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Cardiology Clinics May 2015Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed... (Review)
Review
Familial hypercholesterolemia is a common, inherited disorder of cholesterol metabolism that leads to early cardiovascular morbidity and mortality. It is underdiagnosed and undertreated. Statins, ezetimibe, bile acid sequestrants, niacin, lomitapide, mipomersen, and low-density lipoprotein (LDL) apheresis are treatments that can lower LDL cholesterol levels. Early treatment can lead to substantial reduction of cardiovascular events and death in patients with familial hypercholesterolemia. It is important to increase awareness of this disorder in physicians and patients to reduce the burden of this disorder.
Topics: Anticholesteremic Agents; Blood Component Removal; Genetic Predisposition to Disease; Global Health; Humans; Hyperlipoproteinemia Type II; Lipoproteins; Prevalence
PubMed: 25939291
DOI: 10.1016/j.ccl.2015.01.001 -
Transfusion and Apheresis Science :... Dec 2022
Topics: Humans; COVID-19; Blood Component Removal
PubMed: 36414519
DOI: 10.1016/j.transci.2022.103601 -
Blood Sep 2018Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal disorders associated with elevation of immunoglobulins. Asymptomatic patients with an... (Review)
Review
Plasma hyperviscosity is a rare complication of both monoclonal and polyclonal disorders associated with elevation of immunoglobulins. Asymptomatic patients with an elevation in the serum viscosity do not require plasma exchange, and the majority will have other indications for therapeutic intervention. For patients with hemorrhagic or central nervous system manifestations, plasma exchange is the therapy of choice and is relatively safe. Viscosity measurements are not required to initiate therapy if the index of suspicion is high and the clinical presentation is typical. However, patients should have a sample sent for confirmation of the diagnosis. Whole-blood hyperviscosity is seen in patients with extreme elevation of the red cell and white cell count. Phlebotomy of patients with primary and secondary elevation of the red cell count is a well-established therapy.
Topics: Blood Component Removal; Blood Viscosity; Cryoglobulinemia; Disease Management; Humans; Hypergammaglobulinemia; Male; Middle Aged; Plasma Exchange; Sjogren's Syndrome
PubMed: 30104220
DOI: 10.1182/blood-2018-06-846816 -
Journal of Atherosclerosis and... Jul 2021Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated... (Review)
Review
Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis.Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases.This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system.
Topics: Blood Component Removal; Cholesterol, LDL; Early Medical Intervention; Heart Disease Risk Factors; Homozygous Familial Hypercholesterolemia; Humans; Insurance Coverage; Japan; LDL-Receptor Related Proteins; Lipid Regulating Agents; Prognosis
PubMed: 33867421
DOI: 10.5551/jat.RV17050 -
Kidney & Blood Pressure Research 2023Therapeutic plasmapheresis (TP) is an extracorporeal therapy that allows the removal of pathogens from plasma. The role of TP in immuno-mediated diseases and toxic... (Review)
Review
BACKGROUND
Therapeutic plasmapheresis (TP) is an extracorporeal therapy that allows the removal of pathogens from plasma. The role of TP in immuno-mediated diseases and toxic conditions has been of interest for decades.
SUMMARY
We reviewed the recent literature on the application and the optimal choice of TP technique ranging from plasma exchange, double filtration plasmapheresis, rheopheresis, immunoadsorptions, plasma adsorption perfusion and lipidoapheresis. In addition, we report our experience in the application of TP for various diseases ranging in different medical specialties, following the American Society for Apheresis (ASFA) recommendations.
KEY MESSAGES
Overall patients receiving TP showed an improvement in clinical and laboratory parameters. Our review and single-center experience suggest a benefit of the application of TP in multiple clinical disciplines.
Topics: Humans; United States; Plasma Exchange; Plasmapheresis; Blood Component Removal
PubMed: 36481657
DOI: 10.1159/000528556 -
Atherosclerosis Dec 2019Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the... (Review)
Review
Lipoprotein(a), Lp(a), is a modified atherogenic low-density lipoprotein particle that contains apolipoprotein(a). Its levels are highly heritable and variable in the population. This consensus statement by HEART UK is based on the evidence that Lp(a) is an independent cardiovascular disease (CVD) risk factor, provides recommendations for its measurement in clinical practice and reviews current and emerging therapeutic strategies to reduce CVD risk. Ten statements summarise the most salient points for practitioners and patients with high Lp(a). HEART UK recommends that Lp(a) is measured in adults as follows: 1) those with a personal or family history of premature atherosclerotic CVD; 2) those with first-degree relatives who have Lp(a) levels >200 nmol/l; 3) patients with familial hypercholesterolemia; 4) patients with calcific aortic valve stenosis and 5) those with borderline (but <15%) 10-year risk of a cardiovascular event. The management of patients with raised Lp(a) levels should include: 1) reducing overall atherosclerotic risk; 2) controlling dyslipidemia with a desirable non-HDL-cholesterol level of <100 mg/dl (2.5 mmol/l) and 3) consideration of lipoprotein apheresis.
