Prothrombotic aspects of sickle cell disease

Sickle cell disease (SCD) is a hematologic disorder caused by a well‐characterized point mutation in the β‐globin gene. Abnormal polymerization of hemoglobin tetramers results in the formation of sickle red blood cells that leads to vascular occlusions, hemolytic anemia, vascular inflammation and cumulative, multiple organ damage. Ongoing activation of coagulation is another hallmark of SCD. Recent studies strongly suggested that hypercoagulation in SCD is not just a secondary event but contributes directly to the disease pathophysiology. In this article we summarize mechanisms leading to the activation of coagulation, review data indicating direct contribution of coagulation to the pathology of SCD and, we discuss the anticoagulation as a possible treatment strategy to attenuate the disease progression     

Pulmonary embolism in sickle cell disease: a case–control study

Introduction:  A pulmonary embolism (PE) is a leading cause of mortality in hospitalized patients, yet the prevalence of PE in sickle cell disease (SCD) and its relation to disease severity or intrinsic hypercoagulability are not established. Methods:  We estimated inpatient PE incidence and prevalence among SCD and non‐SCD populations in Pennsylvania, and compared severity of illness and mortality, using Pennsylvania Health Care Cost Containment Council (PHC4) discharge data, 2001–2006. Risk factors for PE were assessed in a case–control study of discharges from the University of Pittsburgh Medical Archival Records System (MARS). Results:  The incidence of inpatient PE was higher in the SCD PA population than in the non‐SCD Pennsylvania population, 2001–2006. The PE prevalence among SCD discharges ≤ 50 years of age, 0.57%, was similar to that in non‐SCD Pennsylvania discharges, 0.60%, and unchanged after adjustment for race. Among SCD discharges, those developing PE were significantly older, with a longer length of stay, greater severity of illness and higher mortality, P < 0.001, than SCD without a PE. Among PE discharges, SCD had a similar severity of illness, P = 0.77, and mortality, P = 0.39, but underwent fewer computerized tomographic scans, P = 0.006, than non‐SCD with PE. In the local case–control study, no clinical or laboratory feature was associated with PE. Conclusions:  The incidence of PE is higher and chest computed tomography (CT) utilization is lower in SCD than non‐SCD inpatients, suggesting that PE may be under‐diagnosed.     

The role of cognitive-behavioural therapy in the management of pain in patients with sickle cell disease

Painful crisis is the most common manifestation of sickle cell disease and accounts for the second greatest number of admissions with an average length of stay of 7 days in central London. Despite this frequency of admissions, the management of pain is fraught with problems. This is not surprising since the psychological challenges presented by sickle cell disease are manifold, resulting in significant psychological distress for some individuals. This paper considers the literature on the psychosocial impact of sickle cell disease, and the American research evidence which suggests that pain management strategies that incorporate a psychological intervention can significantly reduce psychological distress as well as hospital admissions. Britain has been slow to incorporate psychology in the pain management strategies, and we have embarked on research to fill this gap. Although this research constitutes work in progress, an argument is put forward for utilizing the cognitive-behavioural perspective in the management of pain in sickle cell disease and we conclude by giving a brief summary of pilot work which is both the foundation and justification for the current ongoing research.     

Migraine-mimicking headache and sickle cell disease: a transcranial Doppler study

Headache occurs in sickle cell disease (SCD), but its characteristics and frequency have not previously been studied. Our aim was to study patterns of headache in adults with SCD and to correlate its presence with blood flow velocities measured by transcranial Doppler (TCD) and with brain magnetic resonance imaging (MRI) abnormalities. We studied 56 adults with SCD. Twenty-eight patients (50%) had severe and frequent headaches. In 20 patients (35.7%) the headache met the International Headache Society criteria for migraine without aura. Patients with frequent and severe headache presented TCD velocities significantly higher than those without headache, or with milder headache. No correlation was found between headache and abnormalities in brain MRI. A migraine-mimicking headache occurs in SCD but we should not understand it as a primary headache because the blood flow abnormalities secondary to SCD detected by TCD seem to play an important role in these patients.     

