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Coagulopathy

Bleeding Disorders (Coagulopathy)
Classification and external resources
Specialty hematology

A bleeding disorder (coagulopathy) is a condition that affects the way the blood clots. It is characterised by prolonged/excessive bleeding following injury or medical and dental procedures.[1] In some instances spontaneous bleeding can occur into joints, muscles or other parts of the body.[2] Irregular clotting can be due to deficiencies and defects in blood platelets and/or clotting factors.[2] The body produces 13 clotting factors.[3] Blood clotting is affected if any of the clotting factors are deficient or defective.[4]

Bleeding disorders can be inherited or acquired. Some bleeding disorders can occur due to conditions such as anemia, vitamin K deficiency, leukemia, cirrhosis of the liver and HIV.[5] They also can result from certain medications that are used to thin the blood, including antiplatelet and anticoagulant medications. Platelets are a components of blood that stop bleeding by clotting blood at the site of blood vessel injuries.[6]

Examples of inherited bleeding disorders include Haemophilia A, Haemophilia B[7] and von Willebrand Disease.[8] Bleeding disorders can be acquired due to antiplatelet and anticoagulant medications that are taken for the prophylaxis and treatment of medical conditions such as atrial fibrillation, deep vein thrombosis (DVT), Stroke, Pulmonary Embolism and heart attack.[9] Examples of these medications include Aspirin and Clopidogrel (antiplatelets), Warfarin (anticoagulant) and Novel Oral Anticoagulant medications (NOACs) such as Rivaroxaban,[10] Apixaban[11] and Dabigatran.[12]

Thrombocytopenia is a condition characterized by abnormally low levels of platelets (thrombocytes) in the blood.[13] It can be caused by

  1. Decreased platelet production
  2. Increased platelet destruction or consumption
  3. Increased splenic sequestration (capturing of circulating platelets in the spleen)

Signs and symptoms

Signs of bleeding disorders include:[14]

  • Bruising (purpura)
  • Bleeding into muscles and joints which may have symptoms of:
    • an ache
    • swelling
    • pain
    • stiffness
    • stiff joint or muscle if affected[15]
  • Heavy bleeding following dental treatment and small injuries
  • Nosebleeds
  • Bleeding into joints
  • Excessive bleeding following surgery
  • Bleeding gums
  • Menorrhagia
  • Blood in the urine or stools

Coagulopathy may cause excessive external and/or internal bleeding. Uncontrolled bleeding may cause damage to internal organs, joints and muscles. If this is left untreated it may be life-threatening.[16]

Additional signs and symptoms of Thrombocytopenia include:

  • Superficial bleeding into the skin which appears as small red spots (petechiae)
  • Fatigue
  • Jaundice
  • Enlarged spleen

Risk factors

Drugs That Can Cause Bleeding

Aceclofenac

Acenocoumarol

Acetylsalicylic acid (Aspirin)

Citalopram*

Clopidogrel

Dexibrufen

Diclofenac

Dicoumarol

Escitalopram

Fluoxetine*

Fluvoxamine*

Ibuprofen

Indomethacin

Ketoprofen

Ketorolac

Lornoxicam

Meloxicam

Nabumetone

Naproxen

Paroxetine*

Phenprocoumon

Piroxicam

Sertraline*

Sulindac

Tenoxicam

Ticlopidine

Warfarin

Drugs marked with * only have a mild inhibiting effect on the platelet function, which may increase bleeding slightly.[17]

Apixaban, Rivaroxaban and Dabigatran (NOACs) are included in the list of drugs that can cause bleeding.[18]

Mechanism

Platelets

The normal clotting process depends on the interplay of various proteins in the blood called clotting factors.[3] Coagulopathy may be caused by reduced levels or absence of blood-clotting proteins, known as clotting factors or coagulation factors. Genetic disorders, such as hemophilia and Von Willebrand's disease, can cause a reduction in clotting factors.[19]

Anticoagulants such as warfarin will also prevent clots from forming properly.[19] Coagulopathy may also occur as a result of dysfunction or reduced levels of platelets (small disk-shaped bodies in the bloodstream that aid in the clotting process).

