Thrombophilia - Knowledge

827:), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis. In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventive treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent 115: 58: 962: 744: 653: 1052: 856:, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as 34: 1022:

third of those with protein S deficiency. People with activated protein C resistance (usually resulting from factor V Leiden), in contrast, have a slightly raised absolute risk of thrombosis, with 15% having had at least one thrombotic event by the age of sixty. In general, men are more likely than women to experience repeated episodes of venous thrombosis.

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The major ("type 1") thrombophilias are rare. Antithrombin deficiency is present in 0.2% of the general population and 0.5–7.5% of people with venous thrombosis. Protein C deficiency, too, is present in 0.2% of the population, and can be found in 2.5–6% of people with thrombosis. The exact prevalence

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There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most

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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

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may include any combination of abnormalities in the blood vessel wall, abnormalities in the blood flow (as in immobilization), and abnormalities in the consistency of the blood. Thrombophilia is caused by abnormalities in blood consistency, which is determined by the levels of coagulation factors and

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The minor ("type 2") thrombophilias are much more common. Factor V Leiden is present in 5% of the population of Northern European descent, but much rarer in those of Asian or African extraction. In people with thrombosis, 10% have factor V Leiden. In those who are referred for thrombophilia testing,

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Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events,

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In people without a detectable thrombophilia, the cumulative risk of developing thrombosis by the age of 60 is about 12%. About 60% of people who are deficient in antithrombin will have experienced thrombosis at least once by age 60, as will about 50% of people with protein C deficiency and about a

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There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous

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determines thrombosis risk to a significant extent. Those with blood groups other than type O are at a 2- to 4-fold relative risk. O blood group is associated with reduced levels of von Willebrand factor — because of increased clearance — and factor VIII, which is related to thrombotic risk .

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The most common types of congenital thrombophilia are those that arise as a result of overactivity of coagulation factors; hence they are considered "gain-of-function" alterations. They are relatively mild in the usual heterozygous state, and are therefore classified as "type II" defects. The most

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is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as

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results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical need. A 2016 study estimated that more than $ 1 million was wasted on inappropriate thrombophilia testing in a year at one academic medical center.

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Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has had thrombosis, the risk of developing thrombosis is increased. Screening this selected

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In the United Kingdom, professional guidelines give specific indications for thrombophilia testing. It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In

712:, TAFI) that enhance the fibrin clot. The process is inhibited by TFPI (which inactivates the first step catalyzed by factor VIIa/tissue factor), antithrombin (which inactivates thrombin, factor IXa, Xa and XIa), protein C (which inhibits factors Va and VIIIa in the presence of protein S), and 2997:

Stevens SM, Woller SC, Kreuziger LB, Bounameaux H, Doerschug K, Geersing GJ, Huisman MV, Kearon C, King CS, Knighton AJ, Lake E, Murin S, Vintch JR, Wells PS, Moores LK (December 2021). "Antithrombotic Therapy for VTE Disease: Second Update of the CHEST Guideline and Expert Panel Report".

457:(spread to other places in the body), is a recognised risk factor for thrombosis. A number of mechanisms have been proposed, such as activation of the coagulation system by cancer cells or secretion of procoagulant substances. Furthermore, particular cancer treatments (such as the use of 1012:

When women experience recurrent pregnancy loss secondary to thrombophilia, some studies have suggested that low molecular weight heparin reduces the risk of miscarriage. When the results of all studies are analysed together, no statistically significant benefit could be demonstrated.

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When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patient's indicated treatment. In 2013, the

974:, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result. 1039:

30–50% have the defect. The prothrombin mutation occurs at rates of 1–4% in the general population, 5–10% of people with thrombosis, and 15% of people referred for thrombophilia testing. Like factor V Leiden, this abnormality is uncommon in Africans and Asians.

1107:, as genetic abnormalities are typically named after the place where they are discovered. Two years later, the same group described a common mutation in the prothrombin gene that caused elevation of prothrombin levels and a mild increase in thrombosis risk. 1025:

People with factor V Leiden are at a relatively low risk of thrombosis, but may develop thrombosis in the presence of an additional risk factor, such as immobilization. Most people with the prothrombin mutation (G20210A) never develop thrombosis.

531:), have been associated with a 2- to 6-fold increased risk of venous thrombosis. The risk depends on the types of hormones used, the dose of estrogen, and the presence of other thrombophilic risk factors. Various mechanisms, such as deficiency of 1087:

Antiphospholipid syndrome was described in full in the 1980s, after various previous reports of specific antibodies in people with systemic lupus erythematosus and thrombosis. The syndrome is often attributed to the British rheumatologist

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The exact prevalence of antiphospholipid syndrome is not well known, as different studies employ different definitions of the condition. Antiphospholipid antibodies are detected in 24% of those referred to thrombophilia testing.

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Middeldorp S, Nieuwlaat R, Baumann Kreuziger L, Coppens M, Houghton D, James AH, Lang E, Moll S, Myers T, Bhatt M, Chai-Adisaksopha C, Colunga-Lozano LE, Karam SG, Zhang Y, Wiercioch W, Schünemann HJ, Iorio A (November 2023).

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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.

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Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child.

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The rare forms of congenital thrombophilia are typically caused by a deficiency of natural anticoagulants. They are classified as "type I" and are more severe in their propensity to cause thrombosis. The main ones are

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issued new guidelines for thrombophilia testing. One departure from their previous guidelines relates to patients with nonsurgical major transient risk factors; testing may be appropriate. Thrombophilia testing after

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categorized abnormalities in the consistency of the blood as a factor in the development of thrombosis in 1856. The exact nature of these abnormalities remained elusive until the first form of thrombophilia,

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group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.

471:, in which protein from the bloodstream is released into the urine due to kidney diseases, can predispose to thrombosis; this is particularly the case in more severe cases (as indicated by blood levels of 913:

Thrombophilia screening in people with arterial thrombosis is generally regarded as unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by

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has long been regarded as a risk factor for venous thrombosis. It more than doubles the risk in numerous studies, particularly in combination with the use of oral contraceptives or in the period after

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The more common genetic thrombophilias were described in the 1990s. Many studies had previously indicated that many people with thrombosis showed resistance activated protein C. In 1994 a group in

388:. In some cases, antiphospholipid syndrome can cause arterial as well as venous thrombosis. It is also more strongly associated with miscarriage, and can cause a number of other symptoms (such as 864:

in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.

