Anti-s antibody-associated delayed hemolytic transfusion reaction in patients with sickle cell anemia

PURPOSE: Signs and symptoms of delayed hemolytic transfusion reaction (DHTR) may resemble those of vaso-occlusive crises in patients with sickle cell anemia (SCA). The diagnosis of DHTR therefore presents a challenge to the clinician when treating such patients. The current study describes a patient with SCA and DHTR secondary to red cell anti-s antibody, manifesting as painful extremeties, severe hemolytic anemia, and acute oliguric renal failure. PATIENTS AND METHODS: A 17-year-old patient with homozygous hemoglobin S presented 8 days after partial exchange transfusions with severe anemia and signs and symptoms resembling vaso-occlusive crisis. Clinical course was complicated by intravascular hemolysis and acute renal failure. RESULTS: Anti-s antibody was detected in the eluate. Diagnosis of DHTR was made. Treatment included single volume whole blood exchange transfusion and continuous veno-venous hemofiltration with dialysis. CONCLUSIONS: The possibility of DHTR should be considered in a patient with SCA with hemolytic anemia. Acute renal failure is a rare complication of anti-s antibody-associated DHTR. Such reactions can be successfully managed with exchange transfusion and continuous hemofiltration with dialysis.     

Less intensive long-term transfusion therapy for sickle cell anemia and cerebrovascular accident.

To determine the efficacy of a less intensive transfusion regimen in preventing recurrent cerebrovascular accidents and reducing transfusion requirements in patients with sickle cell anemia, we offered to 14 patients who had been undergoing aggressive transfusion therapy (sickle hemoglobin concentration kept less than 30% of total) for a mean of 9 years the option of either diminishing or stopping transfusion therapy. Thirteen patients chose to continue a modified transfusion regimen to maintain sickle hemoglobin concentration less than 60%; 10 of these patients have now been followed for 1 year or more (12 to 27 months, mean 15.5 months). There have been no recurrent neurologic events, although two patients have died of complications of hemochromatosis. All patients had a reduction in donor exposure, and there was a mean reduction in net transfusion requirement of 31.4% during the first year after modification. The greatest reduction was achieved in the single patient managed by small-volume (5 ml/kg) simple transfusion rather than partial packed cell exchange. We conclude that although long-term consequences of less aggressive transfusion therapy are unknown, the use of such a regimen may be reasonable, particularly in patients with significant transfusional hemochromatosis.     

Outcomes of a preoperative risk-based transfusion assignment protocol in sickle cell disease patients: a single-center retrospective study from Saudi Arabia

Abstract

Many patients with sickle cell disease (SCD) need surgical management during their lifetime. The best approach for preoperative transfusion in SCD is still to be determined. In this single-center retrospective study, we included HBSS/HBS-Beta⁰-thalassemia patients younger than 16?years of age who underwent surgery between January 2008 and July 2019. Preoperative transfusion assignment (PTA) was based on SCD severity and surgical risk. Patients were assigned to no transfusion, simple transfusion, or exchange transfusion. A total of 284 patients were identified and 66 (23%) underwent 78 procedures. Mean age at the time of procedure was 8 (5–11) years, mean baseline hemoglobin was 8.5 (7.8–9.3) g/dl, and mean hemoglobin F was 18.4?±?8.2%. SCD severity was low-risk in 57 (73%) and high-risk in 21 (27%) patients. Surgical risk was low-risk in 20 (25.6%) and medium-risk in 58 (74.4%) procedures. PTA was no transfusion in 17 (22%), simple transfusion in 40 (51%), and exchange transfusion in 21 (27%) procedures. Postoperative complications occurred in five (6.4%) of procedures only in the simple transfusion group (three acute chest syndrome, one hemolytic anemia, one pain crisis) undergoing medium-risk surgery. Preoperative risk-based transfusion assignment is feasible. Despite a high baseline hemoglobin level in the no transfusion group, none of the patients developed postoperative complications. It is possible that the high baseline hemoglobin F phenotype was protective and indicates the need to study the risk/benefit of interventions used in this phenotype.     

