Materiały źródłowe

• #1 Hypercoagulability – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538251/

  Hypercoagulability or thrombophilia is the increased tendency of blood to thrombose. […] Hypercoagulability describes the pathologic state of exaggerated coagulation or coagulation in the absence of bleeding. […] Different constituents of the blood interact to create a thrombus. […] Pathophysiology and treatment differ for arterial and venous thrombosis, but risk factors overlap. […] A hypercoagulable state and subsequent thromboembolism is a result of overactivity of pro-coagulant factors or a deficiency in anti-coagulants. […] The interplay of factors is complicated – coagulation activators and inhibitors and their production and degradation (quantitative) and functional properties (qualitative) all influence thrombosis. […] The triad of hypercoagulability, vascular stasis and vascular trauma as described by Virchow in 1856 still holds and remains the harbinger of vascular thrombosis.

• #2 Thrombophilia pathophysiology – wikidoc

  https://www.wikidoc.org/index.php/Thrombophilia_pathophysiology

  The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with endothelial injury or stasis (Virchow’s Triad) can predispose to clot formation. Multiple genetic mutations and predisposing conditions have been associated with the increased risk of thrombosis due to abnormalities in the coagulation cascade. The most common genes involved in the pathogenesis of acquired thrombophilias are Factor V Leiden and prothrombin gene mutations. […] Coagulation is an inherent property of the hematologic system and normal blood flow is maintained by the balance between the pro-coagulant and anti-thrombotic factors under healthy conditions. A hypercoagulable state and subsequent thromboembolism is a result of overactivity of pro-coagulant factors or a deficiency in anti-coagulants. Anticoagulants that regulate thrombin include antithrombin, protein C, and protein S. The primary mechanism for thrombus formation in common inherited thrombophilic states involves thrombin dysregulation. However, the interplay of these factors is complicated process consisting of coagulation activators and inhibitors and their production and degradation (quantitative) and functional properties (qualitative) influencing the thrombosis process. […] In thrombophilia, procoagulant and anticoagulant factors are dysregulated leading to thrombus formation.

• #3 Thrombophilia: the dermatological clinical spectrum

  https://oatext.com/Thrombophilia-the-dermatological-clinical-spectrum.php

  The term thrombophilia was introduced in 1965 by Egeberg and is currently used to describe conditions resulting from hereditary (or primary) and/or acquired hyper-coagulation of the blood that increase the predisposition to thromboembolic events. […] Various risk factors, whether genetic or acquired, make up the pathogenesis of thrombosis in both arteries and veins. […] Hereditary thrombophilia can be classified into three large groups according to the pathogenic mechanism: Reduction of anticoagulant capacity, Increase in coagulant capacity, and Other conditions. […] Inherited deficiencies in antithrombin (AT), protein C (PC), and its co-factor protein S (PS) were the first identified causes of thrombophilia. […] Over the last decade, two common genetic polymorphisms were recognized as causes of hypercoagulability: mutant factor V and factor V G1691A (factor V Leiden), which make factor V resistant to the anticoagulant action of protein C, and mutation of the prothrombin gene (prothrombin G20210A), which is associated with an increase in circulating levels of prothrombin.

• #4 Thrombophilia – Wikipedia

  https://en.wikipedia.org/wiki/Thrombophilia

  Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as deep vein thrombosis in the leg) that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor. […] Thrombophilia is caused by abnormalities in blood consistency, which is determined by the levels of coagulation factors and other circulating blood proteins that participate in the „coagulation cascade”. […] In thrombophilia, the balance between „procoagulant” and „anticoagulant” activity is disturbed. The severity of the imbalance determines the likelihood that someone develops thrombosis. Even small perturbances of proteins, such as the reduction of antithrombin to only 70-80% of the normal level, can increase the thrombosis risk; this is in contrast with hemophilia, which only arises if levels of coagulation factors are markedly decreased. […] Thrombosis is a multifactorial problem because there are often multiple reasons why a person might develop thrombosis.

