Giorgio Gandini

Non-ABO red blood cell alloantibodies following allogeneic hematopoietic stem cell transplantation

Summary:Immune-mediated hemolysis is a well-recognized occurrence which complicates the period following a bone marrow transplant (BMT). However, although many studies have investigated the hemolytic anemia following ABO-incompatible BMT, data regarding the occurrence of alloantibodies against red blood cell (RBC) antigens other than ABO in patients undergoing hematopoietic stem cell transplantation are limited. In this review, we briefly analyze the most important non-ABO red blood cell (RBC) antigen systems involved in the development of post-BMT alloimmune hemolytic anemia, paying particular attention to the pathogenic mechanisms and the clinical significance of the alloantibodies involved. Among the non-ABO RBC antigens, RhD antigen is the one most frequently implicated in the development of post-BMT alloimmune hemolytic anemia. Although less frequent than hemolysis following transplants with ABO incompatibility, non-ABO-incompatible allograft hemolysis may severely complicate the post-BMT period creating difficult clinical management issues. For this reason, we advise careful pre-transplant donor and recipient checks for the most important RBC antigen systems and close post-BMT immunohematological monitoring in those patients undergoing allogeneic hematopoietic stem cell transplant with RBC antigen incompatibility.

Preoperative autologous blood donation by 1073 elderly patients undergoing elective surgery : a safe and effective practice

BACKGROUND: Preoperative autologous blood donation (PABD) aims at avoiding the risks associated with exposure to allogeneic blood. While its use is extremely common among adult patients in connection with elective surgery, it is still uncommon in elderly patients, because of a series of coexisting pathologies.

Adverse reactions in blood and apheresis donors: experience from two Italian transfusion centres.

BACKGROUND Blood and apheresis donations are widely considered to be safe with a low incidence of adverse reactions and injuries; however, data reported in the medical literature on the prevalence of adverse events in donors and studies on the predictive risk factors for donor reactions are limited and contradictory. METHODS From January 2002 to December 2006 we recorded every adverse reaction verified during 240,596 consecutive blood and apheresis donations (183,855 homologous whole blood donations, 6,669 autologous whole blood donations, 38,647 plasmapheresis, 2,641 plateletpheresis and 8,784 multicomponent donations) at the Italian Transfusion Centres of Verona and Ragusa,. RESULTS Using a special, pre-arranged form within the quality system, a total of 686 adverse reactions (related to 0.28% of all donations) were recorded. Vasovagal reactions, mostly of mild intensity, were the most commonly observed adverse reactions, with a frequency of 0.20% (487/ 240,596). The frequency of the vasovagal reactions varied according to the different types of donation, being 0.19% (346/183,855) for homologous whole blood donations, 0.24% (16/6,669) for autologous whole blood donations, 0.16% (63/38,647) for plasmapheresis, 0.68% (18/2,641) for plateletpheresis and 0.49 (43/8,784) for multicomponent donations. Citrate toxicity was reported in 0.38% (189/50,072) of apheresis donations. Severe adverse reactions were very rare, as they occurred in 0.004% of the donations (10/240,596). CONCLUSIONS In conclusion, the results of our 5-year survey document that apheresis and blood donation are safe procedures for the donor with a low incidence of adverse reactions; the adverse reactions that did occur were mostly mild and resolved rapidly.

Mature CD10+ and immature CD10- neutrophils present in G-CSF-treated donors display opposite effects on T cells

The identification of discrete neutrophil populations, as well as the characterization of their immunoregulatory properties, is an emerging topic under extensive investigation. In such regard, the presence of circulating CD66b+ neutrophil populations, exerting either immunosuppressive or proinflammatory functions, has been described in several acute and chronic inflammatory conditions. However, due to the lack of specific markers, the precise phenotype and maturation status of these neutrophil populations remain unclear. Herein, we report that CD10, also known as common acute lymphoblastic leukemia antigen, neutral endopeptidase, or enkephalinase, can be used as a marker that, within heterogeneous populations of circulating CD66b+ neutrophils present in inflammatory conditions, clearly distinguishes the mature from the immature ones. Accordingly, we observed that the previously described immunosuppressive neutrophil population that appears in the circulation of granulocyte colony-stimulating factor (G-CSF)-treated donors (GDs) consists of mature CD66b+CD10+ neutrophils displaying an activated phenotype. These neutrophils inhibit proliferation and interferon γ (IFNγ) production by T cells via a CD18-mediated contact-dependent arginase 1 release. By contrast, we found that immature CD66b+CD10- neutrophils, also present in GDs, display an immature morphology, promote T-cell survival, and enhance proliferation and IFNγ production by T cells. Altogether, our findings uncover that in GDs, circulating mature and immature neutrophils, distinguished by their differential CD10 expression, exert opposite immunoregulatory properties. Therefore, CD10 might be used as a phenotypic marker discriminating mature neutrophils from immature neutrophil populations present in patients with acute or chronic inflammatory conditions, as well as facilitating their isolation, to better define their specific immunoregulatory properties.