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Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the

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Chong LY, Fenu E, Stansby G, Hodgkinson S, Guideline Development G (2012). "Management of venous thromboembolic diseases and the role of thrombophilia testing: Summary of NICE guidance".

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A mutation of coagulation factor V (schematic representation drawn here) is much more common in people with thrombosis than in those without, but is only regarded as a weak risk factor.

242:, a severe clotting disorder in the newborn that leads to both tissue death and bleeding into the skin and other organs. The condition has also been described in adults. Protein C and 2778:

Baglin T, Gray E, Greaves M, Hunt BJ, Keeling D, Machin S, MacKie I, Makris M, Nokes T, Perry D, Tait RC, Walker I, Watson H, British Committee for Standards in Haematology (2010).

891:(VTE) provoked by surgery, on the other hand, is not recommended, because the risk of recurrence is low. Some experts argue that unprovoked VTE requires indefinite (lifelong) 3173:"Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)" 3519:"A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis" 2434:

Gomes MP, Deitcher SR (October 2004). "Risk of venous thromboembolic disease associated with hormonal contraceptives and hormone replacement therapy: a clinical review".

1103:, The Netherlands, identified the most common underlying defect—a mutation in factor V that made it resistant to the action of activated protein C. The defect was called 965:

People considered to be at a high risk of repeated thrombosis due to thrombophilia are often advised to take warfarin for prolonged periods of time or even indefinitely.

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Exner T, Rigano J, Favaloro EJ (June 2020). "The effect of DOACs on laboratory tests and their removal by activated carbon to limit interference in functional assays".

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and therefore performing thrombophilia testing will not affect management. Nearly all recommendations in the guidelines were based on "very low certainty" evidence.

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Crowther MA, Kelton JG (2003). "Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system".

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A number of conditions that have been linked with venous thrombosis are possibly genetic and possibly acquired. These include: elevated levels of factor VIII,

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Rudolf Virchow, the German pathologist who distinguished the various causes of thrombosis, and whose work led to the development of thrombophilia as a concept

938:. Therefore, most thrombophilia testing should be done after the patient has completed the initial treatment course of anticoagulation. Efforts to remove 3127:"Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)" 831:, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results. 3466:

Bertina RM, Koeleman BP, Koster T, et al. (May 1994). "Mutation in blood coagulation factor V associated with resistance to activated protein C".

406:(or its derivatives). Though it is named for associated low platelet counts, HIT is strongly associated with risk of venous and arterial thrombosis. 205:) is less well established. However, more recent data suggest some forms of inherited thrombophilia are associated with increased risk for arterial 1068:, was recognized in 1965 by the Norwegian hematologist Olav Egeberg. Protein C deficiency followed in 1981, when described by researchers from the 819:

thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the

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There is no specific treatment for most thrombophilias, but recurrent episodes of thrombosis may be an indication for long-term preventive

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Brodsky RA (April 2008). "Narrative review: paroxysmal nocturnal hemoglobinuria: the physiology of complement-related hemolytic anemia".

341:, for instance, mainly causes eye symptoms and sometimes problems in other organs, but the link with thrombosis has been more uncertain. 608:

and thrombosis, although this has not been reported consistently in all studies. Homocysteine levels are determined by mutations in the

3172: 3126: 1073: 997:(amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion. 2864:"Analysis of Thrombophilia Test Ordering Practices at an Academic Center: A Proposal for Appropriate Testing to Reduce Harm and Cost" 3710: 2303:"Defining venous thromboembolism and measuring its incidence using Swedish health registries: a nationwide pregnancy cohort study" 118:

A right-sided acute deep vein thrombosis (to the left in the image). The leg is swollen and red due to venous outflow obstruction.

86:(blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as 807:

levels. Testing may be more or less extensive depending on clinical judgement and abnormalities detected on initial evaluation.

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Thrombosis is a multifactorial problem because there are often multiple reasons why a person might develop thrombosis. These

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that is not attributable to factor V mutations is probably caused by other factors and remains a risk factor for thrombosis.

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aggregation may be increased, and there are higher levels of coagulation proteins such as von Willebrand factor, fibrinogen,

553:, an inhibitor of fibrinolysis, is present in higher levels in people with obesity. Obese people also have larger numbers of 871:

offered one testing-related recommendation in its venous thromboembolism guidelines. They recommended to consider positive

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Comp PC, Esmon CT (December 1984). "Recurrent venous thromboembolism in patients with a partial deficiency of protein S".

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Papadakis E, Hoffman R, Brenner B (November 2010). "Thrombohemorrhagic complications of myeloproliferative disorders".

990:. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia. 788: 134:(VTE). DVT usually occurs in the legs, and is characterized by pain, swelling and redness of the limb. It may lead to 2712: 1555:

Chiasakul T, De Jesus E, Tong J, Chen Y, Crowther M, Garcia D, Chai-Adisaksopha C, Messé SR, Cuker A (October 2019).

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It is suspected that other genetic abnormalities underlying familial thrombosis will in future be discovered through

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Sanna G, D'Cruz D, Cuadrado MJ (August 2006). "Cerebral manifestations in the antiphospholipid (Hughes) syndrome".

399: 182: 170: 3216:"A meta-analysis of low-molecular-weight heparin to prevent pregnancy loss in women with inherited thrombophilia" 2708: 2350:

Bourjeily G, Paidas M, Khalil H, Rosene-Montella K, Rodger M (February 2010). "Pulmonary embolism in pregnancy".

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Quera R, Shanahan F (October 2004). "Thromboembolism--an important manifestation of inflammatory bowel disease".

594: 536: 520: 498: 302: 217: 3043:"American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing" 2915:"Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis" 2301:

Abdul Sultan A, West J, Stephansson O, Grainge MJ, Tata LJ, Fleming KM, Humes D, Ludvigsson JF (November 2015).

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is associated with an increased risk of thrombosis of 2- to 7-fold. This probably results from a physiological

377: 142:) to arteries in the lungs. Depending on the size and the location of the clot, this may lead to sudden-onset 4084: 4070: 1111: 476: 491:) predispose to thrombosis, particularly when the disease is active. Various mechanisms have been proposed. 4058: 4021: 3891: 1520:

de Moerloose P, Boehlen F (April 2007). "Inherited thrombophilia in arterial disease: a selective review".

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Hematologic conditions associated with sluggish blood flow can increase risk for thrombosis. For example,

4211: 3787: 1557:"Inherited Thrombophilia and the Risk of Arterial Ischemic Stroke: A Systematic Review and Meta-Analysis" 764: 616: 436: 373: 305:

of the gene). Compound heterozygotes and homozygotes, while rare, are at significant risk of thrombosis.

