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Coagulopathy
Other namesBleeding disorder
Platelets in a Giemsa-stained blood film.
Platelets
SpecialtyHematology
SymptomsChronic presentation: Frequent nosebleeds, easy bruising, feeling tired and anaemia, prolonged bleeding, petechiae and purpura, heavy periods and bleeding gums
Acute presentation: Fast heartrate, chest pain, difficulty breathing, feeling faint when standing and dizziness, nausea and vomiting, delirium, difficulty speaking, double vision, loss of co-ordination and seizures
ComplicationsUncontrolled hemorrhage and internal bleeding, soft tissue bleeding, joint damage from hemarthrosis, low blood volume, shock, abnormally low levels of platelets, ante- and postpartum bleeding, blood-borne infections from treatment, intracerebral hemorrhage, subarachnoid hemorrhage, multiple organ dysfunction syndrome, organ damage and death from blood loss

Coagulopathy (also known as a bleeding disorder) is a condition where the blood's ability to coagulate (form clots) is impaired,[1] a critical factor in preventing severe blood loss. This can cause prolonged or excessive bleeding (bleeding diathesis), which may occur following an injury, during menstruation, due to medical (including dental) procedures or without obvious cause.[2][3] Coagulopathies can be hereditary or acquired.

Coagulopathies are sometimes erroneously referred to as "clotting disorders"; a clotting disorder is a predisposition to clot formation (thrombus), also known as a hypercoagulable state or thrombophilia.[4]

Overview

[edit]

Normally, blood clotting begins within seconds after any vascular injury, but this process depends on the interplay of various proteins in the blood. Coagulopathies can result from deficiencies of any of the key components in hemostasis (the process to prevent and stop bleeding) such as platelets (small disk-shaped bodies in the bloodstream that aid in the clotting process) or blood-clotting proteins, known as coagulation or clotting factors. The body produces thirteen clotting factors; if any of these are reduced or absent, a bleeding disorder can result.

Acquired

[edit]

Causes of acquired coagulopathies are broad and can include chronic kidney disease (involving delayed formation of clots, but decreased clot breakdown),[5] acquired coagulation factor antibodies (autoantibodies or alloantibodies),[6] traumatic injury, liver disease (cirrhosis also causes reduced levels of prothrombin and factor II, VII, IX and X)[7], autoimmune disease, chronic inflammation, surgical procedures, infections,[8] and Vitamin K deficiency.[9] Medications which impede clotting such as warfarin,[10] heparin or oral factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) can lead to coagulopathy.[11] More rarely, medications which impede platelet clumping like aspirin[12] and clopidogrel can cause coagulopathy.[13]

Traumatic

[edit]

Coagulopathies after traumatic injuries are a potentially preventable (with early recognition and treatment) cause of fatality.[14] Up to 40% of trauma deaths are due to uncontrolled bleeding or its consequences.[15][16] In 2003, Karim Brohi, Professor of Trauma Sciences at Queen Mary University of London, introduced the term Acute Traumatic Coagulopathy (ATC),[17] establishing that coagulopathy induced by trauma results in more severe bleeding, multiple organ dysfunction syndrome and high mortality. Traumatic coagulopathies are also associated with hypothermia, acidosis (increased acidity in the blood), blood protein and clotting factor dilution, and tissue destruction.[18]

Hereditary

[edit]

Hereditary coagulopathies are genetic disorders that include Von Willebrand disease, which involves the deficiency or dysfunction of von Willebrand factor (a protein that mediates adherence of platelets into clots);[19] hemophilia and other factor deficiencies, which involves the fixed reduction or absence of certain clotting factors and proteins (depending on which type);[10] and congenital Vitamin K-dependant clotting factors deficiency which involves variably decreased levels of clotting factors and the natural anticoagulants protein C, protein S and protein Z.[20]

Von Willebrand disease is the most common type of hereditary coagulopathy.[21]

