Inventory management.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.

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

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.

Transmission of an anti-RhD alloantibody from donor to recipient after ABO-incompatible BMT.

We report a bone marrow transplant which was HLA matched, with major and minor ABO and minor RhD incompatibility (anti-RhD antibody) between the donor and recipient. When engraftment occurred, the recipient developed an anti-RhD antibody of donor origin detected by direct and indirect antiglobulin tests (DAT, IAT) and showed signs of mild hemolytic anemia. With the disappearance of the recipient RBCs, the DAT became negative and the hemolysis disappeared, while the anti-RhD alloantibody persisted in the patient's serum. This case emphasizes the importance of close immuno-hematological monitoring in patients undergoing allogeneic BMT with ABO-RhD incompatibility between recipient and donor.

Detection of an anti-RhD antibody 2 years after sensitization in a patient who had undergone an allogeneic BMT.

We describe an HLA matched bone marrow transplantation with minor ABO incompatibility and RhD mismatch (donor RhD negative and recipient RhD positive). GVHD appeared on day +96 and therapy with steroid and cyclosporin was started. When GVHD disappeared and immunosuppressive therapy was stopped (2 years after BMT), an anti-RhD antibody was detected in the patient's serum. The delayed appearance of this antibody may have been associated with the prolonged immunosuppression that was required for treatment of the patient's GVHD.

Unrelated allogeneic bone marrow donation: short- and long-term follow-up of 103 consecutive volunteer donors.

Between 1992 and 1999, 105 unrelated allogeneic bone marrow collections from 103 volunteer donors (65 males and 38 females; median age 33 years) were carried out in three northern Italian centers (Verona, Bolzano and Padova) affiliated with the Italian Bone Marrow Donor Registry (IBMDR). The average volume of BM collected was equivalent in both genders (1143.1 ml for males and 1054.2 ml for females; P = 0.1), although the average volume collected for unit of body weight and the average post-collection blood volume depletion was higher in females (respectively 17.1 ml/kg and 14.2% in females, 14.8 ml/kg and 12% in males; P= 0.01 and 0.03). There was no statistically significant difference between males and females in the total number of nucleated cells collected. We did not record any acute life-threatening event during or after the bone marrow collections. The most frequent complaint was pain at the collection site (77%) followed by the onset of fatigue (38%) and nausea and vomiting (25%); all of these were short-term problems. Hospitalization was short (average 20.2 h) and donors started their normal daily activities after an average of 5.4 days. We also monitored Hb, serum ferritin levels, WBC and platelet counts in the post-collection period (average follow-up 40.1 months). All donors signed a written informed consent for a further bone marrow collection, if needed. Our findings confirm the short- and long-term safety of allogeneic bone marrow collection in volunteer donors.

Alternative pathway for complement activation triggered by human liver plasma membranes.

Liver plasma membranes (LPM) prepared from normal hepatocytes by centrifugation in sucrose discontinuous gradient, are capable of haemolysing PNH-like cells in the presence of complement or complement plus EGTA or MG2+ ions. In contrast, EDTA or Ca2+ ions inhibit the lysis. The total complement lytic activity is reduced by some 40% when fresh serum is incubated with LPM, whereas the total amount of C4 remains constant. The cross-immunoelectrophoresis studies of fresh serum incubated with LPM demonstrate the appearance of C3 breakdown products, which suggests the activation of the alternative complement pathway. In contrast, the sucrose test, which proceeds mainly through the classical complement pathway, is inhibited by LPM. The possible role of complement in liver disease is discussed.

[Menorrhagia and inherited disorders of coagulation]. / Menorragia e disturbi ereditari della coagulazione.

Menorrhagia, a common complaint among women, may be a manifestation of an underlying inherited disorder of coagulation. In this review, the most frequent hereditary bleeding disorders associated with menorrhagia are briefly analyzed. Particularly, the epidemiological, clinical and diagnostic characteristics of von Willebrand disease, factor VIII, factor IX and factor XI deficiencies are examined. The influence of external factors (age, phase of menstrual cycle and hormonal therapy) on coagulation factor levels is also analyzed. Finally, the main therapeutic options (such as hormonal therapy, tranexamic acid and desmopressin), for the treatment of menorrhagia in women with hereditary bleeding disorders are reviewed. Since inherited bleeding disorders are frequently associated with menorrhagia, the conclusion is drawn that an underlying congenital bleeding disorder should be ruled out in any woman with menorrhagia.