F8 gene mutation profile and ITT response in a cohort of Italian haemophilia A patients with inhibitors

Summary.  Anti factor VIII (FVIII) antibodies represent the main complication of replacement therapy in severe cases of haemophilia and most patients with inhibitor have gross gene rearrangements or point mutations that hamper the production of normal circulating FVIII. In this study we have investigated 82 haemophilia A patients with inhibitors. Seventy six were severe, three were moderate and three were mild. We screened the patients for the causative mutations using long range PCR for the recurrent intron 22 inversion (invint22), multiplex PCR for intron 1 inversion (invint1) and conformation sensitive gel electrophoresis followed by DNA sequencing for all other mutation types in the F8 gene. Diverse genetic defects were detected in the severe cases (with a predominance of severe molecular defects): F8 gene inversions, large deletions and non‐sense mutations account for 71% of the mutations. Only missense and splicing mutations were identified in the non‐severe patients and we confirmed that the presence of inhibitors correlates well with the presence of severe mutations, but a proportion of severe patients develops inhibitors despite the presence of diverse less severe mutations. When we have analysed the subgroup of patients who underwent immunetolerance, we have found that F8 gene large deletions are likely to be a high risk factor also for immunetolerance therapy unresponsiveness, while no clear evidence has been demonstrated for other mutation types.

Recombinant human erythropoietin facilitates autologous blood collections in children undergoing corrective spinal surgery

We did not discuss the chimeric complex in our original report 1 because it was not possible to test all family members. Therefore, we can provide some additional data in response to Denomme’s questions but a few cannot be answered clearly. Two Y-chromosome-specific variants of the amelogenin system 2 were detected in the twin sister, indicating the presence of “male” white blood cells in her Blackwell Science, LtdOxford, UKTRFTransfusion0041-11322004 American Association of Blood BanksJuly 2004447••••Letters to the Editor LETTERS TO THE EDITORLETTERS TO THE EDITOR

Clinical effectiveness of platelets in additive solution treated with two commercial pathogen-reduction technologies

Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen‐reduction technologies versus standard platelets.

Tyr2105Cys mutation in exon 22 of FVIII gene is a risk factor for the development of inhibitors in patients with mild/moderate haemophilia A.

Summary.  We report the case of a patient with mild haemophilia A, due to a Tyr2105Cys mutation in exon 22 of the C1 domain, who developed a high‐titre factor VIII inhibitor (maximum titre 1600 BU) with recurrent severe haemorrhages and fatal intracranial bleeding. Based on published data, it appears that although this mutation occurs rarely in patients with mild or moderate haemophilia A, it is frequently associated with the development of high‐titre inhibitors.

Efficacy of desmopressin as surgical prophylaxis in patients with acquired von Willebrand disease undergoing thyroid surgery

Coagulation abnormalities may occur in patients with thyroid diseases. We report on 14 patients undergoing thyroid surgery for a thyroid disease with an alteration of coagulation parameters resembling von Willebrand disease. Subcutaneous desmopressin was first tested and then used successfully in these patients as surgical prophylaxis, with no side‐effects or bleeding complications during or after surgery. This study highlights the need for coagulation studies in patients with thyroid diseases undergoing thyroid surgery. Subcutaneous desmopressin may be used in these patients in order to prevent a surgically related bleeding risk.

Preoperative autologous blood donation by elderly patients undergoing orthopaedic surgery

To assess the feasibility of a programme of predeposit in elderly patients undergoing elective orthopaedic surgery.