Pulmonary Complications of Sickle Cell Disease

The pulmonary complications of sickle cell disease are a major cause of morbidity and mortality in affected patients. The acute chest syndrome (ACS) is a leading cause of death in patients with sickle cell disease and has a multifactorial etiology. Hydroxyurea (HU), stem cell transplantation (SCT) and chronic transfusions are known to prevent the recurrence of ACS. Careful management of patients admitted for pain crises and surgery including use of incentive spirometry is critical in preventing this complication. Pulmonary hypertension is well known to be associated with sickle cell disease and patients with pulmonary hypertension have increased mortality. Asthma is also commonly seen in patients with sickle cell disease and is associated with a more complicated course. Chronic lung disease develops in a significant proportion of patients with sickle cell disease.     

Sickle cell ‘girdle syndrome’ progressing to ischaemic colitis and colonic perforation

Abdominal pain of presumed vasocclusive origin, often termed ‘girdle syndrome’ because of the circumferential distribution of the pain, is common in sickle cell anaemia (SCA). Evidence of progression to bowel infarction is rare. A 27‐year‐old man with SCA developed chest and abdominal pain unresponsive to opiate analgesia. Abdominal X‐ray showed dilated bowel loops because of partial obstruction. Despite reduction of HbS to 23% by automated red cell exchange, abdominal pain worsened. A CT scan was the most informative investigation and showed free peritoneal air. He underwent emergency hemicolectomy and reversible ileostomy formation. Histology of the resected colon was consistent with acute ischaemic colitis. Early surgical intervention remains essential in SCA when abdominal pain does not respond to maximal therapy including red cell exchange: as this case illustrates, sickle girdle syndrome has the capacity to progress to irreversible ischaemic colitis and necrotic perforation of the bowel wall.     

Exacerbation of Sickle Cell Disease Itself as a Cause of Abnormal Liver Chemistry Tests

Liver pathology occurring in patients with sickle cell disease is commonly related to viral hepatitis or hepatic iron deposition due to repeated transfusions; cholestasis and cirrhosis may also occur. Consequently, the differential diagnosis of abnormal liver tests in patients with sickle cell anemia is often complicated. We report the case of a patient presenting with jaundice and abnormal liver biochemistries, without typical evidence of the liver diseases associated with sickle cell anemia. Biochemical markers for viral hepatitis were negative. CT scan only showed hepatomegaly. The liver biopsy revealed marked sinusoidal congestion with red blood cells without significant steatosis or increased iron deposition. The patient's medical history corroborated with biochemical tests and histological examination of the liver suggested that worsening hemolysis related to increased sickling of erythrocytes intrahepatically led to sinusoidal dilatation and probably caused the abnormal liver tests.     

Pulmonary Function and Airway Hyperresponsiveness in Adults with Sickle Cell Disease

Study Objectives Pulmonary involvement is a major cause of morbidity and mortality in patients with sickle cell disease (SCD). Although a high prevalence of airway hyperresponsiveness (AHR) has been reported, there are no studies demonstrating the relationship between AHR and acute chest syndrome (ACS) in adults with SCD. We investigated AHR prevalence, lung function abnormalities, and the relationships of these variables with ACS in SCD patients. Method Thirty-one adult patients without asthmatic symptoms were compared with 31 matched controls. Expiratory flow rates, lung volumes, carbon monoxide diffusion capacity (DLCO), and methacholine provocation test (MPT) results were assessed. Results Forced vital capacity (FVC), forced expiratory volume in one second, forced expiratory flow rate at 25% to 75% of FVC (FEF_25%–75%), peak expiratory flow rate, total lung capacity, and DLCO values were significantly lower in the patient group than in the controls. No significant difference in pulmonary function test results was found between patients with and without a history of ACS. Fifteen patients with SCD (48%) and only 5 controls (16%) had AHR (p = 0.007). A significant correlation was found between the number of ACS episodes and MPT positivity (r = 0.379, p = 0.035). The FEF_25%–75% values were significantly lower in patients with positive MPT results than in patients with negative MPT results (p = 0.027). Conclusion The prevalence of AHR was high in adult patients with SCD. A significant correlation was found between AHR and recurrent ACS episodes. Anti-inflammatory controller agents can be used routinely to decrease pulmonary morbidity associated with SCD, even in the absence of asthmatic symptoms.     