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Kyrle PA, Rosendaal FR, Eichinger S (December 2010). "Risk assessment for recurrent venous thrombosis".

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Borissoff JI, Spronk HM, ten Cate H (2011). "The hemostatic system as a modulator of atherosclerosis".

1069: 939: 861: 524: 480: 424:(anemia resulting from destruction of red blood cells). Both HIT and PNH require particular treatment. 326: 2666:"Screening for thrombophilia in high-risk situations: a meta-analysis and cost-effectiveness analysis" 1719:

Stevens SM, Woller SC, Bauer KA, Kasthuri R, Cushman M, Streiff M, Lim W, Douketis JD (January 2016).

4282: 3853: 3834: 979: 784: 357: 337:(the system that destroys clots) are major contributors to thrombosis risk. Congenital deficiency of 2100: 1035:

of protein S deficiency in the population is unknown; it is found 1.3–5% of people with thrombosis.

439:, in which the bone marrow produces too many blood cells, predispose to thrombosis, particularly in 57: 4252: 3995: 3824: 3625: 3538: 3518: 983: 727:

In addition to its effects on thrombosis, hypercoagulable states may accelerate the development of

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Skeith L, Carrier M, Kaaja R, Martinelli I, Petroff D, Schleußner E, Laskin CA, Rodger MA (2016).

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Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA (October 2010). "Antiphospholipid syndrome".

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into thrombin. Thrombin is a central enzyme in the coagulation process: it generates fibrin from

458: 99: 2543: 447:(excess platelets). Again, these conditions usually warrant specific treatment when identified. 4156: 4131: 4089: 2472:

Tchaikovski SN, Rosing J (July 2010). "Mechanisms of estrogen-induced venous thromboembolism".

2095: 1081: 888: 344: 174: 131: 1009:) is generally used as an alternative. Warfarin and LMWH may safely be used in breastfeeding. 4151: 4141: 3959: 898: 810:

For hereditary cases, the patient must have at least two abnormal tests plus family history.

732: 516: 502: 213: 198: 186: 2109: 1848: 1802: 3907: 3802: 3792: 3475: 1077: 824: 768: 752: 318: 314: 270:" may be used) that increase the tendency to develop thrombosis, while, on the other hand, 243: 235: 178: 123: 87: 8: 4146: 4136: 3932: 3812: 3665: 3603: 950: 903: 780: 657: 590: 428: 365: 294: 194: 159: 3479: 3067: 3042: 2823:"The ASH Choosing Wisely(R) campaign: five hematologic tests and treatments to question" 569:. Obesity also increases the risk of recurrence after an initial episode of thrombosis. 114: 4272: 3954: 3912: 3886: 3759: 3499: 3408: 3383: 3280: 2979: 2890: 2863: 2766: 2416: 2375: 2327: 2302: 2283: 2235: 2210: 2121: 2021: 1860: 1814: 1745: 1720: 1640: 1589: 1556: 1533: 1415: 1390: 1269: 828: 660:, consists of a group of proteins that interact in the formation of a fibrin-rich clot. 488: 484: 468: 389: 385: 356:

A number of acquired conditions augment the risk of thrombosis. A prominent example is

229: 155: 127: 3608: 3324: 3299: 2363: 2187: 1999: 1628: 1257: 4161: 3937: 3846: 3702: 3636: 3543: 3491: 3448: 3413: 3364: 3329: 3272: 3237: 3192: 3146: 3107: 3072: 3058: 3015: 2971: 2936: 2895: 2844: 2801: 2796: 2779: 2758: 2687: 2682: 2665: 2646: 2600: 2565: 2524: 2489: 2451: 2420: 2406: 2367: 2332: 2275: 2271: 2240: 2191: 2156: 2113: 2065: 2060: 2043: 2013: 1961: 1956: 1939: 1920: 1852: 1806: 1750: 1698: 1693: 1676: 1632: 1594: 1576: 1537: 1499: 1494: 1477: 1455: 1420: 1371: 1366: 1349: 1317: 1261: 1219: 1153: 440: 417: 247: 239: 79: 46: 3284: 2983: 2770: 2287: 2174:

Prandoni P, Falanga A, Piccioli A (June 2005). "Cancer and venous thromboembolism".

2125: 2025: 1864: 1818: 1721:"Guidance for the evaluation and treatment of hereditary and acquired thrombophilia" 1644: 1273: 1214: 1197: 3987: 3927: 3922: 3782: 3691: 3533: 3503: 3483: 3440: 3403: 3395: 3356: 3319: 3311: 3264: 3227: 3184: 3138: 3099: 3062: 3054: 3007: 2963: 2954:

Wu O, Greer IA (September 2007). "Is screening for thrombophilia cost-effective?".

2926: 2885: 2875: 2834: 2791: 2750: 2677: 2636: 2592: 2555: 2516: 2485: 2481: 2443: 2398: 2393:

Daughety MM, Samuelson Bannow BT (2019). "Hemostasis and Thrombosis in Pregnancy".

2379: 2359: 2322: 2314: 2267: 2230: 2222: 2183: 2148: 2105: 2055: 2003: 1995: 1951: 1910: 1844: 1798: 1740: 1732: 1688: 1624: 1584: 1568: 1529: 1489: 1447: 1410: 1402: 1361: 1307: 1253: 1209: 760: 421: 16:

Abnormality of blood coagulation increasing the risk of blood clotting (thrombosis)

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Egeberg O (June 1965). "Inherited antithrombin deficiency causing thrombophilia".

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Shen YM, Tsai J, Taiwo E, Gavva C, Yates SG, Patel V, Frenkel E, Sarode R (2016).

1915: 1898: 435:) is regarded as a mild prothrombotic state induced by impaired flow. Similarly, 4267: 4101: 3942: 3807: 3630: 3232: 3215: 2967: 2880: 2839: 2822: 2721: 2717: 2641: 2624: 2447: 2402: 1312: 1295: 946: 915: 892: 840: 796: 728: 284: 206: 103: 3676: 3360: 3011: 2318: 2226: 669:

other circulating blood proteins that participate in the "coagulation cascade".

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Kearon C, Kahn SR, Agnelli G, Goldhaber S, Raskob GE, Comerota AJ (June 2008).

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due to damage to valves in the veins. The clot may also break off and migrate (

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An ultrasound image demonstrating a blood clot in the left common femoral vein.