Effects of intravascular, intrauterine transfusion on prenatal and postnatal hemolysis and erythropoiesis in severe fetal isoimmunization

In an investigation of the effects of intrauterine, intravascular transfusions (IUT) on fetal and neonatal hemolysis and erythropoiesis, 12 fetuses who received IUT for treatment of severe isoimmunization had serial measurements of hemoglobin concentration, Kleihauer-Betke stains to detect fetal hemoglobin-containing erythrocytes, and determination of plasma erythropoietin (EPO) concentration before each IUT, at birth, and postnatally. Reticulocyte counts and sensitizing antibody titers were measured in five fetuses. Mean values before the first IUT, before the final IUT, and at birth were as follows: hemoglobin level, 6.1, 9.1, and 11.3 gm/dl; reticulocyte count, 22.7%, 0.5%, and 0.9%; fetal hemoglobin-containing erythrocytes, 100%, 1.6%, and 1.5%; and EPO level, 12, 56, and 756 mU/ml, respectively. Only one neonate required exchange transfusion. In the first month postnatally, all infants had a profound anemia. All but one infant required simple blood transfusions postnatally. Before the first postnatal transfusion, mean hemoglobin concentration was 6.2 gm/dl, mean reticulocyte count was 0.8%, mean erythropoietin concentration was 23 mU/ml, and the sensitizing antibody titer remained markedly elevated. Except for the surge of EPO at birth, EPO levels did not rise prenatally or postnatally unless marked anemia (hemoglobin level less than 5 gm/dl) occurred. These observations suggest that the intrauterine and postnatal anemia in fetuses who receive IUTs may be explained both by hemolysis of newly formed erythrocytes by circulating antibody, which typically persisted for more than a month after birth, and by suppressed erythropoiesis.     

Fulminant liver failure in a 12-year-old girl with sickle cell anaemia: Favourable outcome after exchange transfusions

Acute liver failure is unusual unusual in sickle cell anaemia. We describe a child with homozygous sickle cell anaemia who developed acute liver disease of abrupt onset during an episode of limb pain. She presented with sudden onset of persistent vomiting, headache, lethargy, epistaxis, and painful liver enlargement. Laboratory investigations were indicative of cholestasis and severe liver failure with profound prolonged clotting times, hypofibrinogenaemia, elevated serum ammonia and lactic acidosis. The symptoms were promptly and completely reversed by two partial exchange transfusions. No evidence of viral infection was found. Cholelithiasis was ruled out by ultrasonography. The child recovered from what appeared to be massive hepatic sickling with no apparent sequelae.Conclusion Massive hepatic sickling should be considered in the differential diagnosis of a child with homozygous sickle cell disease who suddenly develops acute liver failure. Exchange transfusion should be promptly carried out so as to reverse ischaemic hepatic injury.     

Sickle cell hepatopathy: clinical presentation, treatment, and outcome in pediatric and adult patients

BACKGROUND: Standard diagnostic criteria and therapy are lacking for sickle cell hepatopathy, an uncommon complication of sickle cell disease. Here we propose diagnostic and therapeutic guidelines based on our experience and on reported cases. METHODS: We defined sickle hepatopathy by a total serum bilirubin concentration >13 mg/dl not explained by severe acute hemolysis, viral hepatitis, extrahepatic obstruction, or hepatic sequestration. We reviewed the records of all children with sickle hepatopathy seen at our institution during the past 20 years and the reported cases from the literature. Patients were categorized into two groups based on whether hepatic dysfunction at presentation was mild (Group I) or severe (Group II). RESULTS: Seven patients were identified from our institution and 37 patients from the literature. The 44 patients were evenly divided between the two groups. Group I patients had a significantly lower mean age (11.8 years vs. 24.5 years, P = 0.0001), maximum bilirubin level (36.2 mg/dl vs. 76.8 mg/dl, P = 0.0008), and frequency of treatment with exchange transfusions (P = 0.03). Overall, mortality was 4% in Group I and 64% in Group II (P = 0.0001). Gender and recurrence rate did not differ. Among Group II patients, only two of nine who received exchange transfusion died, whereas 12 of 13 who did not receive exchange transfusion died (P = 0.0015). CONCLUSIONS: Sickle cell hepatopathy is an uncommon complication characterized by extreme hyperbilirubinemia and either mild or severe hepatic dysfunction. Children and adults can present with either form; however, adults have a higher frequency of the severe form. Exchange transfusion may be the only effective management for initial episodes of severe sickle cell hepatopathy.     

