Red cell antibodies in patients with homozygous sickle cell disease: a comparison of patients in Jamaica and the United Kingdom

The transfusion history and frequency of red cell antibodies in patients with homozygous sickle cell (SS) disease have been compared in 190 subjects from the Jamaican cohort study and 37 patients attending a sickle cell clinic in Manchester, England. The proportion of patients transfused did not differ between the groups although the number of units transfused and the frequency of red cell antibodies were significantly greater in the Manchester group. Immune antibodies occurred in three Jamaicans (2.6% of those transfused) and 16 UK subjects (76% of those transfused). Multiple antibodies occurred in 10 (63%) UK subjects but in no Jamaicans. Indications for transfusion also differed between the groups, Jamaican patients typically receiving 1-2 units for acute anaemia or acute chest syndrome, whereas UK patients frequently had multiple transfusions in preoperative exchange or prophylaxis programmes. The greater red cell alloimmunization among UK patients probably reflects both the greater use of transfusion and the disparity between donor and recipient populations in the UK.     

Effect of red cell exchange transfusion on plasma levels of inflammatory mediators in sickle cell patients with acute chest syndrome

Red cell exchange transfusion is the recommended therapy for patients with sickle cell disease (SCD) who have severe, progressive acute chest syndrome (ACS). A double-volume red cell exchange transfusion decreases the percentage of hemoglobin S (Hgb S) containing red blood cells to less than 20%, improving vascular perfusion. We speculated that reduction of pro-inflammatory mediators might also contribute to the therapeutic effect of an exchange transfusion. We measured white blood cell count (WBC), absolute neutrophil count (ANC), platelet concentration as well as plasma levels of interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), interleukin-8 (IL-8), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 8 sickle cell patients with 9 episodes of ACS who received a manual, double-volume exchange transfusion. Six patients with SCD seen during a routine clinic visit were used as controls. The mean number of hospitalization days was 6, with an average of 2 days in the intensive care unit. All patients recovered without complication. Sickle cell patients with ACS had a higher WBC and ANC at baseline but lower sVCAM-1 levels compared to controls. TNF-alpha, IL-1alpha, IL-1beta, and IL-8 levels were not significantly different from controls. WBC, ANC, platelet, and sVCAM-1 measurements were significantly decreased immediately post-exchange in patients with ACS; however, this effect was not persistent as levels trended towards pre-exchange values by 24 hr post-exchange. Due to wide inter-individual variability, a consistent pattern was not seen for TNF-alpha, IL-1alpha, IL-1beta, or IL-8. We conclude that in sickle cell patients with ACS, a manual, double-volume exchange transfusion lowers WBC, ANC, platelets, and sVCAM-1 levels, but the effect is short-lived.     

Blood transfusion usage among adults with sickle cell disease - a single institution experience over ten years

Transfusion of red blood cells is a major therapeutic option in sickle cell disease (SCD). There is strong evidence for its efficacy, particularly in primary and secondary stroke prevention in children, however, its use in other areas remains controversial. This study assessed the patterns of transfusion in the adult cohort attending King's College Hospital over a 10-year period, from 2000 to 2009. Total blood usage has increased significantly (P = 0·006) during this time, with 78% of the blood received by only 6% of the patients. The increase is explained by increased automated red cell exchange and increased usage for planned and acute transfusions for sickle-related complications.     

Effect of erythrocytapheresis on arterial oxygen saturation and hemoglobin oxygen affinity in patients with sickle cell disease

