Evaluation of a diagnostic platelet aggregation test strategy for platelet rich plasma samples with low platelet counts.

INTRODUCTION: Light transmission aggregometry (LTA) is important for diagnosing platelet function disorders (PFD) and von Willebrand disease (VWD) affecting ristocetin-induced platelet aggregation (RIPA). Nonetheless, data is lacking on the utility of LTA for investigating thrombocytopenic patients and platelet rich plasma samples with low platelet counts (L-PRP). Previously, we developed a strategy for diagnostic LTA assessment of L-PRP that included: (1) acceptance of referrals/samples, regardless of thrombocytopenia severity, (2) tailored agonist selection, based on which are informative for L-PRP with mildly or severely low platelet counts, and (3) interpretation of maximal aggregation (MA) using regression-derived 95% confidence intervals, determined for diluted control L-PRP (C-L-PRP). METHODS: To further evaluate the L-PRP LTA strategy, we evaluated findings for a subsequent patient cohort. RESULTS: Between 2008 and 2021, the L-PRP strategy was applied to 211 samples (11.7% of all LTA samples) from 192 unique patients, whose platelet counts (median [range] × 109 /L) for blood and L-PRP were: 105 [13-282; 89% with thrombocytopenia] and 164 [17-249], respectively. Patient-L-PRP had more abnormal MA findings than simultaneously tested C-L-PRP (p-values <0.001). Among patients with accessible electronic medical records (n = 181), L-PRP LTA uncovered significant aggregation abnormalities in 45 (24.9%), including 18/30 (60%) with <80 × 109 platelets/L L-PRP, and ruled out PFD, and VWD affecting RIPA, in others. The L-PRP LTA strategy helped diagnose VWD affecting RIPA, Bernard Soulier syndrome, familial platelet disorder with myeloid malignancy, suspected ITGA2B/ITGB3-related thrombocytopenia, and acquired PFD. CONCLUSION: Diagnostic LTA with L-PRP, using a strategy that considers thrombocytopenia severity, is feasible and informative.

An unusual non-hematopoietic bone marrow finding.

We present an interesting case that showed a non-hematopoietic structure embedded in the bone marrow biopsy. Given the clinical and morphological difficulties, it was challenging to identify this artifact's nature. Publishing this case would familiarize pathologists with this artifact and save additional testing and delays in reporting.

Favorable outcome of PML-RARα short isoform and FLT3-ITD mutation in a patient with several adverse prognostic markers: A case report.

Key Clinical Message: Complete molecular remission in a "variant APL" patient with short isoform of PML-RARα and FLT3-ITD mutation was achieved in response to ATRA and ATO plus IDA instead of standard treatment protocol. The use of FLT3 inhibitor in APL induction management is implicated to prevent differentiation syndrome and coagulopathy experienced in in patients with FLT3-ITD. Abstract: FLT3-ITD mutations are the most common activating mutations in FLT3 gene, occurring in about 12 to 38% of acute promyelocytic leukemia cases, and are mainly associated with high white blood cell counts and poor clinical outcomes. Here, we present a case of APL variant with adverse prognostic features who showed short isoform [bcr3] of PML-RARα and FLT3-ITD mutation at diagnosis. The patient received all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) plus idarubicin (IDA) instead of standard treatment protocol, and achieved a complete morphological, cytogenetic and molecular response. However, the patient experienced differentiation syndrome, and coagulopathy that was subsequently resolved by continuous oxygen therapy, dexamethasone, and enoxaparin. The use of FLT3 inhibitor in APL induction management is implicated to prevent differentiation syndrome and coagulopathy in patients with FLT3-ITD mutation.

Relapsed Angioimmunoblastic T Cell Lymphoma with Fulminant Leukemic Involvement.