• #5 Thrombophilia overview – wikidoc

  https://www.wikidoc.org/index.php/Thrombophilia_overview

  Thrombophilia is a complex condition which increases the risk of thrombosis or thromboembolic disease. The predisposition to clotting, or thrombotic risk, can be multi-factorial, and is due to an abnormality in coagulation described as hypercoagulability. Hypercoagulability is a component of Virchow’s Triad, which by itself or in synergy with stasis or trauma can predispose to clot formation. […] The pathogenesis of thrombophilia is multi-factorial. It is characterized by hypercoagulability, which by itself or in synergy with endothelial injury or stasis (Virchow’s Triad) can predispose to clot formation. Multiple genetic mutations and predisposing conditions have been associated with the increased risk of thrombosis due to abnormalities in the coagulation cascade. The most common genes involved in the pathogenesis of acquired thrombophilias are Factor V Leiden and prothrombin gene mutations.

• #6 A Comprehensive Review of Risk Factors and Thrombophilia Evaluation in Venous Thromboembolism

  https://www.mdpi.com/2077-0383/13/2/362

  Venous thromboembolism (VTE), which encompasses deep vein thrombosis (DVT) and pulmonary embolism (PE), is a significant cause of morbidity and mortality worldwide. There are many factors, both acquired and inherited, known to increase the risk of VTE. Most of these result in increased risk via several common mechanisms including circulatory stasis, endothelial damage, or increased hypercoagulability. […] A major theory describing the pathogenesis of VTE is Virchow’s triad which consists of the stasis of blood flow, vascular endothelial injury, and hypercoagulability. With this, most identified risk factors for the development of VTE have at least one element of Virchow’s triad. […] Understanding the risk factors associated with VTE is important for understanding a patient’s risk of VTE development and recurrence, and thus guides providers on the best management strategies moving forward. Importantly, risk factors do not carry an equal risk of VTE development.

• #7 Thrombophilia: What It Is, Causes, Diagnosis, and Treatment – Synlab

  https://www.synlab-sd.com/en/blog/womens-health-en/thrombophilia-in-pregnancy-what-it-is-and-the-risks-for-pregnancy/

  The coagulation system typically maintains a balance between pro-coagulant and anticoagulant factors. However, this balance can shift toward a prothrombotic state, resulting in thromboembolic disease. […] Understanding the mechanisms behind this shift characterized by excessive thrombin generation is clinically complex due to the interplay among various coagulation factors and their interactions with blood vessels, endothelial cells, platelets, and other circulating cells. […] Thrombophilia has a multifactorial and complex etiology, being both hereditary and acquired. The presence of a thrombophilic defect is just one of several factors influencing the risk of developing the condition. […] Hereditary thrombophilia commonly refers to conditions where genetic mutations or variants affect the quantity or function of proteins involved in coagulation. Hereditary thrombophilias include a group of genetic disorders, with the most notable being Factor V Leiden mutation, prothrombin (Factor II) gene mutation, and deficiencies in antithrombin III, protein C, or protein S. These conditions disrupt the natural balance of coagulation, favoring clot formation.

• #8 Factor V Leiden – Wikipedia

  https://en.wikipedia.org/wiki/Factor_V_Leiden

  Factor V Leiden is a variant (mutated form) of human factor V (one of several substances that helps blood clot), which causes an increase in blood clotting (hypercoagulability). Due to this mutation, protein C, an anticoagulant protein that normally inhibits the pro-clotting activity of factor V, is not able to bind normally to factor V, leading to a hypercoagulable state, i.e., an increased tendency for the patient to form abnormal and potentially harmful blood clots. […] The condition results in a factor V variant that cannot be as easily degraded by activated protein C. […] The mutation prevents efficient inactivation of factor V. When factor V remains active, it facilitates overproduction of thrombin leading to generation of excess fibrin and excess clotting. […] The excessive clotting that occurs in this disorder is almost always restricted to the veins, where the clotting may cause a deep vein thrombosis (DVT). If the venous clots break off, these clots can travel through the right side of the heart to the lung where they block a pulmonary blood vessel and cause a pulmonary embolism.