3593: 3589: 3444: 3399: 2520: 1736: 4333: 4302: 4124: 4119: 4114: 1580: 935: 772: 724:, which only arises if levels of coagulation factors are markedly decreased. 673: 225: 98:. The first major form of thrombophilia to be identified by medical science, 95: 4045: 2625:"Should patients with venous thromboembolism be screened for thrombophilia?" 2507:

Stein PD, Goldman J (September 2009). "Obesity and thromboembolic disease".

1572: 1296:"Advances in understanding pathogenic mechanisms of thrombophilic disorders" 4312: 3754: 3452: 3276: 3268: 3241: 3196: 3150: 3111: 3076: 3039: 3019: 2975: 2940: 2899: 2848: 2805: 2762: 2691: 2650: 2604: 2569: 2528: 2493: 2455: 2371: 2336: 2279: 2244: 2195: 2160: 2117: 2069: 2017: 1965: 1924: 1856: 1810: 1754: 1702: 1636: 1598: 1541: 1503: 1459: 1424: 1375: 1321: 1265: 1223: 820: 804: 605: 510: 462: 334: 310: 151: 3547: 3495: 3417: 3368: 3333: 3188: 3142: 2596: 1451: 970:

important decision is whether to use anticoagulation medications, such as

505:. This hypercoagulability in turn is likely related to the high levels of 420:. PNH increases the risk of venous thrombosis but is also associated with 4109: 3917: 3749: 3738: 3298:

Griffin JH, Evatt B, Zimmerman TS, Kleiss AJ, Wideman C (November 1981).

2560: 1478:"Does thrombophilia testing help in the clinical management of patients?" 1198:"Thrombophilia: common questions on laboratory assessment and management" 879:

may suggest that the ongoing thrombotic tendency has not fully resolved.

800: 709: 701: 693: 665: 647: 632: 566: 402:(HIT) is due to an immune system reaction against the anticoagulant drug 338: 322: 298: 102:, was identified in 1965, while the most common abnormalities (including 3572: 2008: 1406: 4297: 4262: 4237: 3881: 3863: 3671: 3103: 1006: 961: 792: 756: 721: 697: 677: 625: 621: 586: 562: 454: 432: 361: 330: 221: 147: 83: 51: 3315: 2754: 1825: 875:

in the decision to continue or discontinue anticoagulation. Positive

743: 549:. Various coagulation abnormalities have been described in the obese. 4287: 4232: 3819: 3660: 3487: 3384:"Thrombosis, abortion, cerebral disease, and the lupus anticoagulant" 2931: 2914: 1985: 713: 705: 685: 582: 578: 532: 506: 494: 410:(PNH) is a rare condition resulting from acquired alterations in the 2349: 266:

refers to inborn conditions (and usually hereditary, in which case "

4201: 4196: 4186: 3876: 3734: 2544:"Is thrombin a key player in the 'coagulation-atherogenesis' maze?" 971: 689: 681: 652: 558: 416:

gene, which plays a role in the protection of blood cells from the

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Simpson EL, Stevenson MD, Rawdin A, Papaioannou D (January 2009).

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below 25 g/L) and if the syndrome is caused by the condition

4247: 4206: 2912: 1899:"Venous thrombosis: the role of genes, environment, and behavior" 1051: 987: 876: 872: 546: 542: 472: 403: 143: 3619: 3517:

Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (November 1996).

2996: 1833:"Congenital Causes of Venous Thrombosis—A Classification System" 1438:

Agnelli G, Becattini C (July 2010). "Acute pulmonary embolism".

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Several thrombophilia assays can be impacted by the presence of

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campaign, cautioned against overuse of thrombophilia screening;

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Venous thrombosis may also occur in more unusual places: in the

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Bates SM, Greer IA, Pabinger I, Sofaer S, Hirsh J (June 2008).

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Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "Chapter 4".

2780:"Clinical guidelines for testing for heritable thrombophilia" 1677:"Clinical guidelines for testing for heritable thrombophilia" 122:

The most common conditions associated with thrombophilia are

3516: 3213: 2386: 1843:(2). American College of Physicians: I39. January 21, 2003. 1475: 3297: 412: 3300:"Deficiency of protein C in congenital thrombotic disease" 3124: 2740: 2664:

Wu O, Robertson L, Twaddle S, et al. (October 2005).

1718: 216:, and possibly various complications of pregnancy such as 1554: 942:

using activated carbon may prove helpful in this regard.

700:, and activates a number of other enzymes and cofactors ( 3170: 2542:

Borissoff JI, Spronk HM, Heeneman S, ten Cate H (2009).

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are unaffected by the physiologic state of the patient.

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from damaged tissue. Tissue factor binds to circulating

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against constituents of the cell membrane, particularly

33: 3430: 2582: 2173: 2138: 1675:

Baglin T, Gray E, Greaves M, et al. (April 2010).

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Rai R, Regan L (August 2006). "Recurrent miscarriage".

1243: 720:

increase the thrombosis risk; this is in contrast with

3732: 557:(fragments of damaged cells) that bear tissue factor. 3465: 2777: 2713:"Five Things Physicians and Patients Should Question" 2041: 3562: 2044:"The management of heparin-induced thrombocytopenia" 604:

There is an association between the blood levels of

246:

have also been associated with an increased risk of

3089: 2821:Hicks LK, Bering H, Carson KR, et al. (2013). 1981: 1979: 1977: 1975: 1519: 372:but often detected in people without the disease), 193:. Whether thrombophilia also increases the risk of 2861: 2663: 1476:Middeldorp S, van Hylckama Vlieg A (August 2008). 1343: 1341: 1339: 1337: 1335: 1333: 1331: 1080:followed in 1984, described by researchers at the 672:Normal coagulation is initiated by the release of 2820: 2471: 1674: 1391:"Diagnosis and treatment of deep-vein thrombosis" 926:, fails because of rapid occlusion of the graft. 333:). It is unclear whether congenital disorders of 4331: 1972: 1892: 1890: 1888: 1886: 1884: 1882: 1880: 1878: 1876: 1874: 1437: 1347: 1328: 922:) and those in whom revascularization, such as 465:) may increase the risk of thrombosis further. 274:refers to conditions that arise later in life. 3539:10.1182/blood.V88.10.3698.bloodjournal88103698 1788: 1388: 3718: 2433: 2257: 2208: 1871: 1515: 1513: 688:to factor IXa. Factor Xa (in the presence of 656:The coagulation system, often described as a 262:Thrombophilia can be congenital or acquired. 2506: 2467: 2465: 2294: 2042:Keeling D, Davidson S, Watson H (May 2006). 1937: 1896: 1784: 1471: 1469: 321:. Milder rare congenital thrombophilias are 130:(PE), which are referred to collectively as 3035: 3033: 3031: 3029: 1782: 1780: 1778: 1776: 1774: 1772: 1770: 1768: 1766: 1764: 1670: 1668: 1666: 1664: 1662: 1660: 1658: 1656: 1654: 1610: 1608: 735:and other forms of cardiovascular disease. 591:thrombin-activatable fibrinolysis inhibitor 250:on commencing anticoagulant treatment with 3725: 3711: 2703: 2701: 2085: 2081: 2079: 2037: 2035: 1903:Hematology Am. Soc. Hematol. Educ. Program 1714: 1712: 1510: 1293: 1289: 1287: 1285: 1283: 1202:Hematology Am. Soc. Hematol. Educ. Program 56: 32: 3537: 3407: 3381: 3346: 3323: 3254: 3231: 3066: 2930: 2889: 2879: 2838: 2795: 2681: 2640: 2559: 2462: 2326: 2234: 2099: 2059: 2007: 1955: 1914: 1744: 1692: 1588: 1561:Journal of the American Heart Association 1493: 1466: 1414: 1382: 1365: 1311: 1239: 1237: 1235: 1233: 1213: 3166: 3164: 3026: 2622: 2618: 2616: 2614: 2167: 1761: 1651: 1614: 1605: 1152:(8th ed.). Philadelphia: Saunders. 1143: 1141: 1139: 1137: 1135: 1133: 1131: 1050: 960: 742: 651: 368:(first found in people with the disease 113: 3979: 2953: 2698: 2110:10.7326/0003-4819-148-8-200804150-00003 2076: 2032: 1849:10.7326/0003-4819-138-2-200301210-00005 1803:10.7326/0003-4819-138-2-200301210-00014 1709: 1280: 1195: 1191: 1189: 4332: 3375: 3118: 1431: 1389:Scarvelis D, Wells PS (October 2006). 1348:Rosendaal FR, Reitsma PH (July 2009). 1230: 1187: 1185: 1183: 1181: 1179: 1177: 1175: 1173: 1171: 1169: 982:, the presence of cancer, symptoms of 731:, the arterial disease that underlies 3706: 3161: 2611: 1938:Mehta R, Shapiro AD (November 2008). 1128: 109: 929: 869:American College of Chest Physicians 839:, as part of recommendations in the 2132: 1166: 408:Paroxysmal nocturnal hemoglobinuria 13: 2209:Hull RP, Goldsmith DJ (May 2008). 1534:10.1053/j.seminhematol.2007.01.008 1112:studies of the entire genetic code 791:, activated protein C resistance, 197:(which is the underlying cause of 14: 4351: 3558: 551:Plasminogen activator inhibitor-1 384:; it is therefore regarded as an 212:Thrombophilia has been linked to 4079:platelet storage pool deficiency 4031:Heparin-induced thrombocytopenia 3059:10.1182/bloodadvances.2023010177 2797:10.1111/j.1365-2141.2009.08022.x 2683:10.1111/j.1365-2141.2005.05715.x 2272:10.1111/j.1572-0241.2004.40923.x 2061:10.1111/j.1365-2141.2006.06018.x 1957:10.1111/j.1365-2516.2008.01825.x 1694:10.1111/j.1365-2141.2009.08022.x 1495:10.1111/j.1365-2141.2008.07339.x 1367:10.1111/j.1538-7836.2009.03394.x 751:Tests for thrombophilia include 400:Heparin-induced thrombocytopenia 136:long-term swelling and heaviness 3510: 3459: 3424: 3340: 3291: 3248: 3207: 3083: 2990: 2947: 2906: 2855: 2814: 2657: 2576: 2535: 2500: 2427: 2343: 2251: 2202: 1931: 1548: 1350:"Genetics of venous thrombosis" 1215:10.1182/asheducation-2007.1.127 1029: 852:particular situations, such as 789:anti-β2 glycoprotein 1 antibody 595:tissue factor pathway inhibitor 537:tissue factor pathway inhibitor 521:combined hormonal birth control 499:hypercoagulability in pregnancy 218:intrauterine growth restriction 106:) were described in the 1990s. 3798:Activated protein C resistance 2784:British Journal of Haematology 2727:American Society of Hematology 2709:American Society of Hematology 2486:10.1016/j.thromres.2010.01.045 2211:"Nephrotic syndrome in adults" 1092:, and is often referred to as 918:or use of estrogen-containing 884:American Society of Hematology 837:American Society of Hematology 599:Activated protein C resistance 539:, are said to be responsible. 