Immunophenotyping is indispensable in the differential diagnosis of B-cell chronic lymphoproliferative disorders (B-CLPDs). However, B-CLPDs often show overlapping immunophenotypic profiles and may be diagnostically challenging. CD1d is an HLA class I-like molecule that presents glycolipids to invariant natural killer T cells. Normal mature B cells constitutively express CD1d, but with the exception of some conflicting data, its expression in B-CLPDs is unknown. We demonstrate that in 222 B-CLPD cases, CD1d expression of less than 45% is strongly predictive of CLL (likelihood ratio, 32.3; specificity, 97.4%; sensitivity, 84.1%). In addition, CD1d showed significantly higher staining intensity in splenic marginal zone lymphoma compared with atypical hairy cell leukemia, lymphoplasmacytic lymphoma, and mantle cell lymphoma, thus allowing the discrimination of the former from the latter immunophenotypically overlapping B-CLPDs. It is important to note that in a given patient, CD1d expression on malignant B cells was similar between tissues and remained unaffected by disease stage and treatment status. Our findings strongly argue for the incorporation of CD1d into routine lymphoma panels.

Acquired haemophilia is a rare phenomenon and prompt diagnosis is essential for successful treatment. Early laboratory detection could minimize its potentially devastating consequences and reduce mortality but when a masking element such as anticoagulant therapy is present, delay in diagnosis is not uncommon. A prolonged activated partial thromboplastin time (APTT) may be falsely attributed to warfarin alone, particularly when it is associated with oral anticoagulant overdose. We describe two patients on treatment with warfarin who presented with a bleeding diathesis and disproportionately prolonged APTT, which led to the diagnosis of antibodies directed against factor VIII.

Functional transcranial Doppler (fTCD) has been used for the identification of cerebral hemispheric dominance in various cognitive tasks. In our study, we have used fTCD with the aim to compare blood flow patterns in the hemispheres not only during the task activation periods but also in the post-stimulus phase. Normal volunteers, 25 right and 25 left-handed, were included. Mean flow velocities (FVs) in the bilateral middle cerebral arteries were recorded during the performance of six cognitive tasks and during the intervals between tasks. The lateralization index (LI) was calculated separately for each test (LI1-6), on the basis of the percent change of blood FV from baseline. To estimate flow fluctuations, a novel index, the LI-variability, was also calculated using a formula constituted by the minimum and maximum mean values recorded at specific time intervals during the entire procedure. Laterization indices, LI-3 and LI-4, corresponding to word generation and reading aloud tasks, produced the highest degree of activation. A perfect agreement (Cohen's j = 1.000, P < 0.001) was observed among LI-3, LI-4, and LI-V. The repetition of recordings gave excellent test-retest reliability in 10 randomly selected participants. Our results suggest that the hemisphere that is characterized as dominant by fTCD maintains a more stable flow pattern during the performance of successive cognitive tasks. Although it could not be considered as a clinically useful tool as yet, this observation introduces a novel parameter such as the stability of blood flow over time, which could potentially provide insight in the study of cerebral functions.

Background/Aims: Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) share the same acquired lesion JAK2^V617F and may exhibit substantial overlap. Variability in JAK activation and allele burden, complemented by host, genetic and non-genetic modifiers, determine the phenotype. The aim of this study was to investigate the presence of the JAK2 mutation in association with the ratio of metallopeptidases inhibitors (TIMPs) to tissue metallopeptidases (MMPs) in MPNs, where inhibitory rather than proteolytic activity in marrow microenvironment appears to predominate. Methods: 94 patients with polycythemia vera, essential thrombocythemia and primary myelofibrosis, and 102 healthy individuals were evaluated. Allele-specific PCR and RFLP were used to detect JAK2 and genomic status. Serum concentrations of MMP and TIMP were measured by ELISA. The parameters were assessed with covariance analysis, and adjusted for gender, age and co-morbidity. Results: Mutation frequency was 81.91%. Abnormal TIMP/MMP ratios were identified in all three diseases. JAK2 mutation was correlated with significant changes in TIMP concentrations. Conclusions: Identification of an abnormal TIMP/MMP ratio in all three diseases, regardless of the JAK2 status, indicates invariable marrow remodeling. In this particular group of patients, presence of a JAK2^V617F mutation, being associated with even higher ratios, appears to be a concurring participant in bone marrow-reforming processes. Additional research may delineate correlates with the JAK2 allelic burden.