• #9 Hereditary and Acquired Hypercoagulability: Practice Essentials, COVID-19, Pathophysiology

  https://emedicine.medscape.com/article/211039-overview

  Patients with acquired hypercoagulable states or hereditary thrombophilia are more likely to develop clots, venous thrombosis, and arterial thrombosis, than healthy individuals. […] About 50% of patients presenting with a first idiopathic venous thrombosis have an underlying thrombophilia. […] Hereditary thrombophilias should be suspected in individuals with a history of recurrent thromboembolism, thrombosis at a young age ( 40 years), and/or a family history of thrombosis. […] Hypercoagulability can result from the release of procoagulants from tumor cells or the presence of antiphospholipid antibodies (lupus anticoagulants). […] Insufficient inactivation of procoagulants due to impaired regulatory antithrombotic pathways can result in hypercoagulability. […] The presence of factor V Leiden or a mutant prothrombin can cause hypercoagulability.

• #10

  https://www.alliedacademies.org/articles/evaluation-of-clinical-outcome-of-cancer-related-thrombophilia-a-review.html

  The delicate balance between the coagulation and fibrinolytic systems can easily shift to induce a prothrombotic state, perhaps via an excess of procoagulant proteins such as tissue factor, fibrinogen, and plasminogen activator inhibitor, or deficiencies in other molecules, such as antithrombin III, proteins C and S, and tissue plasminogen activator. […] The presence of inhibitors of fibrinolysis was observed in cancer patients long before the plasminogen activator inhibitor type I (PAI- 1) was identified. […] Tumor cells can express all proteins of the fibrinolytic system, including the urokinase-type (u-PA) and tissue type (t- PA) plasminogen activators, and their inhibitors PAI-1 and PAI-2. […] Tumor cells synthesize and release inflammatory cytokines, including TNF- and IL-1 which can induce the expression of TF procoagulant activity by endothelial cells and monocytes. […] The expression of TF by tumor cells upregulates the transcription of VEGF in the same cells. […] The pathogenesis of thrombosis in cancer is different and reflects the activation of the various components of the hemostatic system, triggered by tumor cell-associated prothrombotic properties.

• #11

  https://haematologica.org/article/view/1277

  Venous thrombosis is a common disease annually affecting 1 in 1000 individuals. The multifactorial nature of the disease is illustrated by the frequent identification of one or more predisposing genetic and/or environmental risk factors in thrombosis patients. Most of the genetic defects known today affect the function of the natural anticoagulant pathways and in particular the protein C system. This presentation focuses on the importance of the genetic factors in the pathogenesis of inherited thrombophilia with particular emphasis on those defects which affect the protein C system. The risk of venous thrombosis is increased when the hemostatic balance between pro- and anti-coagulant forces is shifted in favor of coagulation. When this is caused by an inherited defect, the resulting hypercoagulable state is a lifelong risk factor for thrombosis. Resistance to activated protein C (APC resistance) is the most common inherited hypercoagulable state found to be associated with venous thrombosis. It is caused by a single point mutation in the factor V (FV) gene, which predicts the substitution of Arg506 with a Gln. Arg506 is one of three APC-cleavage sites and the mutation results in the loss of this APC-cleavage site. The mutation is only found in Caucasians but the prevalence of the mutant FV allele (FV:Q506) varies between countries. It is found to be highly prevalent (up to 15%) in Scandinavian populations, in areas with high incidence of thrombosis. FV:Q506 is associated with a 5-10-fold increased risk of thrombosis and is found in 20-60% of Caucasian patients with thrombosis. The second most common inherited risk factor for thrombosis is a point mutation (G20210A) in the 3′ untranslated region of the prothrombin gene. This mutation is present in approximately 2% of healthy individuals and in 6-7% of thrombosis patients, suggesting it to be a mild risk factor of thrombosis. Other less common genetic risk factors for thrombosis are the deficiencies of natural anticoagulant proteins such as antithrombin, protein C or protein S. Such defects are present in less than 1% of healthy individuals and together they account for 5-10% of genetic defects found in patients with venous thrombosis. Owing to the high prevalence of inherited APC resistance (FV:Q506) and of the G20210A mutation in the prothrombin gene, combinations of genetic defects are relatively common in the general population. As each genetic defect is an independent risk factor for thrombosis, individuals with multiple defects have a highly increased risk of thrombosis. As a consequence, multiple defects are often found in patients with thrombosis.

• #12 Thrombophilia (Hypercoagulable States) – Bleeding Disorders – Hematology – Diseases – McMaster Textbook of Internal Medicine

  https://empendium.com/mcmtextbook/chapter/B31.II.15.22.

