Challenge of Managing Sickle Cell Disease in a Pediatric Population Living in Kinshasa,Democratic Republic of Congo: A Sickle Cell Center Experience

In the Democratic Republic of Congo (DRC), sickle cell disease is not yet really regarded as a health care priority. The patterns of sickle cell disease in patients living in Kinshasa, DRC are discussed and the difficulties encountered in their management are highlighted. The cross-sectional survey is of sickle cell patients and their families attending the Centre de Médecine Mixte et d’Anémie SS de Yolo (CMMASS), Kinshasa, DRC, between January and April 2009. Completed questionnaires were received from 168 respondents (111 girls; 57 boys). Seventy-one percent of the subjects were diagnosed before the age of 2 years but none in the neonatal period. Sickle cell disease was diagnosed in 54.8% of the patients after they had suffered pain crises. Of the 168 subjects, 74.0% had previously received blood transfusions. Seventy-five (45.0%) had more than three severe pain crises per year. A minority of 35.0% reported that they regularly took an antibioprophylaxis. Seventy-five (45.0%) subjects were eligible for hydroxyurea (HU) therapy but in all cases this drug was taken irregularly. Eighty-two percent of drugs were purchased by the parents. One hundred and sixty-three children (97.0%) were vaccinated according to the Expanded Programme on Immunization (EPI), 61.0% against Streptococcus pneumoniae and 16.0% against the Hepatitis B virus (HBV). No case of immunization against Hemophilus influenzae and Salmonella sp was reported. Neonatal screening programs, early educational detection programs for families, use of current method treatments and an implementation of a health insurance system for sickle cell disease will improve detection and management for these and future patients in our population.     

Prevalence and Characteristics of Priapism in Sickle Cell Disease

Priapism is a pathological condition of persistent penile erection in the absence of sexual arousal or desire. It is an urological emergency and its identification is important as lack of prompt treatment can result in erectile dysfunction. The aim of this study was to estimate and describe the characteristics (number of episodes, duration, time of occurrence and evolution) of priapism in patients with sickle cell disease. A bibliographical research was carried out in PubMed, searching for papers published in the last 5 years. Thirteen scientific articles were included in this review. The main results were: 1) the highest prevalence of priapism in males reported was 48.0% and the lowest 0.67%; 2) six studies were carried out on the African Continent (46.1%), three in America (23.1%), two in Europe (15.4%) and two in Asia (15.4%); 3) the main goal of ～50.0% of the studies was to determine the rate of priapism in patients with sickle cell disease; 4) there was predominance of sickle cell anemia patients [homozygous Hb S (HBB: c.20A>T) genotype]; 5) the minimum age of patients with priapism was 7 years old and the maximum 30 years. In general, the episodes of priapism occurred during sleep, were recurrent and had variable duration. The prevalence of priapism are not real and the explanations include underreporting by patients, lack of awareness by physicians and lack of proper prospective studies. Priapism is a complication that deserves close attention due to its significant impact on the life of the patient with sickle cell disease and, therefore, should be further clarified.     

The Assessment and Sustainable Management of Sickle Cell Disease in the Indigenous Tharu Population of Nepal

Sickle cell disease is an inherited hemoglobinopathy associated with significant morbidity and mortality. Reports suggest a high sickle cell disease burden among the indigenous Tharu population of Nepal, who for centuries have inhabited regions where malaria is endemic. Unfortunately, health care resources are limited and often inaccessible for Tharu individuals suffering from sickle cell disease. We conducted a large-scale screening effort to estimate the prevalence of Hb S (HBB: c.20A>T) among the Tharu population and delivered community-based education sessions to increase sickle cell disease awareness. A total of 2899 Tharu individuals aged 6 months to 40 years in the rural district of Dang in Western Nepal were screened using a sickling test, of whom, 271 [9.3%; 95% confidence interval (95% CI): 8.3–10.4%] screened positive for Hb S. Those who screened positive were offered diagnostic gel electrophoresis testing. Of the 133 individuals who underwent diagnostic testing, 75.9% (n?=?101) were confirmed to be Hb AS heterozygotes, 4.5% (n?=?6) were confirmed to be Hb SS homozygotes and 19.5% (n?=?26) were false positives. These findings support a large burden of sickle cell disease among the Tharu population and highlight the importance of appropriate resource allocation and management. With a positive predictive value of 80.0% (95% CI: 73.0-87.0%), the sickling test in conjunction with raising local sickle cell disease awareness may be a simple and sustainable way to promote access to health resources.     