1: 2364:10.1016/S0140-6736(09)60996-X 2188:10.1016/S1470-2045(05)70207-2 2000:10.1016/S0140-6736(10)60709-X 1916:10.1182/asheducation-2005.1.1 1629:10.1016/S0140-6736(06)69204-0 1258:10.1016/S0140-6736(10)60962-2 1121: 978:male sex, the presence of an 620:genes, but also by levels of 513:that occur during pregnancy. 443:(excess red blood cells) and 277: 3892:Trousseau sign of malignancy 3388:Br. Med. J. (Clin. Res. Ed.) 3233:10.1182/blood-2015-12-626739 2968:10.1097/MOH.0b013e32825f5318 2881:10.1371/journal.pone.0155326 2840:10.1182/blood-2013-07-518423 2642:10.1016/j.amjmed.2007.10.042 2448:10.1001/archinte.164.18.1965 2403:10.1007/978-3-030-19330-0_30 1313:10.1182/blood-2008-01-077909 1016: 1003:Low molecular weight heparin 956: 813: 738: 716:(which inhibits factor Xa). 680:. The combination activates 641: 437:myeloproliferative disorders 370:systemic lupus erythematosus 7: 4212:Nonthrombocytopenic purpura 3788:Antithrombin III deficiency 3361:10.1056/NEJM198412133112401 3012:10.1016/j.chest.2021.07.055 2319:10.1136/bmjopen-2015-008864 2227:10.1136/bmj.39576.709711.80 1837:Annals of Internal Medicine 1116:small alternations in genes 862:quality-adjusted life years 765:partial thromboplastin time 374:anti-cardiolipin antibodies 351: 293:gene at position 1691) and 82:that increases the risk of 10: 4356: 4167:Congenital afibrinogenemia 4071:Glanzmann's thrombasthenia 3433:Rheum. Dis. Clin. North Am 3382:Hughes GR (October 1983). 2153:10.1016/j.blre.2010.08.002 1074:Centers of Disease Control 1070:Scripps Research Institute 1046: 940:direct oral anticoagulants 645: 593:, and decreased levels of 572: 525:menopausal hormone therapy 481:Inflammatory bowel disease 382:-glycoprotein 1 antibodies 327:familial dysfibrinogenemia 301:(at position 20210 in the 154:and may be complicated by 4283:Gastrointestinal bleeding 4222: 4179: 4100: 4085:Hermansky–Pudlak syndrome 4044: 3986: 3972: 3900: 3862: 3854:Antiphospholipid syndrome 3835:Essential thrombocythemia 3775: 3768: 3745: 3651: 3566: 3445:10.1016/j.rdc.2006.05.010 3400:10.1136/bmj.287.6399.1088 2521:10.1016/j.ccm.2009.05.006 2395:Hemostasis and Thrombosis 1737:10.1007/s11239-015-1316-1 980:inferior vena cava filter 860:. If cost-effectiveness ( 785:anti-cardiolipin antibody 755:(with examination of the 555:circulating microvesicles 358:antiphospholipid syndrome 257: 45: 40: 31: 26: 4253:Subconjunctival bleeding 4059:Bernard–Soulier syndrome 4022:Upshaw–Schulman syndrome 3996:Thrombocytopenic purpura 3825:Sticky platelet syndrome 1940:"Plasminogen deficiency" 1294:Dahlbäck B (July 2008). 984:post-thrombotic syndrome 945:Molecular tests such as 924:coronary arterial bypass 638:, which depend on diet. 459:central venous catheters 445:essential thrombocytosis 431:(caused by mutations of 268:hereditary thrombophilia 264:Congenital thrombophilia 4243:Intracranial hemorrhage 3257:Thromb. Diath. Haemorrh 2720:: an initiative of the 1573:10.1161/JAHA.119.012877 1150:Robbins Basic Pathology 1066:antithrombin deficiency 920:hormonal contraceptives 854:retinal vein thrombosis 179:hepatic vein thrombosis 100:antithrombin deficiency 78:) is an abnormality of 4157:Factor XIII deficiency 4137:Hypoprothrombinemia/II 4132:von Willebrand disease 4090:Gray platelet syndrome 3269:10.1055/s-0038-1656297 3183:(6 Suppl): 844S–886S. 3137:(6 Suppl): 454S–545S. 2925:(2): iii, ix–x, 1–91. 2919:Health Technol. Assess 2623:Dalen JE (June 2008). 1082:University of Oklahoma 1056: 966: 889:venous thromboembolism 748: 661: 501:that protects against 477:membranous nephropathy 303:3' untranslated region 272:acquired thrombophilia 175:portal vein thrombosis 132:venous thromboembolism 119: 4152:Factor XII deficiency 4142:Factor VII deficiency 3960:Renal vein thrombosis 3189:10.1378/chest.08-0761 3143:10.1378/chest.08-0658 2597:10.1056/NEJMra1011670 1897:Rosendaal FR (2005). 1725:J Thromb Thrombolysis 1452:10.1056/NEJMra0907731 1054: 964: 899:Recurrent miscarriage 746: 733:myocardial infarction 655: 527:(in combination with 503:postpartum hemorrhage 360:, which is caused by 214:recurrent miscarriage 191:the veins of the arms 187:renal vein thrombosis 117: 3908:Deep vein thrombosis 3803:Protein S deficiency 3793:Protein C deficiency 2397:. pp. 197–206. 2260:Am. J. Gastroenterol 1078:Protein S deficiency 825:Budd-Chiari syndrome 803:mutation, and basal 769:thrombodynamics test 753:complete blood count 453:, particularly when 319:protein S deficiency 315:protein C deficiency 244:protein S deficiency 236:Protein C deficiency 124:deep vein thrombosis 88:deep vein thrombosis 4147:Factor X deficiency 4036:May–Hegglin anomaly 3813:Prothrombin G20210A 3480:1994Natur.369...64B 2956:Curr. Opin. Hematol 2515:(3): 489–93, viii. 1407:10.1503/cmaj.060366 951:Prothrombin G20210A 904:thromboelastography 781:lupus anticoagulant 429:sickle-cell disease 366:lupus anticoagulant 295:prothrombin G20210A 287:(a mutation in the 195:arterial thrombosis 144:shortness of breath 76:prothrombotic state 4273:Pulmonary hematoma 4180:Signs and symptoms 3955:Pulmonary embolism 3760:Bleeding diathesis 3652:External resources 3104:10.1111/ijlh.13196 3098:(Suppl 1): 41–48. 