  Thrombophilia is a genetic or acquired tendency to the development of venous (VTE) or arterial thromboembolism. […] In many cases, a thromboembolic event in a patient with thrombophilia develops in the presence of a concomitant acquired risk factor. […] The presence of a thrombophilia may influence the duration of treatment. […] Thrombophilia in a patient with no episodes of thrombosis requires no prophylactic treatment outside periods of a particularly high risk.

• #13 Hereditary thrombophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1592479/

  Thrombophilia can be defined as a predisposition to form clots inappropriately. […] The predisposition to form clots can arise from genetic factors, acquired changes in the clotting mechanism, or, more commonly, an interaction between genetic and acquired factors. […] A hereditary thrombophilia results when an inherited factor, such as antithrombin or protein C deficiency, requires interaction with components that are inherited or acquired before onset of a clinical disorder. […] The imbalance between reduced inhibitors of coagulation and/or increased activation of coagulation factors lead to thrombosis. […] Deficiencies of these proteins result in an increased generation of thrombin and a predisposition to thrombosis. […] The understanding of factor V inactivation was almost immediately followed by reports on how activated protein C in patients’ plasma failed to prolong the activated partial thromboplastin time, hence the term „activated protein C resistance” was developed.

• #14 Hereditary thrombophilia | Thrombosis Journal | Full Text

  https://thrombosisjournal.biomedcentral.com/articles/10.1186/1477-9560-4-15

  Thrombophilia can be defined as a predisposition to form clots inappropriately. […] The predisposition to form clots can arise from genetic factors, acquired changes in the clotting mechanism, or, more commonly, an interaction between genetic and acquired factors. […] A hereditary thrombophilia results when an inherited factor, such as antithrombin or protein C deficiency, requires interaction with components that are inherited or acquired before onset of a clinical disorder. […] The imbalance between reduced inhibitors of coagulation and/or increased activation of coagulation factors lead to thrombosis. […] Deficiencies of these proteins result in an increased generation of thrombin and a predisposition to thrombosis. […] The understanding of factor V inactivation was almost immediately followed by reports on how activated protein C in patients’ plasma failed to prolong the activated partial thromboplastin time, hence the term „activated protein C resistance” was developed.

• #15 Pathogenesis & Laboratory approach to Thrombophilia [Eastern J Med]

  https://eastjmed.org/jvi.aspx?pdir=ejm&plng=eng&un=EJM-38654&look4=

  Thrombophilia is a term used for any hypercoagulable state, either inherited or acquired. […] It frequently results from interplay of genetic and acquired factors. […] Inherited hypercoagulable states may be secondary to deficiency of natural clotting inhibitors or elevated procoagulants or increased fibrinolytic factors. […] Amongst these, activated protein C resistance, is the commonest underlying cause.

• #16 Hypercoagulability – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538251/

  Mutations influence coagulation depending on whether they are present in heterozygous or homozygous genotype. […] The most common genetic risk factor for thrombophilia is Factor V Leiden mutation. It increases the risk of thrombosis by enhanced thrombin production. […] The prothrombin G20210A mutation is the second most common inherited risk factor for thrombosis and leads to increased levels of prothrombin which demonstrates a higher risk for arterial and venous thrombotic events. […] Hyperhomocysteinemia is associated with premature atherosclerosis and thrombosis and caused by defects of the methionine metabolic pathway. […] The most common acquired thrombophilia is the antiphospholipid syndrome (APS) in which antibodies are directed against natural constituents of cell membranes, the phospholipids.

• #17 Factor V Leiden and activated protein C resistance – UpToDate

  https://www.uptodate.com/contents/factor-v-leiden-and-activated-protein-c-resistance

  Factor V Leiden (FVL) results from a point mutation in the F5 gene, which encodes the factor V protein in the coagulation cascade. FVL renders factor V (both the activated and inactive forms) insensitive to the actions of activated protein C (aPC), a natural anticoagulant. As a result, individuals who carry the FVL variant are at increased risk of venous thromboembolism (VTE). […] Mechanism of factor V Leiden.

