Blood Research最新文献

Background: Light-chain amyloidosis (AL) is the most common form of systemic amyloidosis. This study aimed to evaluate the usefulness of laboratory tests for light-chain clonality and bone marrow (BM) findings in AL amyloidosis.

Methods: We retrospectively enrolled patients newly diagnosed with AL amyloidosis on pathological examination who underwent a BM biopsy. Laboratory test data for light-chain clonality were collected and compared. Amyloid deposits were identified with H&E, Congo red, and PAS stains.

Results: We reviewed 98 patients with AL amyloidosis. Light chain clonality (λ, 64 cases; κ, 34 cases) was detected by serum immunofixation electrophoresis (IFE) (63.3%), urine IFE (70.8%), serum protein electrophoresis (PEP) (44.9%), urine PEP (44.8%), serum free light chain (SFLC) ratio (79.5%), and BM immunohistochemistry (IHC) (85.7%). Flow cytometric (FCM) assay identified aberrant BM plasma cells in 92.9% of cases. BM amyloid deposits were identified in 35 of the 98 cases (35.7%); 71.4% (25/35) were Congo red-positive, and 100.0% (35/35) were PAS-positive.

Conclusion: Laboratory tests for detecting light-chain clonality in AL amyloidosis in order of sensitivity include FCM assay for aberrant plasma cells, IHC for light chains on BM biopsy or clot section, SFLC ratio, and serum and urine IFE. Congo red staining of BM samples remains an important tool for identifying amyloid deposits in BM. Periodic acid-Schiff (PAS) staining can be useful in diagnosing some cases of Congo red-negative amyloidosis.

This study aimed to delineate the possible impact of COVID-19 on acute myeloid leukemia (AML) patients in terms of diagnosis, chemotherapy, bone marrow transplant, and vaccination response. Allogeneic stem cell transplantation is markedly affected by the COVID-19 pandemic, as both donors and recipients must be healthy for transplantation to be feasible and successful. Delays in the identification of well-matched donors have been predicted, and represent a special challenge. Therefore, future donors should be tested for COVID-19. The outcome of delayed transplantation is vague and masked by variations in stem cell source along with disease subtype. However, if transplant delay results in recurrence of minimal residual disease, a negative impact on survival is anticipated.

Background: The clinical phenotype of hemophilia A (HA) does not always correlate with severity. Similarly, the presence of inhibitors does not necessarily increase the risk of bleeding. This paradox between clinical and laboratory findings may be partially attributed to non-modifiable factors, such as blood group, which is known to influence FVIII levels in healthy individuals. Our aim was to assess the effect of ABO blood group antigens on FVIII levels across the severity spectrum of HA and risk of inhibitor development.

Methods: Data of consecutive patients with HA who visited the coagulation unit of a northern Indian tertiary care hospital between 2010‒2021 were reviewed. Patients with missing blood group data, transfusion histories, or baseline FVIII levels were excluded.

Results: Mild, moderate, and severe HA was present in 41 (6.9%), 72 (12.2%), and 479 (80.9%) patients, respectively. There were no differences in the FVIII levels among the various blood groups across the HA severity spectrum. Inhibitors were administered to 35 patients (5.9%). In the multivariate analysis, blood group A was an independent risk factor for the development of inhibitors (adjusted odds ratio 2.70, P=0.04) after adjusting for age at onset of bleeding, FVIII transfusion, age at first FVIII transfusion, and severity of HA.

Conclusion: Unlike what is observed in healthy individuals, blood group did not influence residual FVIII levels across the severity spectrum of HA. Patients in group A had a higher risk of developing inhibitors.

Background: The PLASMIC score is a convenient tool for predicting ADAMTS13 activity of <10%. Lactate dehydrogenase (LDH) is widely used as a marker of haemolysis in thrombotic thrombocytopenic purpura (TTP) monitoring, and could be used as a replacement marker for lysis. We aimed to validate the PLASMIC score in a multi-centre Asia Pacific region, and to explore whether LDH could be used as a replacement marker for lysis.

Methods: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.

Results: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.

Conclusion: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.

Background: Acquired von Willebrand syndrome (AVWS) has not been investigated in Korean patients with Philadelphia chromosome-negative myeloproliferative neoplasm.

Methods: This study analyzed the prevalence at diagnosis and clinical features of AVWS in patients with essential thrombocythemia (ET), polycythemia vera (PV), prefibrotic/early primary myelofibrosis (pre-PMF), or overt PMF (PMF) diagnosed between January 2019 and December 2021 at Chungam National University Hospital, Daejeon, Korea. AVWS was defined as below the lower reference limit (56%) of ristocetin cofactor activity (VWF:RCo).

Results: Sixty-four consecutive patients (36 with ET, 17 with PV, 6 with pre-PMF, and 5 with PMF; 30 men and 34 women) with a median age of 67 years (range, 18‒87 yr) were followed for a median of 25.1 months (range, 2.6‒46.4 mo). AVWS was detected in 20 (31.3%) patients at diagnosis and was most frequent in ET patients (41.4%), followed by patients with pre-PMF (33.3%) and PV (17.6%) patients. VWF:RCo was negatively correlated with the platelet count (r=0.937; P=0.002). Only one episode of minor bleeding occurred in a patient with ET and AVWS. Younger age (<50 yr) [odds ratio (OR), 7.08; 95% confidence interval (CI), 1.27‒39.48; P=0.026] and thrombocytosis (>600×10⁹/L) (OR, 13.70; 95% CI, 1.35‒138.17; P=0.026) were independent risk factors for developing AVWS.