An important purpose of blood transfusion in patients with sickle cell disease is to improve arterial oxygen saturation (SaO₂) and thereby reduce red cell sickling. To investigate the degree of improvement in SaO₂ by blood transfusion, we determined the hemoglobin oxygen affinity, transcutaneous oxygen saturation (Tc-SO₂), and pulse rate before and after automated partial exchange transfusion (erythrocytapheresis). In 13 patients with sickle cell disease who underwent 24 erythrocytapheresis procedures, the mean oxygen tension at half saturation (P50) was significantly reduced from 30.4 ± 2.2 to 26.0 ± 1.6 mm Hg (P < 0.01) immediately after exchange transfusion. Mean Tc-SO₂ values increased from 96.2 ± 2.8 to 98.5 ± 2.1% (P < 0.01). Approximately 50% of the increase in Tc-SO₂ after erythrocytapheresis could be explained by the increase in hemoglobin oxygen affinity. An increase in arterial oxygen pressure (PaO₂) following erythrocytapheresis, suggested by the calculated PaO₂ in this study, may explain some of the increase in Tc-SO₂. We conclude that improvement in Tc-SO₂ in patients with sickle cell disease resulted from changes in hemoglobin oxygen affinity as well as blood oxygen pressure following erythrocytapheresis. Am. J. Hematol. 59:5–8, 1998. © 1998 Wiley-Liss, Inc.     

Oxygen Saturation and Hemoglobin A Content in Patients with Sickle Cell Disease Undergoing Erythrocytapheresis

Abstract: Severe hypoxia occurs in patients with acute chest syndrome, and erythrocytapheresis has been shown to improve oxygenation. Patients with sickle cell anemia also have decreased baseline oxygen saturation values, but the effect of erythrocytapheresis on steady‐state oxygenation has not been well studied. We investigated the changes in oxygen saturation versus hematocrit, fraction of hemoglobin A, and transfusion volume during 71 prophylactic erythrocytapheresis procedures performed in 5 stable patients with sickle cell anemia. Each patient had a history of either acute chest syndrome or stroke, but no serious events occurred while enrolled in the chronic exchange program. The oxygen saturation improved from 1% to 6% during erythrocytapheresis in each of our patients (p < 0.001) regardless of preprocedure saturation level or total hematocrit. We have shown that decreased baseline oxygen saturation in sickle cell disease is related to abnormal hemoglobin S levels, and oxygen saturation can be improved with erythrocytapheresis, independent of any change in the total hematocrit.     

Techniques for blood administration in sickle cell patients

Transfusion therapy provides many benefits to individuals with sickle cell disease but may lead to cardiovascular complications, alloimmunization, exposure to infection, and iron overload. Simple transfusion is used to increase oxygen-carrying capacity. Chronic simple transfusion is useful in preventing a number of complications in sickle cell disease. Acute erthrocyte exchange transfusion can reduce the percentage of cells containing sickle hemoglobin while decreasing volume overload and minimizing hyperviscosity. Chronic erythrocyte exchange transfusion reduces iron loading but increases donor exposure. Directed odnation may reduce alloimmunization and exposure to infection.     

Heart valve surgery in patients with homozygous sickle cell disease: A management strategy

Background:

Patients with the homozygous sickle cell disease have increased perioperative mortality. Some indications like heart valve surgery, may justify an exchange blood transfusion to reduce the proportion of hemoglobin S (HbS) and complications.

Subjects and Methods:

We report two female cases aged 20 and 27, of African origin with homozygous sickle cell anemia who underwent heart valve surgery to treat mitral valve regurgitation. This presentation describes the perioperative considerations including anesthesia and postoperative care.

Results:

A partial exchange blood transfusion decreased HbS levels from respectively, 90% and 84%, 9% to 27% and 34%, and simultaneously treated the anemia. Neither sickling crisis nor acidosis occurred in any patient, and no special postoperative complication occurred. Average hospital stay was 10 days. Currently, the two patients remain alive and free of cardiac symptoms.

Discussion:

Although the presence of sickle cell disorders is associated with increased risk of sickling and thus vaso-occlusive complications, they should not be taken as a contraindication for heart valve surgery. Nevertheless, monitoring of certain parameters such as venous, arterial oxygen content, pH, and body temperature is mandatory for a better outcome. Furthermore, preoperative exchange transfusion has a positive influence on the outcome of surgery and on the survival of patients undergoing heart valves surgery. Avoiding intraoperative hypoxia, hypothermia, and vaso-constrictive agents, minimizing HbS levels with preoperative exchange transfusion, and ensuring a stress-free environment with the judicious use of sedatives made surgery relatively safe in these cases.     

