Relevance of RH variants in transfusion of sickle cell patients

Transfusion is a life sustaining therapy in sickle cell disease. Allo-immunization against red blood cells remains an important side effect responsible for post transfusion hemolysis. Numerous RH variant antigens are encountered in these patients of African descent. These RH variants can be associated with allo-immunization when the variant belongs to the partial type and when the carrier of this partial variant is exposed to the normal antigen through transfusion or pregnancy. Variants can be characterized by molecular typing, and many commercial tools have been developed. In this review, we will discuss the involvement of RH variants in sickle cell disease transfusion, with regards to their clinical significance in term of allo-immunization and haemolytic transfusion reaction.     

HLA-B35 is associated with red cell alloimmunization in sickle cell disease

HLA-A, -B, -C, and DR antigens were determined in 33 patients with sickle cell disease (SCD), who had received red blood cell (RBC) transfusions. Twenty-one patients formed red cell alloantibodies after transfusions (responders) while 12 multitransfused SCD patients did not form any RBC antibodies (non-responders). We found that 67% of the SCD responder participants had HLA-B35 versus 25% of the non-responders (chi 2 = 5.3079, P = 0.0212). The frequency of B35 in non-responder SCD patients was similar to that of a normal healthy Black population consisting of 139 individuals. Calculation of the relative risk showed that sickle cell patients with B35 are six times more likely to form RBC alloantibodies after transfusion than those lacking that HLA antigen. We found no significant increase or association between any HLA-DR antigens and sickle cell disease.     

Viral seroprevalence, transfusion and alloimmunization in adults with sickle cell anemia in Guadeloupe]

We retrospectively studied the prevalence of anti HIV 1 and 2, anti-HTLV-I, anti-Hepatitis B and C viruses (HBV and HCV) antibodies, anti-HBV vaccinal coverage, transfused patients and alloimmunizations frequencies among adult sickle cell patients attending the sickle cell center (SCC) of Guadeloupe. The data were collected from the medical files of the centre. Among the studied samples (n = 331) no transfusional HIV contamination was observed. All patients with HTLV-I (n = 11, 3.3% of whole sample) and anti-HCV (n = 9, 2.7%) positive serology had transfusion history. Five patients (1.5%) had an active hepatitis B. Vaccination against HBV efficiently protected 247 patients (74.4%) and 57 had post-hepatitis B antibodies. We observed that 213 patients (64%) had a history of transfusion (88% of SS patients and 36% of the SC patients, p < 0.05). Fifty-four patients (16%) presented alloimmunization, 4 of them have never been transfused. These results show that it is still necessary to optimise transfusion protocol and their safety, and to diagnose viral contamination in transfused sickle cell patients.     

Management of delayed hemolytic transfusion reaction in sickle cell disease: Prevention,diagnosis, treatment

Transfusion remains a key treatment of sickle cell disease complications. However, delayed hemolytic transfusion reaction, the most serious complication of transfusion, may be life-threatening if hyperhemolysis develops. This syndrome is generally underdiagnosed because its biological and clinical features resemble those of vaso-occlusive crisis, and red blood cell antibodies are frequently absent. Further transfusions may aggravate the symptoms, leading to severe multiple organ failure and death. It is therefore essential to prevent, diagnose and treat this syndrome efficiently. Prevention is based principally on the attenuation of allo-immunization through the provision of extended-matched RBCs or the use of rituximab. However, such treatment may be insufficient. Early diagnosis might make it possible to implement specific treatments in some cases, thereby avoiding the need for secondary transfusion. Diagnosis is dependent on the knowledge of the medical staff. Finally, many treatments, including steroids, immunoglobulins, erythropoietin and eculizumab, have been used to improve outcome. Improvements in our knowledge of the specific features of DHTR in SCD should facilitate management of this syndrome.     