Limitations of Hb F as a Phenotypic Modifier in Sickle Cell Disease: Study of Kuwaiti Arab Patients

Sickle cell disease is characterized by phenotypic heterogeneity and many genetic modifiers have been identified with elevated Hb F being the most recognized ameliorating factor. Kuwaiti sickle cell disease patients carry the India/Arab chromosomal haplotype, which is associated with elevated Hb F (on average ～22%) on account of the Xmn1 site in the ^Gγ-globin gene promoter. Most patients had either Hb SS or Hb S-β⁰-thalassemia (β⁰-thal) and there are a few Hb SD compound heterozygotes. We have carried out longitudinal clinical studies of these patients to document the pattern of morbidity, spleen function, brain and hip magnetic resonance imaging (MRI) for prevalence of silent brain infarcts and avascular necrosis of the femoral head (AVNFH), respectively. In addition, pulmonary function, SPECT (single photon emission computerized tomography) brain cerebral blood flow and response of selected patients to hydroxyurea (HU) treatment were also studied. The Hb SS and Hb S-β-thal patients have a generally mild phenotype compared to sickle cell disease in other populations and most patients do not have their first pain crisis until about the age of 4 years. Spleen function is retained till late childhood; pneumococcemia and other severe bacterial infections are rare. Overt stroke and silent brain infarcts are uncommon in childhood (～3% prevalence) although SPECT reveals cerebral blood flow deficits in ～30%. Avascular necrosis of the femoral head is, however, common with a prevalence of ～26% in children and 50% in adults. There is brisk response to HU in patients with frequent pain crises, with marked increases in Hb F levels. Patients who are compound heterozygotes for Hbs S and D-Los Angeles, have the most severe phenotype despite Hb F levels of >20% and Hb S <30%. In conclusion, although the patients have a uniformly elevated Hb F level, there are still considerable phenotypic heterogeneity and other modulating genetic factors that require further studies.     

Uric Acid as a Potential Biomarker of Pulmonary Arterial Hypertension in Patients with Sickle Cell Disease

Serum uric acid (UA) is emerging as a strong and independent marker for pulmonary arterial hypertension (PAH). PAH is well recognized as a life threatening complication of sickle cell disease (SCD). However, the association between UA and PAH in SCD is unknown. We reviewed electronic medical records (EMR) of 559 consecutive adult SCD patients from Kings County Hospital Center (KCHC) between January 2005 and February 2010. Patients (n = 96) with measurement of UA in close temporal proximity to the transthoracic echocardiography (TTE) were identified. PAH was defined as pulmonary artery systolic pressure (PASP) ≥30 mm Hg. Patients (n = 16) with other risk factors which may cause PAH and chronic renal insufficiency were excluded. In 18 patients, TTE could not measure PASP. Finally, 62 patients were selected. Statistical analysis was performed using Student t tests, Pearson correlation coefficient and multivariate regression analysis. Out of 62 patients, 30 had PAH. Patients with PAH had a higher UA level (8.67 ± 4.8 vs. 5.35 ± 2.1, P = 0.001). We found strong positive correlation between the UA level and PASP (r = 0.71; P < 0.0001). This correlation was independent of diuretic use. UA could be a potential marker for PAH in SCD. However, its’ prognostic and pathophysiologic role in SCD patients with PAH needs to be further investigated.     

Tuberculous myocarditis presenting as long QT syndrome

An increasing QT interval can precipitate life-threatening tachyarrhythmias such as ventricular fibrillation. Tuberculous myocarditis is a very unusual diagnosis commonly made at autopsy. Mycobacterium tuberculosis can invade the cardiac conduction system and produce potentially dangerous arrhythmias. This case presents an HIV-infected man with tuberculous infection and long QT syndrome. We comment on the pathology, clinical features and outcome of this rare form of tuberculous infection.     

