Ristocetin, a Laboratory and Clinical Evaluation in Children:

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Ristocetin, a glycopeptide antibiotic, was isolated from Amycolatopsis orientalis shortly after the discovery of vancomycin, a similar glycopeptide. Ristocetin's antibacterial properties were described in 1955,¹ and the drug was widely used as an antistaphylococcal drug until the early 1960s. In this 1960 article, Pries and Koch describe the clinical response to ristocetin in 55 children, including pharmacokinetic studies. Serious staphylococcal infections were effectively treated, but one-third of the patients had mild toxicities (eosinophilia, leukopenia, skin rash, and local reactions). Interestingly, none developed thrombocytopenia, but other reports of ristocetin-induced severe thrombocytopenia eventually led to ristocetin's discontinuation as an antimicrobial drug.²

Although platelet toxicity was risocetin's clinical undoing as an antibiotic, years later the drug found a role in the investigation of von Willebrand disease (VWD), as the key reagent for testing functional interactions between von Willebrand factor (VWF) and the platelet GPIb-IX-V complex. In this VWF ristocetin cofactor assay (VWF:RCo), ristocetin induces measurable platelet aggregation in the presence of VWF. The VWF:RCo assay is sensitive to the presence of large and intermediate VWF multimers and is abnormal in patients with VWD and also in those with Bernard-Soulier disease, an inherited deficiency of the GPIb-IX-V complex. Although this assay has multiple shortcomings (ie, cumbersome, lack of optimal control of reagent platelets, high coefficient of variation, inaccurate at low levels of VWF, and significant interlaboratory variation), it remains central to the evaluation for VWD, because ristocetin remains the sole reagent capable of assessing this specific VWF function.

It is noteworthy that ristocetin and vancomycin have biological and structural similarities. But the ristocetin aglycon methyl ester derivative lacks the platelet side effect while conserving the antimicrobial property, thus making ristocetin a lead compound for developing new antibiotics against vancomycin-resistant bacteria.³

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References 

1. Philip JE, Schenck JR, Hargie MP. Ristocetins A and B, two new antibiotics: isolation and properties. Antibiot Annu. 1956;699–705
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2. Gangarosa EJ, Landerman NS, Rosch PJ, Herndon EG. Hematologic complications arising during ristocetin therapy: relation between dose and toxicity. N Engl J Med. 1958;259:156–161
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3. McComas CC, Crowley BM, Hwang I, Boger DL. Synthesis and evaluation of methyl ether derivatives of the vancomycin, teicoplanin, and ristocetin aglycon methyl esters. Bioorg Med Chem Lett. 2003;13:2933–2936
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