The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention of this phenomena among 64 transfused thalassemia patients (75% Asian) were evaluated. The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients. Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a splenectomy (36% vs 12.8%; P = .06). Erythrocyte autoantibodies, as determined by a positive Coombs test, developed in 25% or 16 of the 64 patients, thereby causing severe hemolytic anemia in 3 of 16 patients. Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. Autoimmunization was associated with alloimmunization and with the absence of spleen (44% and 56%, respectively). Transfused RBCs had abnormal deformability profiles, more prominent in the patients without a spleen, which possibly stimulated antibody production. Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P = .0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.

HCS should be recognized as a distinct thalassemia syndrome with a high risk of life-threatening anemia during febrile illnesses. HbH was not associated with an increased rate of severe anemia with infections and was managed without blood transfusions. Many patients with these disorders had mixed ethnic backgrounds, which highlights the need for extended newborn screening in populations that are traditionally considered to be at low risk for hemoglobin H disease.

SUMMARY Red blood cell (RBC) transfusion is the primary treatment for severe forms of thalassaemia. Pre-storage screening has resulted in decreased transfusion-transmitted infections, but anti-RBC antibodies remain a major problem. We report on 697 participants who had ever received transfusions. Allo- and autoantibody rates were compared with respect to splenectomy status, ethnicity, diagnosis, duration of transfusions, treatment centre, and age at transfusion initiation, together with rates before and after 1990, when leucoreduction methods were routine at thalassaemia treatment centres. Allo- and autoantibodies were reported in 115 (16.5%) and 34 (4.9%) subjects, respectively. Splenectomized patients were more likely to have alloantibodies (Odds Ratio [OR] = 2.528, p = <0.0001), or autoantibodies (OR = 2.590, p = 0.0133). Alloantibodies occurred in 19 of 91 (21%) splenectomized subjects who started transfusion after 1990, and only 18 of 233 (7.7%) nonsplenectomized subjects (p<0.001). Data from this study demonstrate that RBC antibodies continue to develop in chronically transfused thalassaemia patients at a high rate. Splenectomy preceded the development of antibodies in most cases. Increased rates of RBC sensitization among splenectomized patients is concerning and deserves further study.

The development of hemolytic alloantibodies and erythrocyte autoantibodies complicates transfusion therapy in thalassemia patients. The frequency, causes, and prevention of this phenomena among 64 transfused thalassemia patients (75% Asian) were evaluated. The effect of red blood cell (RBC) phenotypic differences between donors (mostly white) and Asian recipients on the frequency of alloimmunization was determined. Additional transfusion and patient immune factors were examined. 14 (22%) of 64 patients (75% Asian) became alloimmunized. A mismatched RBC phenotype between the white population, comprising the majority of the donor pool, and that of the Asian recipients, was found for K, c, S, and Fyb antigens, which accounts for 38% of the alloantibodies among Asian patients. Patients who had a splenectomy had a higher rate of alloimmunization than patients who did not have a splenectomy (36% vs 12.8%; P = .06). Erythrocyte autoantibodies, as determined by a positive Coombs test, developed in 25% or 16 of the 64 patients, thereby causing severe hemolytic anemia in 3 of 16 patients. Of these 16, 11 antibodies were typed immunoglobulin G [IgG], and 5 were typed IgM. Autoimmunization was associated with alloimmunization and with the absence of spleen (44% and 56%, respectively). Transfused RBCs had abnormal deformability profiles, more prominent in the patients without a spleen, which possibly stimulated antibody production. Transfusion of phenotypically matched blood for the Rh and Kell (leukodepleted in 92%) systems compared to blood phenotypically matched for the standard ABO-D system (leukodepleted in 60%) proved to be effective in preventing alloimmunization (2.8% vs 33%; P = .0005). Alloimmunization and autoimmunization are common, serious complications in Asian thalassemia patients, who are affected by donor-recipient RBC antigen mismatch and immunological factors.

The pathogenesis of pulmonary hypertension (PAH), a serious complication in thalassemia, is not well understood. Thromboembolism has been postulated as one of the causative factors; however, there are currently limited specific data on its role. To examine whether increased platelet activation and hypercoagulability are linked to PAH, 25 b-thalassemia major and b-thalassemia intermedia patients were evaluated with Doppler echocardiograms for estimation of pulmonary artery pressure and with laboratory assays for indications of a prothrombotic state. The association of clinical variables and abnormal coagulation assays with PAH was determined. PAH was identified in 17 (68%) patients; mean pulmonary artery systolic pressure was 39.8 ± 5.4 mm Hg. PAH was significantly associated with prior splenectomy, older age, and evidence for chronic hemolysis, diagnosed in both transfused (n 5 10) and nontransfused (n 5 7) patients. Increased platelet activation, measured by P-selectin, was significantly associated with PAH (P 5 0.001). Increased thrombin-antithrombin III level was more prevalent in the presence of PAH, but increased fibrinolysis or low protein C levels were not. This study underscores the role of platelet activation in the development of PAH and stresses its occurrence even among patients who are regularly transfused, especially those who are older and have had splenectomies. Am. J. Hematol. 81:670-675, 2006. V V C 2006 Wiley-Liss, Inc.

