Iron deficiency anaemia revisited.

Iron deficiency anaemia is a global health concern affecting children, women and the elderly, whilst also being a common comorbidity in multiple medical conditions. The aetiology is variable and attributed to several risk factors decreasing iron intake and absorption or increasing demand and loss, with multiple aetiologies often coexisting in an individual patient. Although presenting symptoms may be nonspecific, there is emerging evidence on the detrimental effects of iron deficiency anaemia on clinical outcomes across several medical conditions. Increased awareness about the consequences and prevalence of iron deficiency anaemia can aid early detection and management. Diagnosis can be easily made by measurement of haemoglobin and serum ferritin levels, whilst in chronic inflammatory conditions, diagnosis may be more challenging and necessitates consideration of higher serum ferritin thresholds and evaluation of transferrin saturation. Oral and intravenous formulations of iron supplementation are available, and several patient and disease-related factors need to be considered before management decisions are made. This review provides recent updates and guidance on the diagnosis and management of iron deficiency anaemia in multiple clinical settings.

Raised haematocrit concentration and the risk of death and vascular complications after major surgery.

BACKGROUND: Preoperative anaemia is associated with adverse postoperative outcomes. Data on raised preoperative haematocrit concentration are limited. This study aimed to evaluate the effect of raised haematocrit on 30-day postoperative mortality and vascular events in patients undergoing major surgery. METHODS: This was a cohort study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Thirty-day mortality and vascular events, demographics and perioperative risk factors were obtained for adults undergoing major surgery. The adjusted effect of raised (over 0·50) compared with normal (0·41-0·50, American Medical Association reference range) preoperative haematocrit concentration on postoperative outcomes was assessed. Separate sex-specific analyses were also conducted, using haematocrit concentration thresholds commonly used in the diagnosis and management of apparent or absolute erythrocytosis. RESULTS: Some 3961 (2·0 per cent) of 197 469 patients had a raised haematocrit concentration before surgery. After adjustment, the 30-day postoperative mortality rate was higher in patients with raised haematocrit than in those without (odds ratio (OR) 2·23, 95 per cent confidence interval 1·77 to 2·80). Thirty-day rates of deep vein thrombosis (OR 1·95, 1·44 to 2·64) and pulmonary embolism (OR 1·79, 1·17 to 2·73), but not myocardial infarction or stroke, were also higher in patients with a raised haematocrit concentration. The effect on mortality was noted beyond the haematocrit thresholds of 0·48 in women and 0·52 in men; the effect estimates were considerably higher for values exceeding 0·54. Values between 0·41 and 0·45 were not associated with increased mortality risk. Similar observations were noted for venous thrombosis, although with apparent sex differences. CONCLUSION: A raised haematocrit concentration was associated with an increased risk of 30-day mortality and venous thrombosis following major surgery.

The effect of maternal fasting during Ramadan on preterm delivery: a prospective cohort study.

OBJECTIVE: To determine the effect of fasting during the month of Ramadan on the rate of preterm delivery (PTD). DESIGN: A prospective cohort study of women with singleton pregnancies who elected to fast and matched controls. SETTING: Four medical centres in Beirut, Lebanon. POPULATION: Women presenting for prenatal care (20-34 weeks of gestation) during the month of Ramadan, September 2008. METHODS: Data were collected prospectively. The frequency of PTD was evaluated in relation to the duration of fasting and the stage of gestation at the time of fasting. MAIN OUTCOME MEASURES: The primary endpoint was the percentage of pregnant women who had PTD, defined as delivery before 37 completed weeks of gestation. RESULTS: A total of 468 women were approached, of whom 402 were included in the study. There were no differences in smoking history and employment. There was no difference in the proportion of women who had PTD at <37 weeks (10.4% versus 10.4%) or PTD at <32 weeks (1.5% versus 0.5%) in the Ramadan-fasted group and the controls, respectively. The PTD rate was also similar in those who fasted before or during the third trimester. The mean birthweight was lower (3094 ± 467 g versus 3202 ± 473 g, P = 0.024) and the rate of ketosis and ketonuria was higher in the Ramadan-fasted women. On multivariate stepwise logistic regression analysis, fasting was not associated with an increased risk of PTD (odds ratio 0.72; 95% confidence interval 0.34-1.54; P = 0.397). The only factor that had a significant effect on the PTD rate was body mass index (odds ratio 0.43; 95% confidence interval 0.20-0.93; P = 0.033). CONCLUSIONS: Fasting during the month of Ramadan does not seem to increase the baseline risk of preterm delivery in pregnant women regardless of the gestational age during which this practice is observed.