Hemophilia

[edit]
See also: Hemophilia

Hemophilia is the overarching term for mostly hereditary coagulopathies as a result of deficiencies of clotting factor VIII, factor IX or factor XI. Factor VIII deficiency is known as hemophilia A (classic hemophilia), factor IX deficiency is known as hemophilia B (Christmas disease),[22] and factor XI is known as hemophilia C (plasma thromboplastin antecedent (PTA) deficiency or Rosenthal syndrome). The severity of hemophilia is measured by how much of the clotting factor affected is present; mild disease is considered more than 5%, moderate is 1-5% and severe is less than 1%.[23]

Acquired hemophilia is a rare autoimmune disorder found in people with no history of bleeding disorders who develop autoantibodies (inhibitors) to clotting factors. The most common type is autoantibodies to factor VIII, mimicking congenital hemophilia A. In 50% of cases, an underlying cause can be identified (including, but not limited to, childbirth, cancer, other autoimmune conditions, inflammatory bowel disease or diabetes), but in the others it is idiopathic.[24] Acquired hemophilia C is found in individuals with systemic lupus erythematosus and other immunological disorders, because of developing autoantibodies to factor XI.[25]

Severe disorders

[edit]

Autosomal recessive platelet function abnormalities such as Glanzmann thrombasthenia and Bernard–Soulier syndrome are rare disorders that present with severe symptoms. Glanzmann thrombasthenia is when the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), a receptor for fibrinogen (the base protein that creates fibrin-based blood clots), thus blood clotting is severely affected and bleeding time is significantly prolonged. Bernard–Soulier syndrome is a giant platelet disorder where there's a deficiency of the glycoprotein Ib-IX-V complex (GPIb-IX-V), resulting in poor platelet adhesion to von Willebrand factor.

Mild bleeding disorders

[edit]

Mild bleeding disorders (MBD) is a term used to signify a laboratory marker of disease such as deficiencies in clotting factors or parts of the hemostatic system without significant clinical signs or a clear phenotype. These disorders may be characterised by the presence of more frequent bleeding symptoms than in the normal population, but without serious complications.[26]

Signs and symptoms

[edit]

Symptoms of coagulopathies can range from mild to severe. Some of the most common ones are:

Not all coagulopathies show obvious outward signs. For instance, Von Willebrand disease type 1 often involves non-specific mild bleeding symptoms and reduced von Willebrand factor levels show low heritability, with weak risk factors for bleeding, making it difficult to classify for diagnosis.[29] However, although Von Willebrand disease is theorised to affect an equal number of men and women, more women are diagnosed than men because the bleeding associated is more easily detected in menstruation and childbirth.[30]

Another coagulopathy that is often asymptomatic and found incidentally on routine bloodwork (such as pre-surgery assessments) is Factor XII deficiency; it's frequently called benign as other clotting factors compensate for the reduction so it doesn't cause excessive bleeding.[31] However, paradoxically, it's been linked in rare cases to thromboembolic (formation of clots which block blood vessels) complications.[32]

Furthermore, over 25% of healthy controls have been found to have at least one bleeding symptom[29] and it's estimated that 26% to 45% people have a history of nose bleeds, easy bruising, or gum bleeding,[33] making it difficult to determine if this is incidental or the result of an underlying disorder.

Diagnosis

[edit]

The investigation of a patient with a bleeding symptoms begins with a full history and physical examination. It is important to look for any indications of hemostatic abnormalities such as bruising or petechiae. In cases of acute symptoms, it is important to assess for neurologic impairment, evidence of hematomas or internal bleeding, gastrointestinal bleeding and a history of recent trauma.[34]

History

[edit]

A positive history of abnormal bleeding is a prerequisite for inherited coagulopathy diagnosis and should guide further investigations. When inherited coagulopathies are suspected, standardised assessments such as Bleeding Assessment Tools (BAT) can be used to quickly assess presence and severity of bleeding symptoms. The ISTH-SSC Bleeding Assessment Tool consists of fourteen categories which allows diagnosticians to assess the presence and severity of bleeding symptoms retrospectively; a high score has high sensitivity for the presence of an inherited bleeding disorder. However, it is insensitive in children with a possible inherited bleeding disorder as they may not yet have experienced the events (eg, prior surgery) asked about.

