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Blood Sep 2004Deficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with... (Review)
Review
Deficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500 000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. We investigated more than 1000 patients with recessively inherited coagulation disorders from Italy and Iran, a country with a high rate of recessive diseases due to the custom of consanguineous marriages. Based upon this experience, this article reviews the genetic basis, prevalent clinical manifestations, and management of these disorders. The steps and actions necessary to improve the condition of these often neglected patients are outlined.
Topics: Blood Coagulation Disorders, Inherited; Genes, Recessive; Humans
PubMed: 15138162
DOI: 10.1182/blood-2004-02-0595 -
Hamostaseologie Feb 2023Platelets play an important role regarding coagulation by contributing to thrombus formation by platelet adhesion, aggregation, and α-/δ-granule secretion. Inherited...
Platelets play an important role regarding coagulation by contributing to thrombus formation by platelet adhesion, aggregation, and α-/δ-granule secretion. Inherited platelet disorders (IPDs) are a very heterogeneous group of disorders that are phenotypically and biochemically diverse. Platelet dysfunction (thrombocytopathy) can be accompanied by a reduction in the number of thrombocytes (thrombocytopenia). The extent of the bleeding tendency can vary greatly. Symptoms comprise mucocutaneous bleeding (petechiae, gastrointestinal bleeding and/or menorrhagia, epistaxis) and increased hematoma tendency. Life-threatening bleeding can occur after trauma or surgery. In the last years, next-generation sequencing had a great impact on unrevealing the underlying genetic cause of individual IPDs. Because IPDs are so diverse, a comprehensive analysis of platelet function and genetic testing is indispensable.
Topics: Female; Humans; Blood Platelet Disorders; Blood Coagulation Disorders; Blood Platelets; Hemorrhagic Disorders; Thrombocytopenia
PubMed: 36807820
DOI: 10.1055/a-1987-3310 -
Clinical and Applied... 2023Sepsis-induced coagulopathy (SIC) is a life-threatening complication characterized by the systemic activation of coagulation in sepsis. The diagnostic criteria of SIC... (Review)
Review
Sepsis-induced coagulopathy (SIC) is a life-threatening complication characterized by the systemic activation of coagulation in sepsis. The diagnostic criteria of SIC consist of three items, including Sequential Organ Failure Assessment (SOFA) score, platelet count, and prothrombin time (PT)-international normalized ratio (INR). SIC has a high prevalence and it can lead to a higher mortality rate and longer length of hospital and ICU stay. Thus, the early detection of SIC is extremely important. It is unfortunate that there is still no precise biomarker for early diagnosis and assessment of the prognosis of SIC. We reviewed the current literature and discovered that some potential biomarkers, such as soluble thrombomodulin (sTM), thrombin-antithrombin complex (TAT), tissue plasminogen activator-inhibitor complex (t-PAIC), α2-plasmin inhibitor-plasmin complex (PIC), C-type lectin-like receptor 2 (CLEC-2), neutrophil extracellular traps (NETs), prothrombin fragment 1.2 (F1.2), Angiopoietin-2 (Ang-2), plasminogen activator inhibitor-1 (PAI-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) may be useful for early diagnosis, evaluation, and prognosis of SIC. Early initiation of treatment without missing any therapeutic opportunities may improve SIC patients' prognosis. Further large-scale clinical studies are still needed to confirm the role of these biomarkers in the diagnosis and prognosis assessment of SIC.
Topics: Humans; Tissue Plasminogen Activator; Tissue Inhibitor of Metalloproteinase-1; Blood Coagulation Disorders; Prognosis; Biomarkers; Early Diagnosis; Sepsis; Disseminated Intravascular Coagulation
PubMed: 37605466
DOI: 10.1177/10760296231195089 -
International Journal of Molecular... Jun 2021Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors... (Review)
Review
Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors that, by regulating fibrin degradation, maintain the hemostatic balance. A dysregulation of fibrinolysis is associated with various pathological processes that result, depending on the type of abnormality, in prothrombotic or hemorrhagic states. This narrative review is focused on the congenital and acquired disorders of primary fibrinolysis in both adults and children characterized by a hyperfibrinolytic state with a bleeding phenotype.