2711:(September 2013), 2561:10.1093/cvr/cvp066 1994:(9751): 1498–509. 1360:(Suppl 1): 301–4. 1354:J. Thromb. Haemost 1090:Graham R.V. Hughes 1057: 967: 829:orthopedic surgery 749: 662: 485:ulcerative colitis 469:Nephrotic syndrome 390:livedo reticularis 386:autoimmune disease 254:or related drugs. 230:abruptio placentae 171:veins of the brain 128:pulmonary embolism 120: 110:Signs and symptoms 72:hypercoagulability 70:(sometimes called 4327: 4326: 4323: 4322: 4175: 4174: 4162:Dysfibrinogenemia 4046:Platelet function 3968: 3967: 3847:Purpura fulminans 3686: 3685: 3394:(6399): 1088–89. 3316:10.1172/JCI110385 3092:Int J Lab Hematol 2755:10.1136/bmj.e3979 2436:Arch. Intern. Med 2412:978-3-030-19329-4 1159:978-1-4160-2973-1 1096:for that reason. 1059:German physician 930:Timing of Testing 684:to factor Xa and 441:polycythemia vera 418:complement system 240:purpura fulminans 80:blood coagulation 65: 64: 21:Medical condition 4347: 3988:Thrombocytopenia 3984: 3983: 3977: 3976: 3933:Lowenberg's sign 3783:Clotting factors 3773: 3772: 3727: 3720: 3713: 3704: 3703: 3699: 3564: 3563: 3552: 3551: 3541: 3532:(10): 3698–703. 3523: 3514: 3508: 3507: 3488:10.1038/369064a0 3463: 3457: 3456: 3428: 3422: 3421: 3411: 3379: 3373: 3372: 3344: 3338: 3337: 3327: 3295: 3289: 3288: 3252: 3246: 3245: 3235: 3211: 3205: 3204: 3199:. Archived from 3168: 3159: 3158: 3153:. Archived from 3122: 3116: 3115: 3087: 3081: 3080: 3070: 3037: 3024: 3023: 3006:(6): e545–e608. 2994: 2988: 2987: 2951: 2945: 2944: 2934: 2932:10.3310/hta13020 2910: 2904: 2903: 2893: 2883: 2859: 2853: 2852: 2842: 2818: 2812: 2809: 2799: 2774: 2736: 2735: 2733: 2705: 2696: 2695: 2685: 2661: 2655: 2654: 2644: 2620: 2609: 2608: 2580: 2574: 2573: 2563: 2539: 2533: 2532: 2504: 2498: 2497: 2469: 2460: 2459: 2431: 2425: 2424: 2390: 2384: 2383: 2358:(9713): 500–12. 2347: 2341: 2340: 2330: 2298: 2292: 2291: 2255: 2249: 2248: 2238: 2221:(7654): 1185–9. 2206: 2200: 2199: 2171: 2165: 2164: 2136: 2130: 2129: 2103: 2088:Ann. Intern. Med 2083: 2074: 2073: 2063: 2039: 2030: 2029: 2011: 1983: 1970: 1969: 1959: 1935: 1929: 1928: 1918: 1894: 1869: 1868: 1829: 1823: 1822: 1791:Ann. Intern. Med 1786: 1759: 1758: 1748: 1716: 1707: 1706: 1696: 1672: 1649: 1648: 1623:(9535): 601–11. 1612: 1603: 1602: 1592: 1552: 1546: 1545: 1517: 1508: 1507: 1497: 1473: 1464: 1463: 1435: 1429: 1428: 1418: 1386: 1380: 1379: 1369: 1345: 1326: 1325: 1315: 1291: 1278: 1277: 1252:(9757): 2032–9. 1241: 1228: 1227: 1217: 1196:Heit JA (2007). 1193: 1164: 1163: 1145: 761:prothrombin time 422:hemolytic anemia 392:of the skin and 311:antithrombin III 297:, a mutation in 283:common ones are 61: 60: 36: 24: 23: 4355: 4354: 4350: 4349: 4348: 4346: 4345: 4344: 4330: 4329: 4328: 4319: 4268:Hemopericardium 4218: 4171: 4102:Clotting factor 4096: 4040: 3964: 3913:Bancroft's sign 3896: 3887:Virchow's triad 3858: 3808:Factor V Leiden 3764: 3741: 3731: 3692:"Thrombophilia" 3690: 3687: 3682: 3681: 3647: 3646: 3575: 3561: 3556: 3555: 3521: 3515: 3511: 3464: 3460: 3429: 3425: 3380: 3376: 3349:N. Engl. J. Med 3345: 3341: 3304:J. Clin. Invest 3296: 3292: 3253: 3249: 3226:(13): 1650–55. 3212: 3208: 3169: 3162: 3123: 3119: 3088: 3084: 3053:(22): 7101–38. 3038: 3027: 2995: 2991: 2952: 2948: 2911: 2907: 2874:(5): e0155326. 2860: 2856: 2833:(24): 3879–83. 2819: 2815: 2731: 2729: 2722:ABIM Foundation 2718:Choosing Wisely 2706: 2699: 2670:Br. J. Haematol 2662: 2658: 2621: 2612: 2591:(18): 1746–60. 2585:N. Engl. J. Med 2581: 2577: 2548:Cardiovasc. Res 2540: 2536: 2509:Clin. Chest Med 2505: 2501: 2470: 2463: 2442:(18): 1965–76. 2432: 2428: 2413: 2391: 2387: 2348: 2344: 2313:(11): e008864. 2299: 2295: 2256: 2252: 2207: 2203: 2172: 2168: 2137: 2133: 2101:10.1.1.668.4942 2084: 2077: 2048:Br. J. Haematol 2040: 2033: 1984: 1973: 1936: 1932: 1895: 1872: 1831: 1830: 1826: 1787: 1762: 1717: 1710: 1681:Br. J. Haematol 1673: 1652: 1613: 1606: 1567:(19): e012877. 