• #18 Hereditary thrombophilia

  https://pmc.ncbi.nlm.nih.gov/articles/PMC1592479/

  The consequence of this is a hypercoagulable state as more factor Va is available within the prothrombinase complex, thereby increasing the generation of thrombin. […] The presence of an inherited thrombophilia should not alter the intensity of anticoagulant therapy, given that antithrombin, protein C, or protein S deficiency, factor V Leiden, and the prothrombin G20210A mutation are not unusually anticoagulant resistant. […] However, they can increase the optimal treatment duration after a first thromboembolic event.

• #19 Increased efficiency of mRNA 3′ end formation: a new genetic mechanism contributing to hereditary thrombophilia | Nature Genetics

  https://www.nature.com/articles/ng578

  The GA mutation at position 20210 of the prothrombin or coagulation factor II gene (F2) represents a common genetic risk factor for the occurrence of thromboembolic events. This mutation affects the 3-terminal nucleotide of the 3 untranslated region (UTR) of the mRNA and causes elevated prothrombin plasma concentrations by an unknown mechanism. […] Enhanced mRNA 3 end formation efficiency emerges as a novel principle causing a genetic disorder and explains the role of the F2 20210 GA mutation in the pathogenesis of thrombophilia. This work also illustrates the pathophysiologic importance of quantitatively minor aberrations of RNA metabolism.

• #20 Hereditary and Acquired Hypercoagulability: Practice Essentials, COVID-19, Pathophysiology

  https://emedicine.medscape.com/article/211039-overview

  The neutralization of activated factor Xa and thrombin are impaired in antithrombin (AT) deficiency. […] The formation of activated protein C (APC), which is a key down-regulator of factor V and factor VIII, may be impaired by protein C deficiency or protein S deficiency. […] Such deficiencies may be hereditary or acquired. […] The ability of APC to inactivate factor V and factor VIII can be impaired in individuals with mutant factor V, such as factor V Leiden. […] Individuals with a mutant prothrombin (variously termed prothrombin 20210A, prothrombin G2010A, and mutant factor II) generate excess prothrombin that is associated with hypercoagulability. […] Lupus anticoagulants are antiphospholipid antibodies that are associated with acquired hypercoagulability. […] The mechanisms for hypercoagulability in these patients remains poorly understood, but alteration of the regulation of hemostasis and endothelial cell injury might be responsible.

• #21 The

  https://derangedphysiology.com/main/required-reading/haematology-and-oncology/Chapter-311/thrombophilic-screen

  The „Thrombophilic Screen” is as series of tests launched when the question arises as to why a person is found to be clotting excessively. […] A good article exists to guide investigations of inherited thrombophilia. […] The consequences of AT-III deficiency are thrombosis and loss of heparin effect. Heparin needs antithrombin to act upon as its primary mode of action. No AT, and heparin becomes pointless. […] The management of AT-III deficiency is, predictably, supplementation with AT-III. If the expensive purified factor is not available, FFP will suffice.

• #22 Thrombophilia (Hypercoagulable States) – Warde Medical Laboratory

  https://wardelab.com/warde-reports/thrombophilia-hypercoagulable-states/

  In 1856, Rudolf Virchow, a German pathologist, proposed a hypothesis to explain the pathogenesis of thrombosis. He suggested there were three primary causes of venous and arterial thrombosis: stasis, injury to the vessel wall and abnormalities in the circulating blood. […] Thrombophilia may be defined as hereditary or acquired conditions which predispose individuals to thromboembolic events. […] Deficiencies of these proteins result in an increased generation of thrombin and a predisposition to thrombosis. […] Dahlback concluded there was an abnormality in the protein C/protein S regulatory system. […] The identification of FVL significantly changed the way clinicians and laboratories approach the diagnosis of thrombophilia. […] The risk of recurrent thromboembolism is significantly higher in carriers of FVL than in patients without this hereditary abnormality.

• #23 Thrombophilia and pregnancy | Reproductive Biology and Endocrinology | Full Text

  https://rbej.biomedcentral.com/articles/10.1186/1477-7827-1-111

  Homozygosity for the cytosine 677 thymine (C677T) mutation in methylenetetrahydrofolate reductase (MTHFR) results in decreased synthesis of 5-methyltetrahydrofolate, the primary methyl donor in the conversion of homocysteine to methionine and the resulting increase in plasma homocysteine concentrations is a risk factor for thrombosis. […] The known thrombotic nature of the placental vascular lesions and the increased thrombotic risk associated with the existence of thrombophilias strongly suggest a cause-and-effect relationship between inherited and acquired thrombophilias and the listed severe obstetric complications.