Erythropoietin Levels in Patients with Sickle Cell Disease Do Not Correlate with Known Inducers of Erythropoietin

Previous studies have suggested that erythropoietin (Epo) levels may be inappropriately low in patients with sickle cell disease compared to the extent of the related anemia they demonstrate. Here, we evaluate Epo level vs. renal function, oxygenation, and markers of inflammation for patients treated for sickle cell disease at our institution. Blood was drawn from 54 patients with sickle cell disease during routine visits to the outpatient hematology office and analyzed for hemoglobin (Hb) level, Epo, markers of inflammation, oxygenation, and renal function. Erythropoietin levels were lower than expected for patients with sickle cell disease, compared to the degree of anemia demonstrated in these patients. In addition, a correlation between Hb level and Epo was not consistently observed. Higher Epo levels were seen in patients receiving hydroxyurea (HU), but no correlation with oxygenation, hemolysis, renal function, or inflammation was observed.     

Enhancing Effect of Hydroxyurea on Hb F in Sickle Cell Disease: Ten-Year Egyptian Experience

Patients with sickle cell disease experience hemolytic anemia and vaso-occlusions that result in pain, organ injury, and premature mortality. Several prospective studies have verified the efficacy and tolerability of hydroxyurea (HU), and demonstrated its efficacy in reducing painful vaso-occlusive crises (VOCs) in addition to its ability to increase Hb F levels. We aimed to evaluate the long-term effects of HU therapy on Hb F and assess its long term efficacy and safety in sickle cell disease patients. A retrospective study on 60 sickle cell disease patients was conducted. We studied the laboratory changes, frequency of VOCs per year, frequency of hospital admisions per year and number of transfusions per year, both before and after HU therapy. The follow-up period was 4 to 120 months. Hb F levels after HU therapy positively correlated with the duration of HU therapy, baseline Hb F levels and baseline total hemoglobin (Hb) (r?=?0.4, p?=?0.04; r?=?0.45, p?=?0.001; r?=?0.5, p?=?0.019, respectively) and inversely correlated with baseline total leucocyte count (r?=?–0.33, p?=?0.034). Hydroxyurea therapy was associated with an increase in the total Hb and mean corpuscular volume (MCV) (p?=?0.009, p?=?0.000; respectively) and with a decrease in total leucocyte count, platelet count and reticulocyte count (p?=?0.00, p?=?0.03, p?=?0.02, respectively). Moreover, a significant reduction in the frequency of VOCs, transfusion frequency and hospital admissions per year after HU therapy was shown in the studied subjects. Hydroxyurea induced an increase in Hb F level, which was maintained over time and was associated with clinical efficacy and acceptable safety.     

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.     

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases

Abstract

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients’ charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.     

Non‐transferrin bound labile plasma iron and iron overload in Sickle Cell Disease: a comparative study between Sickle Cell Disease and β thalassemic patients

Background: Blood transfusions are the standard of care in β thalassemia and transfusions are also indicated in sickle cell disease (SCD) patients with hypersplenism, recurrent vaso‐occlusive crises and for stroke prevention. Iron overload caused by blood transfusions in thalassemia and in SCD may affect morbidity and mortality. Recent studies of iron overload in SCD suggest that the biologic features of SCD and the chronic inflammatory state may protect SCD patients from iron damage. Designs and methods: In view of the controversy regarding the effect of iron overload in patients with SCD we studied the iron status, including non‐transferrin bound iron (NTBI) and labile plasma iron (LPI) levels in a cohort of 36 SCD patients and compare the results with 43 thalassemia patients. Results: Our results indicate that none of the SCD patients had clinical symptoms of iron overload. Only two SCD patients had NTBI values in the gray zone (0.4 units) and none had positive values. By contrast, 14 patients with thalassemia major and three with thalassemia intermedia had NTBI values above 0.6, level that are in the positive pathological range. Similarly, four thalassemia patients, but only one SCD patient had positive LPI levels. Conclusions: The parameters of iron status in SCD patients, even after frequent transfusions are different when compared to patients with thalassemia. The low NTBI and LPI levels found in patients with SCD are in keeping with the absence of clinical signs of iron overload in this disease.     