Physical examination

[edit]

Scars on the elbows and knees are a feature of hemophilia A. Grey Turner's sign is discolouration (bruising) of the skin on the flanks due to bleeding, which have been found in people with coagulopathies or who have taken much anticoagulative medication.[35]

Laboratory tests

[edit]

Certain laboratory blood tests can be used to assess both acquired and inherited coagulopathies. These include bleeding time, a complete blood count, prothrombin time (PT) along with a calculation of the international normalized ratio (INR) to standardize for different reagents, activated partial thromboplastin time (aPTT) and a fibrinogen level.[36] It's important not to place too much emphasis on only laboratory tests as these may show reduced clotting factors without a clear etiology, and there isn't a reliable relationship between partial deficiency and residual activity or bleeding severity.[26]

Laboratory findings in various platelet and coagulation disorders[citation needed]
Condition Prothrombin time Partial thromboplastin time Bleeding time Platelet count
Vitamin K deficiency or warfarin Prolonged Normal or mildly prolonged Unaffected Unaffected
Disseminated intravascular coagulation Prolonged Prolonged Prolonged Decreased
Von Willebrand disease Unaffected Prolonged or unaffected Prolonged Unaffected
Hemophilia Unaffected Prolonged Unaffected Unaffected
Aspirin Unaffected Unaffected Prolonged Unaffected
Thrombocytopenia Unaffected Unaffected Prolonged Decreased
Liver failure, early Prolonged Unaffected Unaffected Unaffected
Liver failure, end-stage Prolonged Prolonged Prolonged Decreased
Uremia Unaffected Unaffected Prolonged Unaffected
Congenital afibrinogenemia Prolonged Prolonged Prolonged Unaffected
Factor V deficiency Prolonged Prolonged Unaffected Unaffected
Factor X deficiency as seen in amyloid purpura Prolonged Prolonged Unaffected Unaffected
Glanzmann's thrombasthenia Unaffected Unaffected Prolonged Unaffected
Bernard–Soulier syndrome Unaffected Unaffected Prolonged Decreased or unaffected
Factor XII deficiency Unaffected Prolonged Unaffected Unaffected
C1INH deficiency Unaffected Shortened Unaffected Unaffected

Complications

[edit]

Coagulopathies can cause uncontrolled internal bleeding, such as gastrointestinal bleeding, or external bleeding. Left untreated, uncontrolled bleeding (hemorrhage) may cause damage to joints, muscles, or internal organs and may be life-threatening. People should seek urgent medical care for serious symptoms like heavy external bleeding, blood in the urine or stool. They should seek prompt medical care if they experience mild but unstoppable external bleeding or joint swelling and stiffness.[citation needed]

Double vision, severe headache of rapid onset, neck stiffness and meningism, fever, repeated vomiting, difficulty walking, difficulty speaking, loss of co-ordination and balance, altered level of consciousness, convulsions, seizures, stroke symptoms (such as weakness, numbness, facial paralysis) or other neurologic deficits could be a sign of a subarachnoid haemorrhage or intracerebral hemorrhage which can be fatal and require immediate medical care.[37][38]

Chronic

[edit]

Hemophilic arthropathy (joint disease) is a known complication from chronic or repeated bleeding into joints (hemarthrosis),[39][40] which is found in hemophilia A and B.

Acute

[edit]

Coagulopathies heighten the risk of acute compartment syndrome (a build-up of blood increasing pressure within a fascial compartment), even without clear cause or trauma. This can cause irreversible tissue damage and cell death and is a medical emergency.[41]

Treatment

[edit]

Treatment of coagulopathies varies depending on their cause, severity or whether there is any active bleeding. The primary goal is to prevent excessive or dangerous bleeding in the least invasive way, which may be with medications or replacement therapy.