• #23 Thrombophilia and pregnancy | Reproductive Biology and Endocrinology | Full Text

  https://rbej.biomedcentral.com/articles/10.1186/1477-7827-1-111

  Pregnancy is hypercoagulable state. The field of thrombophilia; the tendency to thrombosis, has been developed rapidly and has been linked to many aspects of pregnancy. It is recently that severe pregnancy complications such as severe preeclampsia intrauterine growth retardation abruptio placentae and stillbirth has been shown to be associated with thrombophilia. […] Thrombophilias are inherited or acquired conditions which predispose an individual to thromboembolism. […] Resistance to activated protein C caused by an adenine 506 guanine (A506G) mutation in factor V (factor V Leiden) has been linked with an increased risk for venous thromboembolism. […] A recently described guanine 20210 adenine mutation in prothrombin is associated with higher plasma prothrombin concentrations and increased risk for venous thromboembolism and cerebral-vein thrombosis.

• #24 Thrombophilia: What It Is, Causes, Diagnosis, and Treatment – Synlab

  https://www.synlab-sd.com/en/blog/womens-health-en/thrombophilia-in-pregnancy-what-it-is-and-the-risks-for-pregnancy/

  Acquired thrombophilia refers to conditions that develop over a person’s lifetime without a genetic predisposition. It is characterized by immune system alterations that result in the production of antibodies attacking blood vessel walls, thereby increasing thrombosis risk. […] Thrombophilia during pregnancy and the postpartum period is exacerbated by the pro-coagulant characteristics of these conditions, affecting approximately 15% of the general population. Physiological adaptations in the body, blood circulation, and coagulation system during pregnancy increase the risk of thrombosis. This risk is influenced by various factors. […] Among the possible obstetric complications associated with thrombophilic defects, preeclampsia, often related to antithrombin or protein S deficiency, and fetal growth restriction, associated with the Factor V Leiden mutation and the prothrombin gene mutation, stand out. […] Effective monitoring and management are vital to reducing risks, requiring an interdisciplinary approach involving gynecologists, midwives, anesthesiologists, and hematologists throughout pregnancy, delivery, and postpartum. This collaboration ensures maternal-fetal safety.

• #25 Thrombophilia (Hypercoagulable States) – Warde Medical Laboratory

  https://wardelab.com/warde-reports/thrombophilia-hypercoagulable-states/

  A polymorphism in the prothrombin gene (20210 G A) was described in 1996. […] In addition to hereditary disorders predisposing to venous thrombosis, there are many acquired conditions which amplify hereditary thrombophilia or represent significant risk factors in the absence of genetic risk. […] Recently, another ELISA assay has been introduced to detect antibodies to 2 Glycoprotein I. […] Recent studies have emphasized patients who present with thrombosis secondary to APA are at very high risk for developing recurrent events if they are not adequately anticoagulated. […] However, with recent advances, one can make a strong argument to evaluate for other risk factors predisposing to thrombosis. […] The laboratory diagnosis of thrombophilia has changed dramatically within the last five years.

• #26 Hypercoagulability – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK538251/

  Malignancy is the second most common acquired hypercoagulability and leads to a prothrombotic state through the production of procoagulant factors (tissue factor and cancer procoagulant) and the interaction of tumor cells with blood and vascular endothelium. […] There is an interplay between inflammation and the coagulation system. Inflammation triggers a hypercoagulable state. […] Trauma is another acquired hypercoagulable state. […] Other conditions associated with a hypercoagulable state include myeloproliferative disorders, multiple myeloma, paroxysmal nocturnal hemoglobinuria, heart failure.

