Ristocetin is a

glycopeptide antibiotic Glycopeptide antibiotics are a class of drugs of microbial origin that are composed of glycosylated cyclic or polycyclic nonribosomal peptides. Significant glycopeptide antibiotics include the anti-infective antibiotics vancomycin, teicoplanin, ...

, obtained from ''

Amycolatopsis ''Amycolatopsis'' is a genus of high GC-content bacteria within the family Pseudonocardiaceae. The genus is known for producing many types of antibiotics, including * Epoxyquinomicin, related to ''Amycolatopsis sulphurea'', are a class of weak ...

lurida'', previously used to treat

staphylococcal infection A staphylococcal infection or staph infection is an infection caused by members of the '' Staphylococcus'' genus of bacteria. These bacteria commonly inhabit the skin and nose where they are innocuous, but may enter the body through cuts or abrasi ...

s. It is no longer used clinically because it caused

thrombocytopenia Thrombocytopenia is a condition characterized by abnormally low levels of platelets, also known as thrombocytes, in the blood. It is the most common coagulation disorder among intensive care patients and is seen in a fifth of medical patients an ...

and

platelet Platelets, also called thrombocytes (from Greek θρόμβος, "clot" and κύτος, "cell"), are a component of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping, thereby ini ...

agglutination In linguistics, agglutination is a morphological process in which words are formed by stringing together morphemes, each of which corresponds to a single syntactic feature. Languages that use agglutination widely are called agglutinative lang ...

. It is now used solely to assay those functions ''in vitro'' in the diagnosis of conditions such as

von Willebrand disease Von Willebrand disease (VWD) is the most common hereditary blood-clotting disorder in humans. An acquired form can sometimes result from other medical conditions. It arises from a deficiency in the quality or quantity of von Willebrand factor ( ...

(vWD) and

Bernard–Soulier syndrome Bernard–Soulier syndrome (BSS) is a rare autosomal recessive bleeding disorder that is caused by a deficiency of the ''glycoprotein Ib-IX-V complex'' (GPIb-IX-V), the receptor for von Willebrand factor. The incidence of BSS is estimated to be ...

. Platelet agglutination caused by ristocetin can occur only in the presence of

von Willebrand factor Von Willebrand factor (VWF) () is a blood glycoprotein involved in hemostasis, specifically, platelet adhesion. It is deficient and/or defective in von Willebrand disease and is involved in many other diseases, including thrombotic thrombocytopen ...

multimers, so if ristocetin is added to blood lacking the factor (or its receptor—see below), the platelets will not clump. Through an unknown mechanism, the antibiotic ristocetin causes von Willebrand factor to bind the platelet receptor glycoprotein Ib (GpIb), so when ristocetin is added to normal blood, it causes agglutination. In some types of vWD (types 2B and platelet-type), even very small amounts of ristocetin cause platelet aggregation when the patient's platelet-rich

plasma Plasma or plasm may refer to: Science * Plasma (physics), one of the four fundamental states of matter * Plasma (mineral), a green translucent silica mineral * Quark–gluon plasma, a state of matter in quantum chromodynamics Biology * Blood pla ...

is used. This paradox is explained by these types having gain-of-function mutations which cause the vWD high molecular-weight multimers to bind more tightly to their receptors on platelets (the alpha chains of

glycoprotein Ib (GPIb) Glycoprotein Ib (GPIb), also known as CD42, is a component of the GPIb-V-IX complex on platelets. The GPIb-V-IX complex binds von Willebrand factor, allowing platelet adhesion and platelet plug formation at sites of vascular injury. It is defic ...

receptors). In the case of type 2B vWD, the gain-of-function mutation involves von Willebrand's factor (VWF gene), and in platelet-type vWD, the receptor is the object of the mutation (GPIb). This increased binding causes vWD because the high-molecular weight multimers are removed from circulation in plasma since they remain attached to the patient's platelets. Thus, if the patient's platelet-poor plasma is used, the ristocetin cofactor assay will not agglutinate standardized platelets (i.e., pooled platelets from normal donors that are fixed in formalin), similar to the other types of vWD. In all forms of the ristocetin assay, the platelets are fixed in

formalin Formaldehyde ( , ) (systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section Fo ...

prior to the assay to prevent von Willebrand's factor stored in platelet granules from being released and participating in platelet aggregation. Thus, the ristocetin cofactor activity depends only upon high-molecular multimers of the factor present in circulating plasma.

References

{{Cell wall disruptive antibiotics Antibiotics Glycopeptide antibiotics Chemical pathology