More than 60 deaths during a 14-month period that began in January 2007 were caused by allergic reactions to a heparin-like contaminant.
Heparin structure.
A recent report from NEJM identifies the trigger in the heparin-related anaphylaxis as oversulphated chondroitin sulphate (OSCS).
Chondroitin sulphate.
OSCS directly activated the kinin–kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins.
Complement system is a cascade of enzymes which leads to a membrane attack complex (MAC) which causes osmotic lysis of cells. Different fragments of the complement cascade act as inflammatory mediators.
There are 3 pathways for activation of complement:
CAM
Classical
Alternative
Mannose-binding lectin (MBL)
The 3 pathways (CAM) converge at the point of cleavage of C3. Then C3b becomes an acceptor site for C5, and C5-9 form the membrane attacking complex (MAC). Thus, CAM leads to MAC:
CAM --> MAC
A complement protein attacking the cell membrane. Image source: Wikipedia.
Classical and alternative complement pathways. Image source: Wikipedia.
Oversulphated chondroitin sulphate is a complex sugar molecule, similar to heparin, and hence it had not been possible to distinguish the two substances in ordinary screening tests done previously.
Read more in Anaphylaxis Due to Contaminated Heparin Causes Multiple Deaths, Trigger Found from Allergy Notes.
References:
Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System. NEJM.
Trigger in heparin deaths confirmed. Nature.
Innate Immune System: A Short Review. Allergy Cases.
Images source: Wikipedia, public domain.
Heparin structure.
A recent report from NEJM identifies the trigger in the heparin-related anaphylaxis as oversulphated chondroitin sulphate (OSCS).
Chondroitin sulphate.
OSCS directly activated the kinin–kallikrein pathway in human plasma, which can lead to the generation of bradykinin, a potent vasoactive mediator. In addition, OSCS induced generation of C3a and C5a, potent anaphylatoxins derived from complement proteins.
Complement system is a cascade of enzymes which leads to a membrane attack complex (MAC) which causes osmotic lysis of cells. Different fragments of the complement cascade act as inflammatory mediators.
There are 3 pathways for activation of complement:
CAM
Classical
Alternative
Mannose-binding lectin (MBL)
The 3 pathways (CAM) converge at the point of cleavage of C3. Then C3b becomes an acceptor site for C5, and C5-9 form the membrane attacking complex (MAC). Thus, CAM leads to MAC:
CAM --> MAC
A complement protein attacking the cell membrane. Image source: Wikipedia.
Classical and alternative complement pathways. Image source: Wikipedia.
Oversulphated chondroitin sulphate is a complex sugar molecule, similar to heparin, and hence it had not been possible to distinguish the two substances in ordinary screening tests done previously.
Read more in Anaphylaxis Due to Contaminated Heparin Causes Multiple Deaths, Trigger Found from Allergy Notes.
References:
Contaminated Heparin Associated with Adverse Clinical Events and Activation of the Contact System. NEJM.
Trigger in heparin deaths confirmed. Nature.
Innate Immune System: A Short Review. Allergy Cases.
Images source: Wikipedia, public domain.