Antiphosphatidylserine antibodies as diagnostic indicators of antiphospholipid syndrome.

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune condition that is diagnosed by the presence of at least one of the clinical manifestations (thrombosis and/or pregnancy failure) and one of antiphospholipid antibodies (aPL) laboratory tests. The most relevant aPL are lupus anticoagulant (LA), anti-beta2 glycoprotein I (aß2GPI) and anticardiolipin (aCL). The clinical significance of other antibodies like anti-phosphatidylserine antibodies (aPS) is still under investigation. OBJECTIVES: The aim of the study was to assess the diagnostic value of aPS antibodies, and to compare their utility to that of other aPL antibodies. METHODS: We conducted a prospective observational study consisting of 212 patients with suspected thrombosis, pregnancy failure, or unexplained, prolonged clotting time. Data on demography, clinical presentation and autoantibody levels were assessed. Descriptive analysis, accuracy analysis, sensitivity, specificity, predictive value and likelihood ratio were calculated for aPS in comparison to other aPL. RESULTS: The diagnostic value of aPS versus other aPL antibodies revealed the high specificity of aPS (87%), with 70% of aPS-positive patients being confirmed APS. When the aPS test was used as a single test, it was effective for detection of confirmed APS cases (p < 0.01). Among 28 confirmed primary APS cases, 75% of patients were positive for aPS (p < 0.003). Moreover, by using aPS we detected three additional confirmed APS cases and another three probable cases. CONCLUSION: Our findings reveal a significant association between aPS and APS, especially when used to diagnosis clinical cases with other negative aPL tests. There is an independent association between aPS and primary APS. In addition, these results demonstrated the advantages of using aPS as a diagnostic test for APS.

The value and practicality of granulocyte transfusion: a single oncology centre experience.

There is an increased risk of infection in patients with neutropaenia, especially in those with neutrophil counts of less than 0.5 x 10(9)/L, and neutropaenia-associated infection remains a limiting factor in treating malignancy especially of haematopoietic origin. Transfusing donor neutrophils is a logical approach to these problems, but granulocyte transfusion (GTx), a practice first advocated in the 1960s, is underused and although now enjoying resurgence, remains controversial. The aim of this study was to determine the practical aspects of GTx and clinical responses in patients receiving them. This is an observational retrospective review of GTx in patients undergoing therapy for predominantly haematological malignancies. We reviewed blood bank records and identified patients who received therapeutic granulocytes procured by leukapheresis and linked these recipients with their granulocyte donors. We determined the reasons for GTx and their clinical and relevant haematological responses to the transfusions. We identified 22 patients receiving at least three continuous days of GTx and who had adequate clinical and haematological data. Most donors were relatives and ABO matched with their respective recipients. Mean age of the patients was 28.8 years. Severe aplastic anaemia was the most common diagnosis, occurring in 9 patients (40.9%), followed by acute myeloid leukaemia in 6 (27.3%). Disseminated fungal infection was the most common reason for GTx, occurring in 16 patients (73%), followed by febrile neutropaenia in 7 patients. Fifteen (68.2%) patients showed clinical improvement. This uncontrolled retrospective observational study provides some evidence that procurement and use of GTx is safe for both donors and recipients and is probably an effective supportive therapy for patients with febrile neutropaenia.

Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system.