Pharmacological

[edit]

Medication options for the treatment of coagulopathies remain limited. Desmopressin can be used in mild forms of hemophilia A (factor VIII coagulant activity of more than 5%) or mild to moderate type 1 von Willebrand disease (factor VIII coagulant activity of more than 5%), but is not suitable for hemophilia B, severe hemophilia A or patients with factor VIII antibodies.[42] Antifibrinolytics, which prevent the breakdown of blood clots (fibrinolysis), can be used although this is frequently off-label. These include aprotinin, tranexamic acid and aminocaproic acid/epsilon-aminocaproic acid. Major side effects of antifibrinolytics include hypotension, cardiac arrhythmias, rhabdomyolysis, and obstructive or dangerous blood clots. Other medications used are aprotinin and concentrated oestrogens.

Topical agents

[edit]

In cases of external bleeding or intraoperative bleeding, some local hemostatic agents and tissue adhesives can be applied to support the defective clotting process; for example, topical thrombin or fibrin glue provide exogenous thrombin or fibrinogen, making them effective in congenital or acquired coagulopathies.[43] In surgery, these can be used in addition to other surgical hemostasis techniques like compression, sutures or electrocoagulation. Other mechanical hemostatic agents like Bovine microfibrillar collagen are not considered effective as they rely on the body's plasma constituents and fibrin to achieve hemostasis, which requires a normal coagulation system.[44] However, there has been some success with the use of mechanical hemostatic agents in hemophilic patients recently treated with supplementary clotting factor concentrates.

Replacement therapy

[edit]

In replacement therapy, the affected clotting factors are replaced clotting factor concentrates (CFCs) derived from either human blood (plasma-derived factor concentrates) or created in the laboratory (recombinant factor concentrates). Plasma-derived concentrates are collected from many different donors who have been screened for viruses, then they're separated into components, freeze-dried, and finally tested and treated once again to kill viruses before use.

Recombinant factor concentrates are genetically engineered using DNA. This therapy may be given either to treat bleeding that has already begun (on-demand (OD) therapy) or to prevent bleeding from occurring (prophylactic therapy).[citation needed] Prophylactic administration is utilised frequently in more severe coagulopathies.

Risks

[edit]

Because between 10,000-50,000 different donations have to be pooled into a single lot before precipitating out fractions with cold ethanol,[45] the major risk of human-derived plasma in replacement therapy is blood-borne infections. Prior to the development of widely available tests to screen donors such as nucleic acid amplification testing and antigen testing, there was a high incidence of post-transfusion virus infections such as hepatitis and HIV.[46] By 1984, around 80% of all hemophilia A and 50% of all hemophilia B patients were infected with HIV via blood[47] and 100% of those who received more than 500,000 units of Factor VIII were infected; by 1990, antibodies to hepatitis C virus were detected in up to 80% of hemophiliacs tested.[48] However, modern safety techniques, donor testing and viral inactivation steps have made this exceedingly rare; in the United States, for example, the chance of HIV infection around 1:5 to 1:8 million products transfused.[49]

In some cases, replacement therapy can have a serious complication of developing neutralizing antibodies (inhibitors), known as alloantibodies, due to exposure to foreign proteins (rather than an individual's own proteins). These alloantibodies may be directed against clotting factors, such as hemophilia-related factor VIII or IX inhibitors, or alloantibodies against von Willebrand factor, and make it harder to treat the patient in question as the original treatment is no longer effective.

There are several other possible risks, such as transfusion-related acute lung injury, acute respiratory distress syndrome, multiple organ dysfunction syndrome, major hemorrhage, and venous thromboembolism.

Critical care

[edit]

An important area in the treatment of coagulopathies is managing people with major bleeding in a critical setting, such as an emergency department.[1] This is a time-sensitive medical emergency in which all facets of care should be performed simultaneously; initial treatment focuses on stabilising a bleeding patient with intravenous (IV) access, airway management, fluid resuscitation, and control of active bleeding sites.[36]

Further treatment can be transfusing a combination of red cells with one of the following options:[citation needed]

Tranexamic acid reduces bleeding by inhibiting lysine binding sites on the zymogen plasminogen, preventing its conversion to the enzyme plasmin, a serine protease that degrades blood plasma proteins like fibrin clots.[50] Thus, tranexamic acid inhibits clot breakdown, and can help control blood loss. Administration of tranexamic acid within one hour of bleeding onset in trauma significantly reduces risk of death (and between one and three hours moderately reduces risk of death) without increased thromboembolic events. When given after three hours has elapsed, there are no recorded benefits, and it may in fact be detrimental.[51]