Neonatal hyperviscosity: randomized study of effect of partial plasma exchange transfusion on long-term outcome

The use of partial plasma exchange transfusion in newborns with polycythemia and hyperviscosity was evaluated. Ninety-three infants with polycythemia and hyperviscosity were randomly assigned to receive either partial plasma exchange transfusion or symptomatic treatment; the infants were matched with control infants without polycythemia. Neonatal course and outcome at 1 and 2 years were evaluated for each of the three groups. Polycythemic infants had more fine motor and speech problems at 1 year of age than did control infants. At 2 years of age, polycythemic infants had more gross motor delays, neurologic diagnoses, fine motor abnormalities, and speech delays than did the control infants. There was no significant difference at 1 year between the polycythemic infants who had received partial plasma exchange transfusion and those given only symptomatic care. At 2 years, the group receiving partial plasma exchange transfusion had fewer neurologic diagnoses and fine motor abnormalities.     

Transfusion therapy for cerebrovascular abnormalities in sickle cell disease.

Cerebral angiograms were performed in patients with sickle cell disease and symptoms of stroke to evaluate transfusion therapy for cerebrovascular accidents. Three patients who were transfused repeatedly for one year to maintain less than 30% hemoglobin S were compared to two patients who were not transfused. All patients had abnormal angiograms initially. After one year the angiographic abnormalities resolved in two and improved in one transfused child. The two children who were not transfused showed progressive vascular disease. For all arteriograms, the patients were prepared by transfusion with normal red cells and careful hydration.     

Factors associated with stroke following the Fontan procedure

We reviewed the results of 68 consecutive Fontan procedures from 1978 to 1993 to determine the frequency of late central neurologic complications of the Fontan procedure in patients living at a mean altitude of 4500 feet. Two surviving patients had transient neurologic symptoms or signs with no corresponding evidence of brain injury by magnetic resonance imaging (MRI), whereas six surviving patients had strokes defined by sustained neurologic symptoms or signs with areas of brain injury identified by MRI [8.8% (6.0–13.0%; 70% confidence limits)]. Collectively, patients with neurologic symptoms had normal hemoglobin values, platelet counts, partial thromboplastin times, and prothrombin times at the onset of clinical neurologic findings. Two patients were taking antiplatelet agents, and one patient was taking warfarin. One of the patient's with transient neurologic findings and all of the stroke patients had residual right-to-left shunts. Thus strokes were not uncommon in our patients after the Fontan procedure. Brain injury may result. from thromboembolic events associated with residual right-to-left shunts, but our total number of asymptomatic patients with a residual shunt or brain abnormalities by MRI is not known.     

Acute chest syndrome in children with sickle cell disease

Acute chest syndrome (ACS) is an acute pulmonic process in patients with sickle cell disease. We prospectively studied 50 patients with ACS admitted to the Pediatric Medical Ward during one year period (Jan. 1993 through Dec: 1993). Twenty eight of them were males and twenty two were females giving a male: female ratio of 1.2: 1. The age ranged between one and 12 years. Twelve (24%) of the patients had chest pain on presentation. Twenty seven (54%) patients had significant temperature (>38°C). The x-ray findings showed that the right lung was involved in 30 patients, the left in 10 patients and both lungs in 10 patlents. Three patients had pleural effusion that required chest tube insertion. Laboratory profiles showed that the erythrocyte sedimentation rate ranged between 15 and 90mm/h, and their hemoglobin ranged between 4.2 gm and 12 gm/dl. Seven (14%) patients had significantly positive mycoplasma pneumoniae titer. None of the blood cultures was positive. All of our patient received antibiotic, usually either Cefuroxime or Ceftriaxone with Erythromycin in addition to other supportive measures such as blood transfusion, oxygen therapy and hydration therapy.     

