Hemostatic system and COVID-19 crosstalk: A review of the available evidence

Table 1 The various hematological parameters in significant relation to coronavirus disease 2019 and their mechanisms

Hematological parameter	Significant relation to COVID-19	Mechanism
High RDW (greater than 14.5%)	Increase in mortality risk (from 11% to 31%)[86]	Not completely understood however reports suggested elevated RDW was attributed to affection of RBC production kinetics[86]
Leucopenia or lymphopenia (ALC < 1.0 × 109/L)	Observed in most of COVID cases especially hospitalized patients and associated with poor prognosis[86]	(1) Defective immune response; and (2) Drug induced as with steroids[87]
Normal or increased platelet count	Found in some cases of COVID-19	May be caused by to the large amounts of platelets produced in response to increased thrombopoietin formation from liver stimulation and megakaryocytes in the lung[88]
Prolonged PT and aPTT, elevations of D dimer, fibrinogen and FDP and decreased levels of antithrombin III	Direct relationship was observed between severity of COVID and affection of coagulation profile, Overt DIC (ISTH score of 5 and higher) is seen more frequently in non-survivors[89]	aPTT prolongation is caused by increased Factor VIII level and Factor XII deficiency secondary to the presence of factor XII inhibitors. Von Willebrand factor is quantitatively increased. LA is positive in 91% of those with prolonged aPTT. The presence of both LA and Factor XII deficiency are not associated with bleeding tendency

ALC: Absolute lymphocyte count; aPTT: Activated partial thromboplastin time; COVID-19: Coronavirus disease 2019; DIC: disseminated intravascular coagulation; ISTH: International Society on Thrombosis and Hemostasis; LA: Lupus anticoagulant; PT: Prothrombin time; RBC: Red blood cell; RDW: Red cell distribution width.

Table 2 Various laboratory parameters that are altered in severe acute respiratory syndrome coronavirus 2 and their implications in coronavirus disease 2019 severity

Clinical index	Alterations with COVID-19 severity	Ref.
Neutrophil-to-lymphocyte ratio	Increased	[84,122-124,131,134-136]
CRP	Increased	[122,124,125,128,129,131,134-136,137-144]
Platelets	Decreased	[78,83,122,126,129,131-133,136,145,146]
Lymphocytes	Decreased	[78,128,129,131,134-136,147,148]
D-dimer	Increased	[55,83,84,127,128,131,137,144-146,149-152]
Ferritin	Increased	[91,94,128,129,131,134,135,137-139,144,153-155]
Procalcitonin	Increased	[83,84,128,144,156-158]
Lactate dehydrogenase	Increased	[106,129-131,152,159-173]
Albumin	Decreased	[111,116,128,129,136,148,174-186]

COVID-19: Coronavirus disease 2019; CRP: C-reactive protein.

Table 3 Frequency of venous thromboembolic complications in coronavirus disease 2019 patients

Ref.	Proportion	Cumulative incidence	Median follow-up	Patients
Cui et al[59]	20/81 (25%)	NR	NR	ICU patients
Klok et al[60]	68/184 (37%)	57% or 49% adjusted for competing risk of death	14 d	ICU patients only.19 PE were limited to subsegmental arteries.65/68 venous events were PE (95.6%)
Poissy et al[61]	VTE 22.2% of 54 ICU admitted
Helms et al[44]	27/150 (18%)	NR	NR	ICU patients with ARDS 25/27 events were PE (92.5%)
Poissy et al[61]	PE only 22/107 (20.6%)	20.4% calculated at ICU day 15	6 d	ICU only
Middeldorp et al[63]	Venous thromboembolism 39% of COVID-19 ICU cases 74 patients
Llitjos et al[64]	DVT: 18/26 (69%); PE: 6/26 (23%)	NR	NR	ICU patients. Systematic ultrasound screening
Léonard-Lorant et al[183]	PE only 32/106 (30%)	NR	NR	24/32 (75%) PE-positive patients were in the ICU
Grillet et al[184]	PE only 23/100 (23%)	NR	NR	Ward: 6/61 (9.8%); ICU: 17/39 (43.6%)
Middeldorp et al[63]	33/198 (17%)	15% at 7 d; 34% at 14 d	5 d	Ward: 4/123 (3.3%); ICU: 35/75 (47%); 11 (5.4%) clots detected on screening 11/33 events were PE (33%)
Lodigiani et al[185]	16/362 (4.4%)	21% (time not reported)	10 d	ICU 4/48(8.3%); Ward 12/314 (3.8%)
Thomas et al[186]	6/63 (9%)	27%	8 d	ICU patients
Cattaneo et al[108]	DVT only 0/388 (0%)	NR	NR	Non-ICU Ward 64 patients had screening ultrasound. All negative

DVT: Deep vein thrombosis; ICU: Intensive care unit; NR: Not reported; PE: Pulmonary embolism.