Three patients highlighting potential pitfalls in platelet refractory testing.

BACKGROUND: Platelet-transfusion refractory (PR) patients do not achieve expected post-transfusion platelet counts. We investigate suspected PR patients with post-transfusion platelet counts, indirect platelet antibody screens (ind-PAS), Class I HLA antibody tests (HLA-Scr), and physical platelet crossmatch (PXM) studies. STUDY DESIGN AND METHODS: The three following cases describe possible pitfalls of laboratory tests used in PR workup and management. RESULTS: Case #1: Antibody testing detected antibodies to only HLA-B13, corresponding to a 4% calculated panel reactive antibodies (CPRA; 96% predicted donor compatibility). However, PXM showed the patient compatible with 11/14 (79%) donors; two of the PXM-incompatible units were ABO-incompatible. Case #2: PXM revealed compatibility with 1/14 screened donors; however, the patient did not respond to the product from the compatible donor. The patient did respond to HLA-matched product. Dilution studies provided evidence of the prozone effect, which caused negative PXM despite clinically relevant antibodies. Case #3: There was a discrepancy between the ind-PAS and HLA-Scr. Ind-PAS was negative for HLA antibodies, while HLA-Scr was positive and specificity testing corresponded to 38% CPRA. Per the package insert, the sensitivity of ind-PAS is ~85% compared to HLA-Scr. DISCUSSION: These cases highlight the importance of investigating incongruent results. Cases #1 and #2 demonstrate PXM pitfalls: ABO incompatibility can result in positive PXM and false-negative PXM can occur in the setting of the prozone effect. Case #3 reveals the importance of knowing a test's sensitivity. Centers that only perform ind-PAS may fail to detect HLA antibodies.

Risk Stratification of Prostatic Adenocarcinoma Metastatic to the Lymph Nodes.

CONTEXT.­: The pathologic nodal staging of prostatic adenocarcinoma is binary for regional lymph nodes. Stages pN0 and pN1 indicate the absence or presence of regional nodal metastasis, respectively, whereas patients with metastasis to nonregional lymph nodes are staged as pM1a. OBJECTIVE.­: To determine the risk of recurrence of pN1 prostatic adenocarcinoma patients based on the extent of nodal tumor burden. DESIGN.­: We retrospectively reviewed pN1 patients with prostatic adenocarcinoma managed with radical prostatectomy seen between 2011 and 2019. Kaplan-Meier and Cox regression analyses were performed to compare disease-free survival. RESULTS.­: Ninety-six patients were included (median [interquartile range] age, 62 years [57-67 years]; 70 of 96 [73%] White). On univariate analysis, age >65 years (P = .008), ≥2 positive regional lymph nodes (P < .001), and a maximum size of the tumor deposit ≥2 mm (P = .004) were significantly associated with an unfavorable outcome. Controlling for age, stage, metastatic deposit size, margin status, and the presence of extranodal extension, patients with ≥2 positive regional lymph nodes were 3.03 times more likely (95% confidence interval, 1.39-6.60; P = .005) to have an unfavorable outcome. Patients with pN1M1a stage showed a disease-free survival similar to that of pN1M0 patients, after controlling for the number of positive regional lymph nodes (P = .36). CONCLUSIONS.­: Overall, pN1 patients with ≥2 positive regional lymph nodes are 3 times more likely to have an unfavorable outcome. The results suggest a benefit in further stratifying patients with metastatic prostatic adenocarcinoma to the lymph nodes into prognostically significant risk categories that could help the treating clinicians tailor subsequent patient follow-up and therapy.

Sildenafil attenuates placental ischemia-induced hypertension.

Preeclampsia is a complication of pregnancy that is marked by hypertension, proteinuria, and maternal endothelial dysfunction. A central factor in the etiology of the disease is the development of placental hypoxia/ischemia, which releases pathogenic soluble factors. There is currently no effective treatment for preeclampsia, but the phosphodiesterase-5 (PDE-5) inhibitor sildenafil has been suggested, as PDE-5 is enriched in the uterus, and its antagonism could improve uteroplacental function. Here, we report in the reduced uterine perfusion pressure (RUPP) rat model that administration of oral sildenafil is effective in attenuating placental ischemia-induced hypertension during gestation. RUPP animals have significantly elevated arterial pressure compared with control animals (132 ± 3 vs. 100 ± 2 mmHg; P < 0.05). Administration of oral sildenafil (45 mg·kg⁻¹·day⁻¹) had no effect on blood pressure in control rats but decreased pressure in RUPP rats (115 ± 1 mmHg; P < 0.05). RUPP induced changes in placental sFlt-1, and vascular endothelial growth factor (VEGF) was unaffected by sildenafil administration, as was the decrease in free plasma VEGF. RUPP animals had a significant increase in medullary PDE-5/ß-actin ratio (1 ± 0.14 vs. 1.63 ± 0.18; P < 0.05) expression with a resulting reduction in renal medullary cGMP (1.5 ± 0.15 vs. 0.99 ± 0.1 pmol/µg protein, P < 0.05) compared with controls. Although sildenafil had no effect on renal medullary cGMP in control animals, it significantly increased cGMP in RUPP animals (1.3 ± 0.1 pmol/µg protein; P < 0.05). These data suggest that sildenafil might provide an effective therapeutic option for the management of hypertension during preeclampsia.