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

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.

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.

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.

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.

The natural history of chronic hepatitis C in a cohort of HIV-negative Italian patients with hereditary bleeding disorders.

This study looked at 102 anti-hepatitis C virus (HCV)-positive, hepatitis B virus (HBV)-negative, and HIV-negative patients (median age, 45.1 years; range, 15-71) affected by hereditary bleeding disorders who have been infected with HCV for 15 to 34 years (median, 25.1). All these patients were infected before the mid 1980s because of non-virally inactivated pooled blood products. Fourteen patients (13.7%) were HCV-RNA negative with no signs of liver disease and were considered to have cleared the virus. Eighty-eight patients (86.3%) were HCV-RNA positive. The HCV genotype distribution was 1a in 20.5%, 1b in 36.4%, 2 in 17.0%, 3 in 15.9%, 4 in 3.4%, and mixed in 6.8% of cases. Twenty-four patients (23.5%) had serum cryoglobulins, symptomatic in 4 cases, and associated with liver disease and with genotype 1. Among the 88 HCV-RNA-positive patients, 15 (17.0%) had normal alanine aminotransferase levels and abdominal ultrasound, 61 (69.3%) had nonprogressive chronic hepatitis, and 12 (13.7%) had severe liver disease (6 [6.9%] liver cirrhosis, 4 [4.5%] hepatic decompensation, and 2 [2.3%] hepatocellular carcinoma) after a follow-up period of 25 years. There were 3 (3.4%) liver-related deaths. HCV genotype 1, patient's age at evaluation, duration of infection, and severity of congenital bleeding disorder were associated with more advanced liver disease. The results confirm the slow progression of HCV infection in HIV-negative hemophiliacs.

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.

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.

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)

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.

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.

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.

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.

Regulation of GRO alpha production in human granulocytes.

GRO alpha, a member of the chemokine superfamily, exerts potent stimulatory actions on granulocytes. In this report, we show that activated human polymorphonuclear leukocytes (PMN) are able to produce significant amounts of GRO alpha. Lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF alpha), and yeast particles opsonized with IgG (Y-IgG) had the ability to induce GRO alpha release, with Y-IgG being the most potent stimulus. The extracellular production of GRO alpha was also modulated by both interferon-gamma (IFN gamma) and interleukin-10 (IL-10). IFN gamma significantly inhibited the production of GRO alpha by PMN stimulated for 2 hr with LPS, TNF alpha, or Y-IgG, but potentiated the production of GRO alpha in cells stimulated for 18 hr with LPS and TNF alpha. IL-10 moderately suppressed the Y-IgG-induced production of GRO alpha, but strongly inhibited the action of LPS and potentiated the effect of TNF alpha. As revealed by Northern blot analysis, the extracellular production of GRO alpha under the experimental conditions used did not always correlate with parallel changes at the level GRO alpha mRNA expression, suggesting that production of GRO alpha by PMN might be regulated at post-transcriptional, translational, or post-translational level. These findings identify a novel biological function of PMN, likely involved in the modulation of the acute inflammatory response.

Potassium loss and cellular dehydration of stored erythrocytes following incubation in autologous plasma: role of the KCl cotransport system.

We studied the regulation of cell volume and cation content in erythrocytes stored at 4 degrees C under blood bank conditions for various lengths of time and subsequently incubated in autologous plasma at 37 degrees C for 4 or 24 h. Cell swelled during storage at 4 degrees C whereas marked K+ loss and cell shrinkage were observed when erythrocytes were incubated at 37 degrees C in autologous plasma. The cell shrinkage was inhibited only by the K+ Cl- cotransport-specific inhibitor, [(dihydroindenyl)oxy] alkanoic acid, and not by other specific inhibitors of cation transport systems such as ouabain (Na(+)-K+ ATPase pump), bumetanide (Na(+)-K(+)-Cl- cotransport) or carbocyanine (Ca+(+)-activated K+ channel). Acidification and swelling of the erythrocytes are well known to be able to activate the K+ Cl cotransport; such conditions, which were demonstrated to occur during the storage, could lead to activation of the K+ Cl- cotransport in reinfused cells. These data strongly support the evidence that K+ Cl- cotransport plays a role in K+ loss and dehydration of stored erythrocytes, when incubated in autologous plasma.

Membrane fatty acids, glutathione-peroxidase activity, and cation transport systems of erythrocytes and malondialdehyde production by platelets in Laurence Moon Barter Biedl syndrome.

The fatty acid composition of erythrocyte membrane, the glutathione-peroxidase activity of erythrocytes and platelets, the production of malondialdehyde by platelets and the activity of the main systems of transmembrane cation transport have been studied in 5 members of a family, 2 of whom affected by Laurence-Moon-Barter-Biedl Syndrome. A remarkable increase of polyunsaturated fatty acids (particularly arachidonic acid) and of cholesterol/phospholipid molar ratio has been noted. This pattern of membrane lipids was associated to an increment of malondialdehyde production and an increase activity of glutathione-peroxidase. Serum retinol and a-tocopherol were in the normal range, whereas serum selenium was low in 3 out of 5 members. Moreover, the alteration of membrane lipids was associated to a decrease of the maximal velocity of Li-Na countertransport. We speculate that the enrichment of polyunsaturated fatty acids on the cell membranes may represent a condition favoring the lipoperoxidation and therefore the development of the retinitis pigmentosa characteristic feature of Laurence-Moon-Barter-Biedl Syndrome.

Membrane fatty acids and erythrocyte Li-Na countertransport in nephrotic syndrome and their relationship.

Cholesterol/phospholipids molar ratio and fatty acid composition have been estimated in erythrocyte membrane of 12 patients suffering from nephrotic syndrome and compared to values obtained in 23 normal subjects matched for sex and age. The membrane lipid composition has been correlated with the activity of erythrocyte Li-Na countertransport of the same subjects. The results show a significant increase in cholesterol/phospholipids ratio and total saturated fatty acids when erythrocytes of nephrotic patients are compared to normal erythrocytes, whereas total unsaturated fatty acids were lower in nephrotics (p less than 0.002). Li-Na countertransport was higher in nephrotics (p less than 0.001) and it was positively correlated with the total amount of saturated fatty acids of the erythrocyte membrane (r = +0.451; p less than 0.01). On the contrary, Li-Na countertransport was negatively correlated with the total amount of unsaturated fatty acids (r = -0.468; p less than 0.01).