Table 1. Therapeutic strategies... | American Society of Hematology

Table 1.

Therapeutic strategies targeting the interplay between bacterial components, the contact pathway of coagulation, and immunothrombosis

Therapeutic strategy	Target	Mechanism	Clinical status
FXI inhibitors	FXI	Inhibit FXI activation or activity to prevent thrombosis	Phase 2/3 trials²⁴^,^112-115
FXII inhibitors	FXII	Block FXII activation	Phase 2 trials¹¹²^,¹¹⁶
PK inhibitors	Prekallikrein	Inhibit kallikrein-kinin system	Approved for HAE, not yet tested in sepsis^117-119
Complement inhibitors	Complement components	Reduce inflammatory response, limit LPS release	Preclinical to early clinical trials¹⁰¹; some agents approved for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome¹²⁰
Antiendotoxin therapies	LPS	Remove endotoxins	Investigational/clinical use in select cases⁹⁶^,⁹⁷^,¹⁰²^,¹¹⁰
Broad-spectrum antibiotics	Bacteria	Target pathogens to reduce infection burden	Standard of care⁹⁵^,⁹⁸
Immunomodulatory therapies	Cytokines, immune receptors	Modulate immune response	Clinical trials/variable efficacy^102-106

Therapeutic strategy	Target	Mechanism	Clinical status
FXI inhibitors	FXI	Inhibit FXI activation or activity to prevent thrombosis	Phase 2/3 trials²⁴^,^112-115
FXII inhibitors	FXII	Block FXII activation	Phase 2 trials¹¹²^,¹¹⁶
PK inhibitors	Prekallikrein	Inhibit kallikrein-kinin system	Approved for HAE, not yet tested in sepsis^117-119
Complement inhibitors	Complement components	Reduce inflammatory response, limit LPS release	Preclinical to early clinical trials¹⁰¹; some agents approved for paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome¹²⁰
Antiendotoxin therapies	LPS	Remove endotoxins	Investigational/clinical use in select cases⁹⁶^,⁹⁷^,¹⁰²^,¹¹⁰
Broad-spectrum antibiotics	Bacteria	Target pathogens to reduce infection burden	Standard of care⁹⁵^,⁹⁸
Immunomodulatory therapies	Cytokines, immune receptors	Modulate immune response	Clinical trials/variable efficacy^102-106

The table summarizes the primary targets, mechanisms of action, examples of therapeutic agents, and their current status in clinical development or use.

HAE, hereditary angioedema.

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