Topics: Adult; Blood Coagulation Disorders; Child; Fibrinolysis; Gene Regulatory Networks; Hemorrhage; Humans
PubMed: 34209949
DOI: 10.3390/ijms22137027 -
Experimental Biology and Medicine... Jun 2021Despite the relative frequency of both bleeding and clotting disorders among patients treated in the neonatal intensive care unit, few clear guidelines exist for... (Review)
Review
Despite the relative frequency of both bleeding and clotting disorders among patients treated in the neonatal intensive care unit, few clear guidelines exist for treatment of neonatal coagulopathies. The study and treatment of neonatal coagulopathies are complicated by the distinct hemostatic balance and clotting components present during this developmental stage as well as the relative scarcity of studies specific to this age group. This mini-review examines the current understanding of neonatal hemostatic balance and treatment of neonatal coagulopathies, with particular emphasis on emerging treatment methods and areas in need of further investigative efforts.
Topics: Animals; Blood Coagulation Disorders; Hemorrhage; Hemostasis; Humans; Infant, Newborn; Infant, Newborn, Diseases
PubMed: 33858204
DOI: 10.1177/15353702211006046 -
Critical Care (London, England) Apr 2013According to the World Health Organization, traumatic injuries worldwide are responsible for over 5 million deaths annually. Post-traumatic bleeding caused by traumatic... (Review)
Review
According to the World Health Organization, traumatic injuries worldwide are responsible for over 5 million deaths annually. Post-traumatic bleeding caused by traumatic injury-associated coagulopathy is the leading cause of potentially preventable death among trauma patients. Despite these facts, awareness of this problem is insufficient and treatment options are often unclear. The STOP the Bleeding Campaign therefore aims to increase awareness of the phenomenon of post-traumatic coagulopathy and its appropriate management by publishing European guidelines for the management of the bleeding trauma patient, by promoting and monitoring the implementation of these guidelines and by preparing promotional and educational material, organising activities and developing health quality management tools. The campaign aims to reduce the number of patients who die within 24 hours after arrival in the hospital due to exsanguination by a minimum of 20% within the next 5 years.
Topics: Awareness; Blood Coagulation Disorders; Exsanguination; Health Promotion; Hemorrhage; Hemostasis; Hospital Mortality; Humans
PubMed: 23635083
DOI: 10.1186/cc12579 -
Journal of Thrombosis and Haemostasis :... Dec 2007Plasminogen (plg) deficiency has been classified as (i) hypoplasminogenemia or 'true' type I plg deficiency, and (ii) dysplasminogenemia, also called type II plg... (Review)
Review
Plasminogen (plg) deficiency has been classified as (i) hypoplasminogenemia or 'true' type I plg deficiency, and (ii) dysplasminogenemia, also called type II plg deficiency. Both forms, severe hypoplasminogenemia and dysplasminogenemia, are not causally linked to venous thrombosis. Dysplasminogenemia does not lead to a specific clinical manifestation and probably represents only a polymorphic variation in the general population, mainly in Asian countries. Severe hypoplasminogenemia is associated with compromised extracellular fibrin clearance during wound healing, leading to pseudomembraneous (ligneous) lesions on affected mucous membranes (eye, middle ear, mouth, pharynx, duodenum, upper and lower respiratory tract and female genital tract). Ligneous conjunctivitis is by far the most common clinical manifestation. More than 12% of patients with severe hypoplasminogenemia exhibit congenital occlusive hydrocephalus. In milder cases of ligneous conjunctivitis, topical application of plg-containing eye drops, fresh frozen plasma, heparin, corticosteroids or certain immunosuppressive agents (such as azathioprine) may be more or less effective. Oral treatment with sex hormones was successful in two female patients with ligneous conjunctivitis. In severe cases with possibly life-threatening multi-organ involvement, true therapeutic options are not available at present. The plg-knockout mouse is a useful tool to study the many different properties of plg in a variety of settings, such as wound healing, tissue repair and tissue remodeling, virulence and invasiveness of certain bacteria in the human host, tumor growth and dissemination, as well as arteriosclerosis.