ADAMTS-13 activity and autoantibodies classes and subclasses as prognostic predictors in acquired thrombotic thrombocytopenic purpura.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare life-threatening disease. Of surviving patients, 45% develops an exacerbation or a late recurrence. Severe ADAMTS-13 deficiency, both during the acute episode and remission, is a well-established predictor of recurrence. The predictive value of anti-ADAMTS-13 antibodies, their inhibitory activity and Ig class subtype for disease recurrence is still to be established. OBJECTIVES: To analyze ADAMTS-13-related biomarkers (ADAMTS-13 and anti-ADAMTS-13 immunoglobulins, classes and subclasses) and their potential relationship with prognosis. PATIENTS/METHODS: In 115 patients with TTP, we assessed the association between levels of these biomarkers and the severity of acute episodes; we analysed also the hazard ratio (HR) and 95% confidence interval (CI) of recurrence in association with biomarkers levels retrieved at the previous acute episode or during remission, using Cox regression models. RESULTS: During the acute phase, higher IgA, IgG1 and IgG3 titers showed the strongest association with acute episode severity. In the survival analyzes, the only biomarker significantly associated with a high hazard of recurrence after an acute episode was the presence of IgG. Conversly, low ADAMTS-13 activity or antigen levels (<10%), the presence of ADAMTS-13 inhibitor or IgG during remission were all significantly associated with a higher hazard of recurrence. CONCLUSIONS: Both the Ig class and subclass are of predictive value for acute episode severity in patients with TTP. Although markers that could predict the risk of recurrence in the acute phase are limited, a thorough assessment of ADAMTS-13-related parameters during remission is warranted.

Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders.

BACKGROUND: The European Network of Rare Bleeding Disorders (EN-RBD) was established to bridge the gap between knowledge and practise in the care of patients with RBDs. OBJECTIVES: To explore the relationship between coagulation factor activity level and bleeding severity in patients with RBDs. PATIENTS/METHODS: Cross-sectional study using data from 489 patients registered in the EN-RBD. Coagulation factor activity levels were retrieved. Clinical bleeding episodes were classified into four categories according to severity. RESULTS: The mean age of patients at data collection was 31 years (range, 7 months to 95 years), with an equal sex distribution. On linear regression analysis, there was a strong association between coagulation factor activity level and clinical bleeding severity for fibrinogen, factor (F) X, FXIII, and combined FV and FVIII deficiencies. A weaker association was present for FV and FVII deficiencies. There was no association between coagulation factor activity level and clinical bleeding severity for FXI. The coagulation factor activity levels that were necessary for patients to remain asymptomatic were: fibrinogen, > 100 mg dL(-1); FV, 12 U dL(-1); combined FV + VIII, 43 U dL(-1); FVII, 25 U dL(-1); FX, 56 U dL(-1) ; FXI, 26 U dL(-1); FXIII, 31 U dL(-1). Moreover, coagulation factor activity levels that corresponded with Grade III bleeding were: undetectable levels for fibrinogen, FV and FXIII, < 15 U dL(-1) for combined FV + VIII; < 8 U dL(-1) for FVI; < 10 U dL(-1) for FX; and < 25 U dL(-1) for FXI. CONCLUSIONS: There is a heterogeneous association between coagulation factor activity level and clinical bleeding severity in different RBDs. A strong association is only observed in fibrinogen, FX and FXIII deficiencies.

The surgeon and the patient with ß-thalassaemia intermedia.

BACKGROUND: Unlike patients with ß-thalassaemia major, where lifelong transfusion and iron chelation therapy are necessary for survival, patients with ß-thalassaemia intermedia (TI) generally have a milder course and anaemia. The underlying pathophysiology of the disease still allows several complications to manifest. Surgical management during the course of the disease is common but relevant data from the literature have never been reviewed constructively. This aim of this review was to highlight this clinical entity to the surgeon, and ensure optimal and timely intervention. METHODS: The review was based on potentially relevant studies identified from an electronic search of MEDLINE and PubMed databases. There were no language or publication year restrictions. References in published articles were also reviewed. RESULTS: Surgical intervention is often essential to ensure optimal control of the associated morbidity in TI. Several general considerations are necessary before surgical intervention with regard to anaemia, cardiovascular disease, thromboembolic events and the effects of iron overload. Splenectomy, cholecystectomy, leg ulcers, fractures and extramedullary pseudotumours are the most commonly encountered surgical problems related to TI. CONCLUSION: Awareness of TI and its associated morbidity is important so that appropriate preoperative care can occur.