Topics: Biomarkers; Blood Component Removal; Cardiovascular Diseases; Clinical Decision-Making; Consensus; Down-Regulation; Dyslipidemias; Humans; Hypolipidemic Agents; Lipoprotein(a); Risk Assessment; Risk Factors
PubMed: 31704552
DOI: 10.1016/j.atherosclerosis.2019.10.011 -
JAMA Neurology Nov 2021Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE);... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Overall, immunotherapy has been shown to improve outcomes and reduce relapses in individuals with N-methyl-d-aspartate receptor (NMDAR) antibody encephalitis (NMDARE); however, the superiority of specific treatments and combinations remains unclear.
OBJECTIVE
To map the use and safety of immunotherapies in individuals with NMDARE, identify early predictors of poor functional outcome and relapse, evaluate changes in immunotherapy use and disease outcome over the 14 years since first reports of NMDARE, and assess the Anti-NMDAR Encephalitis One-Year Functional Status (NEOS) score.
DATA SOURCES
Systematic search in PubMed from inception to January 1, 2019.
STUDY SELECTION
Published articles including patients with NMDARE with positive NMDAR antibodies and available individual immunotherapy data.
DATA EXTRACTION AND SYNTHESIS
Individual patient data on immunotherapies, clinical characteristics at presentation, disease course, and final functional outcome (modified Rankin Scale [mRS] score) were entered into multivariable logistic regression models.
MAIN OUTCOMES AND MEASURES
The planned study outcomes were functional outcome at 12 months from disease onset (good, mRS score of 0 to 2; poor, mRS score greater than 2) and monophasic course (absence of relapse at 24 months or later from onset).
RESULTS
Data from 1550 patients from 652 articles were evaluated. Of these, 1105 of 1508 (73.3%) were female and 707 of 1526 (46.3%) were 18 years or younger at disease onset. Factors at first event that were significantly associated with good functional outcome included adolescent age and first-line treatment with therapeutic apheresis, corticosteroids plus intravenous immunoglobulin (IVIG), or corticosteroids plus IVIG plus therapeutic apheresis. Factors significantly associated with poor functional outcome were age younger than 2 years or age of 65 years or older at onset, intensive care unit admission, extreme delta brush pattern on electroencephalography, lack of immunotherapy within the first 30 days of onset, and maintenance IVIG use for 6 months or more. Factors significantly associated with nonrelapsing disease were rituximab use or maintenance IVIG use for 6 months or more. Adolescent age at onset was significantly associated with relapsing disease. Rituximab use increased from 13.5% (52 of 384; 2007 to 2013) to 28.3% (311 of 1100; 2013 to 2019) (P < .001), concurrent with a falling relapse rate over the same period (22% [12 of 55] in 2008 and earlier; 10.9% [35 of 322] in 2017 and later; P = .006). Modified NEOS score (including 4 of 5 original NEOS items) was associated with probability of poor functional status at 1 year (20.1% [40 of 199] for a score of 0 to 1 points; 43.8% [77 of 176] for a score of 3 to 4 points; P = .05).
CONCLUSIONS AND RELEVANCE
Factors influencing functional outcomes and relapse are different and need to be considered independently in development of evidence-based optimal management guidelines of patients with NMDARE.
Topics: Adrenal Cortex Hormones; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Blood Component Removal; Female; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunotherapy; Male; Rituximab
PubMed: 34542573
DOI: 10.1001/jamaneurol.2021.3188 -
Current Atherosclerosis Reports Mar 2023Apheresis is a treatment option for severe dyslipidemia which has been introduced approximately 40 years ago to clinical practice. This article reviews recent apheresis... (Review)
Review
PURPOSE OF REVIEW
Apheresis is a treatment option for severe dyslipidemia which has been introduced approximately 40 years ago to clinical practice. This article reviews recent apheresis research progresses, including apheresis for elevated LDL-cholesterol and elevated lipoprotein(a).
RECENT FINDINGS
While the role of apheresis in treating more common forms of LDL-hypercholesterolemia has been reduced due to the development of new, very potent LDL-lowering drugs, it still plays an important role in treating patients with homozygous familial hypercholesterolemia and patients with severe lipoprotein(a) elevation. One apheresis session can decrease LDL-cholesterol, apoB, and lipoprotein(a) by approximately 65%, which results in a time averaged reduction of 30-50%. Although time-consuming, and expensive regular apheresis is very well tolerated and has been proven safe for decades. Apheresis remains a treatment option for severe dyslipidemia, especially in homozygous familial hypercholesterolemia and elevated lipoprotein(a), if other forms of therapy fail to achieve targets.
