Five injections at 1. The inset in panel B provides a visualization of the extent of plasma hemoglobin in maximally dosed guinea pigs vs control. Quantification of schistocytes in the peripheral blood 24 hours postinjection is presented as number per high power field. Maximum plasma free hemoglobin levels were reached 8 hours after the first injection in both single and repeatedly dosed guinea pigs. With evidence of microangiopathic hemolytic anemia and decreased platelet counts, we next characterized the VWF multimer distribution using SDS agarose gel electrophoresis.
Increased quantities of low-molecular-weight VWF species were instead seen in multidosed animals, reflected by decreased VWF collagen-binding activity to antigen ratios Figure 2H. The iron content within the renal cortex tissue of single-dose and multidosed animals was significantly elevated Figure 3C , depositing primarily within the proximal and distal tubules Figure 3D. B Quantitation of T 24h urine hemoglobin. E Western blot of HO-1 expression in kidney tissue and its quantitative densitometric analysis.
Kidney sections from multidosed animals demonstrated signs of glomerular and tubular damage. Proximal tubular epithelial cells showed hyaline droplet deposition and patchy necrosis, resulting in the filling of tubular lumens with cellular debris and protein casts.
Ectatic glomerular capillary loops were frequently seen Figure 4A top panel. A dose-dependent increase in glomerular capillary fibrinogen content was also identified by immunohistochemistry Figure 4A bottom panel. Glomeruli did not stain positively for VWF or platelet antigen data not shown. To better define the extent of kidney damage, common markers of acute kidney injury were quantified Figure 4B-D. Only repeatedly dosed groups 5 times, 0.
NGAL or Lcn2 is rapidly induced and secreted from renal distal tubules following ischemic or nephrotoxic injury. The endothelium of interlobular arteries as well as the vasa recta straight capillaries of the medulla showed positive staining for PEO Figure 4E top and bottom right panels.
Although this may result in endothelial activation or injury in vivo, the presence of the inert ingredients in the culture medium of HUVECs did not directly stimulate release of sVCAM, a marker of endothelial activation Figure 4G.
Microangiopathic hemolytic anemia, thrombocytopenia, renal injury, and vision loss have been described in prior published cases of TMA associated with extended-release oxymorphone abuse. However, this report introduces the first descriptions of cardiac involvement and atypical clinical features of TMA eg, pulmonary involvement, dyspnea. Although serum complements were found to be normal in at least 1 other case report, 7 the patients described here were found to have decreasing levels across the course of hospitalization.
IV infusion of the solubilized inert ingredient mixture elicited hallmark features of TMA. Microangiopathic hemolytic anemia, declines in platelet count, and renal injury were all observed with dose dependence in our animal model. These findings speak to the utility of the guinea pig model, which are increasingly recognized for their nephrotoxic sensitivity to hemoglobin 19 , 34 and also confirm the inert ingredients as a casual factor in the development of TMA.
Infusion rate and polymer concentration may be influential in determining the impact of IV HMW PEO, which is reflected in the stepwise gradient of pathology seen in the current animal study. Although shear-driven hemolysis appeared in all animal groups in a dose-dependent manner, end organ damage was only observed in animals given repeated doses. This may also explain why only a minority of individuals approximately one-third at Wake Forest Baptist Medical Center; P.
Renal injury, although seen in many forms of TMA, is also a recognized consequence of acute and chronic hemolysis. Once outside of the confines of an erythrocyte, hemoglobin can extravasate into tissue compartments where it becomes oxidized and denatured, resulting in heme loss and iron release. Its scavenging of nitric oxide, a potent vasodilator within the microcapillary bed, can result in hypertension and endothelial dysfunction.
The long-term consequences for renal function in humans have ranged from complete recovery to chronic renal insufficiency necessitating renal replacement therapy. Although the supporting body of evidence is limited, initial plasma exchange therapy has been applied in several cases and may be appropriate in the setting of severe TMA. However, the resolution of symptoms in patients managed with supportive care alone is noteworthy, which may stem from the natural degradation of PEO polymers under flow.
Although injection abuse of prescription opioids is highly concentrated in certain regions of the United States, particularly in rural Appalachia, 57 all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.
The publication costs of this article were defrayed in part by page charge payment. Contribution: R. Conflict-of-interest disclosure: E. The remaining authors declare no competing financial interests.
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A related article has been published: Opana ER—induced thrombotic microangiopathy. Cite Icon Cite. Plasma creatinine levels were determined by a colorimetric assay kit Abcam.
Table 1. Patient 1. Patient 2. Patient 3. Age, y 24 28 48 Sex Female Male Female Presenting symptoms Numbness of extremities, vision loss Angina, dyspnea, abdominal pain, vision loss Angina, dyspnea, abdominal pain, diarrhea, numbness of extremities, vision loss Treatment 5 times plasma exchange 9 times plasma exchange 5 times plasma exchange. View Large. Table 2. Test result.
Peak or nadir. WBC, 4. Figure 1. View large Download PPT. Figure 2. Figure 3. Figure 4. The online version of this article contains a data supplement. Search ADS. Resurgence of intravenous Opana as a cause of secondary thrombotic thrombocytopenic purpura. Successful treatment of intravenously abused oral Opana ER-induced thrombotic microangiopathy without plasma exchange. Opana-ER used the wrong way: intravenous abuse leading to microangiopathic hemolysis and a TTP-like syndrome.
Thrombotic microangiopathy and acute kidney injury associated with intravenous abuse of an oral extended-release formulation of oxymorphone hydrochloride: kidney biopsy findings and report of 3 cases. Thrombotic microangiopathy associated with Opana ER intravenous abuse: a case report.
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US Food and Drug Administration. Accessed 7 July Down selection of polymerized bovine hemoglobins for use as oxygen releasing therapeutics in a guinea pig model. Hemoglobinuria-related acute kidney injury is driven by intrarenal oxidative reactions triggering a heme toxicity response.
Labordiagnostische referenzbereiche bei meerschweinchen. Tieraerztl Prax. Enhanced proteolysis of plasma von Willebrand factor in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Hypertrophic obstructive cardiomyopathy, bleeding history, and acquired von Willebrand syndrome: response to septal myectomy.
Acquired and reversible von Willebrand disease with high shear stress aortic valve stenosis. Fluid shear stress modulates von Willebrand factor release from human vascular endothelium.
Shear-induced platelet aggregation can be mediated by vWF released from platelets, as well as by exogenous large or unusually large vWF multimers, requires adenosine diphosphate, and is resistant to aspirin.
Involvement of large plasma von Willebrand factor vWF multimers and unusually large vWF forms derived from endothelial cells in shear stress-induced platelet aggregation. Many who are addicted to opiates will abuse the drugs with the express intent of getting high.
Long-term opiate addicts will often go to extremes in order to get the biggest impact out of their drugs of choice. Rather than just swallowing the pills, they will crush them, dissolve the crushed substance in water, and then inject the solution.
Especially when using an extended-release version of the drug or multiple pills, this can mean a huge dose injected straight into the bloodstream — an extremely dangerous practice. Abusing Opana in any way comes with a set of risks, and injecting any illicit substance comes with a host of risks as well. Together, the practice of shooting up with Opana can compound the risks associated with opiate drug abuse or dependence and expose the user to a number of health problems. Users who opt to shoot Opana will often experience a high that is quicker in onset but shorter in length as compared to those who swallow the pills whole.
The short-term effects of use may be a feeling of euphoria and blocking of the experience of pain but it may also mean:.
Opana abuse can occur in a number of different ways, and using the drug in any manner or amount that is not prescribed by a doctor is a form of abuse.
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