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Gaceta Medica de Mexico 2021Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor...
Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a correlation with the various degrees of severity. Hemorrhagic manifestations are related to levels of circulating factor, mainly affecting the musculoskeletal system and specifically the large joints (knees, ankles, and elbows). This document is a review and consensus of the main genetic aspects of hemophilia, from the inheritance pattern to the concept of women carriers, physiopathology and classification of the disorder, the basic and confirmation studies when hemophilia is suspected, the various treatment regimens based on infusion of the deficient coagulation factor as well as innovative factor-free therapies and recommendations for the management of complications associated with treatment (development of inhibitors and/or transfusion-transmitted infections), or secondary to articular hemorrhagic events (hemophilic arthropathy). Finally, relevant reviews of clinical and treatment aspects of hemorrhagic pathology characterized by acquired deficiency of FVIII secondary to neutralized antibodies named acquired hemophilia.
Topics: Algorithms; Hemophilia A; Mexico
PubMed: 33819260
DOI: 10.24875/GMM.M21000463 -
Blood Apr 2019Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights,... (Review)
Review
Since the comprehensive recommendations for the management of acute promyelocytic leukemia (APL) reported in 2009, several studies have provided important insights, particularly regarding the role of arsenic trioxide (ATO) in frontline therapy. Ten years later, a European LeukemiaNet expert panel has reviewed the recent advances in the management of APL in both frontline and relapse settings in order to develop updated evidence- and expert opinion-based recommendations on the management of this disease. Together with providing current indications on genetic diagnosis, modern risk-adapted frontline therapy, and salvage treatment, the review contains specific recommendations for the identification and management of the most important complications such as the bleeding disorder APL differentiation syndrome, QT prolongation, and other all- retinoic acid- and ATO-related toxicities, as well as recommendations for molecular assessment of the response to treatment. Finally, the approach to special situations is also discussed, including management of APL in children, elderly patients, and pregnant women. The most important challenges remaining in APL include early death, which still occurs before and during induction therapy, and optimizing treatment in patients with high-risk disease.
Topics: Aged; Arsenic Trioxide; Disease Management; Female; Hemorrhagic Disorders; Humans; Leukemia, Promyelocytic, Acute; Practice Guidelines as Topic; Pregnancy; Recurrence; Tretinoin
PubMed: 30803991
DOI: 10.1182/blood-2019-01-894980 -
Journal of Thrombosis and Haemostasis :... Aug 2016Mild inherited bleeding disorders are relatively common in the general population. Despite recent advances in diagnostic approaches, mild inherited bleeding disorders... (Review)
Review
Mild inherited bleeding disorders are relatively common in the general population. Despite recent advances in diagnostic approaches, mild inherited bleeding disorders still pose a significant diagnostic challenge. Hemorrhagic diathesis can be caused by disorders in primary hemostasis (von Willebrand disease, inherited platelet function disorders), secondary hemostasis (hemophilia A and B, other (rare) coagulant factor deficiencies) and fibrinolysis, and in connective tissue or vascular formation. This review summarizes the currently available diagnostic methods for mild bleeding disorders and their pitfalls, from structured patient history to highly specialized laboratory diagnosis. A comprehensive framework for a diagnostic approach to mild inherited bleeding disorders is proposed.
Topics: Blood Coagulation; Blood Platelet Disorders; Blood Platelets; Coagulants; Fibrinolysis; Genetic Testing; Hematology; Hemophilia A; Hemophilia B; Hemorrhage; Hemorrhagic Disorders; Hemostasis; Humans; Mutation; von Willebrand Diseases
PubMed: 27208505
DOI: 10.1111/jth.13368 -
Haematologica Aug 2020The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike... (Review)
Review
The acquired von Willebrand syndrome (AvWS) is a rare bleeding disorder with laboratory findings similar to those of inherited von Willebrand disease. However, unlike the inherited disease, AvWS occurs in persons with no personal and family history of bleeding and is often associated with a variety of underlying diseases, most frequently lymphoproliferative, myeloproliferative and cardiovascular disorders. After the presentation of a typical case, in this narrative review we discuss the more recent data on the pathophysiology, clinical, laboratory and therapeutic aspects of this acquired bleeding syndrome. We chose to focus particularly on those aspects of greater interest for the hematologist.
Topics: Cardiovascular Diseases; Hemorrhage; Hemorrhagic Disorders; Humans; Syndrome; von Willebrand Diseases; von Willebrand Factor
PubMed: 32554559
DOI: 10.3324/haematol.2020.255117 -
Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective.Haematologica Sep 2018Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The... (Review)
Review
Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria. Genetic mutations that have been identified include , , and , among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high-output heart failure. Families with the same mutation exhibit considerable phenotypic variation. Optimal treatment is best delivered a multidisciplinary approach with appropriate diagnosis, screening and local and/or systemic management of lesions. Anti-angiogenic agents such as bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review discusses the biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.
