Table 1. Studies examining the... | American Society of Hematology

Table 1.

Studies examining the procoagulant effects of cell-free DNA on coagulation in vitro

Reference	Cellular origin	Method of purification	Coagulation Assay	Type of DNA	Conclusions
Kannemeier et al 2007⁵²	China Hamster ovarian cell line	Silica-based affinity chromatography	Thromboelastography	Genomic	DNA shortens clotting times in whole blood and plasma, activates FXII and amplifies thrombin-dependent FXIa generation in buffer
			Clotting times in plasma
			Chromogenic assay in plasma
			Chromogenic assay in purified system
Oemcke et al 2009⁵³	Normal human neutrophils	Guanidinium isothiocyanate detergent + ethanol precipitation	Chromogenic assay for PK hydrolysis in plasma	Genomic	DNA binds FXII and HK and promotes PK hydrolysis in plasma
Swystun et al 2011⁵⁴	Chemotherapy-treated normal whole blood or neutrophils	Silica-based affinity chromatography	Thrombin generation in PPP	Genomic	Extracellular DNA released from chemotherapy-treated blood cells increases thrombin generation in plasma
Vu et al 2015⁵⁵	A549 cells	Silica-based affinity chromatography	Clotting times in plasma	Genomic	DNA shortens clotting times, increases TG in plasma, promotes FXII activation and FXIa generation in buffer
			Thrombin generation in PPP
			FXII activation, FXIIa-dependent and thrombin-dependent FXIa generation in purified systems
Bhagirath et al 2015⁵⁶	HEK297 cells	Silica-based affinity chromatography.	Thrombin generation in PPP	Genomic	All types of DNA enhance TG in plasma
	Bacteria	Bacterial DNA was purchased.		Mitochondrial
				Bacterial
Kokoye et al 2016¹⁴	Normal human leukocytes	Phenol-chloroform extraction	Western blot for FXII and PK activation in purified systems	Genomic	DNA enhances FXII and PK activation in buffer and enhances thrombin generation in plasma.
Kokoye et al 2016¹⁴	Normal human leukocytes	Phenol-chloroform extraction	Thrombin generation in PPP	Genomic
Noubouossie et al 2017²⁴	Normal human neutrophils	Silica-based affinity chromatography	ELISA for FXIa-C1INH complexes in purified contact system	Genomic	DNA triggers contact activation in buffer and thrombin generation in PFP and PRP
			Chromogenic assays for FXIa generation in buffer		DNA amplifies FXIIa- and thrombin-dependent FXIa generation in buffer
			Thrombin generation in PFP or PRP		DNA amplifies TF-initiated TG in plasma
Ivanov et al 2017⁵⁷	Normal human leukocytes	Phenol-chloroform extraction	Chromogenic assays for PK and FXI activation	Genomic	DNA promotes PK (in the presence of HK) and FXI activation
Ivanov et al 2017⁵⁷	Normal human leukocytes	Phenol-chloroform extraction	Thrombin generation in plasma	Genomic	DNA initiates thrombin generation in plasma independently of TF, and amplifies TF-initiated TG in plasma

Reference	Cellular origin	Method of purification	Coagulation Assay	Type of DNA	Conclusions
Kannemeier et al 2007⁵²	China Hamster ovarian cell line	Silica-based affinity chromatography	Thromboelastography	Genomic	DNA shortens clotting times in whole blood and plasma, activates FXII and amplifies thrombin-dependent FXIa generation in buffer
			Clotting times in plasma
			Chromogenic assay in plasma
			Chromogenic assay in purified system
Oemcke et al 2009⁵³	Normal human neutrophils	Guanidinium isothiocyanate detergent + ethanol precipitation	Chromogenic assay for PK hydrolysis in plasma	Genomic	DNA binds FXII and HK and promotes PK hydrolysis in plasma
Swystun et al 2011⁵⁴	Chemotherapy-treated normal whole blood or neutrophils	Silica-based affinity chromatography	Thrombin generation in PPP	Genomic	Extracellular DNA released from chemotherapy-treated blood cells increases thrombin generation in plasma
Vu et al 2015⁵⁵	A549 cells	Silica-based affinity chromatography	Clotting times in plasma	Genomic	DNA shortens clotting times, increases TG in plasma, promotes FXII activation and FXIa generation in buffer
			Thrombin generation in PPP
			FXII activation, FXIIa-dependent and thrombin-dependent FXIa generation in purified systems
Bhagirath et al 2015⁵⁶	HEK297 cells	Silica-based affinity chromatography.	Thrombin generation in PPP	Genomic	All types of DNA enhance TG in plasma
	Bacteria	Bacterial DNA was purchased.		Mitochondrial
				Bacterial
Kokoye et al 2016¹⁴	Normal human leukocytes	Phenol-chloroform extraction	Western blot for FXII and PK activation in purified systems	Genomic	DNA enhances FXII and PK activation in buffer and enhances thrombin generation in plasma.
Kokoye et al 2016¹⁴	Normal human leukocytes	Phenol-chloroform extraction	Thrombin generation in PPP	Genomic
Noubouossie et al 2017²⁴	Normal human neutrophils	Silica-based affinity chromatography	ELISA for FXIa-C1INH complexes in purified contact system	Genomic	DNA triggers contact activation in buffer and thrombin generation in PFP and PRP
			Chromogenic assays for FXIa generation in buffer		DNA amplifies FXIIa- and thrombin-dependent FXIa generation in buffer
			Thrombin generation in PFP or PRP		DNA amplifies TF-initiated TG in plasma
Ivanov et al 2017⁵⁷	Normal human leukocytes	Phenol-chloroform extraction	Chromogenic assays for PK and FXI activation	Genomic	DNA promotes PK (in the presence of HK) and FXI activation
Ivanov et al 2017⁵⁷	Normal human leukocytes	Phenol-chloroform extraction	Thrombin generation in plasma	Genomic	DNA initiates thrombin generation in plasma independently of TF, and amplifies TF-initiated TG in plasma

HK, high-molecular-weight kininogen; PK, prekallikrein; PPP, platelet-poor plasma; PRP, platelet-rich plasma; C1INH, C1 esterase inhibitor; TG, thrombin generation.

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