The use of tranexamic acid is the only option supported by reliable evidence of effectiveness from a randomized controlled trial for major traumatic bleeding,[52] with the greatest benefit to patients with severe injuries and those who receive massive transfusions.[53] However, a trial of 12,000 patients showed it's ineffective and can increase side effects in severe gastrointestinal bleeding.[54] Furthermore, there isn't any evidence for the use of tranexamic acid in children and it's not indicated for isolated head injuries.[53]

The most common acquired coagulopathy disorder seen in emergency care is thrombocytopenia, which can be the result of dilution from massive blood transfusions, and in these cases it is important not to dilute the clotting factors with further transfusions without replacement therapy.

See also

[edit]

References

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  1. ^ a b Hunt, Beverley J. (27 February 2014). "Bleeding and Coagulopathies in Critical Care". New England Journal of Medicine. 370 (9): 847–859. doi:10.1056/NEJMra1208626. ISSN 0028-4793. PMID 24571757.
  2. ^ "What is a Bleeding Disorder?". National Hemophilia Foundation. Retrieved 11 April 2021.
  3. ^ Rodeghiero, F.; Tosetto, A.; Abshire, T.; Arnold, D.M.; Coller, B.; James, P.; Neunert, C.; Lillicrap, D. on behalf of the ISTH/SSC Joint VWF and perinatal/pediatric hemostasis subcommittees working group (2010). "ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders: Supplementary material to the official communication of the SSC" (PDF). Journal of Thrombosis and Haemostasis. 8 (9). Retrieved 12 April 2021.
  4. ^ Kundel, Vaishnavi; Richman, Lisa (2021). "Anticoagulation-Related Bleeding". In Mayer, Stephan A.; Shapiro, Janet M.; Gidwani, Umesh K.; Oropello, John M. (eds.). Mount Sinai Expert Guides: Critical Care. Hoboken, NJ: John Wiley & Sons. p. 561. ISBN 978-1-119-29327-9. OCLC 1182019415.
  5. ^ Nunns, Geoffrey R.; Moore, Ernest E.; Chapman, Michael P.; Moore, Hunter B.; Stettler, Gregory R.; et al. (6 September 2017). "The hypercoagulability paradox of chronic kidney disease: The role of fibrinogen". The American Journal of Surgery. 214 (6). doi:10.1016/j.amjsurg.2017.08.039. ISSN 0002-9610.
  6. ^ Macik, B. Gail; Crow, Peter (September 1999). "Acquired autoantibodies to coagulation factors". Current Opinion in Hematology. 6 (5). doi:10.1097/00062752-199909000-00009. ISSN 1065-6251.
  7. ^ Caldwell, Stephen H.; Hoffman, Maureane; Lisman, Ton; Macik, B. Gail; Northup, Patrick G.; et al. (27 September 2006). "Coagulation disorders and hemostasis in liver disease: Pathophysiology and critical assessment of current management". Hepatology. 44 (4): 1039. doi:10.1002/hep.21303. ISSN 0270-9139. Retrieved 12 April 2021.
  8. ^ Tanaka, Kenichi A; Bolliger, Daniel (28 November 2014). "Acquired Coagulopathy". Reference Module in Biomedical Sciences. doi:10.1016/B978-0-12-801238-3.00068-4.
  9. ^ Wojciechowski, Valery V.; Calina, Daniela; Tsarouhas, Konstantinos; Pivnik, Alexander V.; Sergievich, Alexander A.; et al. (17 April 2017). "A guide to acquired vitamin K coagulophathy diagnosis and treatment: the Russian perspective". DARU Journal of Pharmaceutical Sciences. 25 (1). Springer Science and Business Media LLC. doi:10.1186/s40199-017-0175-z. ISSN 2008-2231.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  10. ^ a b Spahn, DR.; Bouillon, B.; Cerny, V.; Coats, TJ.; Duranteau, J.; et al. (19 April 2013). "Management of bleeding and coagulopathy following major trauma: an updated European guideline". Crit Care. 17 (2): R76. doi:10.1186/cc12685. PMC 4056078. PMID 23601765.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  11. ^ Critical Care 2021, p. 553.