Anemia and thrombocytopenia in children with Plasmodium vivax malaria

Clinico-epidemiological features of pediatric patients with malaria due Plasmodium vivax that developed anemia and thrombocytopenia requiring hospitalization are herein reported. Over a 3-year period, 78 children with P. vivax infection were admitted to our Hospital in Sucre, Venezuela. Clinical manifestations at admission were 93.59 per cent fever, 41.03 per cent chills and 14.10 per cent headache, among others. On paraclinical evaluations 94.87 percent presented with anemia (10.26 per cent severe), 25.64 percent with malnutrition, and 10.26 percent had intestinal parasitosis. The mean hemoglobin levels on admission were 8.09 g/dl and mean platelet counts 127 402 cells/mm3. Among these patients 58.97 per cent developed thrombocytopenia (24.36 per cent severe) requiring transfusion in 25.64 per cent of patients. After antimalarial treatment with chloroquine and primaquine and supportive care all patients were successfully discharged. No deaths or further complications were seen, except for persistent mild thrombocytopenia in 17.95 per cent of the patients.     

Cholecystectomy and cholelithiasis in sickle cell anemia

Elective cholecystectomy was performed on 12 children (eight male and four female; age range, 4 to 19 years; and mean age, 11.2 years) with abdominal pain that was related to gallstones. Seven patients had jaundice, six had nausea, five had fat intolerance, and three had biliary colic. Two simple transfusions (10 mL/kg of packed red blood cells), designed to decrease the hemoglobin S content to less than 30% and to increase the total hemoglobin level to greater than 100 g/L, were given preoperatively two to three weeks apart. A third transfusion was given on the day before surgery if the total hemoglobin level was less than 100 g/L. The preoperative mean hemoglobin S content was decreased from 88% to 31%, and the mean total hemoglobin level was raised to 122 g/L. There were no preoperative or intraoperative complications. Post-operatively, no patients developed complications that were related to sickle cell anemia. Hospitalization averaged 6.3 days. Recurrent abdominal pain resolved shortly after surgery in all patients. With proper preoperative transfusions, elective cholecystectomy is safe in children with sickle cell anemia. Elective cholecystectomy should be recommended at the time of diagnosis of cholelithiasis.     

Exchange transfusion for severe autoimmune hemolytic anemia

A 10-year-old patient with severe autoimmune hemolytic anemia (AIHA) presented with heart failure. Hemoglobin levels remained dangerously low despite multiple blood transfusions and corticosteroid therapy. A two-volume exchange transfusion promptly restored and maintained satisfactory hemoglobin levels. An exchange transfusion should be considered in selected patients with AIHA when severe hemolysis results in life-threatening anemia, and repeated blood transfusions are unsuccessful in maintaining safe hemoglobin levels. Such an approach may be especially applicable in children in whom plasma-pheresis may not be suitable because of technical limitations.     

Cerebral blood flow in sickle cell cerebrovascular disease

Cerebral blood flow (CBF) has been studied by the xenon-133 (133Xe) inhalation method in 16 children with suspected sickle cell cerebrovascular disease. Abnormalities consisting of decreases in total, hemispheral, or regional CBF were found in 17 of 26 studies. Eleven studies performed immediately after stroke, transient ischemic attack, or depression of state of alertness showed abnormalities. In addition to confirming regional cerebrovascular insufficiency in children with stroke due to major cerebral artery occlusion, the method detected diffuse decrease in CBF in children with stupor, coma, and seizures who had normal angiographic findings. In contrast, six of seven studies obtained after exchange transfusion or during maintenance on hypertransfusion therapy showed normal findings. The difference between results in patients with acute neurologic disturbances and those receiving transfusion therapy was statistically significant (P less than .005). The data indicate that the 133Xe method reliably demonstrates cerebrovascular impairment in sickle cell disease. They also suggest that CBF changes in patients with sickle cell disease can be reversed by exchange transfusion and by hypertransfusion therapy. The 133Xe CBF method may be useful for following up children with sickle cell disease who are at high risk for recurrent stroke.     