Warfarin is a vitamin K antagonist. It decreases blood clotting by blocking an enzyme called vitamin K epoxide reductase which blocks vitamin K activation. In turn, clotting factors II, VII, IX, and X have decreased clotting ability.[20]

Rivaroxaban is an anticoagulant and is a direct factor Xa inhibitor.[21]

Apixaban is an anticoagulant - factor Xa inhibitor for the prevention and treatment of thromboembolic diseases.[22]

Aspirin inhibits platelet function by acetylation of the platelet cyclooxygenase (COX).[23]

Diagnosis

Routine screening tests include:

  • Complete blood cell count[24]
  • Platelet count
  • Evaluation of a peripheral blood sample
  • Prothrombin time (PT)[25] also known as 'International Normalised Ration' (INR) - a test that measures how long it takes a blood clot to form[26]
  • Activated Partial Thromboplastin Time (APTT)[25]
  • Partial Thromboplastin Time
  • Platelet aggregation test[27]

The PTT or APTT is a medical test that characterises blood coagulation (clotting).[28] The PTT and PT tests are also used to monitor oral anticoagulant therapy[29] such as Warfarin.[30] People who take Warfarin will have their INR routinely monitored to ensure it is within the therapeutic range. The longer it takes blood to clot, the higher the INR will be.[31]

The PTT is used in conjunction with another test that measures how quickly blood clotting takes place called the prothrombin time (PT). The prothrombin time measures the speed of clotting by means of the extrinsic pathway (also known as the tissue factor pathway).[28]

Hemophilia is diagnosed by measuring the level of factor activity in a blood sample:

  • Hemophilia A is diagnosed by testing the level of factor VIII activity
  • Hemophilia B is diagnosed by measuring the level of factor IX activity[15]

Testing for von Willebrand Disease involves measuring the level and activity of VWF, and that of another blood clotting protein, factor VIII (FVIII). in an individual's blood.[32]

Treatment

If someone has coagulopathy, their health care provider may help them manage their symptoms with medications or replacement therapy. In replacement therapy, the reduced or absent clotting factors are replaced with proteins derived from human blood or created in the laboratory. This therapy may be given either to treat bleeding that has already begun or to prevent bleeding from occurring.[33]

For people who require rapid reversal of warfarin in cases of serious bleeding or emergency surgery, the effects of warfarin can be reversed with vitamin K, prothrombin complex concentrate (PCC), or fresh frozen plasma (FFP). Blood products should not be routinely used to reverse warfarin overdose when vitamin K could work alone.[20]

Treatment for haemophilia requires the missing clotting factor to be administered into the bloodstream. People with mild hemophilia A may sometimes use desmopressin (also called DDAVP) to treat minor bleeding. DDAVP is a synthetic hormone that stimulates the release of factor VIII.[34]

VWD can be treated with Desmopressin or with a clotting factor concentrate that contains VWD.[35]

Critical Care

One area of treatment is managing people with major bleeding in a critical setting, like an emergency department.[36] In these situations, the common treatment is transfusing a combination of red cells with one of the following options:[citation needed]

The use of tranexamic acid is the only option that is currently supported by a large, randomized, controlled clinical trial, and is given to people with major bleeding after trauma.[37] There are several possible risks to treating coagulopathies, such as transfusion-related acute lung injury, acute respiratory distress syndrome, multiple organ dysfunction syndrome, major hemorrhage, and venous thromboembolism.

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
Haemophilia 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