Biphenotypic acute leukemia (BAL) is a rare, difficult to diagnose entity. Its identification is important for risk stratification in acute leukemia (AL). The scoring proposal of the European Group for the Classification of Acute Leukemia (EGIL) is useful for this purpose, but its performance against objective benchmarks is unclear. Using the EGIL system, we identified 23 (3.4%) BAL from among 676 newly diagnosed AL patients. Mixed, small and large blast cells predominated, with FAB M2 and L1 constituting the majority. All patients were positive for myeloid (M) markers and either B cell (B) (17 or 74%) or T cell (T) (8 or 34%) markers with two exceptional patients demonstrating trilineage phenotype. Six (50%) of studied M-B cases were positive for both IGH and TCR. In six (26%) patients myeloid lineage commitment was also demonstrable by electron cytochemistry. Abnormal findings were present in 19 (83%) patients by cytogenetics/FISH/molecular analysis as follows: t(9;22) (17%); MLL gene rearrangement (26%); deletion(6q) (13%); 12p11.2 (9%); numerical abnormalities (13%), and three (13%) new, previously unreported translocations t(X;6)(p22.3;q21); t(2;6)(q37;p21.3); and t(8;14)(p21;q32). In conclusion, the EGIL criteria for BAL appear robust when compared against molecular techniques that, if applied routinely, could aid in detecting BAL and help in risk stratification.

Diagnosis of Glanzmann thrombasthenia by whole blood impedance analyzer (MEA) vs. light transmission aggregometry.

BACKGROUND: Glanzmann thrombasthenia (GT) is a rare inherited platelet disorder that is characterized by spontaneous or postprocedural bleeding. The diagnosis of GT depends on identifying the dysfunction of the platelets. AIM: The aim of this study was to compare a whole blood impedance Multiplate analyzer (MEA) with the standard method, light transmission aggregometry (LTA) in diagnosis of GT. METHODS: Fifteen patients with GT were assessed on MEA and LTA using arachidonic acid (ASPI: 15 mm), (TRAP: 1 mm), collagen (100 µg/mL), ADP (0.2 mm), and ristocetin (Risto: 10 mg/mL). Whole blood samples were collected in sodium citrate and hirudin vacuum, blood collection tubes and tested within 4 h. Platelet-rich plasma was used for LTA using platelet agonists (ristocetin 1.5 mg/mL) (arachidonic acid 0.5 mg/mL) (ADP 2.5 mg/mL) and (collagen 1 mg/mL). RESULTS: The platelet count and PFA-100 results were (average and SD) 319 ± 93 × 10(9) L and 252 ± 34 s, respectively. Flow cytometry analysis showed that all samples are positive for CD42a and CD42b, whereas 9/15 samples were negative for CD61 and CD41. The other six patients had either partial or full expression of CD61/CD41. Aggregation analysis using both methods showed that all samples had no aggregation response to any of the agonists used apart from six samples which, using only the MEA, showed minimal aggregation in response to collagen (average = 14.3 ± 7 µg, which may suggest ability to detect qualitative abnormality of GPIIb/IIIa). CONCLUSION: These results suggest that the MEA is sensitive for the detection of Glanzmann thrombasthenia. Furthermore, MEA may also be able to differentiate between the subtypes of Glanzmann thrombasthenia.

Hemophagocytic syndrome.

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High efficacy and low toxicity of APL induction with concurrent idarubicin/ATRA followed by a novel and simplified outpatient post-remission therapy using single doses of idarubicin and intermittent ATRA.

Acute promyelocytic leukemia (APL) is one of the most curable myeloid malignancies because of its great sensitivity to all-trans retinoic acid (ATRA) and response to anthracycline therapy. In an attempt to simplify post-remission therapy, deliver adequate dose of anthracycline and reduce treatment related toxicity, we entered 26 consecutively newly diagnosed, previously untreated APL patients in a pilot treatment program consisting of concurrent induction using idarubicin/ATRA followed by an exclusive outpatient post-remission therapy using single dose of idarubicin and intermittent ATRA, every 4 weeks. Of 25 evaluable patients, two (8%) died early during induction due to hemorrhagic complications, and 23 (92%) achieved complete remission. Overall survival at 4.2 years was 90% (CI 76.4-100), and 3.6 years disease-free survival was 78% (CI 60.6-95.4). The treatment outcome of this program is encouraging; however, the result of this study needs to be validated in larger cohort of patients and optimally in a randomized comparison with other current post-remission approaches.