  12. ^ Mielke, C.Harold (14 June 1983). "Influence of aspirin on platelets and the bleeding time". The American Journal of Medicine. 74 (6). Elsevier BV. doi:10.1016/0002-9343(83)90532-6. ISSN 0002-9343.
  13. ^ Critical Care 2021, p. 554.
  14. ^ Martini, Wenjun Z. (22 November 2016). "Coagulation complications following trauma". Military Medical Research. 3. doi:10.1186/s40779-016-0105-2. PMC 5120509. PMID 27895932.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  15. ^ Kauvar, David S.; Lefering, Rolf; Wade, Charles E. (June 2006). "Impact of Hemorrhage on Trauma Outcome: An Overview of Epidemiology, Clinical Presentations, and Therapeutic Considerations". Journal of Trauma: Injury, Infection & Critical Care. 60 (6). doi:10.1097/01.ta.0000199961.02677.19. ISSN 0022-5282.
  16. ^ Ruiz, Carolina; Andresen, Max (3 June 2013). "Treatment of Acute Coagulopathy Associated with Trauma". ISRN Critical Care. 2013: 1. doi:10.5402/2013/783478. ISSN 2090-5610.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  17. ^ Brohi, Karim; Singh, Jasmin; Heron, Mischa; Coats, Timothy (June 2003). "Acute Traumatic Coagulopathy". The Journal of Trauma: Injury, Infection, and Critical Care. 54 (6): 1127–1130. doi:10.1097/01.TA.0000069184.82147.06. ISSN 0022-5282. PMID 12813333.
  18. ^ Kaufmann, Christoph R.; Dwyer, Kevin M.; Crews, John D.; Dols, Sheila J.; Trask, Arthur L. (April 1997). "Usefulness of Thrombelastography in Assessment of Trauma Patient Coagulation". The Journal of Trauma: Injury, Infection, and Critical Care. 42 (4). doi:10.1097/00005373-199704000-00023. ISSN 1079-6061.
  19. ^ Pollak, Eleanor S (11 March 2021). Nagalla, Srikanth (ed.). "von Willebrand Disease: Practice Essentials, Etiology, Epidemiology". Medscape Reference. Retrieved 12 April 2021.
  20. ^ Tie, Jian-Ke; Carneiro, Jorge D. A.; Jin, Da-Yun; Martinhago, Ciro D.; Vermeer, Cees; Stafford, Darrel W. (2016). "Characterization of vitamin K–dependent carboxylase mutations that cause bleeding and nonbleeding disorders". Blood. 127 (15). doi:10.1182/blood-2015-10-677633. ISSN 0006-4971. Retrieved 11 April 2021. {{cite journal}}: |archive-date= requires |archive-url= (help)CS1 maint: url-status (link)
  21. ^ Bharati, K Pavani; Prashanth, U. Ram (2011). "Von Willebrand disease: an overview". Indian Journal of Pharmaceutical Sciences. 73 (1). doi:10.4103/0250-474X.89751. PMC 3224412. PMID 22131616.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  22. ^ Amin, Chirag; Sharathkumar, Anjali; Griest, Anne (21 December 2013). "Bleeding diathesis and hemophilias". Handbook of Clinical Neurology. 120: 1046. doi:10.1016/B978-0-7020-4087-0.00070-X. ISSN 0072-9752.
  23. ^ White II, Gilbert; Rosendaal, Frits; Aledort, Louis M.; Lusher, Jeanne M.; RothschilD, Chantal; et al. (29 March 2001). "Definitions in Hemophilia Scientific and Standardization Committee Communication: On behalf of the Subcommittee on Factor VIII and Factor IX of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis" (PDF). International Society on Thrombosis and Haemostasis. p. 1. Retrieved 12 April 2021.
