Cerebral Infarction in Children with Sickle Cell Disease: A Concise Overview

Cerebral infarction is a common complication in sickle cell disease. Both overt and silent infarcts evident on neuroimaging have been described. In this article we overview the current knowledge of cerebral infarction in this patient population and discuss recent updates on the role of preventive intervention.     

胸部钝性外伤性急性心肌梗塞2例报告及文献复习

本文报告2例青年于胸部钝性外伤后出现心肌异常Q波和损伤性ST段抬高，其心电图和心肌酶学的演变与典型的急性心肌梗塞（AMI）相同。胸部钝性外伤致AMI的主要机理为冠状动脉内膜扯裂、内膜下出血、血栓形成以及粥样斑块扯裂而导致冠状动脉阻塞，受累最多的是左前降支。由于常伴体表、心脏或其它脏器的挫伤或损伤，全身抗凝或静脉溶栓治疗通常为禁忌。如病人条件允许，可施行冠脉搭桥、PTCA或冠状动脉内溶栓等治疗。     

Diagnosis of Myocardial Abscess After Acute Myocardial Infarction by Transesophageal Echocardiography: Case Report and Short Review of Published Data

A 56-year-old man received thrombolysis for an anterior myocardial infarction after chest pain for 18 hours. Ten days later he was readmitted with fever and hemodynamic deterioration. Transesophageal echocardiography demonstrated a thin-walled cavity at the apex of the left ventricle. At operation he was found to have a myocardial abscess, and after excision and antibiotics his subsequent clinical course was uneventful. We review the echocardiographic diagnosis and clinical features of myocardial abscess complicating acute infarction. Presumed etiologic factors in our patient included late thrombolysis, mural thrombus, and poor dental hygiene leading to septicaemia.     

The Role of Inflammation and Leukocytes in the Pathogenesis of Sickle Cell Disease

Acute and chronic vascular occlusion underlies much of the morbidity and mortality in sickle disease. Abnormal polymerization of deoxygenated hemoglobin S (HbS) resulting in stiff, non-deformable erythrocytes is central to sickle cell pathogenesis. However, a complex interplay of many factors determines the balance between adequate blood flow and vessel obstruction. Serum markers of inflammation have provided evidence for a state of chronic inflammation in sickle cell disease (SCD). Inflammation promotes endothelial adherence to sickle erythrocytes. Studies demonstrating a beneficial effect of steroid therapy for painful episodes and acute chest syndrome provide indirect evidence for the role of inflammation in this disease. Leukocytosis, in the absence of infection, is common in SCD patients and predicts for stroke, acute chest syndrome, and overall mortality. Neutrophils and monocytes have been shown to be activated in these patients. Activated leukocytes further promote vascular inflammation and vessel damage. A reduction in leukocytes, and thus inflammation, may partially explain the beneficial effects of hydroxyurea in this disease. These data provide a strong rationale for clinical studies of therapy directed at inflammation and/or leukocytes in sickle cell disease.     

Acute Myocardial Infarction in Systemic Mastocytosis: Case Report With Literature Review on the Role of Inflammatory Process in Acute Coronary Syndrome

Background Systemic Mastocytosis (SM) is a disorder of excessive mast cell infiltration in multiple organ tissues. Atherosclerosis is a major risk factor for developing acute coronary syndrome. In addition to lipid accumulation in the arterial wall, inflammation plays an important role in the pathogenesis of plaque rupture and activating the thrombosis cascade. The Mast cells contribution to plaque destabilization has been well established in multiple animal and human studies. In a recent study, SM has been proven to be associated with a higher incidence of acute coronary syndrome even with lower plasma lipids levels. The study showed that 20% of patients with SM had cardiovascular events compared to only 6% in the control group with adjustment to all cardiac risk factors.Case We presented a patient with no risk factors for heart disease other than old age and history of SM who developed acute myocardial infarction.Conclusion SM can be life-threatening and can result in ACS, anaphylactic reaction, syncope, or cardiac arrest. Clinicians should have a high index of suspicion of acute coronary syndrome (ACS) occurrence in the setting of inflammatory conditions, such as SM and KS, and vice versa, where SM should be considered or ruled out in patients who suffer from anaphylaxis and cardiac arrest or myocardial infarction.     