Secretory Phospholipase A2 Levels in Patients with Sickle Cell Disease and Acute Chest Syndrome

In a multicenter study (eight centers), we determined secretory phospholipase A₂ (sPLA₂) levels in patients with sickle cell disease and acute chest syndrome (ACS). The diagnosis of ACS was made according to established criteria. The sPLA₂ levels were determined in blood samples collected at baseline (time of diagnosis) and serially thereafter up to day 22–35 follow-up visits. Thirty-four of 43 (80%) patients with ACS had enzyme levels ≥1.00 AU at baseline. The enzyme levels decreased significantly on Days 2 through Days 25–35 after baseline. Nine of 43 (20%) patients had baseline sPLA₂ values of <1.00 AU with six of them never exceeding 1.00 AU at any point in time during follow-up. The data indicate that the reliability of sPLA₂ for predicting the development of ACS is not perfect (100%) as was previously reported but occurs in about 80% of the patients.     

Sweet's syndrome as the presenting symptom of hairy cell leukemia with concomitant infection by Mycobacterium kansasii

Summary A patient with Sweet's syndrome and leukopenia is reported. Hematological evaluation revealed hairy cell leukemia (HCL). The clinical picture was dominated by persistent fever, which is a common feature of both Sweet's syndrome and HCL. Since fever frequently reflects concomitant infection in HCL, a thorough search for infectious disease was performed. Blood cultures grewMycobacterium kansasii. The patient recovered after treatment with recombinant interferon- (r-IFN-) and tuberculostatic drugs. Remarkably, the skin lesions completely regressed within 1 week after the start of r-IFN-. In the literature, Sweet's syndrome is rarely mentioned as a feature of HCL. Mycobacterial disease, especially atypical mycobacteria, is relatively often seen in HCL.     

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.     

Intravascular lymphomatosis presenting as adult respiratory distress syndrome

An unusual case of intravascular lymphomatosis caused by small noncleaved, non-Burkitt's lymphoma, which presented with adult respiratory distress syndrome, is described. Extensive invasion of the small- and medium-size blood vessels of the lung, liver, spleen, kidneys, heart, esophagus, stomach, small and large intestines, bladder, and brain—but not the bone marrow or peripheral blood—is documented. The possible mechanism and the unusual features of this case are discussed in comparison with previously reported cases. The pertinent literature is reviewed. The problem of diagnosing this pathological entity is emphasized. Am. J. Hematol. 56:155–160, 1997. © 1997 Wiley-Liss, Inc.     

Sickle cell trait in a white Jewish family presenting as splenic infarction at high altitude

We report the presence of sickle cell trait in several members of a white Jewish family. The trait was discovered when the propositus developed massive splenic infarction at high altitude. No erythrocyte markers characteristic of African ancestry were detected in any of the family members. This is the first bona fide documentation of sickle trait among white Jews.     

Acute appendicitis presenting as a fall (geriatric syndrome)

Falls are common among elderly patients who present at the emergency department (ED). When elderly patients suffer from an acute illness or the exacerbation of a chronic condition, they are frail, and, consequently, their balance may be affected. However, falls are not yet reported as the initial presentation of acute appendicitis. This is a case report of such. A 70-year-old gentleman called for emergency medical services help due to a fall. He presented at the ED with abrasion and contusion to his forehead and bilateral knees. He was taken to the traumatic division of the ED. However, some hours later, he developed fever and right lower abdominal pain. Acute appendicitis was diagnosed and appendectomy was performed. He had a smooth recovery without complications. Because surgical intervention is the only definitive treatment for acute appendicitis, emergency physicians should be aware of this rare presentation.     