  24. ^ "Acquired Hemophilia". NORD (National Organization for Rare Disorders). 14 January 2020. Retrieved 11 April 2021.
  25. ^ "Factor XI Deficiency". NORD (National Organization for Rare Disorders). 14 January 2020. Retrieved 11 April 2021.
  26. ^ a b Rodeghiero, F.; Tosetto, A.; Castaman, G. (9 July 2007). "How To Estimate Bleeding Risk In Mild Bleeding Disorders". Journal Of Thrombosis And Haemostasis. 5. doi:10.1111/J.1538-7836.2007.02520.X. ISSN 1538-7933. Retrieved 12 April 2021.
  27. ^ ISTH Supplementary Material 2010,  "Any bleeding episode caused by superficial cuts [...] or that requires frequent bandage changes is considered significant. Insignificant bleeding from wounds includes those of duration < 10 minutes and lesions that usually require stitches in normal subjects (e.g., under the chin)."
  28. ^ ISTH Supplementary Material 2010, "In general, epistaxis [nosebleeds] should not be considered significant when it lasts less than 10 minutes, has a frequency of < 5 episodes/year."
  29. ^ a b Sadler, J. Evan (15 March 2003). "Von Willebrand disease type 1: a diagnosis in search of a disease". Blood. 101 (6): 2089. doi:10.1182/blood-2002-09-2892. ISSN 1528-0020. Archived from the original on 11 April 2021.
  30. ^ James, Andra H. (November 2009). "Von Willebrand disease in women: awareness and diagnosis". Thrombosis Research. 124. doi:10.1016/S0049-3848(09)70151-3. ISSN 0049-3848. PMID 19944259.
  31. ^ Krishnadasan, Ravi (1 April 2016). "Diagnosis and Treatment of Benign Bleeding Disorders". Journal of the Advanced Practitioner in Oncology. 7 (3). doi:10.6004/jadpro.2016.7.3.17. PMC 5679052. PMID 29152400.
  32. ^ Chaudhry, Liaqat Ali; El-Sadek, Wael Yasin Mohamed; Chaudhry, Ghazala Aslam; Al-Atawi, Feddha Eid (2019). "Factor XII (Hageman Factor) Deficiency: a rare harbinger of life threatening complications". The Pan African Medical Journal. 33. PMC 6658145. PMID 31384354. {{cite journal}}: |archive-date= requires |archive-url= (help); |archive-url= requires |url= (help)CS1 maint: url-status (link)
  33. ^ Neutze, Dana; Roque, Jodi (15 February 2016). "Clinical Evaluation of Bleeding and Bruising in Primary Care". American Family Physician. 93 (4): 279–286. ISSN 0002-838X. PMID 26926815. Retrieved 11 April 2021.
  34. ^ Critical Care 2021, p. 556.
  35. ^ Green, David; Ludlam, Christopher A. (2013). Fast Facts: Bleeding Disorders (2nd ed.). Abingdon, Oxford: Health Press. ISBN 978-1-908541-38-3. OCLC 846987961.
  36. ^ a b Hurwitz, Alisheba; Massone, Richard; Lopez, Bernard L. (December 2017). "Acquired Bleeding Disorders". Hematology/Oncology Clinics of North America. 31 (6). doi:10.1016/j.hoc.2017.08.012.
  37. ^ Chong, Ji Y. (April 2020). "Subarachnoid Hemorrhage (SAH) - Neurologic Disorders". MSD Manual Professional Edition. Retrieved 12 April 2021.
  38. ^ Chong, Ji Y. (April 2020). "Intracerebral Hemorrhage - Neurologic Disorders". MSD Manual Professional Edition. Retrieved 12 April 2021.
  39. ^ Melchiorre, Daniela; Manetti, Mirko; Matucci-Cerinic, Marco (25 June 2017). "Pathophysiology of Hemophilic Arthropathy". Journal of Clinical Medicine. 6 (7). doi:10.3390/jcm6070063. PMID 28672826.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  40. ^ Zhou, Jenny Y.; Barnes, Richard F. W.; Foster, Gary; Iorio, Alfonso; Cramer, Thomas J.; von Drygalski, Annette (1 January 2019). "Joint Bleeding Tendencies in Adult Patients With Hemophilia: It's Not All Pharmacokinetics". Clinical and Applied Thrombosis/Hemostasis. 25 (1). doi:10.1177/1076029619862052. PMID 31298044.