Defining the Phenotypes of Sickle Cell Disease

The sickle cell gene is pleiotropic in nature. Although it is a single gene mutation, it has multiple phenotypic expressions that constitute the complications of sickle cell disease. The frequency and severity of these complications vary considerably both latitudinally in patients and longitudinally in the same patient over time. Thus, complications that occur in childhood may disappear, persist or get worse with age. Dactylitis and stroke, for example, occur mostly in childhood, whereas leg ulcers and renal failure typically occur in adults. It is essential that the phenotypic manifestations of sickle cell disease be defined accurately so that communication among providers and researchers facilitates the implementation of appropriate and cost-effective diagnostic and therapeutic modalities. The aim of this review is to define the complications that are specific to sickle cell disease based on available evidence in the literature and the experience of hematologists in this field.     

Amputations in Sickle Cell Disease: Case Series and Literature Review

In this study, we describe four new patients with sickle cell disease who had limb amputations. Two of the patients had sickle cell anemia [Hb S (HBB: c.20A?>?T) (β^S/β^S)] with refractory leg ulcers that required amputations. The third patient had sickle cell trait with an extensive leg ulcer that was associated with epidermoid carcinoma. The fourth patient had amputations of both forearms and feet due to a misdiagnosis of dactylitis. Review of the literature showed that the indications for amputations in sickle cell disease included three distinct categories: mythical beliefs, therapeutic and malpractice. All therapeutic amputations were for severely painful, large, recalcitrant leg ulcers that failed non-interventional therapies. Amputation resulted in pain relief and better quality of life. Phantom neuropathic pain was not a major issue post-operatively. It was absent, transient or well controlled with antidepressants. Limb function was restored post-amputation with prosthetic artificial limbs, wheelchairs or crutches. Malpractice amputations were due to misdiagnosis or to cryotherapy by exposing the painful limb to ice water resulting in thrombosis, gangrene and amputation. We strongly suggest that leg amputations should be considered in the management of certain patients with severe extensive refractory leg ulcers, and topical cryotherapy should never be used to manage sickle cell pain.     

Cytokines in Sickle Cell Disease

Sickle red cells express adhesion molecules including integrin ₄β₁, CD36, band 3 protein, sulfated glycolipid, Lutheran protein, phosphatidylserine and integrin-associated protein. The proadhesive sickle cells may bind to endothelial cell P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), CD36 and integrins leading to its activation. Monocytes also activate endothelium by releasing proinflammatory cytokines like tumor necrosis factor alpha (TNF-) and interleukin 1β (IL-1β). Sickle monocytes also express increased surface CD11b and cytoplasmic cytokines TNF and IL-1β indicating activated state. Polymorphonuclear leukocytes (PMNs) are also activated with reduced L-selectin expression, enhanced CD64 expression and elevated levels of sL-selectin, sCD16 and elastase resulting in increased adhesiveness to the endothelium. Platelets are also activated and secrete thrombospondin (TSP) and cytokine IL-1. They also form platelet- monocytes aggregates causing endothelial cell P-selectin expression. Endothelial cell activation by these multiple mechanisms leads to a loss of vascular integrity, expression of leukocyte adhesion molecules, change in the surface phenotype from antithrombotic to prothrombotic, excessive cytokine production and upregulation of HLA molecules. Furthermore, contraction of these activated endothelial cells leads to exposure of extracellular matrix proteins, such as TSP, laminin, and fibronectin and their participation in adhesive interactions with bridging molecules from the plasma such as von Willebrand factor (vWf) released from endothelial cells, ultimately culminating in vasoocclusion and local tissue ischemia, the pathognomonic basis of vasoocclusive crisis.     

新型冠状病毒肺炎疫情对急性心肌梗死诊治的影响

新型冠状病毒肺炎成为世界卫生体系的严峻挑战,国内外均采取了前所未有的严格防控措施,肺炎疫情对急性心肌梗死的急诊救治流程产生了深刻的影响,国内外制定了一系列的相关文件以指导疫情期间急性心肌梗死的救治工作,本文对此进行综述。     

Blood Transfusion in Sickle Cell Disease

Sickle cell anemia is an inherited disease that causes chronic hemolytic anemia. Its pathognomonic signs and symptoms are caused by hemoglobin (Hb) S, which results from a single nucleotide substitution in the β-globin gene that places the amino acid valine with glutamic acid at codon 6 of the β-globin chain. Hb S is an insoluble Hb that crystalizes at low oxygen tension and other precipitating conditions leading to rigidity of red cells and clumping in small blood vessels.