Clinical relevance of serum cryoglobulins in hemophilic patients with hepatitis C virus infection.

Twenty-four hemophilic patients positive for hepatitis C virus were evaluated for the presence of serum cryoglobulins and associated symptoms. Eight (33.3%) of them had serum cryoglobulins (type II mixed cryoglobulinemia in all cases). The average time lapse between infection and appearance of serum cryoglobulins was 14.4 years (range 7-22 years). Two (25%) out of the 8 patients presented symptoms: one had systemic vasculitis, the other mild purpura. Hemophiliacs are a particularly suitable model for studying cryoglobulinemia in patients with hepatitis C virus infection since the onset of the infection is known and there is a long-term follow-up period.

[Transfusional therapy of hemodialyzed patient with anti-Cartwright antibodies: case report and review of the literature]. / Terapia trasfusionale in un emodializzato con anticorpi anti-Cartwright: descrizione di un caso e revisione della litteratura.

BACKGROUND: Red cell Cartwright antigen (Yta) is very common in the general population therefore patients without red cell Cartwright antigen and with anti-Yta alloantibodies due to previous exposure to the antigen are rare. Report about clinical significance of Yta red cell alloantibodies in hemodialysis (HD) patients are scarce. CASE REPORT: We report a cirrhotic uremic patient with anti-Yta antibodies who received Yta positive red cells. No adverse reactions nor hemolysis were detected. CONCLUSIONS: We concluded that dialysis patients with anti-Yta antibodies could be safely transfused with blood from Cartwright positive donors.

Preoperative autologous blood donation in primary total knee arthroplasty: a single-centre experience on 214 consecutive patients.

BACKGROUND AND OBJECTIVES: Although preoperative autologous blood donation (PABD) is a widespread practice in elective orthopedic surgery, it is controversial whether this procedure avoids allogeneic blood transfusions in patients undergoing total knee arthroplasty (TKA). PATIENTS AND METHODS: We performed a retrospective study on 214 consecutive patients undergoing PABD before elective primary TKA. RESULTS: Thirty-eight patients (17.8%) were transfused with autologous red blood cells (RBC), while four of them (10.5% of those requiring transfusions, 1.9% of all patients) also received allogeneic RBC. The transfused patients were, in most cases, female and had significantly lower basal and preoperative haemoglobin levels. CONCLUSIONS: Based on the results of this study, PABD is not necessary in most patients undergoing TKA, although older female patients with low basal haemoglobin levels could benefit from a predeposit programme and/or erythropoietin support in order to reduce the risk of exposure to allogeneic blood.

Presence and significance of cold agglutinins in patients with HIV infection.

BACKGROUND: HIV-infected patients may contract a variety of other concurrent infections, including Mycoplasma pneumoniae, cytomegalovirus (CMV) and Epstein-Barr virus (EBV), that are known to be causes of transient cold agglutinins (CA). The aim of this study was to search for the prevalence, the persistence and the significance of CA in HIV antibody-positive patients. METHODS: Ninety patients belonging to different risk groups (drug addicts, homosexuals and hemophiliacs), including 15 with AIDS, 20 with ARC, 25 with PGL, 30 symptom-free individuals and 100 healthy blood donors were assessed for the presence of CA for at least six months. RESULTS: In 20 cases (22%) CA were found: 3, 7, 5 and 5 respectively, in each of the above mentioned HIV-positive groups, while the group used as control was CA-negative. There were no differences between CA-negative and CA-positive patients with regard to the presence of anemia, frequency of other infections, or development of lymphatic malignancy during the follow-up period. Serological specificity of CA included 14 of type anti-I, 5 of anti-i and 1 of anti-Pr specificity. CONCLUSIONS: It appears that CA production is another immune disorder of patients with HIV infection.

Activation of complement by stroma from normal and paroxysmal nocturnal haemoglobinuria red cells.