Acute Myocardial Infarction in Sickle Cell Disease: Case Report and Review of the Literature

Although vascular occlusion is a hallmark of sickle cell disease, documented myocardial infarction is an uncommon event in these patients. We report a case of an acute lateral myocardial infarction in a 25 year old male homozygous for HbS, who had previously had a relatively benign course of his sickle cell disease. Management of the case included an exchange transfusion and a 6 month period of chronic simple transfusions (2 units packed red cells every 3–4 weeks). We review here the available literature on cardiovascular manifestations of sickle cell disease.     

The management of crisis in sickle cell disease

Abstract: The symptoms and signs of sickle cell disease are exacerbated in times of crisis, characterized by tissue infarction or worsening anaemia. Prompt medical intervention is required in these distressing situations to provide relief and comfort to the patient. Effective analgesia is crucial in treating the painful crisis of sickle cell disease. The haemoglobinopathy may cause hyposthenuria with reduced ability to excrete the sodium load in normal saline. A 5% dextrose solution or 5% dextrose in 25% normal saline is therefore recommended for intravenous hydration. As the leading cause of morbidity and mortality in sickle cell disease, infections call for vigorous antibiotic therapy. Oxygen administration should be reserved for hypoxic patients, and blood transfusion given only when really indicated. Acute chest syndrome and cerebrovascular accidents are life-threatening complications of sickle cell disease whereas priapism can cause important long-term sequelae; all deserve urgent attention. In the long term, comprehensive care is cost-effective in reducing the frequency and adverse effects of sickle cell crisis.     

Erythrocytapheresis limits iron accumulation in chronically transfused sickle cell patients

Cerebrovascular accidents (CVA) as a complication of sickle cell disease occur most frequently in childhood. Life-long transfusion prevents recurrent stroke, but inevitably leads to iron overload. Although effective chelation exists, many patients are not compliant. Erythrocytapheresis, an automated method of red blood cell exchange, was evaluated as an alternative to control transfusion-related iron load. Eleven patients with sickle cell anemia and a history of stroke were converted from simple transfusion to pheresis. Total time on pheresis for the group averaged 19 months (range 4–36 months). No significant complications occurred with a mean pre-pheresis hemoglobin S (Hb S) level of 44%. Blood utilization increased by an average of 50%. The effect of pheresis on serum ferritin depended on the patient's pre-pheresis ferritin level and chelation regimen. Ferritin levels remained stable for chelated patients with ferritin levels ⩾5,000 ng/ml, but decreased in a chelated patient with a pre-pheresis ferritin level of 4,000 ng/ml. For non-chelated patients with significant pre-pheresis iron load, ferritin levels remained stable. No patient on chelation prior to pheresis was able to discontinue deferoxamine. However, one patient with pre-pheresis ferritin of 500 ng/ml maintained serum ferritin levels <200 ng/ml for 36 months of pheresis without chelation. Pheresis is more expensive than simple transfusion unless the cost of chelation and organ damage from iron overload are considered. Erythrocytapheresis is a safe method of controlling Hb S levels and limiting or preventing iron load in chronically transfused sickle cell patients. Am. J. Hematol. 59:28–35, 1998. © 1998 Wiley-Liss, Inc.     

Acute chest syndrome in sickle cell disease

Acute chest syndrome is a common cause of death among patients with sickle cell disease, and an unfamiliar condition to most Australian medical practitioners. We present a case of acute chest syndrome successfully treated with inhaled nitric oxide and exchange transfusion. In the discussion we review current and future management options of acute chest syndrome.     