1553: 1549: 1518: 1511: 1482:Br. J. Haematol 1474: 1467: 1440:N. Engl. J. Med 1436: 1432: 1387: 1383: 1346: 1329: 1292: 1281: 1242: 1231: 1194: 1167: 1160: 1146: 1129: 1124: 1105:factor V Leiden 1094:Hughes syndrome 1049: 1032: 1019: 1005:(LMWH, such as 959: 947:Factor V Leiden 932: 893:anticoagulation 841:Choosing Wisely 816: 797:factor V Leiden 741: 729:atherosclerosis 708:, factor V and 650: 644: 636: 629: 575: 519:, when used in 489:Crohn's disease 381: 354: 285:factor V Leiden 280: 260: 207:ischemic stroke 183:mesenteric vein 112: 104:factor V Leiden 96:anticoagulation 55: 22: 17: 12: 11: 5: 4353: 4343: 4342: 4340:Coagulopathies 4325: 4324: 4321: 4320: 4318: 4317: 4316: 4315: 4307: 4306: 4305: 4300: 4295: 4293:Hemoperitoneum 4290: 4285: 4277: 4276: 4275: 4270: 4265: 4257: 4256: 4255: 4250: 4245: 4240: 4235: 4226: 4224: 4220: 4219: 4217: 4216: 4215: 4214: 4204: 4199: 4194: 4189: 4183: 4181: 4177: 4176: 4173: 4172: 4170: 4169: 4164: 4159: 4154: 4149: 4144: 4139: 4134: 4129: 4128: 4127: 4122: 4117: 4106: 4104: 4098: 4097: 4095: 4094: 4093: 4092: 4087: 4075: 4074: 4073: 4063: 4062: 4061: 4050: 4048: 4042: 4041: 4039: 4038: 4033: 4027: 4026: 4025: 4024: 4019: 4009: 4008: 4007: 4005:Evans syndrome 3992: 3990: 3981: 3974: 3970: 3969: 3966: 3965: 3963: 3962: 3957: 3952: 3951: 3950: 3945: 3940: 3938:Peabody's sign 3935: 3930: 3925: 3920: 3915: 3904: 3902: 3898: 3897: 3895: 3894: 3889: 3884: 3879: 3874: 3868: 3866: 3860: 3859: 3857: 3856: 3851: 3850: 3849: 3839: 3838: 3837: 3832: 3830:Thrombocytosis 3827: 3817: 3816: 3815: 3810: 3805: 3800: 3795: 3790: 3779: 3777: 3770: 3766: 3765: 3763: 3762: 3757: 3752: 3746: 3743: 3742: 3730: 3729: 3722: 3715: 3707: 3701: 3700: 3684: 3683: 3680: 3679: 3668: 3666:article/211039 3656: 3655: 3653: 3649: 3648: 3645: 3644: 3633: 3622: 3611: 3596: 3576: 3571: 3570: 3568: 3567:Classification 3560: 3559:External links 3557: 3554: 3553: 3509: 3474:(6475): 64–7. 3458: 3423: 3374: 3355:(24): 1525–8. 3339: 3290: 3247: 3206: 3203:on 2013-01-12. 3160: 3157:on 2013-01-12. 3117: 3082: 3025: 2989: 2946: 2905: 2854: 2813: 2811: 2810: 2790:(2): 209–220. 2775: 2737:, which cites 2697: 2656: 2610: 2575: 2554:(3): 392–403. 2534: 2499: 2461: 2426: 2411: 2385: 2342: 2293: 2266:(10): 1971–3. 2250: 2201: 2166: 2131: 2075: 2031: 1971: 1930: 1870: 1824: 1760: 1731:(1): 154–164. 1708: 1650: 1604: 1547: 1522:Semin. Hematol 1509: 1465: 1430: 1401:(9): 1087–92. 1381: 1327: 1279: 1229: 1165: 1158: 1126: 1125: 1123: 1120: 1114:, looking for 1061:Rudolf Virchow 1048: 1045: 1031: 1028: 1018: 1015: 995:antibody titer 958: 955: 936:anticoagulants 931: 928: 858:evidence-based 845:false positive 815: 812: 777:reptilase time 740: 737: 646:Main article: 643: 640: 634: 627: 574: 571: 379: 353: 350: 279: 276: 259: 256: 164:cardiac arrest 111: 108: 63: 62: 49: 43: 42: 38: 37: 29: 28: 20: 15: 9: 6: 4: 3: 2: 4352: 4341: 4338: 4337: 4335: 4314: 4311: 4310: 4308: 4304: 4303:Hematosalpinx 4301: 4299: 4296: 4294: 4291: 4289: 4286: 4284: 4281: 4280: 4278: 4274: 4271: 4269: 4266: 4264: 4261: 4260: 4258: 4254: 4251: 4249: 4246: 4244: 4241: 4239: 4236: 4234: 4231: 4230: 4228: 4227: 4225: 4221: 4213: 4210: 4209: 4208: 4205: 4203: 4200: 4198: 4195: 4193: 4190: 4188: 4185: 4184: 4182: 4178: 4168: 4165: 4163: 4160: 4158: 4155: 4153: 4150: 4148: 4145: 4143: 4140: 4138: 4135: 4133: 4130: 4126: 4123: 4121: 4118: 4116: 4113: 4112: 4111: 4108: 4107: 4105: 4103: 4099: 4091: 4088: 4086: 4083: 4082: 4081: 4080: 4076: 4072: 4069: 4068: 4067: 4064: 4060: 4057: 4056: 4055: 4052: 4051: 4049: 4047: 4043: 4037: 4034: 4032: 4029: 4028: 4023: 4020: 4018: 4015: 4014: 4013: 4010: 4006: 4003: 4002: 4001: 3997: 3994: 3993: 3991: 3989: 3985: 3982: 3978: 3975: 3971: 3961: 3958: 3956: 3953: 3949: 3946: 3944: 3941: 3939: 3936: 3934: 3931: 3929: 3928:Louvel's sign 3926: 3924: 3923:Lisker's sign 3921: 3919: 3916: 3914: 3911: 3910: 3909: 3906: 3905: 3903: 3899: 3893: 3890: 3888: 3885: 3883: 3880: 3878: 3875: 3873: 3872:Thrombophilia 3870: 3869: 3867: 3865: 3861: 3855: 3852: 3848: 3845: 3844: 3843: 3840: 3836: 3833: 3831: 3828: 3826: 3823: 3822: 3821: 3818: 3814: 3811: 3809: 3806: 3804: 3801: 3799: 3796: 3794: 3791: 3789: 3786: 3785: 3784: 3781: 3780: 3778: 3774: 3771: 3767: 3761: 3758: 3756: 3753: 3751: 3748: 3747: 3744: 3740: 3736: 3733:Disorders of 3728: 3723: 3721: 3716: 3714: 3709: 3708: 3705: 3697: 3693: 3689: 3688: 3678: 3677:Thrombophilia 3674: 3673: 3669: 3667: 3663: 3662: 3658: 3657: 3654: 3650: 3643: 3639: 3638: 3634: 3632: 3628: 3627: 3623: 3621: 3617: 3616: 3612: 3610: 3606: 3605: 3601: 3597: 3595: 3591: 3587: 3586: 3582: 3578: 3577: 3574: 3569: 3565: 3549: 3545: 3540: 3535: 3531: 3527: 3520: 3513: 3505: 3501: 3497: 3493: 3489: 3485: 3481: 3477: 3473: 3469: 3462: 3454: 3450: 3446: 3442: 3439:(3): 465–90. 3438: 3434: 3427: 3419: 3415: 3410: 3405: 3401: 3397: 3393: 3389: 3385: 3378: 3370: 3366: 3362: 3358: 3354: 3350: 3343: 3335: 3331: 3326: 3321: 3317: 3313: 3310:(5): 1370–3. 3309: 3305: 3301: 3294: 3286: 3282: 3278: 3274: 3270: 3266: 3263:(2): 516–30. 3262: 3258: 3251: 3243: 3239: 3234: 3229: 3225: 3221: 3217: 3210: 3202: 3198: 3194: 3190: 3186: 3182: 3178: 3174: 3167: 3165: 3156: 3152: 3148: 3144: 3140: 3136: 3132: 3128: 3121: 3113: 3109: 3105: 3101: 3097: 3093: 3086: 3078: 3074: 3069: 3064: 3060: 3056: 3052: 3048: 3044: 3036: 3034: 3032: 3030: 3021: 3017: 3013: 3009: 3005: 3001: 2993: 2985: 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