BACKGROUND Angioimmunoblastic T cell lymphoma (AITL) is an aggressive and rare entity that comprises about 1-2% of all non-Hodgkin lymphomas. This entity carries many challenges that start at the diagnosis, as most patients present with non-specific symptoms affecting different systems. As a result, the optimal approach, reaching the accurate diagnosis, and delivering needed treatment are delayed. Furthermore, it is not surprising that the initial set of biopsies are non-diagnostic given the heavy inflammatory background and scarcity of malignant cells in the early course of the disease. Other challenges include delivering the optimal curative therapy, as there is no such therapeutic option available yet. Although stem cell transplantation (SCT) can be considered a curative option, some patients have comorbidities and are not eligible for this option, and some other patients have relapse despite this aggressive approach, as was seen in our case. CASE REPORT We present an interesting case of AITL with florid leukemic infiltration at the time of relapse. We included a description of the patient's symptoms, diagnostic challenges, and clinical course, and provided therapy with demonstrative peripheral blood and flow cytometry images. Interestingly, there are very few reports in the literature that described leukemic infiltration of this entity. CONCLUSIONS Acknowledging the rarity of this aggressive lymphoma combined with all the challenges that face the involved health care workers, publishing this elaborative case report adds some insight and knowledge and helps improve our understanding of this entity.

The unusual abundance of a rare finding!

We present images (Figure 1A-D) of a preterm girl who had severe anemia due to HDFN caused by maternal anti-C and anti-D alloantibodies. These images show erythrophagocytosis, which is a very interesting and rarely encountered feature. We believe that physicians taking care of such patients should be more aware of this characteristic yet under-detected finding.

Implications of intrachromosomal amplification of chromosome 21 on outcome in pediatric acute lymphoblastic leukemia: Does it affect our patients too?

Intrachromosomal amplification (iAMP) of chromosome 21 entity is associated with a dismal outcome in B cell Acute Lymphoblastic Leukemia (B-ALL). This cytogenetic abnormality is caused by a novel mechanism; breakage-fusion-bridge cycles followed by chromothripsis along with major gross rearrangements in chromosome 21. Charts of B-ALL diagnosed at King Faisal Specialist Hospital and Research Center between 2005 and 2015 were reviewed. iAMP is a rare entity occurring at around 2.4% of all pediatrics BALL. No statistically significant difference was found among patients with iAMP21, patients with extra copies of 21 and other patients with B-ALL. The reported adverse prognostic effect of iAMP21 could be due to other coexistent adverse factors, including older age at the time of diagnosis. The most common associated abnormality in our population in addition to the hyperdiploidy was ETV6/RUNX1.

Non-acute promyelocytic leukemia variant, acute myeloid leukemia with translocation (11;17).

t(11;17) is a rare but recognized finding usually found in Acute Promyelocytic Leukemia with variant RARA translocation (APLv). We present a case of Acute Myeloid Leukemia with t(11;17) that has different break points than those occurring in APLv. The diagnosis of acute myeloid leukemia, not otherwise specified, acute monoblastic leukemia was reached after a thorough investigation. Reaching the correct diagnosis and distinguishing these two entities are essential as they have different management, prognosis, and overall survival.

Molecular yield of targeted sequencing for Glanzmann thrombasthenia patients.

Glanzmann thrombasthenia (GT) is a rare autosomal recessive bleeding disorder. Around 490 mutations in ITGA2B and ITGB3 genes were reported. We aimed to use targeted next-generation sequencing (NGS) to identify variants in patients with GT. We screened 72 individuals (including unaffected family members) using a panel of 393 genes (SHGP heme panel). Validation was done by Sanger sequencing and pathogenicity was predicted using multiple tools. In 83.5% of our cohort, 17 mutations were identified in ITGA2B and ITGB3 (including 6 that were not previously reported). In addition to variants in the two known genes, we found variants in ITGA2, VWF and F8. The SHGP heme panel can be used as a high-throughput molecular diagnostic assay to screen for mutations and variants in GT cases and carriers. Our findings expand the molecular landscape of GT and emphasize the robustness and usefulness of this panel.