Topics: Animals; Biomarkers; Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Disease Susceptibility; Genetic Association Studies; Humans; Mutation; Phenotype; Telangiectasia, Hereditary Hemorrhagic; Treatment Outcome
PubMed: 29794143
DOI: 10.3324/haematol.2018.193003 -
The American Journal of Clinical... Aug 2015Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dietary cholesterol has been suggested to increase the risk of cardiovascular disease (CVD), which has led to US recommendations to reduce cholesterol intake.
OBJECTIVE
The authors examine the effects of dietary cholesterol on CVD risk in healthy adults by using systematic review and meta-analysis.
DESIGN
MEDLINE, Cochrane Central, and Commonwealth Agricultural Bureau Abstracts databases were searched through December 2013 for prospective studies that quantified dietary cholesterol. Investigators independently screened citations and verified extracted data on study and participant characteristics, outcomes, and quality. Random-effect models meta-analysis was used when at least 3 studies reported the same CVD outcome.
RESULTS
Forty studies (17 cohorts in 19 publications with 361,923 subjects and 19 trials in 21 publications with 632 subjects) published between 1979 and 2013 were eligible for review. Dietary cholesterol was not statistically significantly associated with any coronary artery disease (4 cohorts; no summary RR), ischemic stroke (4 cohorts; summary RR: 1.13; 95% CI: 0.99, 1.28), or hemorrhagic stroke (3 cohorts; summary RR: 1.09; 95% CI: 0.79, 1.50). Dietary cholesterol statistically significantly increased both serum total cholesterol (17 trials; net change: 11.2 mg/dL; 95% CI: 6.4, 15.9) and low-density lipoprotein (LDL) cholesterol (14 trials; net change: 6.7 mg/dL; 95% CI: 1.7, 11.7 mg/dL). Increases in LDL cholesterol were no longer statistically significant when intervention doses exceeded 900 mg/d. Dietary cholesterol also statistically significantly increased serum high-density lipoprotein cholesterol (13 trials; net change: 3.2 mg/dL; 95% CI: 0.9, 9.7 mg/dL) and the LDL to high-density lipoprotein ratio (5 trials; net change: 0.2; 95% CI: 0.0, 0.3). Dietary cholesterol did not statistically significantly change serum triglycerides or very-low-density lipoprotein concentrations.
CONCLUSION
Reviewed studies were heterogeneous and lacked the methodologic rigor to draw any conclusions regarding the effects of dietary cholesterol on CVD risk. Carefully adjusted and well-conducted cohort studies would be useful to identify the relative effects of dietary cholesterol on CVD risk.
Topics: Brain Ischemia; Cardiovascular Diseases; Cholesterol; Cholesterol, Dietary; Cholesterol, HDL; Cholesterol, LDL; Coronary Artery Disease; Evidence-Based Medicine; Hemorrhagic Disorders; Humans; Non-Randomized Controlled Trials as Topic; Randomized Controlled Trials as Topic; Reproducibility of Results; Risk Factors; Stroke
PubMed: 26109578
DOI: 10.3945/ajcn.114.100305 -
Clinics in Chest Medicine Sep 2016Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly... (Review)
Review
Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder that is associated with oculocutaneous albinism, bleeding diatheses, granulomatous colitis, and highly penetrant pulmonary fibrosis in some subtypes, including HPS-1, HPS-2, and HPS-4. HPS pulmonary fibrosis shows many of the clinical, radiologic, and histologic features found in idiopathic pulmonary fibrosis, but occurs at a younger age. Despite knowledge of the underlying genetic defects, there are currently no definitive therapeutic or preventive approaches for HPS pulmonary fibrosis other than lung transplant.
Topics: Albinism; Albinism, Oculocutaneous; Arteriovenous Malformations; Blood Coagulation Disorders; Crohn Disease; Epistaxis; Gastrointestinal Diseases; Hemorrhagic Disorders; Hermanski-Pudlak Syndrome; Humans; Hypertension, Pulmonary; Intracranial Arteriovenous Malformations; Liver Diseases; Pulmonary Artery; Pulmonary Fibrosis; Pulmonary Veins; Telangiectasis
PubMed: 27514596
DOI: 10.1016/j.ccm.2016.04.012 -
Current Opinion in Hematology Sep 2012Although recorded evidence of phenotyping bleeding disorders extends back two millennia, standardization of phenotyping has only begun in the past half century. This was... (Review)
Review
PURPOSE OF REVIEW
Although recorded evidence of phenotyping bleeding disorders extends back two millennia, standardization of phenotyping has only begun in the past half century. This was spurred by the need for greater precision in diagnosing disorders in order to select proper laboratory tests and treatment, and the realization that the bleeding history provides prognostic information about the future risk of bleeding with surgery or invasive procedures.