Cerebrovascular accident (CVA) is a major complication of sickle cell disease during childhood. Long‐term transfusion reduces the hemoglobin S level and generally prevents recurrent stroke, but it also results in progressive iron overload that requires regular chelation therapy. Erythrocytapheresis offers an alternative approach aimed at reducing the iron accumulation. We reviewed the results of erythrocytapheresis in eight sickle cell patients (mean age of 12.1 years) at high risk for a first or recurrent stroke. They were maintained at the standard pre‐transfusion hemoglobin S (Hb S) level of 30%. Over an average of 9 months of erythrocytapheresis, none of the patients developed complications related to the procedure or to the increased blood use. Ferritin levels decreased by a mean of 26.5% in all patients. When evaluating the ferritin level in five patients, who remained on chelation therapy with deferoxamine (DFO), the level dropped by a mean of 32%. The levels remained stable in the three patients who were not on DFO. The procedure is safe and effective in reducing iron overload and can obviate the need for chelation therapy, even when the target Hb S is maintained at the standard 30% range. J. Clin. Apheresis 14:122–125, 1999. © 1999 Wiley‐Liss, Inc.

The pathophysiology of iron-induced compromisedfertilityinwomenwiththalassemia major (TM) was evaluated in 26 adult TM females. Low gonadotropin secretion resulted in reduced ovarian antral follicle count and ovarian volume, but levels of anti-mü llerian hormone (AMH), a sensitive marker for ovarian reserve independent of gonadotropin effect, were mostly normal. AMH correlated with nontransferrin-bound iron (NTBI), suggesting a role of labile iron in the pathogenesis of decreased reproductive capacity, possibly occurring in parallel to cardiac iron toxicity, as cardiac iron was associated with the presence of amenorrhea and with NTBI levels. AMH emerges as an important biomarker for assessment of reproductive capacity in TM, demonstrating that fertility is preserved in the majority of those younger than 30 to 35 years. AMH can be useful in future studies aiming at improved chelation for fertility preservation, whereas NTBI and labile plasma iron may be valuable for monitoring iron effect on the reproductive system. (Blood. 2011;118(10):2878-2881) IntroductionDespite progress in chelation regimens, the deleterious effect of excess iron to the reproductive system of women with thalassemia major (TM) is still common. 1,2 Iron toxicity to the anterior pituitary results in declining synthesis of lutenizing hormone (LH) and follicle-stimulating hormone (FSH). 3 The effect of low gonadotropin secretion on the ovarian oocyte maturation has not been explored, and a possible direct effect of iron, in particular that of non-transferrin-bound iron (NTBI) and its redox active form, labile plasma iron (LPI), on the ovaries is unknown. Some have suggested iron-induced ovarian dysfunction 1 ; but with reports of successful ovulation-induction and pregnancies, it has been proposed that ovarian function is preserved even in women with amenorrhea. 2 Ovarian antral follicle pool can predict fertility capacity, and reproductive aging is directly related to the decline in this pool. Low ovarian reserve is associated with low chances for spontaneous pregnancy and poor response to hormonal stimulation. [4][5][6] Antral follicle count (AFC), visualized by ultrasound, and antimüllerian hormone (AMH), which corresponds with AFC, can accurately assess ovarian follicle pool and are used for ovarian reserve testing, identifying women at risk for early ovarian failure. 7,8 The usefulness of ovarian reserve testing for the care of thalassemia females has not been evaluated. Reproductive capacity in TM women cannot be well predicted by means of age, menstrual status, or transfusion and chelation parameters. 1,9 Yet, as overall survival continues to improve, 10,11 attainment of reproductive capacity is crucial for many patients, a concern often brought up to the hematologist.We evaluated the effect of iron burden on hypogonadism and ovarian reserve in TM women, to better understand the pathophysiology of reduced fertility and evaluate the predictive ability of ovarian reserve testing in this unique patient-population. MethodsThalassemia women (Ն...

SummaryIn this study we sought to determine whether factor VUI-reactive T lymphocytes were present in hemophilia A patients with inhibitor antibodies. Peripheral blood mononuclear cells (MNC) were obtained from 12 severe hemophilia A patients having high titer inhibitors, 4 severe hemophilia A patients without inhibitors and 5 normal male subjects. B cell-depleted MNC were cultured in serum-free medium in the absence or presence of 2 µg of recombinant human factor VIII (rFVIII) per ml, and cellular proliferation was assessed after 5 days of culture by measuring 3H-thymidine incorporation. rFVIII induced marked cellular proliferation in cultures of 4 of 12 inhibitor-positive hemophilia patients: fold increase over background (stimulation index, SI) of 7.8 to 23.3. The remaining 8 inhibitor-positive patients, the 4 hemophilia patients without inhibitors and the 5 normal subjects, all had lower proliferative responses to rFVIII, SI range = 1.6 to 6.0. As a group, the inhibitor-positive subjects had significantly higher proliferative responses to rFVIII than did the inhibitor-negative and normal subjects (p < 0.05 by t-test). Cell fractionation experiments showed that T lymphocytes were the rFVIII-responsive cell type, and that monocytes were required for T cell proliferation. Thus, rFVIII-reactive T lymphocytes are present in the peripheral circulation of some inhibitor-positive hemophilia A patients. These T cells may recognize FVIII in an antigen-specific manner and play a central role in the regulation of inhibitor antibody production