See also

References

  1. ^ "What is a Bleeding Disorder?". National Hemophilia Foundation. 2014-03-04. Retrieved 2018-03-13. 
  2. ^ a b "What are bleeding disorders? - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-14. 
  3. ^ a b "Clotting Factors List – Names, Numbers and Actions (Functions) | Healthhype.com". www.healthhype.com. Retrieved 2018-03-14. 
  4. ^ "What is a Bleeding Disorder?". National Hemophilia Foundation. 2014-03-04. Retrieved 2018-03-14. 
  5. ^ "What is a Bleeding Disorder?". National Hemophilia Foundation. 2014-03-04. Retrieved 2018-03-21. 
  6. ^ "Platelet". Wikipedia. 2018-03-16. 
  7. ^ "What is hemophilia? - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-14. 
  8. ^ "What is von Willebrand disease? - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-14. 
  9. ^ "Anticoagulant medicines". nhs.uk. Retrieved 2018-03-14. 
  10. ^ "Rivaroxaban". Wikipedia. 2018-02-20. 
  11. ^ "Apixaban". Wikipedia. 2018-02-16. 
  12. ^ "Dabigatran". Wikipedia. 2018-02-09. 
  13. ^ "Thrombocytopenia". Wikipedia. 2018-03-12. 
  14. ^ "Bleeding Disorders". www.hematology.org. 2017-09-08. Retrieved 2018-03-20. 
  15. ^ a b "Symptoms and diagnosis of hemophilia - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-21. 
  16. ^ "Coagulopathy - Symptoms, Causes, Treatments". 2014-06-26. Retrieved 2018-03-20. 
  17. ^ "Drugs that can cause bleeding - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-20. 
  18. ^ "Novel anticoagulants". www.bhf.org.uk. Retrieved 2018-03-21. 
  19. ^ a b Spahn, DR.; Bouillon, B.; Cerny, V.; Coats, TJ.; Duranteau, J.; Fernández-Mondéjar, E.; Filipescu, D.; Hunt, BJ.; et al. (Apr 2013). "Management of bleeding and coagulopathy following major trauma: an updated European guideline". Crit Care. 17 (2): R76. doi:10.1186/cc12685. PMC 4056078Freely accessible. PMID 23601765. 
  20. ^ a b "Warfarin". Wikipedia. 2018-03-07. 
  21. ^ "Rivaroxaban". www.drugbank.ca. Retrieved 2018-03-21. 
  22. ^ "Apixaban". www.drugbank.ca. Retrieved 2018-03-21. 
  23. ^ Schrör, K. (1997). "Aspirin and platelets: the antiplatelet action of aspirin and its role in thrombosis treatment and prophylaxis". Seminars in Thrombosis and Hemostasis. 23 (4): 349–356. doi:10.1055/s-2007-996108. ISSN 0094-6176. PMID 9263351. 
  24. ^ "Complete blood count (CBC) - About - Mayo Clinic". www.mayoclinic.org. Retrieved 2018-03-20. 
  25. ^ a b "UpToDate". www.uptodate.com. Retrieved 2018-03-20. 
  26. ^ "Prothrombin Time and INR". wa.kaiserpermanente.org. Retrieved 2018-03-20. 
  27. ^ "Bleeding Disorders: Causes, Types, and Diagnosis". Healthline. Retrieved 2018-03-20. 
  28. ^ a b "Partial thromboplastin time". Wikipedia. 2018-01-31. 
  29. ^ Brohi, Karim (2009). "Diagnosis and management of coagulopathy after major trauma". British Journal of Surgery Society. 96: 963–964 – via Wiley Online Library. 
  30. ^ "UpToDate". www.uptodate.com. Retrieved 2018-03-20. 
  31. ^ "Warfarin". nhs.uk. Retrieved 2018-03-21. 
  32. ^ "VWD - Symptoms and diagnosis - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-21. 
  33. ^ "Coagulopathy - Symptoms, Causes, Treatments". 2014-06-26. Retrieved 2018-03-21. 
  34. ^ "Treatment of hemophilia - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-21. 
  35. ^ "Treatment of VWD - World Federation of Hemophilia". www.wfh.org. Retrieved 2018-03-21. 
  36. ^ Hunt, Beverley J. (2014). "Bleeding and Coagulopathies in Critical Care". New England Journal of Medicine. 370 (9): 847–859. doi:10.1056/NEJMra1208626. ISSN 0028-4793. 
  37. ^ Shakur, Haleema; Roberts, Ian; Perel, Pablo (2010). "Tranexamic acid for trauma – Authors' reply". The Lancet. 376 (9746): 1050–1051. doi:10.1016/S0140-6736(10)61479-1. ISSN 0140-6736. 

External links

Classification