Patients with sickle cell disease have a variable Hb level that may range from 7.0 to 11.0 g/dL in their steady state condition. The most common cause of hospital presentation is due to acute painful crisis that results from vaso-occlusion by sickled cells. These episodes are treated with hydration and analgesia and do not require blood transfusion. Blood transfusion should be aimed to increase tissue delivery of oxygen. Hb S is known to be a low affinity Hb and so delivers oxygen at a lower partial pressure of oxygen compared to Hb A. Even with adequate pre transfusion testing and precautions, blood transfusion is never totally safe and short or long term complications may occur.

Blood transfusion in patients with sickle cell disease has only limited indications such as acute hemolytic, aplastic or sequestration crises. Chronic transfusion protocols are implemented in cases of strokes or high cerebral blood flow ultrasonic studies as a prophylactic measure. Exchange blood transfusion is used in some complications of the disease such as acute chest syndrome (ACS), priapism or peri operatively. Once it is decided to transfuse blood, the transfused blood should be Hb S negative, Rh and Kell antigen matched.     

Decompensated Cirrhosis and Sickle Cell Disease: Case Reports and Review of the Literature

Although its prevalence is unknown, liver involvement by sickle cell disease is not uncommon and encompasses different clinical spectra including non cholestatic and cholestatic disorders. Few data have been provided on chronic sickle cell intrahepatic cholestasis (SCIC) clinical course, although cirrhosis has been reported in sickle cell disease. However, no effective therapeutic approaches have been recognized either to prevent or treat this condition. Here we present two cases of adult sickle cell disease patients with decompensated cirrhosis. Their liver biopsies showed sickle cell thrombi within the hepatic sinusoids. Despite erythroexchange (EEX) transfusions, both patients suffered from major sickle cell disease-related events, suggesting that EEX transfusions may not be enough to impact on advanced liver involvement by sickle cell disease.     

Decreased Red Cell Filterability in Patients with Acute Myocardial Infarction

ABSTRACT The red cell filterability was decreased in patients with acute myocardial infarction (AMI) when compared with healthy controls, 14.6 (12.2–16.3) units and 16.9 (15.6–17.4) units respectively, P₅₀ (P₂₅-P₇₅), p<0.001). No significant correlations could be seen within the AMI group between the decrease in filterability and the levels of serum aspartate aminotransferase or serum lactate dehydrogenase. The erythrocyte filterability, however, correlated to the serum concentrations of hepatic enzymes in AMI. The addition of sodium lactate in vitro in physiological concentrations (0.9-3.6 mM/l final concentration) lowered the erythrocyte filterability markedly to 2.7 (0–9.8) units in a dose-dependent manner, supporting the hypothesis that the decrease in erythrocyte filterability in AMI might be caused by an increase in the lactate concentration.     

Fatal Pulmonary Artery Embolism in a Sickle Cell Patient: Case Report and Literature Review

This article reports a rare case of fatal saddle embolism to the pulmonary artery presenting as an Acute Chest Syndrome (ACS) in a Sickle Cell patient. We present a review of the etiology, pathophysiology, clinical manifestation and management of ACS. Clinicians should be aware of the fact that a sickle cell crisis admission may represent a life-threatening process. Such awareness will help physicians to act promptly and execute proper therapeutic interventions. It is important for clinicians to be expectant of impending clinical deterioration and likewise be aware that ACS can develop in patients hospitalized for other medical or surgical conditions.     