Incidence and Predictors of Bacterial infection in Febrile Children with Sickle Cell Disease

Abstract

Children with sickle cell disease are at increased risk of developing bacteremia and other serious bacterial infections. Fever is a common symptom in sickle cell disease and can also occur with sickle cell crises and viral infections. We aimed to evaluate the incidence and predictors of bacteremia and bacterial infection in children with sickle cell disease presenting with fever to a district hospital and sickle cell center in London. A retrospective analysis was performed on all attendances of children (aged under 16 years) with sickle cell disease presenting with a fever of 38.5?°C or higher over a 1-year period. Confirmed bacterial infection was defined as bacteremia, bacterial meningitis, urinary tract infection (UTI), pneumonia, osteomyelitis or other bacterial infection with positive identification of organism. Children were defined as having a suspected bacterial infection if a bacterial infection was suspected clinically, but no organism was identified. Over a 1-year period there were 88 episodes analyzed in 59 children. Bacteremia occurred in 3.4% of episodes and confirmed bacterial infection in 7.0%. Suspected bacterial infection occurred in 33.0%. One death occurred from Salmonella typhirium septicemia. C-reactive protein (CRP) level and white blood cell (WBC) count were both significantly associated with bacterial infection (p?=?0.004 and 0.02, respectively.) In conclusion, bacterial infections continue to be a significant problem in children with sickle cell disease. C-reactive protein was significantly associated with bacterial infections, and could be included in clinical risk criteria for febrile children with sickle cell disease.     

Maternal and Perinatal Outcome of Women With Sickle Cell Disease of a Tribal Population in Central India

Pregnancy in sickle cell disease is associated with increased risk of maternal and fetal morbidity and mortality. Sickle cell disease is very common in tribal populations. The objective of this study was to review the maternal and perinatal outcome in patients with sickle cell disease of tribal populations. This is a retrospective study. The data extracted from the patients’ case files included age, gravidity, family history, complications during pregnancy or at time of delivery or postpartum period, mode of delivery, and fetal outcome. There were 25 deliveries to women with sickle cell disease and 54 with sickle cell trait. Preeclampsia and disseminated intravascular coagulation were common problems associated with sickle cell disease as compared to the sickle cell trait and normal groups. No maternal mortality occurred during the period under study. However, a total of five intrauterine fetal deaths and one early neonatal death did occur. The present study confirms the previous reports, the increased risk of fetal death in women with sickle cell disease, however, in contrast to previous studies, no maternal mortality was found.     

Leg Amputation for an Extensive,Severe and Intractable Sickle Cell Anemia Ulcer in a Brazilian Patient

A 35-year-old African Brazilian patient had sickle cell anemia complicated with recurrent vasoocclusive (VOC) crises and refractory painful leg ulcers for 16 years. The ulcers started over both medial malleoli and expanded gradually. The ulcer on the left leg spread from the foot to the knee circumferentially and was refractory to all forms of therapy within the frame work of multi-disciplinary care. The patient agreed to a below the knee amputation of the left leg. He felt much better after the amputation but developed severe neuropathic phantom pain that was well controlled medically. He could differentiate the sickle cell anemia and ulcer pain from the neuropathic pain. About 6 months after the amputation he had dengue fever with fatal outcome. This is the first report of treatment of refractory sickle cell anemia leg ulcer with amputation and probably the first report of a Brazilian patient with sickle cell anemia and dengue fever.     