Use of a dual lumen port for automated red cell exchange in adults with sickle cell disease

Red cell exchange (RCE) is a common procedure in adults with sickle cell disease (SCD). Implantable dual lumen Vortex (DLV) ports can be used for RCE in patients with poor peripheral venous access. We performed a retrospective cohort study of RCE procedures performed in adults with SCD. The main objective of the study was to compare the inlet speed, duration of procedures and rate of complications performed through DLV ports to those performed through temporary central venous and peripheral catheters. Twenty‐nine adults with SCD underwent a total of 318 RCE procedures. Twenty adults had DLV ports placed and 218 procedures were performed using DLV ports. Mean length of follow‐up after DLV port placement was 397 ± 263 days. Six DLV ports were removed due to infection and 1 for malfunction after a mean of 171 ± 120 days. Compared to temporary central venous and peripheral catheters, DLV port procedures had a greater rate of procedural complications, a longer duration, and a lower inlet speed (all P < 0.01). When accounting for the maximum allowable inlet speed to avoid citrate toxicity, 40% of DLV port procedures were greater than 10% below maximum speed, compared to 7 and 14% of procedures performed through temporary central venous and peripheral catheters (P < 0.0001). In conclusion, DLV ports can be used for RCE in adults with SCD, albeit with more procedural complications and longer duration. The smaller internal diameter and longer catheter of DLV ports compared to temporary central venous catheters likely accounts for the differences noted. J. Clin. Apheresis 30:353–358, 2015. © 2015 Wiley Periodicals, Inc.     

Safety,tolerability, and outcomes of regular automated red cell exchange transfusion in the management of sickle cell disease

We report here our experience with regular automated red cell exchange transfusion for the management of chronic complications of sickle cell disease in 50 patients in our institution from June 2011 to December 2014. The mean sickle hemoglobin level was 44% and 8.5% pre‐ and post‐transfusion, respectively. Platelets were reduced by a mean 70% during the procedure with a count of less than 50 × 10⁹/l in 6% of cases. The alloimmunization rate was 0.065/100 units of red cells with no hemolytic reactions. Patients with no iron overload at baseline showed no evidence of iron accumulation with a mean liver iron concentration of 1.6 mg/g dry tissue and 1.9 mg/g dry tissue at baseline and 36 months, respectively. All six patients with pre‐existing iron overload and on chelation therapy, showed a gradual reduction of their liver iron concentration and two patients could discontinue chelation during the follow‐up period. Seventy percentage of patients who were on the programme for recurrent painful crises showed a sustained reduction in the number of emergency hospital attendances; the mean number of days in hospital for emergency treatment was 103 in the year prior to commencing ARCET and reduced to 62 (40%) after the first 12 months, 51 (50%) after 24 months, and 35 days (66%) after 36 months. J. Clin. Apheresis 31:545–550, 2016. © 2015 Wiley Periodicals, Inc.     

Cerebral oximetry in patients with sickle cell disease

BACKGROUND: There is limited information concerning the brain's oxygen supply and demand in patients with sickle cell disease. DESIGN: We measured near-infrared spectroscopy of brain oxygenation in 27 patients with sickle cell disease regardless of vaso-occlusive crisis, 14 normal healthy controls, and five anaemic patients without sickle cell disease. We also measured pre- and post-transfusion cerebral oximetry in 14 additional sickle cell disease patients who were on transfusion programmes. RESULTS: The mean cerebral oxygen saturation in the combined steady-state and vaso-occlusive crisis population was found to be significantly lower than that in the controls and in anaemic patients without sickle cell disease (47.7% vs. 61.3%, 59.8%, P < 0.0001). Cerebral oxygen saturation failed to correlate with the haemoglobin concentration (r = 0.51, P > 0.5). However, cerebral oxygen saturation increased from 40.4% to 49.6% (P = 0.01) and correlated significantly with the haemoglobin level (r = 0.553, P = 0.003) in 14 subjects studied before and after transfusions. In seven subjects who received simple transfusions, cerebral oxygen saturation correlated strongly and positively with the haemoglobin level (r = 0.811, P = 0.001) and with percent normal haemoglobin (r = 0.786, P = 0.002), and negatively with abnormal sickle haemoglobin (r = -0.775, P = 0.003). None of these correlations was found to be statistically significant in the seven subjects given exchange transfusions. Cerebral oxygen saturation measured in the sickle cell disease subjects after transfusions was still significantly lower than in the anaemic subjects without sickle cell disease and in the normal controls (49.6% vs. 59.8% and 61.3%, P = 0.001). CONCLUSIONS: We found that patients with sickle cell disease have subnormal values of cerebral oxygen saturation. Red cell transfusions significantly increased the brain oxygenation in these patients. Cerebral oximetry may be a useful, noninvasive method for assessing the effect of circulating normal red cells in sickle cell patients after transfusions.     