Red cell transfusion and alloimmunization in sickle cell disease

Red cell transfusion remains a critical component of care for acute and chronic complications of sickle cell disease. Randomized clinical trials demonstrated the benefits of transfusion therapy for prevention of primary and secondary strokes and postoperative acute chest syndrome. Transfusion for splenic sequestration, acute chest syndrome, and acute stroke are guided by expert consensus recommendations. Despite overall improvements in blood inventory safety, adverse effects of transfusion are prevalent among patients with sickle cell disease and include alloimmunization, acute and delayed hemolytic transfusion reactions, and iron overload. Judicious use of red cell transfusions, optimization of red cell antigen matching, and the use of erythrocytapheresis and iron chelation can minimize adverse effects. Early recognition and management of hemolytic transfusion reactions can avert poor clinical outcomes. In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.     

Improved exercise performance after exchange transfusion in subjects with sickle cell anemia

Ten patients with sickle cell anemia underwent partial exchange transfusion with hemoglobin-A-containing cells using a technique that allowed hemoglobin concentration and blood volume to remain constant. The mean fraction of hemoglobin-A in these patients increased from 9% to 55%, but the mean hemoglobin concentration increased by only 1.44 g/dl. The exchange resulted in a large improvement in submaximal exercise capacity: the mean of the anaerobic threshold (the work at which lactic acid begins to accumulate in the blood) increased from 68 to 114 W. The mean work performed at a heart rate of 170/min, an estimation of maximal work capacity, increased from 128 to 187 W. Improved exercise performance after partial exchange transfusion may result from the superior flow properties of hemoglobin-A-containing red cells. Furthermore, we believe that exercise testing in sickle cell anemia has great potential utility as a means to monitor therapy and to evaluate the benefits of exchange transfusion.     

A sickle cell disease patient with dural venous sinus thrombosis: a case report and literature review

Abstract

Dural venous sinus thrombosis (DVST) is a rare disease associated with hypercoagulable states. Patients with sickle cell disease are known to be prothrombotic. We report a case of DVST presenting with anterior neck and facial pain in a 24-year-old female with sickle cell disease, found to have extensive thrombotic disease involving the internal jugular vein. A literature review of DVST in sickle cell disease consisting of 14 case reports was summarized. Headache was a presenting feature in two-thirds of patients. Nine cases were associated with vaso-occlusive crisis (VOC), transfusion, or acute respiratory illness. Most patients were treated with anticoagulation therapy. Over three-quarters either died or suffered from a serious neurological complication, including stroke, seizure, coma, or elevated intracranial pressure. Given its association with life-threatening complications, DVST should be considered when patients with sickle cell disease present with a VOC, especially in the context of headache or neurological deficits.     

How we treat delayed haemolytic transfusion reactions in patients with sickle cell disease

Transfusion therapy is effective in the prevention and treatment of many complications of sickle cell disease (SCD). However, its benefits must be balanced against its risks, including delayed haemolytic transfusion reactions (DHTR). Not only is the relative rate of alloimmunization higher in patients with SCD than in other patient populations, but attendant risks associated with DHTR are even greater in SCD. Clinicians' awareness of DHTR events is poor because symptoms of DHTR mimic acute vaso‐occlusive pain and immunohaematology findings are often negative. Transfusions delivered in the acute rather than elective setting appear to confer a higher risk of DHTR. Management of DHTR in SCD depends on the clinical severity, ranging from supportive care to immunosuppression, and optimization of erythropoiesis. DHTR must be considered in any recently transfused patient presenting with acute sickle cell pain. Meticulous documentation of transfusion and immunohaematology history is key. We anticipate an increase in DHTR events in SCD patients with the increasing use of red blood cell transfusion therapy.     

Sickle cell anemia,right atrial thrombosis,and the antiphospholipid antibody

We report a patient with sickle cell anemia (homozygous Hb SS) and typical features of sickle chest syndrome but with no response to exchange transfusion. A right atrial thrombus was found, and antiphospholipid antibodies were detected in his blood. He responded to thrombolytic therapy. The relationship between right atrial thrombus and massive pulmonary embolus, and the implications of an additional thrombophilic state in sickle cell disease are discussed.     