Phenotypic Diversity of Sickle Cell Disease in Patients with a Double Heterozygosity for Hb S and Hb D-Punjab

Phenotypic heterogeneity for sickle cell disease is associated to several genetic factors such as genotype for sickle cell disease, β-globin gene cluster haplotypes and Hb F levels. The coinheritance of Hb S (HBB: c.20A?>?T) and Hb D-Punjab (HBB: c.364G?>?C) results in a double heterozygosity, which constitutes one of the genotypic causes of sickle cell disease. This study aimed to assess the phenotypic diversity of sickle cell disease presented by carriers of the Hb S/Hb D-Punjab genotype and the Bantu [–?+?– – – –] haplotype. We evaluated medical records from 12 patients with sickle cell disease whose Hb S/Hb D-Punjab genotype and Bantu haplotype were confirmed by molecular analysis. Hb S and Hb D-Punjab levels were quantified by chromatographic analysis. Mean concentrations of Hb S and Hb D-Punjab were 44.8?±?2.3% and 43.3?±?1.8%, respectively. Painful crises were present in eight (66.7%) patients evaluated, representing the most common clinical event. Acute chest syndrome (ACS) was the second most prevalent manifestation, occurring in two individuals (16.7%). Three patients were asymptomatic, while another two exhibited greater diversity of severe clinical manifestations. Medical records here analyzed reported a significant clinical diversity in sickle cell disease ranging from the absence of symptoms to wide phenotypic variety. The sickle cell disease genotype, Bantu haplotype and hemoglobin (Hb) levels did not influence the clinical diversity. Thus, we concluded that the phenotypic variation in sickle cell disease was present within a specific genotype for disease regardless of the β-globin gene cluster haplotypes.     

Renal Failure in Sickle Cell Disease: Prevalence,Predictors of Disease,Mortality and Effect on Length of Hospital Stay

Renal dysfunction in sickle cell disease is not only a chronic comorbidity but also a mortality risk factor. Though renal dysfunction starts early in life in sickle cell patients, the predictors that can identify sickle cell disease patients at risk of developing renal dysfunction is not known. We used the Truven Health MarketScan^® Medicaid Databases from 2007 to 2012. Incidence of new acute renal failure (ARF) and chronic kidney disease (CKD) was calculated in this cohort. There were 9481 patients with a diagnosis of sickle cell disease accounting for 64,201 hospital admissions, during the study period. Both ARF and CKD were associated with higher risk of inpatient mortality, longer duration of the hospital stay and expensive hospitalizations. The yearly incidence of new ARF in sickle cell disease patients was 1.4% and annual CKD incidence was 1.3%. The annual rate of new ARF and CKD in the control group was 0.4 and 0.6%, respectively. The most important predictors of new CKD were proteinuria, ARF and hypertension. Chronic kidney disease, hypertension and sickle cell crisis were the most important predictors of new ARF. The annual rate of incidences of ARF and CKD were 2- to 3-fold higher in sickle cell disease compared to the non sickle cell disease group. Besides the common risk factors for renal disease in the general population, it is imperative to monitor the sickle cell disease patients with more severe disease to prevent them from developing renal dysfunction.     

Comparison of Patients from Nigeria and the USA Highlights Modifiable Risk Factors for Sickle Cell Anemia Complications

To identify factors that affect manifestations of sickle cell anemia we compared patients 11–30 years of age from University of Ibadan, Ibadan, Oyo, Nigeria (n?=?214) and University of Illinois at Chicago, Chicago, IL, USA (n?=?209). Paralleling findings in the general populations of the two countries, the Chicago patients were more often overweight or obese as defined by the Centers for Disease Control and Prevention (Atlanta, GA, USA) guidelines, and more often had elevated blood pressure (BP) as defined by the National Heart, Lung, and Blood Institute (NHLBI), Bethesda, MD, USA guidelines. The Ibadan patients did not receive the pneumococcal vaccine or hydroxyurea (HU) therapy as frequently as the Chicago patients. Consistent with lower rates of elevated BP and increased body mass index (BMI), stroke history was less frequent in the Ibadan patients ≥18 years old. Furthermore, in combined analyses, systolic and diastolic BP directly correlated with BMI, and elevated weight status independently associated with history of stroke. Our findings are consistent with the possibility that higher values for BMI and BP in Chicago sickle cell anemia patients may contribute to an increased risk of stroke and highlights the need for measures to reduce these risk factors. On the other hand, lower pneumococcal vaccination and HU therapy rates in Ibadan patients highlights the need for more improved vaccination coverage and for studies to define the role of HU therapy in Africa.     