Protective effect of HLA-DQB1 alleles against alloimmunization in patients with sickle cell disease

BackgroundAlloimmunization or the development of alloantibodies to Red Blood Cell (RBC) antigens is considered one of the major complications after RBC transfusions in patients with sickle cell disease (SCD) and can lead to both acute and delayed hemolytic reactions. It has been suggested that polymorphisms in HLA genes, may play a role in alloimmunization. We conducted a retrospective study analyzing the influence of HLA-DRB1 and DQB1 genetic diversity on RBC-alloimmunization.Study designTwo-hundred four multi-transfused SCD patients with and without RBC-alloimmunization were typed at low/medium resolution by PCR-SSO, using IMGT–HLA Database. HLA-DRB1 and DQB1 allele frequencies were analyzed using logistic regression models, and global p-value was calculated using multiple logistic regression.ResultsWhile only trends towards associations between HLA-DR diversity and alloimmunization were observed, analysis of HLA-DQ showed that HLA-DQ2 (p = 0.02), -DQ3 (p = 0.02) and -DQ5 (p = 0.01) alleles were significantly higher in non-alloimmunized patients, likely behaving as protective alleles. In addition, multiple logistic regression analysis showed both HLA-DQ2/6 (p = 0.01) and HLA-DQ5/5 (p = 0.03) combinations constitute additional predictor of protective status.ConclusionOur data suggest that particular HLA-DQ alleles influence the clinical course of RBC transfusion in patients with SCD, which could pave the way towards predictive strategies.     

Red blood cell alloimmunization complicating plasma transfusion

Well-known adverse effects of plasma transfusion include viral transmission, allergic complications, and rare anaphylactic reactions. In making clinical decisions to transfuse plasma, a seldom-considered complication is that of red blood cell (RBC) alloimmunization. The authors report a patient in whom strong IgM and IgG anti-E and weak IgG anti-JKa RBC antibodies developed 15 days after infusion of two units of fresh-frozen plasma for volume expansion. These antibodies are potentially hemolytic. This case underscores the importance of considering risks of plasma infusion. Plasma should not be used casually, especially for indications for which alternate therapies, such as crystalloid and colloid solutions, are available.     

Delayed haemolytic transfusion reaction due to Kidd antibodies

A delayed haemolytic transfusion reaction (DHTR) encompasses a positive direct antiglobulin test (DAT) developed anytime between 24 hours to 28 days after cessation of transfusion, a positive eluate or a newly identified alloantibody in the plasma or serum along with features of haemolysis in the patient. Routinely, it is expected that with the transfusion of one unit of packed red cells in a patient of average height and weight, the haemoglobin level and hematocrit increase by 1 g/dL and 3% respectively. However, in a patient with DHTR, an inadequate rise of post-transfusion haemoglobin (< 1 g/dL) or rapid fall in haemoglobin back to pre-transfusion levels is observed. Kidd antibodies are particularly known to cause DHTR, maybe alone or in unison with other antibodies. Detection of these alloantibodies is consequential in providing good transfusion support to these patients. These events may be difficult to detect as they may present as varied clinical features or immunological nuisances. In this case series, we have presented three cases of DHTR with special emphasis on their clinical presentations, immunohaematological evaluations, laboratory parameters and the role of proper transfusion support in these patients to avoid further complications.     

Fatal delayed transfusion reaction in a sickle cell anemia patient with Serratia marcescens sepsis

Patients with sickle cell anemia may require repeated red cell transfusion, putting them at risk for minor blood group alloimmunization and the development of delayed hemolytic transfusion reactions. Although Streptococcus pneumoniae is the most common cause of life-threatening infection in patients with sickle cell anemia, those who have been recently hospitalized are at risk for infection with resistant hospital-associated organisms, and blood transfusion may put the patient at risk of infection with transfusion-associated organisms such as Serratia marcescens and Yersinic enterocolitica. We recently cared for an adolescent with sickle cell anemia who presented to the emergency department with a severe, delayed hemolytic transfusion reaction and Serratia marcescens infection. The patient had been discharged from the hospital five days previously, and had been transfused and treated with antibiotics while hospitalized. In addition to demonstrating the potential severity of delayed hemolytic transfusion reactions, our case illustrates the importance of providing relatively broad-spectrum antibiotic coverage to patients with sickle cell anemia and possible infection who have recently been hospitalized.     

