender	Prior to VTE	VTE treatment (during hospitalization)	Upon discharge	Outcome	Complications
Kenyani Davis	34 M	N/A	N/A	NOAC	Recovery or discharge	N/A
Aoi et al	70 F	Heparin	IV Heparin	N/A	Death	Cardiac arrest
Brüggemann et al	57 M	LMWH (nadroparin)	LMWH (tinzaparin)	N/A	Recovery or discharge	Ischemic stroke
Colombo et al	73 F	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	Obstructive shock
Delcros et al	31 M	LMWH (enoxaparin)	LMWH (enoxaparin)	LMWH (enoxaparin)	Recovery or discharge	N/A
Fiorini et al	26 F	N/A	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
Haider et al	46 F	Heparin	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
Kasinathan et al	20 F	N/A	LMWH (enoxaparin)	LMWH (enoxaparin)	Recovery or discharge	N/A
Mene-Afejuku et al	67 M	Heparin	NOAC	NOAC	Recovery or discharge	N/A
	58 F	Heparin	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
	89 F	Heparin	IV Heparin	NOAC	Recovery or discharge	N/A
	82 F	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
Akel et al	28 F	LMWH (enoxaparin)	tPA, LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
	52 M	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
	62 M	N/A	tPA, IV heparin	NOAC	Recovery or discharge	N/A
	49 M	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
	59 F	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
	69 M	Heparin	IV Heparin	NOAC	Recovery or discharge	N/A
Fortuzi et al	52 M	Heparin	IV Heparin	N/A	Death	AKI, Septic shock
	74 F	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
	31 M	N/A	NOAC	NOAC	Recovery or discharge	N/A
Kanso et la	68 M	LMWH (enoxaparin)	LMWH (enoxaparin)	Warfarin	Recovery or discharge	N/A
Kanso et la	62 M	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC	Recovery or discharge	N/A
Lewis et al	77 M	NOAC (Apixaban)	LMWH (enoxaparin)	N/A	Death	Multi-system organ failure
	70 M	NOAC (Apixaban)	LMWH (enoxaparin)	NOAC (Apixaban), LMWH (enoxaparin), loaded warfarin	Recovery or discharge	N/A
	76 M	NOAC (Rivaroxaban)	LMWH (enoxaparin)	NOAC (Rivaroxaban)	Recovery or discharge	N/A
	80 M	NOAC (Rivaroxaban)	LMWH (enoxaparin)	LMWH (enoxaparin)	Death	N/A
	92 M	NOAC (Apixaban)	Care withdrawn	Care withdrawn	Death	Left-sided facial droop, left-sided hemiplegia and stroke
Manek et al	66 M	N/A	IV heparin	NOAC (Apixaban)	Recovery or discharge	N/A
Mangala et al	55 M	LMWH (enoxaparin)	LMWH (enoxaparin)	NOAC (Apixaban)	Recovery or discharge	aspiration pneumonia
Mangala et al	67 F	LMWH (enoxaparin)	IV heparin	NOAC (Apixaban)	Recovery or discharge	N//A
Nelson et al	61 M	N/A	IV heparin	N/A	Death	Septic shock
Nelson et al	54 M	N/A	tPA, LMWH (enoxaparin)	N/A	Death	N/A.
Overstada et al	55 M	N/A	NOAC (Apixaban)	N/A	Recovery or discharge	N/A
	39 M	N/A	NOAC (Apixaban)	NOAC (Apixaban)	Recovery or discharge	N/A
	57 M	N/A	NOAC (Apixaban)	NOAC (Apixaban)	Recovery or discharge	N/A
	55 M	N/A	LMWH (Dalteparin)	LMWH (Dalteparin)	Recovery or discharge	N/A
Sakr et al	66 M	N/A	tPA and IV heparin	N/A	Death	Progressive multi-organ failure
	65 M	N/A	LMWH (enoxaparin)	LMWH	Recovery or discharge	N/A
	56 M	N/A	LMWH (enoxaparin)	LMWH	Recovery or discharge	N/A
	41 M	N/A	tPA, VA -ECMO, LMWH (tinzaparine)	LMWH	Recovery or discharge	Ventilator-associated pneumonia, severe hypoxemia.
	49 M	LMWH (enoxaparin)	LMWH	N/A	Death	Necrotizing pneumonia
Salam et al	36 M	N/A	tPA , LMWH (enoxaparin)	NOAC (Apixaban)	Recovery or discharge	N/A
Sethi et al	44 M	N/A	tPA, LMWH (enoxaparin), VA -ECMO	LMWH	Recovery or discharge	Bleeding within the oropharynx
Singh et al	69 F	N/A	IV heparin	NOAC (Rivaroxaban) with low dose ASA	Recovery or discharge	N/A
	33 M	N/A	IV heparin	NOAC (Rivaroxaban)	Recovery or discharge	N/A
	69 F	NOAC (Apixaban)	LMWH	N/A	Undetermined	Massive stroke in the territory of the left middle cerebral artery and clinically deteriorated.
Uppuluri et al	32 M	N/A	LMWH (enoxaparin)	NOAC (Apixaban)	Undetermined	N/A

VTE: venous thromboembolism, N/A: not available, M: male, F: female, LMWH: low molecular weight heparin, IV: intravenous; NOAC: novel oral anticoagulants, VA-ECMO: venoarterial extracorporeal membrane oxygenation, AKI: acute kidney injury, tPA: tissue plasminogen activator, ASA: acetylsalicylic acid (aspirin)