Stroma from normal, AET-treated and PNH red cells and their KC1-extracts (partially purified on Sephadex G-200) are able to trigger the activation of the alternative complement pathway. This fact has been demonstrated by: 1 - the lysis of PNH cells incubated in serum treated with stroma from normal or PHN-RBC or with their extracts; the addition of Mg2+ or Ca2+ or of their chelators (EDTA, EGTA) to the extract-treated serum enhances or abolishes the lysis 2 - the reduction of complement acitvity in fresh serum incubated for 60' with PNH-extract 3 - the appearance of C3 breakdown products in serum incubated with PNH-extract, demonstrated by crossed immunoelectrophoresis. In contrast, the same stroma (or extract) inhibits the sucrose lysis test, in which the lysis takes place through the classical complement pathway. No differences on the complement activation were observed between PNH and normal RBC stroma and between their chromatographic extracts. These findings may suggest the possible role of diurnal variation of Mg2+ and Ca2+ concentration in precipitating haemolytic attacks and the possibility that small amount of circulating red cell stroma might maintain the haemolysis on PNH RBC.

Subcutaneous bolus injection of deferoxamine in adult patients affected by onco-hematologic diseases and iron overload.

BACKGROUND AND OBJECTIVE: Chelation therapy is often necessary for patients who undergo chronic transfusion therapy for myelodysplastic syndromes. In these patients, deferoxamine, the most widely used chelating agent, has been reported to be effective in reducing the iron burden and the transfusion requirement. Unfortunately, compliance with the drug, that is usually administered by slow subcutaneous infusion via a battery operated pump, is often poor, especially in elderly patients. DESIGN AND METHODS: To verify efficacy and tolerability of deferoxamine by subcutaneous bolus injection as compared to the conventional pump-driven slow infusion, eleven patients affected by oncohematologic diseases were given 2 g of deferoxamine diluted in 10 mL of distilled water over twelve hours by continuous infusion, or by bolus injection in two divided doses. RESULTS: Mean urinary excretion was comparable with the two methods, being 9,183 +/- 4,349 micrograms/48 h after two daily subcutaneous bolus injections and 8,291 +/- 3,970 micrograms/48 h with the slow infusion. The bolus injection was preferred by all eleven patients, who chose to continue chelation therapy by this method. INTERPRETATION AND CONCLUSIONS: The iron excretion induced by bolus injection is not statistically different from that induced by subcutaneous infusion. The side effects are acceptable. Subcutaneous bolus injection of deferoxamine is an acceptable alternative to slow, pump-driven infusion.

Safety and efficacy of subcutaneous bolus injection of deferoxamine in adult patients with iron overload.

We compared 48-hour urinary iron excretion after a twice-daily subcutaneous bolus injection of deferoxamine and after 12 hours of subcutaneous continuous infusion of the drug in 27 patients with iron overload (mean age, 55.7 years). In most patients, the iron overload was due to multiple transfusions administered during chemotherapy or as part of supportive care for a hematologic or oncologic disorder. One patient had sickle cell anemia and 1 had hereditary hemochromatosis and spherocytosis. Similar urinary iron excretion was observed with the 2 methods of administration; mean +/- SD values were 6935.3 +/- 3832.3 microg/48 hours with subcutaneous bolus injection and 6630.4 +/- 3606.9 microg/48 hours with subcutaneous continuous infusion (P =.3). Twenty-six patients (96.3%) chose to continue therapy with bolus injection. The long-term efficacy of bolus injection was evaluated by measuring the serum ferritin concentration at regular intervals for a follow-up time of 20.1 +/- 4.5 months. Ferritin concentration decreased to below 1000 microg/L in 73% of the patients and to below 500 microg/L in 42% and became normal in 26%. Best results were obtained in patients who were no longer receiving blood transfusions when chelation therapy was initiated. Three of 26 patients (11.5%) had mild, transient side effects after bolus injection. Larger prospective, randomized studies must be conducted before deferoxamine bolus injection can be routinely recommended for patients with iron overload. (Blood. 2000;95:2776-2779)

[Chemotaxis deficiency in patients with HIV infection]. / Deficit della chemiotassi in pazienti con infezione da HIV.