Topics: Humans; Hyperlipoproteinemia Type II; Homozygous Familial Hypercholesterolemia; Cholesterol, LDL; Blood Component Removal; Lipoprotein(a)
PubMed: 36701088
DOI: 10.1007/s11883-023-01081-7 -
European Heart Journal Aug 2014Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein...
Homozygous familial hypercholesterolaemia: new insights and guidance for clinicians to improve detection and clinical management. A position paper from the Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society.
AIMS
Homozygous familial hypercholesterolaemia (HoFH) is a rare life-threatening condition characterized by markedly elevated circulating levels of low-density lipoprotein cholesterol (LDL-C) and accelerated, premature atherosclerotic cardiovascular disease (ACVD). Given recent insights into the heterogeneity of genetic defects and clinical phenotype of HoFH, and the availability of new therapeutic options, this Consensus Panel on Familial Hypercholesterolaemia of the European Atherosclerosis Society (EAS) critically reviewed available data with the aim of providing clinical guidance for the recognition and management of HoFH.
METHODS AND RESULTS
Early diagnosis of HoFH and prompt initiation of diet and lipid-lowering therapy are critical. Genetic testing may provide a definitive diagnosis, but if unavailable, markedly elevated LDL-C levels together with cutaneous or tendon xanthomas before 10 years, or untreated elevated LDL-C levels consistent with heterozygous FH in both parents, are suggestive of HoFH. We recommend that patients with suspected HoFH are promptly referred to specialist centres for a comprehensive ACVD evaluation and clinical management. Lifestyle intervention and maximal statin therapy are the mainstays of treatment, ideally started in the first year of life or at an initial diagnosis, often with ezetimibe and other lipid-modifying therapy. As patients rarely achieve LDL-C targets, adjunctive lipoprotein apheresis is recommended where available, preferably started by age 5 and no later than 8 years. The number of therapeutic approaches has increased following approval of lomitapide and mipomersen for HoFH. Given the severity of ACVD, we recommend regular follow-up, including Doppler echocardiographic evaluation of the heart and aorta annually, stress testing and, if available, computed tomography coronary angiography every 5 years, or less if deemed necessary.
CONCLUSION
This EAS Consensus Panel highlights the need for early identification of HoFH patients, prompt referral to specialized centres, and early initiation of appropriate treatment. These recommendations offer guidance for a wide spectrum of clinicians who are often the first to identify patients with suspected HoFH.
Topics: Anticholesteremic Agents; Arcus Senilis; Atherosclerosis; Blood Component Removal; Cardiovascular Diseases; Cholesterol, LDL; Diagnosis, Differential; Early Diagnosis; Gene Frequency; Genetic Heterogeneity; Homozygote; Humans; Hyperlipoproteinemia Type II; Liver Transplantation; Mutation; Pedigree; Phenotype; Practice Guidelines as Topic; Xanthomatosis
PubMed: 25053660
DOI: 10.1093/eurheartj/ehu274 -
Current Atherosclerosis Reports Feb 2021Lipoprotein apheresis is the most effective means of lipid-lowering therapy. However, it's a semi-invasive, time consuming, and chronic therapy with variable adherence.... (Review)
Review
PURPOSE OF REVIEW
Lipoprotein apheresis is the most effective means of lipid-lowering therapy. However, it's a semi-invasive, time consuming, and chronic therapy with variable adherence. There are still no specific guideline recommendations for the management of patients on lipid apheresis. The purpose of this review is to discuss the clinical indications and major drawbacks of lipid apheresis in the light of recent evidence.
RECENT FINDINGS
Lipoprotein apheresis should be initiated at early ages and performed frequently to receive the expected cardiovascular benefits. However, in clinical practice, most patients experience ineffective apheresis and fail to reach lipid targets. This real-world failure is due to several factors including late diagnosis, delayed referral, and improper frequency of procedures. All these denote that awareness is still low among physicians. Another important factor is the semi-invasive, time consuming nature of the apheresis, leading to high refusal and low adherence rates. Moreover, apheresis decreases quality of life and increases the risk of depression. Mental status is also deteriorated in patients with familial hypercholesterolemia on lipid apheresis. New effective lipid lowering agents are underway with promising cardiovascular results. To overcome the drawbacks, a structured approach, including standardized protocols for lipoprotein apheresis with regular cardiovascular follow-up is warranted. New effective lipid lowering agents with documented cardiovascular benefit, should be integrated into the treatment algorithms of patients on lipoprotein apheresis.
Topics: Blood Component Removal; Humans; Hyperlipoproteinemia Type II; Hypolipidemic Agents; Lipoprotein(a); Lipoproteins; Quality of Life; Treatment Outcome
PubMed: 33594522
DOI: 10.1007/s11883-021-00911-w