RECENT FINDINGS
New bleeding assessment tools (BATs) have been developed, firstly, to evaluate the relative bleeding risks associated with new anticoagulants and antiplatelet agents, secondly, to assess the efficacy of new thrombopoiesis stimulating agents in preventing hemorrhage in patients with immune thrombocytopenia, and finally, to assess complex gene-gene and gene-environment interactions. New web-based systems allow many researchers to collaborate by sharing the same electronic phenotyping infrastructure. Major issues of validation remain, but at present the data indicate that the new BATs have relatively high negative predictive value for excluding a significant bleeding disorder, but disappointingly low positive predictive values.
SUMMARY
New instruments to phenotype bleeding have been developed to address a number of different important clinical and research goals. The improved standardization and opportunities for collaborative studies hold promise for maximizing diagnostic, prognostic, and scientific information.
Topics: Administration, Oral; Anticoagulants; Gene-Environment Interaction; Genotype; Hemorrhagic Disorders; Humans; Phenotype; Predictive Value of Tests
PubMed: 22759628
DOI: 10.1097/MOH.0b013e32835673ab -
Medicine Jan 1997Considerable progress has been made in characterizing the specific molecular defects responsible for the heterogeneous disorder known as von Willebrand disease (VWD). A... (Review)
Review
Considerable progress has been made in characterizing the specific molecular defects responsible for the heterogeneous disorder known as von Willebrand disease (VWD). A large number of molecular defects have been identified and precise characterization may now be possible in the majority of type 2A, type 2B, type 2N, and potentially also type 3 VWD cases. However, the most common variant, type 1 VWD, still remains a major challenge. Continued progress in this area will improve our understanding of the pathogenesis of VWD and lead to more rapid and precise diagnosis and classification for this common disorder. The problems of incomplete VWD penetrance and poor diagnostic sensitivity and accuracy for the currently available clinical laboratory tests provide strong incentives for the development of DNA-based diagnostics. In addition, prenatal diagnosis is now possible either at the level of single point mutations (for some subtypes) or by RFLP analysis (assuming linkage to the von Willebrand factor [VWF] gene) and will probably be applied with increasing frequency for VWD type 3 (17, 133, 175). Understanding the molecular basis of VWD also has important implications for VWF structure and function and is helping to define critical binding domains within the VWF molecule. Insights gained from these studies may eventually lead to improved therapeutic approaches not only for VWD, but also for a variety of other genetic and acquired hemorrhagic and thrombotic disorders.
Topics: DNA Probes; Hemorrhage; Humans; Molecular Biology; Point Mutation; Polymorphism, Restriction Fragment Length; Prenatal Diagnosis; Thrombosis; von Willebrand Diseases; von Willebrand Factor
PubMed: 9064484
DOI: 10.1097/00005792-199701000-00001 -
Clinical Imaging Jul 2021Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a... (Review)
Review
Cerebrovascular malformations occur in both sporadic and inherited patterns. This paper reviews imaging and clinical features of cerebrovascular malformations with a genetic basis. Genetic diseases such as familial cerebral cavernous malformations and hereditary hemorrhagic telangiectasia often have manifestations in bone, skin, eyes, and visceral organs, which should be recognized. Genetic and molecular mechanisms underlying the inherited disorders are becoming better understood, and treatments are likely to follow. An interaction between the intestinal microbiome and formation of cerebral cavernous malformations has emerged, with possible treatment implications. Two-hit mechanisms are involved in these disorders, and additional triggering mechanisms are part of the development of malformations. Hereditary hemorrhagic telangiectasia encompasses a variety of vascular malformations, with widely varying risks, and a more recently recognized association with cortical malformations. Somatic mutations are implicated in the genesis of some sporadic malformations, which means that discoveries related to inherited disorders may aid treatment of sporadic cases. This paper summarizes the current state of knowledge of these conditions, salient features regarding mechanisms of development, and treatment prospects.
Topics: Cerebral Arteries; Diagnostic Imaging; Hemangioma, Cavernous, Central Nervous System; Humans; Skin; Telangiectasia, Hereditary Hemorrhagic
PubMed: 33493737
DOI: 10.1016/j.clinimag.2021.01.020