Search

Vitamin K antagonists (VKA) are the most widely used anticoagulants for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA. The main aim of our study was to explore the association between international normalized ratio (INR) levels and microscopic hematuria in patients with VKA.We performed a cross-sectional study of patients treated with VKA that attended the outpatient clinic for routine INR control. A simple urinalysis was performed on the day of the INR control and the precise number of red cells in the urine sediment was quantified. Demographic data, kidney function tests, comorbidities, anticoagulant dose and concomitant treatment were registered.A total of 337 patients were included with median INR levels of 2.6 (IQR 2.1-3.3). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of red blood cells in the urine sediment (r = 0.201, p = 0.024). In the univariate analysis, microscopic hematuria was associated with having an INR3.5 (19% vs. 10.2%, p = 0.046), bacteriuria (15.2% vs. 3.6%, p = 0.015), leukocyturia (14.8% vs. 6.6%, p = 0.026), hypertension (16.2% vs. 9.5%, p = 0.053), and the use of renin-angiotensin system (RAS) blockers (6.9% vs. 17.2%, p = 0.004). Multivariate logistic regression showed an association between microscopic hematuria and RAS blockade (OR 0.38, CI 95% 0.163-0.886, p = 0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria.INR overdose was significantly associated with the presence of microscopic hematuria. RAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients.

Background and Aims Vitamin K antagonists (VKA) are the most widely used anticoagulants in the daily clinical practice for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA, from hemodynamic effects due to massive urological hemorrhage associated with VKA overdose, to non-hemodynamic effects that include glomerular hemorrhage and renal tubular obstruction due to red cell casts. The main aim of our study was to establish an association between INR levels and microscopic hematuria in patients with VKA, and identify possible risk and protective factors associated with development of microscopic hematuria in these patients. Method We performed a transversal study that included patients with oral anticoagulation with coumarin derivatives (warfarin or acenocoumarol), that attended the Hematology outpatient clinic from October to December 2019 for routine INR control. A urine specimen was collected on the day of the INR control. We performed a simple urinalysis to all patients and quantified the precise number of red cells in the urine sediment by flow cytometry. Demographic data, kidney function tests including serum creatinine and albuminuria, comorbidities, anticoagulant dose and concomitant treatment were registered. Results 337 patients were included in the study, with an average age of 68.6 ± 12.2 years, 51% were females, 95% were treated with acenocoumarol and 5% with warfarin. Median INR levels were 2.6 (IQR 2.1-3.3) and the median number of urine red cells in the sediment were 11 RBCs/µl (IQR 0-13). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of RBCs in the urine sediment (Spearman’s rho= 0.119, p= 0.029), independent from the type of anticoagulant used. This correlation was stronger after excluding those patients who had concomitant bacteriuria (Spearman’s rho= 0.201, p= 0.024). We found no correlation between time elapsed from start of anticoagulation or total weekly dose with the intensity of microscopic hematuria. In the univariate analysis, microhematuria was associated with having an INR >3.5 (19% vs. 10.2%, p=0.046), bacteriuria (15.2% vs. 3.6%, p=0.015), leukocyturia (14.8% vs. 6.6%, p= 0.026), hypertension (16.2% vs. 9.5%, p=0.053), and the use of RAAS blockers (17.2% vs. 6.9%, p=0.004). After performing a multivariate logistic regression that included the aforementioned variables, the association between microhematuria and RAAS blockade with either an ACE inhibitor or ARB was maintained (OR 0.38, CI 95% 0.163-0.886, p=0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria. We found no association between serum creatinine, albuminuria or antiplatelet treatment with the presence of microscopic hematuria. Conclusion INR overdose is significantly associated with the presence of microscopic hematuria, independent from the type of VKA used or the total weekly dose. RAAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients.

The complex [Pt2(Spy−)4Cl2], where Spy− is deprotonated 2-mercaptopyridine, was prepared and analyzed spectroscopically. A single signal in the 195Pt NMR spectrum indicates the equivalence of the two Pt(III) ions. The interaction of this complex with DNA was studied by circular dichroism and the modifications caused by the complex in plasmid pBR322 DNA were imaged by atomic force microscopy. Preliminary results showed higher activity against HeLa and U937 tumor lines for the Pt–2-mercaptopyridine complex in comparison with cisplatin. The values of LC50 were lower than those obtained for cisplatin. Promising perspectives for this compound are expected due to its similarity with the analogous Pt and 2-mercaptopyrimidine antitumor compound.

cis-Diamminedichloroplatinum(II) (cis-DDP) is a widely used antitumour drug which produces important damage on the DNA inducing apoptosis in several cell lines. We have analyzed the cytotoxic activity of novel cyclometallated complexes of p-isopropylbenzaldehyde thiosemicarbazone (p-is.TSCN) and their dimeric chloro-bridged derivatives in murine keratinocytes transformed by the H-ras oncogene which are resistant to cis-DDP (Pam-ras cells). The data show that, in contrast with cis-DDP, the tetrameric cycloplatinated complex [Pt(p-is.TSCN)]4 and its dimeric chloro-bridged derivative [Pt(microCl)(p-is.TSCN)]2 have a good in vitro therapeutic index when comparing the cytotoxicity in Pam-ras cells to normal murine keratinocytes (Pam 212 cells) since they induce cell death in Pam-ras cells at drug concentrations significantly lower than those needed to kill Pam 212 cells. At equitoxic doses (IC90), both complexes produce characteristic features of apoptosis in Pam-ras cells together with a drastic decrease in levels of H-ras protein. These effects are not observed when the cells are treated with the IC90 of the cis-DDP drug nor the p-is.TSCN ligand. Altogether, these results suggest that the platinum compounds [Pt(p-is.TSCN)]4 and [Pt(microCl)(p-is.TSCN)]2 might have potential as antitumour agents in view of their specific induction of apoptosis in cis-DDP resistant cells.