Nontransferrin-bound iron in transfused patients with sickle cell disease.

The value of nontransferrin-bound iron (NTBI) as an index of iron overload in patients with thalassemia has been evaluated; however, data in patients with sickle cell disease (SCD) is limited. NTBI levels were evaluated in a cross-sectional study of 43 transfused patients with SCD. Patient charts were reviewed for demographics, status of the spleen, and total number of lifetime transfusions. All patients were chelation naïve and none of the patients had evidence of hepatitis B or C infection. Blood samples were taken for assessment of NTBI and serum ferritin (SF); liver iron concentration (LIC) was determined by R2 magnetic resonance imaging. NTBI levels were generally low with a median of -0.01 µm (range -2.56 to 6.37 µm). Among study variables, NTBI levels were only significantly correlated to age and total number of lifetime transfusions, whereas LIC and SF only significantly correlated with total number of lifetime transfusions. On multivariate analysis, only total number of lifetime transfusions remained independently correlated with NTBI (P = 0.001), SF (P < 0.001), and LIC (P < 0.001). On multivariate stepwise linear regression analysis, SF was a better predictor of LIC than NTBI. In transfused patients with SCD, NTBI levels are low yet correlate significantly with transfusion burden. However, they offer poor predictability of LIC when compared with SF.

Resistance to aspirin and clopidogrel therapy.

INTRODUCTION: Despite increasing evidence on the roles of aspirin and clopidogrel in decreasing morbidity and mortality from cardiovascular disease, resistance to therapy remains an emerging clinical entity. The aim of this review was to revisit current knowledge of the mechanisms, laboratory evaluation, clinical impact and management of resistance to aspirin and clopidogrel therapy. METHODS: Potentially relevant studies were identified from an electronic search of MEDLINE and PubMed databases. There were no language or publication year restrictions. References in published articles were also reviewed. RESULTS: Several definitions for resistance have been set, and various laboratory testing modalities are available. The pathophysiological mechanisms remain poorly understood; yet, several extrinsic, intrinsic and genetic factors are described. The clinical implications of this phenomenon are alarming and warrant concern. Management is currently limited to dosing alteration and introduction of other antiplatelet agents. CONCLUSION: Data from ongoing and future studies are awaited to better understand this entity and to highlight the most appropriate treatment strategies.

Splenectomy and thrombosis: the case of thalassemia intermedia.

BACKGROUND: Hypercoagulability in splenectomized patients with thalassemia intermedia (TI) has been extensively evaluated. However, clinical and laboratory characteristics of patients who eventually develop overt thromboembolic events (TEE) are poorly studied. PATIENTS/METHODS: Three Groups of TI patients (n=73 each) were retrospectively identified from a registry involving six centers across the Middle East and Italy: Group I, all splenectomized patients with a documented TEE; Group II, age- and sex-matched splenectomized patients without TEE; and Group III, age- and sex-matched non-splenectomized patients without TEE. Retrieved data included demographics, laboratory parameters, clinical complications, and received treatments that may influence TEE development, and reflected the period prior to TEE occurrence in Group I. RESULTS: The mean age of Group I patients at development of TEE was 33.1±11.7years, with a male to female ratio of 33:40. TEE were predominantly venous (95%) while four patients (5%) had documented stroke. Among studied parameters, Group I patients were more likely to have a nucleated red blood cell (NRBC) count ≥300×10(6) L(-1) , a platelet count ≥500×10(9) L(-1) and evidence of pulmonary hypertension (PHT), or be transfusion naïve. The median time to thrombosis following splenectomy was 8years. Patients with an NRBC count ≥300×10(6) L(-1) , a platelet count ≥500×10(9) L(-1) , or who were transfusion naive also had a shorter time to thrombosis following splenectomy. CONCLUSION: Splenectomized TI patients who will develop TEE may be identified early on by high NRBC and platelet counts, evidence of PHT, and transfusion naivety.