Osteonecrosis of the Femoral Head: A Proposed New Treatment in Homozygous Sickle Cell Disease

Possibilities for bone reconstruction in osteonecrosis of the femoral head in sickle cell hemoglobinopathies before the end of growth have not been assessed. The aim of our study was to evaluate the morphological and functional results in 11 osteonecrosis of the femoral head because of homozygous sickle cell disease. Surgical treatment consisted of a triple acetabular osteotomy in seven cases, femoral varus osteotomy in two cases and a combination of both in two cases. The severity of the osteonecrosis was evaluated on radiographs and magnetic resonance imaging (MRI), pre- and postoperative, and function of the hip joint was assessed by Harris and Postel Merle d’Aubigné scores. The anesthetic part (pre- and postoperative) and eventual complications were collected and analyzed. The maximum follow-up was between 1 to 9.6 years. All patients were considered to be satisfactory at maximum follow-up. The severity of the initial damage was not associated with any morphological or functional outcome at maximum follow-up. All patients had an objective functional gain. We found no general complications. We proposed a decision tree for the patient’s management of avascular necrosis of the femoral head in sickle cell hemoglobinopathies before bone maturity, and with an Arlet and Ficat’s stage of 3 or 4. The results of this study confirmed the interest of conservative surgical treatment in children with homozygous sickle cell anemia in case of osteonecrosis of the femoral head. Level of evidence: IV (cases series of our department).     

Successful Use of Veno-Venous Extracorporeal Membrane Oxygenation in an Adult Patient with Sickle Cell Anemia and Severe Acute Chest Syndrome

A 25-year-old female with sickle cell anemia presented with respiratory failure due to acute chest syndrome (ACS). Given her severely compromised cardiopulmonary status, she was started on veno-venous extracorporeal membrane oxygenation (VV-ECMO). After 20 days, the patient’s respiratory status improved and she was successfully decannulated. Veno-venous extracorporeal membrane oxygenation can be utilized for severe ACS in adult patients with sickle cell disease. Prompt initiation of this modality may improve outcomes in adult patients with sickle cell disease complicated by life threatening ACS.     

Lactate Dehydrogenase: A Marker of the Severity of Vaso-Occlusive Crisis in Children with Sickle Cell Disease Presenting at the Emergency Department

The aim of this study was to describe the characteristics of vaso-occlusive crises (VOC) in children with sickle cell disease and to identify factors associated with greater severity. We performed a prospective observational study from August 2012 to January 2014. The study population comprised patients with sickle cell disease who consulted at the emergency department (ED) for VOC. We recorded demographic variables, history of complications related to the disease, and data on usual treatment. We also assessed pain, analgesia at home, need for admission, length of stay, and analgesia during admission. Analytical parameters were collected. A total of 29 patients with VOC were included. The patient’s usual treatment was hydroxyurea (HU) in 69.0%, and 7.0% required chronic transfusions. In the ED, 90.0% had moderate or severe pain, even though 86.0% had received analgesia at home (41.4% minor opioids). Overall, 27 of the 29 patients were admitted, and 56.0% needed major opioids. Higher lactate dehydrogenase (LDH) levels were related to the use of major opioids during admission (p?=?0.038). A significant difference was recorded between the median number of days of admission for patients receiving non-steroidal anti-inflammatory drugs and for those requiring intravenous opioids (p?=?0.005). Most patients with VOC were admitted to hospital. Lactate dehydrogenase level in the ED was a predictor of severity and was associated with the need for major opioids during admission and more days of admission.     