• #27

  https://www.alliedacademies.org/articles/evaluation-of-clinical-outcome-of-cancer-related-thrombophilia-a-review.html

  Acquired thrombophilic state associated with a significant risk of thrombosis is frequently encountered in malignancy. […] The pathogenesis of thrombosis in cancer is multifactorial; however, a relevant role is attributed to the tumor cell capacity to interact with and activate the host haemostatic system. […] Activation of blood coagulation and thrombotic diathesis is a complex phenomenon and that it involves different haemostatic pathways in patients with cancer and many factors which contribute includes non – specific factors, tumor-specific factors, and anticancer therapy-related factors. […] Tumor cells may activate coagulation reactions mainly by the modalities as listed in Table 1. […] In cancer, tumor cells can activate the coagulation system directly, through interactions with platelets, clotting, and fibrinolytic systems to generate thrombin.

• #28 Thrombophilia and Its Associated Health Risks During Pregnancy

  https://67streetobgyn.com/blog/thrombophilia-associated-risks-during-pregnancy/

  Thrombophilia and Pregnancy in Manhattan: […] When the body produces too much blood clots or clots when it is moving through the body when there is no injury, it is called hypercoagulation or thrombophilia. […] During pregnancy, the body goes through some physiological changes that synergistically create a tendency to clot or produce a hyper-coagulated state. […] It is hypothesized that this is the bodys natural way of preventing excessive blood loss during childbirth; the bodys own mechanism to protect the mother. […] This mechanism compounded with a preexisting condition can be fatal for both the mother and child. […] Certain types of thrombophilia can be detrimental to the health of a mother and her baby. […] The earlier diagnosis can be made, the better the odds for a healthy pregnancy.

• #29 Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study | The BMJ

  https://www.bmj.com/content/382/bmj-2022-074450

  Use of hormonal contraception and use of non-steroidal anti-inflammatory drugs (NSAIDs) have individually been associated with an increased risk of venous thromboembolism. […] Use of combined hormonal contraception, containing oestrogen and progestin, is an acknowledged risk factor for lower limb deep venous thrombosis and pulmonary embolism. […] Oestrogen is known to cause hypercoagulability by promoting transcription of genes for multiple coagulation factors. […] Use of systemic non-aspirin NSAIDs has also been positively associated with the development of thrombogenic disease, including venous thromboembolic events. […] Through their targeted inhibition of cyclo-oxygenase enzymes, NSAIDs promote platelet aggregation, which contributes to activation of the coagulation system and thereby potentially to the formation of a venous thrombosis.

• #30 Venous thromboembolism with use of hormonal contraception and non-steroidal anti-inflammatory drugs: nationwide cohort study | The BMJ

  https://www.bmj.com/content/382/bmj-2022-074450

  The observed superadditive joint effect between high/medium risk hormonal contraception and NSAIDs could represent a synergistic drug interaction between the drug classes. […] We found the influence of NSAID use on venous thromboembolic risk to be significantly greater in women using high risk hormonal contraception compared with no use of hormonal contraception and smaller in women using low/no risk hormonal contraception.

• #31 Thrombophilia: the dermatological clinical spectrum

  https://oatext.com/Thrombophilia-the-dermatological-clinical-spectrum.php

  The risk of a first thrombotic event increases in the presence of combined genetic defects. […] An increase in the levels of circulating fibrinogen, lipoprotein, F VIII, F IX, or FXI elevates the risk for VTE by 2 to 4 fold. […] The mechanisms for thrombosis in neoplasms have not yet been fully elucidated. […] The pathogenesis of VTE in nephrotic syndrome seems to stem from urinary loss of natural anticoagulants. […] The occurrence and exact etiopathogenic role of thrombophilias in the origin of ulcers of the lower limbs remains to be established.

• #32 Factor V Leiden thrombophilia | Genetics in Medicine

  https://www.nature.com/articles/gim920112

  Factor V Leiden is the most common inherited form of inherited thrombophilia, accounting for 40-50% of cases. […] The prevalence varies by population. […] The frequency of homozygosity for Factor V Leiden in white populations is approximately 1 in 5000. […] The high prevalence of Factor V Leiden among whites suggests a balanced polymorphism with some type of survival advantage associated with the heterozygous state. […] The presence of a Factor V Leiden allele increases the risk associated with other inherited and acquired thrombophilic disorders. […] The combination of Factor V Leiden heterozygosity and most thrombophilic disorders has a supraadditive effect on overall thrombotic risk.