Conclusion: AVWS based on VWF:RCo was common in patients with ET and pre-PMF, but less common in patients with PV in the Korean population. Clinically significant bleeding is rare in these patients.

Background: In patients with suspected pulmonary embolism (PE), the literature suggests the overuse of computerized tomography pulmonary angiography (CTPA) and underuse of clinical decision rules before imaging request. This study determined the potential for avoidable CTPA using the modified Wells score (mWS) and D-dimer assay in patients with suspected PE.

Methods: This hospital-based retrospective study analyzed the clinical data of 661 consecutive patients with suspected PE who underwent CTPA in the emergency department of a tertiary hospital for the use of a clinical prediction rule (mWS) and D-dimer assay. The score was calculated retrospectively from the available data in the files of patients who did not have a documented clinical prediction rule. Overuse (avoidable) CTPA was defined as D-dimer negativity and PE unlikely for this study.

Results: Of 661 patients' data examined, clinical prediction rules were documented in 15 (2.3%). In total, 422 patients (63.8%) had required information on modified Wells criteria and D-dimer assays and were included for further analysis. PE on CTPA was present in 22 (5.21%) of PE unlikely (mWS ≤4) and 1 (0.24%) of D-dimer negative patients. Thirty patients (7.11%) met the avoidable CTPA (DD negative+PE unlikely) criteria, and it was significantly associated with dyspnea. The value of sensitivity of avoidable CTPA was 100%, whereas the positive predictive value was 90.3%.

Conclusion: Underutilization of clinical prediction rules before prescribing CTPA is common in emergency departments. Therefore, a mandatory policy should be implemented regarding the evaluation of avoidable CTPA imaging to reduce CTPA overuse.

Background: Leukemia is a neoplasm with high incidence and mortality rates. Mitotic death has been observed in tumor cells treated with chemotherapeutic agents. Ras family proteins participate in the transduction of signals involved in different processes, such as proliferation, differentiation, survival, and paradoxically, initiation of cell death.

Methods: This study investigated the effect of H-Ras expression on human T-cell acute lymphoblastic leukemia MOLT-4 cells. Cells were electroporated with either wild-type (Ras^wt) or oncogenic mutant in codon 12 exon 1 (Ras^mut) versions of H-Ras gene and stained for morphological analysis. Cell viability was assessed using trypan blue staining and cell cycle analysis using flow cytometry. H-Ras gene expression was determined using quantitative real-time reverse transcription polymerase chain reaction. The t, ANOVA, and Scheffe tests were used for statistical analysis.

Results: Human T-cell acute lymphoblastic leukemia MOLT-4 cells showed nuclear fragmentation and presence of multiple nuclei and micronuclei after transfection with either wt or mutant H-Ras genes. Cell cycle analysis revealed a statistically significant increase in cells in the S phase when transfected with either wt (83.67%, P<0.0005) or mutated (81.79%, P<0.0001) H-Ras genes. Although similar effects for both versions of H-Ras were found, cells transfected with the mutated version died at 120 h of mitotic catastrophe.

Conclusion: Transfection of human T-cell acute lymphoblastic leukemia MOLT-4 cells with either normal or mutated H-Ras genes induced alterations in morphology, arrest in the S phase, and death by mitotic catastrophe.

Background: Reduced harvest volumes in pediatric donors appear to have the potential to reduce donor-associated risks while maintaining engraftment in recipients; however, the allowable harvest volume reduction remains undefined.

Methods: We retrospectively analyzed the data pairs of 553 bone marrow (BM) harvests from pediatric (age at harvest <18 yr) sibling donors and clinical outcomes of 553 pediatric (age at infusion <14 yr) transplant-naïve recipients to assess the optimal BM harvest volume needed from pediatric donors to obtain the desired CD34+ cell count (≥3.0×10⁶ cells per kg of recipient weight), and to study its impact on the clinical outcomes of transplantation in pediatric recipients.

Results: The minimum desired CD34+ cell count of ≥3.0×10⁶ per kg of recipient weight was achieved for 506 (95.3%) of donor-recipient pairs. The median CD34+ cell yield was 6.4×10⁶ per kg of recipient weight (range, 1.2‒33.8×10⁶) in donors younger than 5 years old at harvest, 4.7×10⁶ (range, 0.3‒28.5×10⁶) in donors aged 5‒10 years and 2.1×10⁶ (range, 0.3‒11.3×10⁶) in donors older than 10 years (P<0.001).

Conclusion: The infused CD34+ cell dose (×10⁶ cells/kg of recipient weight) had no impact on GRFS; however, a CD34+ cell dose of ＞7×10⁶ cells/kg of recipient weight did not improve hematopoietic recovery.