A pseudoaneurysm within a subperiosteal collection in a patient with sickle cell disease

Sickle cell disease involves long bones in the form of infection or subperiosteal collections. Rare pseudoaneurysm/aneurysm formation is also known to occur in the intracranial and visceral territories. We report a small subperiosteal pseudoaneurysm that developed within a subperiosteal abscess in the tibia in a patient with sickle cell disease. This case adds to the known spectrum of musculoskeletal abnormalities resulting from this condition. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2010     

Blood bank issues associated with red cell exchanges in sickle cell disease

Sickle cell disease (SCD) patients are prone to develop complications that include stroke, acute chest syndrome, and other crises. Some of these complications require chronic transfusion therapy or red cell exchange (RCE), either for therapeutic or prophylactic reasons. Due to a discrepancy of red cell antigens between African Americans and Caucasians (majority blood donors), the incidence of alloantibody formation is very high, which makes it difficult to find compatible red cell units, especially for urgent RCE. Some of the above conditions require immediate oxygen delivery to the tissues. Thus, SCD patients undergoing RCE should receive red blood cells with special attributes that include matching for Rh and Kell blood group antigens; RBCs should be fresh in order to provide (1) immediate oxygen delivery and (2) longer surviving cells to reduce the interval between RCE. Also, these units should be pre-storage leukoreduced to prevent febrile non-hemolytic reactions and screened for sickle cell traits to avoid transfusing red cells containing HbS. This requires a concerted effort between the apheresis unit, the local blood bank, and the central blood supplier.     

An acute hemolytic transfusion reaction due to anti-IH in a patient with sickle cell disease

BACKGROUND: A hemolytic transfusion reaction (HTR) due to anti-IH is reported in a patient with sickle cell disease (SCD). CASE REPORT: An 18-year-old woman with SCD and a complete phenotype on file had been identified as group B-positive with negative antibody-screening tests and had received 1 unit of packed RBCs. Ten days later, she was readmitted in painful crisis with a Hb of 4.2 g per dL. Antibody-screening tests and panel cells were positive at all test phases with a negative autocontrol, which suggested alloantibodies. Phenotypically matched group O RBCs were issued emergently. After the transfusion of 100 mL, the patient had an HTR with chills, fever, and tachycardia and laboratory findings of hemoglobinemia, hemoglobinuria, and negative DATs. A high-titer, IgM anti-IH with a high thermal amplitude (reactive with group O, but not group B RBCs at 37 degrees C) was identified. Autologous RBCs appeared to have normal I antigen expression, but less H antigen than pooled group B RBCs. She was given group B RBCs, uneventfully, by use of a blood warmer. CONCLUSIONS: This is a rare case of anti-IH as the cause of a HTR, as a serologic problem that may be seen in SCD, and as an autoantibody that may mimic an alloantibody. Ironically, this HTR resulted from the effort to provide phenotypically matched RBCs, which necessitated the selection of group O RBCs.     

Hyperhemolytic transfusion reaction in sickle cell disease

BACKGROUND: An atypical form of life-threatening hemolytic transfusion reaction (HTR) in patients with sickle cell disease (SCD) has been well described in the literature. Continuation of blood transfusion may be lethal, as it can further exacerbate hemolysis. The pathophysiologic mechanism of HTR is not well understood. CASE REPORTS: Two cases of severe HTR in SCD after the transfusion of compatible RBC units are reported. Hemolysis of both autologous and transfused cells was documented in Case 1 by urine Hb high-performance liquid chromotography. Multispecific HLA antibodies were identified in Case 1. Reticulocytopenia was noted in both cases during the acute hemolytic process. This was followed by a rise in reticulocyte count during receipt of IVIG and steroid therapy. Bone marrow examination during reticulocytopenia in Case 2 showed erythroid hyperplasia. CONCLUSION: In SCD, both mature sickle cells and sickle reticulocytes adhere more readily to macrophages. In view of the bone marrow aspiration results, it appears that the recipients' HbS cells are destroyed by hyperactive macrophages and that the reticulocytopenia observed during HTR is likely to be due to peripheral consumption (i.e., destruction by macrophages), rather than suppression of erythropoiesis. Cessation of hemolysis during IVIG and steroid treatment may be due to IVIG's blocking of the adhesion of sickle cells and reticulocytes to macrophages, together with steroid suppression of macrophage activity.