Asymptomatic brain magnetic resonance imaging abnormalities in splenectomized adults with thalassemia intermedia.

BACKGROUND: A high incidence of thrombotic events in thalassemia intermedia (TI) patients led to the identification of a hypercoagulable state. Brain involvement has not been widely studied in TI, although limited reports confirm a low incidence of overt stroke and high incidence of silent brain infarcts. PATIENTS/METHODS: This was a prospective study conducted on 30 adult, splenectomized TI patients. Patients were screened for absence of neurological signs or symptoms, and stroke-related risk factors. Patient charts were reviewed for demographics, duration since splenectomy, and any history of transfusion therapy. Blood samples were obtained for complete blood counts and serum ferritin. Direct determination of liver iron concentration (LIC) was performed by R2 magnetic resonance imaging (MRI). Brain MRI was performed on all patients, looking for ischemic lesions and/or atrophy. RESULTS: The mean age of patients was 32.1 +/- 11 years (range, 18-54 years), with a male to female ratio of 13:17. Eighteen patients (60%) had evidence of one or more white matter lesions (WMLs) on brain MRI, all involving the subcortical white matter. Fourteen patients had evidence of multiple WMLs, with a mean of 5 +/- 10 lesions (range, 2 to > 40 lesions). The vast majority of patients (94%) had small (< 0.5 cm) to medium (0.5-1.5 cm) WMLs, with only one patient showing evidence of a large (> 1.5 cm) WML. Eleven patients (37%) had mild cerebral atrophy. On multivariate analysis only age and transfusion history were independently and significantly associated with the occurrence of zero, single or multiple WMLs. CONCLUSION: WMLs and brain atrophy are a common finding in adult, splenectomized, TI patients. Increasing age and transfusion naivety are associated with a higher incidence and multiplicity of lesions.

Clinicovirologic analysis of hepatitis C infection in transfusion-dependent beta-thalassemia major children.

Regular blood transfusion puts beta-thalassemia major patients at a higher risk of developing hepatic iron overload and hepatitis C virus (HCV) infection. The association between several transfusion-related factors and an increased risk of developing HCV viremia has been reported. The effect of HCV infection on liver damage in transfusion-dependent thalassemia patients has been poorly described. A sample of 100 Egyptian transfusion-dependent beta-thalassemia major children were studied. Individual patients underwent full history taking, clinical examination and a panel of laboratory tests including HCV ribonucleic acid polymerase chain reaction (HCV-PCR) in blood samples. Liver biopsy was performed for 24 patients. HCV-PCR was positive in 64% of patients. A statistically significant correlation was found between HCV-PCR positivity (HCV viremia) and shorter inter-transfusion interval. There was a significant positive correlation between mean serum ferritin level and mean levels of alanine aminotransferase and aspartase aminotransferase. Histopathologic features of both chronic hepatitis and siderosis were present in 91.7% of biopsy specimens, and fibrosis was present in 41.67%. A higher risk of HCV viremia is noted with a shorter inter-transfusion interval. The reduced role of HCV infection in chronic liver injury in this group of patients may be surpassed by the associated effects of iron overload because of the chronic transfusion. However, the latter finding should be verified in larger studies.

Small bowel intussusception following blunt abdominal trauma in an adult patient.

Blunt abdominal trauma is a rare cause of small bowel intussusception in adults. A patient is described who presented with signs and symptoms of intestinal obstruction following a fall from a ladder. A CT scan revealed evidence of ileo-ileal intussusception. Exploratory laparotomy and resection of a necrotic bowel segment were performed. Rare occurrences like intussusception should be kept in mind in similar presentations with careful examination of the pathognomonic CT findings, as early detection and surgical intervention with manual reduction could preclude the need for small bowel resection and its untoward possible complications.

Childhood stroke in a child with familial Mediterranean fever carrying several prothrombotic risk factors.

Familial Mediterranean fever (FMF) was recently associated with a hypercoagulable state. However, clinically overt thrombosis remains a rare event limited to patients with other predisposing factors. We herein present a child with FMF who experienced a stroke. An extensive thrombophilia work-up revealed multiple inherited and acquired risk factors. In areas with high prevalence of prothrombotic mutations and in children who are products of consanguineous marriages, early screening for concurrent thrombotic risk factors is warranted; as this may help design an optimal management plan and prevent unfavourable outcomes.