• #33

  https://link.springer.com/article/10.1007/s12288-024-01936-2

  The aim of this study is to investigate the relationship of leukocytes DNA methylation in targeted sites and thrombophilia. […] Multivariate correlation analysis was used to estimate targeted gene methylation as an independent risk factor of thrombophilia. […] Target DNA methylation in Protein S.44.CpG.2933 island is associated with an elevated risk of thrombophilia. […] Emerging evidence suggests that aberrant DNA methylation patterns may contribute to dysregulated expression of genes involved in hemostasis and thrombosis pathways. […] Our research suggested that two target DNA methylation sites (F5.24.CpG.10 and Protein S.44.CpG.2933) were associated with thrombophilia. […] The hypo-methylation in F5.24.CpG.10 could up-regulate FV expression, in consequence it would increase the risk of thrombogenesis.

• #34

  https://link.springer.com/article/10.1007/s12288-024-01936-2

  The hyper-methylation in Protein S gene decreases expression of Protein S, which could not help to activate APC and restrain Factor IX activation. […] Understanding the epigenetic landscape of thrombophilia offers insights into the dynamic interplay between genetic predisposition and environmental factors in thrombotic risk. […] The mechanistic link between DNA methylation and thrombophilia lies in its ability to modulate the expression of genes involved in coagulation, fibrinolysis, and platelet function. […] Aberrant DNA methylation patterns within endothelial cells, leukocytes, and platelets have been implicated in endothelial dysfunction, inflammatory signaling, and vascular remodeling processes associated with thrombophilia. […] The identification of DNA methylation biomarkers holds promise for precision medicine in disease management.

• #35 The prevalence and clinical manifestation of hereditary thrombophilia in Korean patients with unprovoked venous thromboembolisms | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0185785

  Hereditary thrombophilia (HT) is a genetic predisposition to thrombosis. […] The mutation spectrum of HT and the subsequent clinical manifestations vary among ethnic groups. […] A deficiency of natural anticoagulants (NAs), including antithrombin (AT), protein C (PC), protein S (PS), and plasminogen, is more likely to occur in Asian populations. […] About 15% of patients with unprovoked VTE had genetically proven HT, and AT-III deficiency and PC deficiency were most frequent subtypes. […] A family history of VTE and young age (age 45 years) were independent predictors for development of unprovoked VTE due to HT.

• #36 Hereditary thrombophilia testing in adults without VTE – UpToDate

  https://www.uptodate.com/contents/screening-for-inherited-thrombophilia-in-asymptomatic-adults

  Hereditary thrombophilia is a risk factor for venous thromboembolism (VTE); however, the absolute increase in risk is low, and management may not differ for many individuals. […] This topic reviews an approach for deciding whether to test for hereditary thrombophilia and which thrombophilia to test for in adults who have not had VTE.

• #37 Factor V Leiden thrombophilia | Genetics in Medicine

  https://www.nature.com/articles/gim920112

  Factor V Leiden is a genetic disorder characterized by a poor anticoagulant response to activated Protein C and an increased risk for venous thromboembolism. […] The current evidence suggests that the mutation has at most a modest effect on recurrence risk after initial treatment of a first venous thromboembolism. […] Factor V Leiden is also associated with a 2- to 3-fold increased relative risk for pregnancy loss and possibly other obstetric complications, although the probability of a successful pregnancy outcome is high. […] The clinical expression of Factor V Leiden is influenced by the number of Factor V Leiden alleles, coexisting genetic and acquired thrombophilic disorders, and circumstantial risk factors. […] Diagnosis requires the activated Protein C resistance assay (a coagulation screening test) or DNA analysis of the F5 gene, which encodes the Factor V protein.

• #38 Hereditary thrombophilia | Thrombosis Journal | Full Text

  https://thrombosisjournal.biomedcentral.com/articles/10.1186/1477-9560-4-15

  The rapidity with which the genetic mutation was identified following the phenotypic observation of APC-R is an example of the dramatic shift to gene-based diagnosis of disease. […] The presence of an inherited thrombophilia should not alter the intensity of anticoagulant therapy, given that antithrombin, protein C, or protein S deficiency, factor V Leiden, and the prothrombin G20210A mutation are not unusually anticoagulant resistant. […] However, they can increase the optimal treatment duration after a first thromboembolic event.

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