成体干细胞移植治疗急性心肌梗死的研究进展

干细胞治疗心血管疾病正处在起步阶段,在治疗急性心肌梗死方面已表现出传统方法无可比拟的优越性。骨髓干细胞、骨骼肌成肌细胞和内皮祖细胞等已被应用于心肌的再生。研究表明,干细胞可在梗死的心肌中分化形成有功能活性心肌、血管等组织,可改善心脏功能,但其作用机制尚不完全明了。本研究对成体干细胞移植治疗心肌梗死研究中取得的成就、有待解决的问题以及临床应用前景做一评述。     

Current Management in Sickle Cell Disease

The number of people in the UK with sickle cell disease continues to rise. Therefore it becomes increasingly important for all clinicians to be cognisant of not only the disorder, but also its complications, prognosis, implications and management. Previously the majority of patients lived within urban areas and attended a few specialist centres, now the young, mobile population of patients are no longer confined to teaching hospitals. In the UK, few centres have experience of many patients but collectively patients' numbers are considerable. This review discusses our view of the current management of the acute and chronic manifestations of this disease, supplemented by international advances, anecdote and current research.     

Acute Painful Crises of Sickle Cell Disease in Egyptian Children: Predictors of Severity for a Preventive Strategy

The objective of this study was to predict which infants with sickle cell disease (SCD) are prone to develop severe painful crises. In a mixed hospital - and community-based population (76 cases), demographic data, SCD diagnostic parameters, and basal blood counts were correlated with 2 indices of SCD severity: pain rate (average number of days of painful episodes per year of follow-up) and serious life-threatening complications, such as hyperhemolytic crises. Data were analyzed blind to these indices. The Student t test, analysis of variance, and Pearson correlation were used to determine association with pain rate. Discriminant analysis was used for the prediction of SCD severity. Pain rate was significantly high in hemoglobin SS patients, especially in those with an early onset of dactylitis. There were statistically significant negative correlations of pain rate with basal hemoglobin level, hematocrit, percent hemoglobin F, and arterial oxygen saturation (P <.01 for all correlations). The top 3 predictors of SCD severity were (in descending order) genotype, basal hemoglobin level, and early dactylitis. Severe forms of SCD could be predicted in early infancy with 100% accuracy by using the basal diagnostic parameters for the disease. These infants should be closely monitored with special attention to ventilation status, even before the development of dactylitis.     

Purulent Pericarditis in Sickle Cell Disease Due to Streptococcus agalactiae; a Unique Case Report and Literature Review

Purulent pericarditis is a localized infection with a thick, fibrinous hypercellular exudate and is historically associated with a high mortality. We describe a case of purulent pericarditis due to Streptococcus agalactiae (S. agalactiae) in a 30-year-old woman with sickle cell disease who presented with fever, dyspnea, and S. agalactiae septicemia. Despite timely initiation of antibiotics, she developed a large purulent pericardial effusion requiring surgical pericardiocentesis followed by a pericardial window. At 14?months follow-up, she has remained asymptomatic without sequelae. A review of the literature contained only four patients with purulent pericarditis in sickle cell patients. We discuss the unique aspects of this case in the context of purulent pericarditis in the age of modern antibiotics and hypothesize on the pathogenesis of delayed pericardial effusion after pericarditis.     

Neurocognitive Testing and Functioning in Adults Sickle Cell Disease

The impact of cerebrovascular events (CVE) on cognitive functioning in adults with sickle cell disease is not well understood. Sequelae of CVEs can adversely impact their quality of life. We reviewed neurocognitive presentation and testing in adults with sickle cell disease. We evaluated the frequency of complaints of memory disturbance using survey methodology in a sample of 109 adult patients with sickle cell disease (48 males, 61 females). A subsample of 24 patients also received a memory questionnaire where specific cognitive functions were assessed.

Overall, we found that males and females did not differ in the frequency of experienced memory disturbance during painful crises. However, the frequency of men reporting that their ability to remember where they place common objects such as keys (p = 0.017) and remembering the item they intended to buy in a grocery store or pharmacy (p = 0.048) was worse now compared to when they were in high school and was greater when compared to women. The frequency of men who reported their memory was worse now than when they were in high school (p = 0.051) was also greater than in women.

We concluded that memory dysfunction predicts global monthly presentation of pain. We suggest incorporating cost-effective neurocognitive screening measures as a standard of practice in sickle cell disease.     

干细胞移植治疗急性心肌梗死的临床研究新进展

干细胞移植已成为治疗心肌梗死的研究热点。大量临床试验已证实干细胞移植能增加左室射血分数,改善心功能等。但要将干细胞移植应用于临床中,仍有许多问题尚未解决。