  41. ^ Donaldson, James; Goddard, Nicholas (29 May 2015). "Compartment syndrome in patients with haemophilia". Journal of Orthopaedics. 12 (4): 237–41. doi:10.1016/j.jor.2015.05.007. PMC 4601993. PMID 26566325.
  42. ^ "Desmopressin Monograph for Professionals". Drugs.com. 22 January 2021. Retrieved 11 April 2021.
  43. ^ Huang, Liang; Liu, Geoffrey L.; Kaye, Alan D.; Liu, Henry (19 August 2020). "Advances in Topical Hemostatic Agent Therapies: A Comprehensive Update". Advances in Therapy. 37 (10). Springer Science and Business Media LLC. Topical Active Hemostats. doi:10.1007/s12325-020-01467-y. ISSN 0741-238X.
  44. ^ Chiara, Osvaldo; Cimbanassi, Stefania; Bellanova, Giovanni; Chiarugi, Massimo; Mingoli, Andrea; et al. (29 August 2018). "A systematic review on the use of topical hemostats in trauma and emergency surgery". BMC Surgery. 18 (1). Mechanical Hemostats. doi:10.1186/s12893-018-0398-z. PMID 30157821. Retrieved 12 April 2021.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  45. ^ Burnouf, Thierry (April 2007). "Modern Plasma Fractionation". Transfusion Medicine Reviews. 21 (2). doi:10.1016/j.tmrv.2006.11.001. PMC 7125842. PMID 17397761.
  46. ^ Farrugia, Albert (1 March 2018). "Factor VIII manufactured from plasma—the ups and downs, and the up again: a personal journey—part 1: history of the development of plasma-derived factor VIII therapies". Annals of Blood. 3 (2). Developments in the manufacture of pd-FVIII in the post-AIDS era. ISSN 2521-361X. Retrieved 11 April 2021.
  47. ^ Donegan, Elizabeth (October 2003). "Transmission of HIV by Blood, Blood Products, Tissue Transplantation, and Artificial Insemination". HIV InSite Gateway to HIV and AIDS Knowledge. Clotting Factor Concentrates. Retrieved 11 April 2021.
  48. ^ Roth, Willi Kurt (April 2019). "History and Future of Nucleic Acid Amplification Technology Blood Donor Testing". Transfusion Medicine and Hemotherapy. 46 (2). doi:10.1159/000496749. ISSN 1660-3796. PMID 31191192. Retrieved 12 April 2021.
  49. ^ Shaz, Beth H. (20 May 2009). "Transfusion Transmitted Diseases". Transfusion Medicine and Hemostasis. Retroviruses. doi:10.1016/B978-0-12-374432-6.00066-X. Retrieved 12 April 2021.
  50. ^ Wells, Jack C.; Stevermer, James J. (May 2013). "PURLs: Trauma care--don't delay with TXA". The Journal of Family Practice. 62 (5). PMC 3646726. PMID 23691542.
  51. ^ Roberts, Ian; Shakur, Haleema; Afolabi, Adefemi; Brohi, Karim; Coats, Tim; et al. (24 March 2011). "The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial". The Lancet. 377 (9771). doi:10.1016/S0140-6736(11)60278-X. PMID 21439633.
  52. ^ Shakur, Haleema; Roberts, Ian; Perel, Pablo (25 September 2010). "Tranexamic acid for trauma – Authors' reply". The Lancet. 376 (9746): 1050–1051. doi:10.1016/S0140-6736(10)61479-1. ISSN 0140-6736.
  53. ^ a b Ackery, Alun; Rizoli, Sandro (21 October 2014). "Tranexamic acid for trauma-related hemorrhage". CMAJ: Canadian Medical Association Journal. 186 (15). doi:10.1503/cmaj.131741. PMID 25047987. Retrieved 12 April 2021.
  54. ^ "Tranexamic acid should not be used for patients with severe gastrointestinal bleeding". National Institute for Health Research. 28 September 2020. Retrieved 12 April 2021.
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