Perinatal Maternal Mortality in Sickle Cell Anemia: Two Case Reports and Review of the Literature

As outcomes of patients with sickle cell anemia improve and survival into adulthood with good quality of life and expectation of long-term survival becomes more common, challenges have developed, including issues related to reproduction. Pregnancy is frequently complicated in patients with sickle cell anemia with mortality up to 4.0%. Here we report maternal perinatal mortality in two women with sickle cell anemia who died post-partum due to acute chest syndrome (ACS), caused by bone marrow fat embolism and review the literature pertinent to this subject. Patient A was a 28-year-old woman with sickle cell anemia with multiple complications. At 30 weeks’ gestation she developed hemolysis associated with poor placental function necessitating delivery by C-section. The fetus was delivered successfully but she died due to multi organ failure after delivery. Autopsy showed pulmonary and amniotic fluid embolization. Patient B was a 37-year-old woman with uncomplicated sickle cell anemia who presented with pre term labor and crisis, then ACS and fetal distress. The infant was delivered successfully but the patient died after cardiovascular collapse. Autopsy results showed fat and bone marrow embolization as the cause of death. Pregnancy continues to be high risk for patients with sickle cell anemia including those with mild disease. Maternal perinatal mortality could be unpredictable due to serious complications of sickle cell disease. More studies to assess maternal perinatal mortality are needed.     

Use of Direct Oral Anticoagulants in Patients with Sickle Cell Disease and Venous Thromboembolism: A Prospective Cohort Study of 12 Patients

Abstract

Patients with sickle cell disease have an increased risk of venous thromboembolism (VTE) and with a mortality 2-fold higher. The anticoagulation of VTE in a young population is an important question. Indeed, hemorrhagic complications of anticoagulation may occur more frequently than in the general population. The use of a direct oral anticoagulant (DOAC) is not recommended for VTE in patients with sickle cell disease because those patients were not included in the clinical studies. We aimed to study the safety of using DOACs in a prospective cohort of patients with sickle cell disease and VTE. We prospectively followed the cohort of all sickle cell disease patients undergoing recent DOAC treatment for VTE at a sickle cell disease reference center. Twelve patients received rivaroxaban for VTE (eight women and four men). The median age was 27?years (20–45). The sickle cell disease variants included homozygous Hb SS (HBB: c.20A>T) in eight patients, Hb S-β⁺-thalassemia (Hb S-β⁺-thal) in two, Hb S-β⁰-thal in one and Hb S-Hb C (HBB: c.19G>A) in one. The cumulative duration of follow-up was 3134?days under rivaroxaban treatment. There were two thrombotic events, including a patient with a double positivity of antiphospholipid antibodies. No major bleeding was observed, and 6/12 patients presented minor bleeding (epistaxis: n?=?4; anal fissure bleeding: n?=?1; menorrhagia n?=?4). Of these, 3/6 required their treatment to be switched to apixaban, which stopped the bleeding. Direct oral anticoagulants may be an alternative treatment for VTE in patients with sickle cell disease, except for an associated antiphospholipid syndrome.     

Low-Molecular-Weight Heparins for Managing Vasoocclusive Crises in People With Sickle Cell Disease: A Summary of a Cochrane Systematic Review

We summarize a Cochrane systematic review that was conducted to assess the effects of low-molecular-weight heparins (LMWH) for managing vasoocclusive crises (VOC) in people with sickle cell disease. Sickle cell disease is one of the most common and severe genetic disorders in the world. It can be divided into three broadly distinct clinical phenotypes characterized by either hemolysis, pain syndromes or organ damage. Pain is the most prominent symptom of vasoocclusion, and hypercoagulability is a well-established pathogenic phenomenon in people with sickle cell disease. Searches included the Cochrane Cystic Fibrosis and Genetic Disorders Group Haemoglobinopathies Trials Register, abstract books of conference proceedings and several online trials registries (December 2012). One study (with an overall unclear to high risk of bias) comprising 253 participants was included. This study provided limited data, but concluded that tinzaparin resulted in a more rapid resolution of pain, and in a statistically significant lower number of hospitalization days compared to a placebo. Two minor bleeding events were reported as adverse events in the tinzaparin group. Based on the results from this single study, there is incomplete evidence to either support or refute the effectiveness of LMWH in people with sickle cell disease.