Case report and review: alloimmunization, delayed hemolytic transfusion reaction, and clinically significant anti-Yt(a) in a patient with Beta-thalassemia/sickle cell anemia

A 26-year-old female with Beta-thalassemia/sickle cell anemia was admitted to the hospital with symptoms of a painful crisis. During the next 4 days her hematocrit decreased to 13 percent, and there was reticulocytopenia. She was transfused with four units of red blood cells that were microscopically incompatible, and the hematocrit increased to 29 percent. Eight days later the patient was readmitted with back pain, hemoglobinuria, and a hematocrit of 27 percent. Anti-E, -c, -Jka, and -Yta were identified. The direct antiglobulin test was positive, and the eluate contained anti-c and -Jka. The patient's hematocrit continued to decrease to 14 percent. Transfusions were withheld and the patient recovered uneventfully. Separate 51Cr red blood cell survival studies showed significantly shortened survival of both autologous and R(1)R(1), Jk(a-), Yt(a+) erythrocytes. This case illustrates the complexity of transfusion management in hemoglobinopathy patients.     

Cerebrovascular accident during a delayed hemolytic transfusion reaction in a patient with sickle cell anemia

A 28-year-old woman with sickle cell anemia suffered a left hemispheric cerebrovascular accident associated with severe right-sided weakness during a delayed hemolytic transfusion reaction owing to anti-rh' (C) and anti-S. The anti-rh' (C) had been identified four years earlier at a different hospital but neither the patient, her family, nor any member of the staff of the hospital where she was transfused was aware of this information. It is postulated that spherocytes, formed during hemolysis, could slow capillary flow, thereby increasing red cell sickling and producing vaso-occlusion. The patient had no clinically apparent neurologic complications during the preceding 24 years and has had no further neurologic events during the subsequent 20 months. This patient's reaction underscores the compelling need for sensitive pre-transfusion tests as well as the obligation to inform patients and their families of the presence and potential consequences of alloantibodies in the event of future transfusion.     

HCV in sickle cell disease

The sickle cell gene is common in the U.S. In fact 8% of African Americans are healthy carriers of the sickle cell trait (HbAS). People who are homozygous (HbSS) have severe disease. They have life-long anemia, chronic hemolysis, and also have at times hematological crises, which can worsen the anemia. Many patients require chronic transfusions and as a result, substantial proportions of sickle cell patients are at high risk for infection with blood-borne diseases-such as Hepatitis C Virus infection (HCV). The HCV antibody positivity is directly related to the number of transfusions given, and on average the prevalence rate in transfused patients is more than 10%. It is known that the combination of iron overload and HCV can lead to a more rapidly progressive liver disease. The treatment of HCV in sickle cell patients poses a challenge to clinicians. A novel approach described by some is the pre-treatment of these patients with hydroxyurea to increase the fetal hemoglobin, therefore decreasing the severity of Ribavirin-related hemolysis. Treatment with Peg-interferon alone has not been used to treat HCV in sickle cell patients, but in the setting of controlled clinical trials it would be feasible. This review explores the impact of HCV in sickle cell patients and the possible therapeutic options available to them.     

Depression in sickle cell disease

PURPOSE: To assess the prevalence of depressive symptoms and examine the contribution of demographics, disease severity, and health care use variables to depressive symptoms in sickle cell patients who had been in stable health for at least one month. PATIENTS AND METHODS: Subjects were a convenience sample of 27 men and 23 women selected during a routine visit to the sickle cell clinic at Howard University Hospital. Depression was assessed using a cut-off score from the Beck Depression Inventory (BDI) and related to a variety of health outcomes. RESULTS: The results of the analyses indicate that 44% (n=22) of the sample scored within the mild to severe (>20) range of depression on the BDI. Depressed sickle cell patients were more frequently treated in emergency rooms and more likely to be hospitalized with vaso-occlusive crises. Patients more likely to be depressed were: those with low family income (<$10,000); less than high school education; female; those who had multiple blood transfusions; poor pain control; inadequate social support; hydroxyurea use; and had histories of frequent vaso-occlusive crises. CONCLUSION: The prevalence of depressive symptoms in sickle cell patients is high compared to the general African American population. Our findings confirmed previous studies examining the occurrence of depression in adults with sickle cell disease. Treatment of depression should be strongly considered to improve the quality of life and probably disease course in sickle cell patients.