Increased susceptibility to bacterial recurrent infection is characteristically associated with impaired B cells function but also with a defective PMN function. We studied PMN CT in 15 HIV positive drug addicts patients with persistent generalized lymphoadenopathy (PGL), in 15 symptom free HIV negative drug addicts (SFDA) and in 15 healthy blood donors to evaluate influence of HIV infection on PMN functions. CT of patients with PGL was reduced to 78% (p < 0.0001) and 75% (p < 0.00001) of CT in SFDA patients and healthy blood donors, respectively. We conclude that HIV infection causes defective PMNL CT and then it can increase susceptibility to bacterial recurrent infections in these patients.

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.

Immunohematological aspects of bone marrow transplantation.

Allogeneic bone marrow transplantation (BMT) is an effective treatment for some severe hematologic or nonhematologic diseases. The blood group antigen mismatch between donor and recipient may cause immunohematological complications during or after BMT. In this review, we analyze the ABO, Rh and other red cell antigen mismatches between donor and recipient, the main immunohematological complications and the techniques to prevent them. The data reported are derived from the experience of the authors and from the medical literature. The clinical implications of the immunohematological aspects of BMT emphasize the importance of close immunohematological monitoring in patients undergoing allogeneic BMT with ABO, Rh or other red cell antigen mismatches between donor and recipient.

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. STUDY DESIGN AND METHODS: A retrospective study was made of 1073 consecutive elderly patients at a city hospital from 1990 to 1996. Their responses to the PABD program were evaluated by analysis of the incidence of complications and the demand for allogeneic blood. RESULTS: The PABD program was interrupted in 79 (7.4%) of 1073 patients because of the onset of anemia, vasovagal reactions, lack of accessible superficial veins, or cardiovascular complications. Seven hundred eighty-four (73.1%) of 1073 patients were given autologous blood; 151 (14.1%) patients also required allogeneic blood. CONCLUSION: The onset of anemia (6.5%) was the main contraindication for continuing the PABD program: incidence increased with age. PABD in connection with elective surgery is both feasible and effective in a high percentage of elderly patients.

Interferon and ribavirin in HIV-negative haemophiliacs with chronic hepatitis C who were nonresponders to a previous interferon treatment.

Between January 1999 and December 2001, 33 HIV-negative haemophiliacs with interferon-nonresponsive chronic hepatitis C were treated with interferon (IFN) alpha2b (5 MU three times weekly) and ribavirin (1-1.2 g daily) for 12 months. Four patients (12.1%) dropped out of the study due to adverse effects. At the end of therapy, normalization of ALT occurred in 14/33 treated patients (42.4%) and HCV-RNA was cleared in 12 (36.4%). Eleven patients (33.3%) became sustained responders. Genotype 1 was the only factor associated with a poor response to therapy (P < 0.001). Our study shows that IFN and ribavirin combination therapy is effective in HIV-negative chronically HCV-infected haemophiliacs who do not respond to a previous IFN treatment.

Preoperative autologous blood donation by elderly patients undergoing orthopaedic surgery.

BACKGROUND AND OBJECTIVES: To assess the feasibility of a programme of predeposit in elderly patients undergoing elective orthopaedic surgery. PATIENTS AND METHODS: We retrospectively studied 789 elderly patient candidates (> 65 years of age) for orthopaedic surgery (total hip and knee replacement and spinal surgery), who were undergoing a programme of preoperative autologous blood donation (PABD) in our city hospital between January 1990 and December 1998. RESULTS: Six hundred and eighty-eight patients (87.2%) were transfused with autologous blood; 128 (16.2%) also received allogeneic blood. Hip arthroplasty revision was characterized by the greatest blood consumption. The predeposit programme was discontinued in 96 patients (12.2%) because of the following complications: the onset of anaemia (11.0%); vasovagal reactions (0.5%); lack of venous access (0.4%); or cardiac complications (0.2%). No episodes of reaction to autologous transfusion were recorded. CONCLUSIONS: Our study confirms the feasibility of PABD in elderly patients undergoing elective orthopaedic surgery.