Safety of Purified Poloxamer 188 in Sickle Cell Disease: Phase I Study of a Non‐ionic Surfactant in the Management of Acute Chest Syndrome

Acute chest syndrome (ACS) is the most common cause of death in patients with sickle cell anemia. Its management is primarily palliative. We performed a Phase I evaluation of purified poloxamer 188 (a non‐ionic surfactant) in the management of ACS. Forty‐three patients with sickle cell disease and ACS were treated with doses as high as 2960 mg/day by continuous intravenous (IV) infusion. The maximum tolerated dose has not been identified. No evidence of renal toxicity or other limiting adverse events were found. One adult patient died due to sepsis and adult respiratory distress syndrome, which were unrelated to treatment. Poloxamer 188 is safe to administer to patients with ACS, and preliminary data suggest that it may shorten its duration and the length of hospitalization in a dose related manner. Children appeared to benefit more than adults. The data and safety profile justify further studies with purified poloxamer 188 in the treatment of ACS.     

Senile systemic amyloidosis presenting as bilateral carpal tunnel syndrome

A 74-year-old woman who had developed numbness in both hands was diagnosed as having bilateral carpal and right cubital tunnel syndrome and underwent bilateral carpal and right cubital tunnel release. Transthyretin immunoreactive amyloid deposits were seen on specimens and were also detected in gastric, duodenal and ileal mucosal biopsies. The transthyretin gene analysis showed no mutation. This is a rare case of senile systemic amyloidosis presenting as carpal tunnel syndrome.     

腔内超声在髂静脉受压综合征中的应用及研究进展

髂静脉受压综合征(IVCS)是指髂静脉受压、且腔内存在异常黏连结构所引起的下肢和盆腔静脉回流障碍性疾病,又称May-Thurner综合征或Cockett综合征.其不仅是造成下肢静脉瓣膜功能不全和浅静脉曲张的原因之一,也是静脉血栓好发的潜在因素.目前临床中的主要检查方式包括彩色多普勒超声(CDFI)、计算机断层扫描静脉造...     

腔内治疗髂静脉压迫综合征的初步体会(附26例报告)

目的:探讨腔内治疗慢性髂静脉压迫综合征的疗效。方法:总结我院26例血栓后综合征伴髂静脉病变(血栓后综合征组)及原发髂静脉病变(非血栓组)的腔内治疗结果。结果:26例均行球囊扩张术,5例支架置入。技术成功100%。21例(81%)获得随访,随访时间4～52个月,平均17个月。其中支架2年通畅率100%(5/5),单纯球囊扩张16例:血栓后综合征组1年通畅率67%(4/6)。非血栓组1年通畅率100%(10/10)。症状体征改善率:血栓后综合征组与非血栓组分别为,酸胀50%,45%;下肢肿63%,46%;色素沉着改善率零,22%;2组静脉曲张均无改善;2组踝部溃疡3例均治疗后1个月内愈合。结论:腔内治疗髂静脉压迫综合征是微创、安全及有效的方法,单纯球囊扩张非血栓病例较血栓后遗症病例通畅率高。对于髂静脉狭窄闭塞扩张后仍存在明显狭窄时,支架置入是治疗的首选,中期通畅率高。慢性髂静脉高压所致的下肢静脉反流病变,应做相应处理以进一步提高患者的生活质量。     

Churg-Strauss syndrome presenting as spontaneous subarachnoid haemorrhage

Churg–Strauss syndrome (CSS) is a systemic small-vessel vasculitis characterised by the presence of asthma and eosinophilia. Central nervous system involvement (cerebral infarctions or intracerebral haemorrhage) is rare in CSS. Spontaneous subarachnoid hemorrhage (SAH) has been described in other systemic vasculitides. SAH is exceptional in CSS. We present a 47-year-old woman with CSS presenting as a spontaneous SAH with cerebral angiography findings consistent with vasculitis of the basilar artery and without aneurysms or arteriovenous malformations. She received treatment with prednisone and cyclophosphamide, and 2 months later the basilar artery was normal on magnetic resonance angiography. Received: 27 May 2001 / Accepted: 17 November 2001