Clinical presentation of sickle cell-hemoglobin C disease

Early symptoms were observed in a representative sample of 166 children with sickle cell-hemoglobin C disease diagnosed at birth. Symptoms were uncommon in the first year of life; in approximately 50% specific symptoms had developed by 5 years, but 22% remained without specific symptoms to 10 years. The age at presentation was significantly earlier in patients with low hemoglobin F levels, but was not influenced by heterozygous alpha-thalassemia-2. Painful crisis was the initial manifestation in 77% of the children; other symptoms included dactylitis (14%) and pneumococcal septicemia and acute splenic sequestration (4% each). The commonest nonspecific symptom was acute chest syndrome. The relatively mild early clinical course of sickle cell-hemoglobin C disease indicates that neonatal diagnosis does not have the same urgency as for homozygous sickle cell disease.     

Severe Mycoplasma Pneumonia in Three Sisters with Sickle Cell Disease

Mycoplasma pneumoniae, which usually causes mild infections in normal children, has been shown to cause isolated cases of severe pneumonia in children with sickle cell disease. We recently observed an outbreak of Mycoplasma pneumonia in three sisters with homozygous sickle cell disease. Two of them required hospitalization, and one progressed to respiratory failure requiring prolonged ventilatory assistance. All eventually recovered without long-term pulmonary complications. Familial outbreaks are not uncommon in Mycoplasma infection, but they have not been described previously in siblings with sickle cell disease. It is assumed that local or systemic host defense abnormalities predispose patients with sickling syndromes to more severe courses of Mycoplasma infections.     

Severe Mycoplasma Pneumonia in Three Sisters with Sickle Cell Disease

Mycoplasma pneumoniae, which usually causes mild infections in normal children, has been shown to cause isolated cases of severe pneumonia in children with sickle cell disease. We recently observed an outbreak of Mycoplasma pneumonia in three sisters with homozygous sickle cell disease. Two of them required hospitalization, and one progressed to respiratory failure requiring prolonged ventilatory assistance. All eventually recovered without long-term pulmonary complications. Familial outbreaks are not uncommon in Mycoplasma infection, but they have not been described previously in siblings with sickle cell disease. It is assumed that local or systemic host defense abnormalities predispose patients with sickling syndromes to more severe courses of Mycoplasma infections.     

ABO hemolytic disease: a comparative study of clinical severity and delayed anemia

The hospital and clinic records of 230 neonates with ABO hemolytic disease (HD) were reviewed. There was no significant difference in clinical severity between AO-HD and BO-HD as measured by (1) number of neonates with hyperbilirubinemia and/or those requiring exchange transfusion; (2) hemoglobin concentration; (3) reticulocyte count; (4) bilirubin concentration; and (5) incidence of anemia after discharge from the hospital. There was no difference in the hemoglobin concentrations measured at between four and eight weeks of age in 39 control infants and infants with either AO-HD or BO-HD who did not require an exchange transfusion. Our data do not indicate a clinical difference in the severity of AO-HD and BO-HD. Infants with ABO-HD who do not require exchange transfusion and/or phototherapy and whose hemoglobin concentration at discharge is greater than 15 gm/dl do not need a hemoglobin measurement before 6 weeks of age.     

Resolution of chronic hepatic sequestration in a patient with homozygous sickle cell disease receiving hydroxyurea

Hepatic sequestration is an uncommon complication in patients with homozygous sickle cell disease. Although transfusion therapy has been effective for the acute condition, no definitive treatment of chronic hepatic sequestration has been identified. We describe a 17-year-old male patient with hemoglobin SS and chronic hepatic sequestration who was treated with long-term (60 months) hydroxyurea. After 36 months of HU therapy, the patient had both an excellent hematologic response and a resolution of hepatic sequestration, as evidenced by disappearance of clinical hepatomegaly, normalization of liver volume on serial computed tomography scans, as well as decreased sinusoidal dilatation and congestion and red blood cell sickling on liver biopsy. The findings in this case suggest that hydroxyurea may benefit patients who have unusual complications of sickle cell disease, such as chronic erythrocyte sickling in the liver.