Ristocetin

Last updated
Ristocetin
Ristocetin.png
Identifiers
3D model (JSmol)
ChEMBL
ChemSpider
ECHA InfoCard 100.014.336 OOjs UI icon edit-ltr-progressive.svg
PubChem CID
UNII
  • InChI=1S/C98H113N7O43/c1-30-50(111)20-39-22-54(30)138-55-21-33(5-12-49(55)110)63(100)88(127)105-67-70(115)35-7-13-52-37(15-35)18-44-62-45-19-38-16-36(8-14-53(38)140-84(45)87(83(44)139-52)148-98-86(78(123)74(119)59(144-98)29-135-94-80(125)75(120)69(114)32(3)137-94)147-97-85(77(122)73(118)58(27-107)143-97)146-95-79(124)71(116)51(112)28-134-95)82(145-60-25-46(99)68(113)31(2)136-60)47-10-9-41(93(132)133-4)42-23-40(108)24-56(141-96-81(126)76(121)72(117)57(26-106)142-96)61(42)43-17-34(6-11-48(43)109)64(89(128)101-47)102-91(130)66(62)104-90(129)65(39)103-92(67)131/h5-8,11-17,20-24,31-32,41,46-47,51,57-60,63-82,85-86,94-98,106-126H,9-10,18-19,25-29,99-100H2,1-4H3,(H,101,128)(H,102,130)(H,103,131)(H,104,129)(H,105,127)/t31-,32+,41-,46+,47?,51-,57+,58-,59-,60+,63?,64?,65?,66?,67+,68-,69+,70+,71-,72+,73-,74-,75-,76-,77+,78+,79+,80-,81-,82+,85+,86-,94-,95+,96+,97-,98+/m0/s1 Yes check.svgY
    Key: SGAHMTIMAXYJKX-JWVHJGEPSA-N Yes check.svgY
  • InChI=1/C98H113N7O43/c1-30-50(111)20-39-22-54(30)138-55-21-33(5-12-49(55)110)63(100)88(127)105-67-70(115)35-7-13-52-37(15-35)18-44-62-45-19-38-16-36(8-14-53(38)140-84(45)87(83(44)139-52)148-98-86(78(123)74(119)59(144-98)29-135-94-80(125)75(120)69(114)32(3)137-94)147-97-85(77(122)73(118)58(27-107)143-97)146-95-79(124)71(116)51(112)28-134-95)82(145-60-25-46(99)68(113)31(2)136-60)47-10-9-41(93(132)133-4)42-23-40(108)24-56(141-96-81(126)76(121)72(117)57(26-106)142-96)61(42)43-17-34(6-11-48(43)109)64(89(128)101-47)102-91(130)66(62)104-90(129)65(39)103-92(67)131/h5-8,11-17,20-24,31-32,41,46-47,51,57-60,63-82,85-86,94-98,106-126H,9-10,18-19,25-29,99-100H2,1-4H3,(H,101,128)(H,102,130)(H,103,131)(H,104,129)(H,105,127)/t31-,32+,41-,46+,47?,51-,57+,58-,59-,60+,63?,64?,65?,66?,67+,68-,69+,70+,71-,72+,73-,74-,75-,76-,77+,78+,79+,80-,81-,82+,85+,86-,94-,95+,96+,97-,98+/m0/s1
    Key: SGAHMTIMAXYJKX-JWVHJGEPBW
  • CC1C(C(CC(O1)OC2C3C(=O)NC(C4=CC(=CC(=C4C5=C(C=CC(=C5)C(C(=O)N3)NC(=O)C6C7=CC(=C(C(=C7)OC8=CC=C2C=C8)OC9C(C(C(C(O9)COC1C(C(C(C(O1)C)O)O)O)O)O)OC1C(C(C(C(O1)CO)O)O)OC1C(C(C(CO1)O)O)O)OC1=CC=C(C=C1)C(C1C(=O)NC(C2=CC(=C(C(=C2)O)C)OC2=C(C=CC(=C2)C(C(=O)N1)N)O)C(=O)N6)O)O)OC1C(C(C(C(O1)CO)O)O)O)O)C(=O)O)N)O
Properties
C94H108N8O44
Molar mass 2053.89052
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Ristocetin is a glycopeptide antibiotic, obtained from Amycolatopsis lurida, previously used to treat staphylococcal infections. It is no longer used clinically because it caused thrombocytopenia and platelet agglutination. It is now used solely to assay those functions in vitro in the diagnosis of conditions such as von Willebrand disease (vWD) and Bernard–Soulier syndrome. Platelet agglutination caused by ristocetin can occur only in the presence of von Willebrand factor 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 is used. [1] 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) 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 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.

Platelet aggregation function by main disorders and agonists   edit
Further information: Platelet § Tests of function
ADP Epinephrine Collagen Ristocetin
P2Y receptor inhibitor or defect [2] DecreasedNormalNormalNormal
Adrenergic receptor defect [2] NormalDecreasedNormalNormal
Collagen receptor defect [2] NormalNormalDecreased or absentNormal
NormalNormalNormalDecreased or absent
DecreasedDecreasedDecreasedNormal or decreased

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von Willebrand disease Medical condition

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 (VWF), a multimeric protein that is required for platelet adhesion. It is known to affect several breeds of dogs as well as humans. The three forms of VWD are hereditary, acquired, and pseudo or platelet type. The three types of hereditary VWD are VWD type 1, VWD type 2, and VWD type 3. Type 2 contains various subtypes. Platelet type VWD is also an inherited condition.

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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 less than 1 case per million persons, based on cases reported from Europe, North America, and Japan. BSS is a giant platelet disorder, meaning that it is characterized by abnormally large platelets.

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<span class="mw-page-title-main">GP1BB</span> Protein-coding gene in the species Homo sapiens

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The ristocetin-induced platelet aggregation (RIPA) is an ex vivo assay for live platelet function. It measures platelet aggregation with the help of von Willebrand factor (vWF) and exogenous antibiotic ristocetin added in a graded fashion. It is similar to the ristocetin cofactor assay but has the added benefit in that it helps in the diagnosis of type 2B/pseudo von Willebrand disease (vWD) and Bernard–Soulier syndrome because it uses patient's live endogenous platelets, whereas ristocetin cofactor assay tests the function of only the vWF and not the platelets. Ristocetin cofactor assay uses the patient's platelet poor plasma and adds ristocetin and exogenous formalin-fixed platelets which can passively agglutinate. Formalin does not allow the extrinsic platelets to secrete the vWF of their α-granules, and thus only the activity of the intrinsic vWF is tested.

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References

  1. ↑ McPherson, Richard A.; Matthew R. Pincus (2006). Henry's Clinical Diagnosis and Management by Laboratory Methods. Philadelphia: W. B. Saunders. pp. 760–2. ISBN   978-1-4160-0287-1.
  2. 1 2 3 4 5 Borhany, Munira; Pahore, Zaen; ul Qadr, Zeeshan; Rehan, Muhammad; Naz, Arshi; Khan, Asif; Ansari, Saqib; Farzana, Tasneem; Nadeem, Muhammad; Raza, Syed Amir; Shamsi, Tahir (2010). "Bleeding disorders in the tribe: result of consanguineous in breeding". Orphanet Journal of Rare Diseases. 5 (1). doi: 10.1186/1750-1172-5-23 . ISSN   1750-1172. PMID   20822539.
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