Topics: Amino Acid Sequence; Animals; Blood Coagulation Disorders; Conjunctivitis; Disease Models, Animal; Fibrinolysin; Fibrinolysis; Genetic Predisposition to Disease; Heterozygote; Homozygote; Humans; Mice; Mice, Knockout; Molecular Sequence Data; Mutation; Phenotype; Plasminogen; Protein Conformation; Risk Assessment; Risk Factors; Venous Thrombosis
PubMed: 17900274
DOI: 10.1111/j.1538-7836.2007.02776.x -
Postgraduate Medical Journal May 1969Three cases of defibrination syndrome and bleeding tendency are described. In each case the aetiology was completely different but thrombocytopenia and fibrinogenopenia...
Three cases of defibrination syndrome and bleeding tendency are described. In each case the aetiology was completely different but thrombocytopenia and fibrinogenopenia were present together. This combination is invariably due to diffuse intravascular clotting and it is suggested that these simple investigations should be asked for in cases of unexplained shock, acute renal failure of obscure origin, severe intravascular haemolysis, septic abortions, etc. Heparin would appear to be of value in these cases of defibrination. However, if there is no thrombocytopenia, defibrination may be due to excessive fibrinolysis. This should be treated with anti-fibrinolytics only when an underlying clotting defect has been excluded.
Topics: Adolescent; Adult; Afibrinogenemia; Blood Coagulation Disorders; Female; Heparin; Humans; Male; Middle Aged; Thrombocytopenia
PubMed: 5790930
DOI: 10.1136/pgmj.45.523.319 -
Current Opinion in Anaesthesiology Apr 2015To provide an overview of acquired coagulopathies that can occur in various perioperative clinical settings. Also described are coagulation disturbances linked to... (Review)
Review
PURPOSE OF REVIEW
To provide an overview of acquired coagulopathies that can occur in various perioperative clinical settings. Also described are coagulation disturbances linked to antithrombotic medications and currently available strategies to reverse their antithrombotic effects in situations of severe hemorrhage.
RECENT FINDINGS
Recent studies highlight the link between low fibrinogen and decreased fibrin polymerization in the development of acquired coagulopathy. Particularly, fibrin(ogen) deficits are observable after cardiopulmonary bypass in cardiac surgery, on arrival at the emergency room in trauma patients, and with ongoing bleeding after child birth. Regarding antithrombotic therapy, although new oral anticoagulants offer the possibility of efficacy and relative safety compared with vitamin K antagonists, reversal of their anticoagulant effect with nonspecific agents, including prothrombin complex concentrate, has provided conflicting results. Specific antidotes, currently being developed, are not yet licensed for clinical use, but initial results are promising.
SUMMARY
Targeted hemostatic therapy aims to correct coagulopathies in specific clinical settings, and reduce the need for allogeneic transfusions, thus preventing massive transfusion and its deleterious outcomes. Although there are specific guidelines for reversing anticoagulation in patients treated with antiplatelet agents or warfarin, there is currently little evidence to advocate comprehensive recommendations to treat drug-induced coagulopathy associated with new oral anticoagulants.
Topics: Antifibrinolytic Agents; Blood Coagulation Disorders; Humans; Intraoperative Complications; Perioperative Care; Postoperative Complications
PubMed: 25734869
DOI: 10.1097/ACO.0000000000000176 -
Anaesthesia Jan 2016Peri-operative anaemia, blood loss and allogeneic blood transfusion are associated with increased postoperative morbidity and mortality, and prolonged hospital stay. A... (Review)
Review
Peri-operative anaemia, blood loss and allogeneic blood transfusion are associated with increased postoperative morbidity and mortality, and prolonged hospital stay. A multidisciplinary, multimodal, individualised strategy, collectively termed 'patient blood management', may reduce or eliminate allogeneic blood transfusion and improve outcomes. This approach has three objectives: the detection and treatment of peri-operative anaemia; the reduction of peri-operative bleeding and coagulopathy; and harnessing and optimising the physiological tolerance of anaemia. This review focuses on the pre-operative evaluation of erythropoiesis, coagulation status and platelet function. Where possible, evidence is graded systematically and recommended therapies follow recently published consensus guidance.
Topics: Anemia; Blood Coagulation Disorders; Blood Loss, Surgical; Humans; Postoperative Complications; Preoperative Care
PubMed: 26620143
DOI: 10.1111/anae.13304