Surgery and anesthesia in sickle cell disease. Cooperative Study of Sickle Cell Diseases

From 1978 to 1988, The Cooperative Study of Sickle Cell Disease observed 3,765 patients with a mean follow-up of 5.3 +/- 2.0 years. One thousand seventy-nine surgical procedures were conducted on 717 patients (77% sickle cell anemia [SS], 14% sickle hemoglobin C disease [SC], 5.7% S beta zero thalassemia, 3% S beta zero + thalassemia). Sixty-nine percent had a single procedure, 21% had two procedures, and the remaining 11% had more than two procedures during the study follow- up. The most frequent procedure was abdominal surgery for cholecystectomy or splenectomy (24% of all surgical procedures, N = 258). Of these, 93% received blood transfusion, and there was no association between preoperative hemoglobin A level and complication rates (except reduction in pain crisis). Overall mortality within 30 days of a surgical procedure was 1.1% (12 deaths after 1,079 surgical procedures). Three deaths were considered to be related to the surgical procedure and/or anesthesia (0.3%). No deaths were reported in patients younger than 14 years of age. Sickle cell diseases (SCD)-related complications after surgery were more frequent in SS patients who received regional compared with general anesthesia (adjusted for risk level of the surgical procedure, patient age, and preoperative transfusion status, P = .058). Non-SCD-related postoperative complications were higher in both SS and SC patients who received regional compared with those who received general anesthesia (P =.095). Perioperative transfusion was associated with a lower rate of SCD- related postoperative complications for SS patients undergoing low-risk procedures (P = .006, adjusted for age and type of anesthesia), with crude rated of 12.9% without transfusion compared with 4.8% with transfusion. In SC patients, preoperative transfusion was beneficial for all surgical risk levels (P = .009). Thus, surgical procedures can be performed safely in patients with SCD.     

Risk of alloimmunization and delayed hemolytic transfusion reactions in patients with sickle cell disease

Blood transfusion is an integral part of the supportive care of patients with sickle cell diseases. The hazards of red blood cell alloimmunization and delayed hemolytic transfusion reactions (DHTRs) complicate the treatment of patients with sickle cell diseases, particularly since such reactions may be misinterpreted as a pain crisis, and, as a result, specific transfusion serologic studies may not be performed. The frequency of alloimmunization in this population has been the subject of several reports; however, the frequency of DHTRs is unknown. To determine the frequency of this event, we retrospectively reviewed the medical and transfusion service records of all adult patients with sickle cell diseases transfused during the six-year period from January 1980 to December 1985. Seventy-three adult patients with sickle cell diseases received transfusions. The prevalence of recognized DHTR was three (4%) of 73. Red blood cell alloimmunization was seen in 22 (30%) of 73 of the patients. The calculated risk of alloimmunization was 3.1% per unit of blood. These observations suggest that alloimmunization and clinically apparent DHTRs occur more frequently in patients with sickle cell diseases and support pretransfusion testing for at least Rh and Kell red blood cell antigens in patients who are at high risk of such events (patients who have formed an alloantibody or who are being enrolled in a transfusion program).     

Post-transfusion alloimmunization in patients with sickle cell disease.

The transfusion histories over a 33-month period of 50 patients with sickle cell disease were reviewed to determine the frequency of alloimmunization to red cell antigens following transfusion in these patients. There were 30 females and 20 males, aged 19--49 years. Eighteen (36%) were immunized of which thirteen were females. Five of the patients have formed only one antibody so far, while the other 13 have formed two or more. Thirty-six antibodies were identified: 16 against various Rh antigens, 12 anti-Lewis, 5 anti-Kell and one each of anti-Jka, -Fya and -M. The immunized patients received, on the average, more transfusions although there was a considerable degree of overlap between the immunized and nonimmunized groups. An approach to the hemotherapy of patients with sickle cell disease (SCD) is discussed.