Coagulation Disorders by David Leather https://padlet.com/dleather2000/20hvge3wjnkzt5n7 en-us 2021-10-03 14:16:13 UTC 2024-10-16 06:37:27 UTC hello@padlet.com Blood components dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787357714 2021-10-03 14:20:12 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787357714 Haemostasis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787359626 - Definition: host defense mechanism that protects this integrity after injury to the vessel wall and tissue injury.


- Primary & Secondary:
  • Primary: vasoconstriction, primary response to injury, platelet plug
  • Secondary: recruitment of clotting factors
]]> 2021-10-03 14:21:18 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787359626 Primary haemostasis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787361269
  • What is the role of the vessel wall? - normally prevents platelet adhesion and thrombus formation via endothelium lining. Injury causes reflex vasoconstriction, endothelium damage results in loss of antithrombic properties, activation of platelets, and coagulation and inhibition of fibrinolysis.

    • Platelets
      • Platelets adhesion:
      • Platelet release:
      • Platelet aggregation:
      • Platelet coagulation:

    ]]>     2021-10-03 14:22:13 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787361269     Secondary haemostasis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787361938
  • Coagulation cascade
    • Coagulation factors: synthesized in the liver. Factor II = prothrombin.
    • Coagulation pathway (explain): Xa initiated by the extrinsic pathway, amplified by the intrinsic pathway.
    • VWF & factor VIII: VWF is a glycoprotein, released from platelet granules and endothelial cells. Prevent premature Factor VIII breakdown.

    • ]]>     2021-10-03 14:22:34 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787361938     Physiological limitations of coagulation dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787368113
  • Antithrombin
  • Activated protein C
  • Protein S
    • ]]>     2021-10-03 14:25:50 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787368113     Fibrinolysis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787369043
  • What is fibrinolysis? (explain)
    • Hemostatic response that helps restore vessel patency after vascular damage.

    Principle component is the serine protease plasmin, which can break down fibrinogen and fibrin to fibrin (and fibrinogen) degradation products.

    ]]>     2021-10-03 14:26:17 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787369043     Investigations of bleeding disorders dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787382862
  • Vascular/platelet bleeding: characterized by bruising and spontaneous bleeding from small vessels. Bleeding into the skin--purpura. Bleeding also occurs from mucous membranes.

    • Coagulation disorders: typically associated with bleeding after injury or surgery. Short delay between precipitating event and overt haemmorhage or haematoma formation.
    ]]>     2021-10-03 14:33:08 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787382862     Thrombocytopenia dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787387358
  • definition: caused by reduced platelet production in the bone marrow, excessive peripheral destruction of platelets, or sequestration in an enlarged spleen.

    • investigations: examine bone marrow (to check number of megakaryocytes)

    • treatment: no treatment needed unless severe.
    ]]>     2021-10-03 14:35:27 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787387358     Thrombcytosis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787388646
  • definition: increased platelet count (acute-phase reaction)

    • causes: slenectomy, malignant disease, inflammatory disorders (eg rheumatoid arthritis, inflammatory bowel disease), major surgery + post haemorrhage, myeloproliferative disorders, iron deficiency
    ]]>     2021-10-03 14:36:05 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787388646     Haemophilia A (Reduced FVIII) dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787390450
  • Aetiology: lack of factor VIII while the VWF is normal.

    • Inheritance: genetic defect. Inversion in intron 22. X-linked disorder.

    • Prevalence: 1 in 5,0000 of the male population.

    • Clinical and laboratory features: severe, moderate, and mild. Ask about the nature of bleeding: severe begins spontaneously, moderate is severe bleeding following an injury, mild is only bleeding after an injury.
      • measure the prothrombin time, thrombin time. (PT, bleeding time.)

    • Treatment: administration of factor VIII.

    • Complications: development of antibodies to factor VIII in 30% of people with severe haemophilia.

    ]]>     2021-10-03 14:37:03 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787390450     Haemophilia B (Reduced FIX) dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787391604 Deficiency of factor IX. Inheritance and clinical features identical to haemophilia a, but incidence is only about 1 in 30,000 males.]]> 2021-10-03 14:37:38 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787391604 Von Willebrand's disease (VWD) dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787392831
  • Aetiology: defective platelet function as well as factor VIII deficiency, both due to a deficiency or abnormality in VWF.

    • Types: Located on chromosome 12.
      • Type 1 is partial quantitative deficiency of VWF and
        significant type 1 VWD is usually inherited as an
        autosomal dominant.
      • Type 2 is due to a qualitative abnormality of VWF, and it too is usually inherited as an autosomal dominant.
      • Type 3 is recessively inherited and patients have
        virtually complete deficiency of VWF. Their parents are often phenotypically normal.

    • Clinical features: Type 3 patients severe bleeding, joint and muscle pains. Types 1 + 2 usually mild clinical factors. Rarely experience joint and muscle bleeds seen in haemophilia A.

    • Treatment: desmopressin, replacement therapy (surgery) in type 3 (severe).
    ]]>     2021-10-03 14:38:14 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787392831     Vitamin K Deficiency dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787394550
  • What role does vitamin K play? - without it, factors II, VII, IX, and X cannot bind to calcium.

    • Aetiology: inadequate stores, malabsorption of vitamin K, oral anticoagulant drugs.

    • Newborn babies? - low levels of vitamin K, all babies given a prophylactic dose of vitamin K.
    ]]>     2021-10-03 14:39:08 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787394550     What is a thrombus? dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787396127 A solid mass formed in the circulation. Fragments (emboli) may break off and block vessels.

    ]]>     2021-10-03 14:39:58 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787396127     Arterial thrombosis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787398442
  • Explanation: "white thrombus," unlike "red thrombus" in venous thrombi. Plaque rupture leads to exposure of blood containing factor VIIa to tissue factor within the plaque, which may trigger blood coagulation and thrombus formation.

    • Prevention and treatment of arterial thrombosis: minimizing factors predisposing to atherosclerosis. Treatment includes antiplatelet drugs + thrombolytic therapy.

    • Antiplatelet drugs:
      • aspirin: COX inhibitor
      • dipyridamole: inhibits platelet phosphodiesterase, causing increase in cAMP.
      • glycoprotein IIb/IIIa receptor antagonists: block receptor on platelet for fibrinogen and von Willebrand factor.
    ]]>     2021-10-03 14:41:09 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787398442     Venous thrombosis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787400108
  • Where does it occur?

    • Major causes of venous thrombosis?

    • How does it differ from arterial thrombosis? ("red thrombus")

    • Risk factors (table 8.26)
      • Inherited
        • Thrombophilia
        • Coagulation abnormalities
      • Acquired

    • Investigations
      • Haemostatic screening test: full blood count (including platelet count). Coagulation screen (including fibrinogen level) will detect erythrocytes, thrombocytosis, and dysfibrinogenaemia.
      • Testing for specific causes of thrombophilia: Assays for naturally occurring anticoagulants, assay for activated protein C and molecular testing for factor V Leiden and the prothrombin variant, screen for coagulation factor

    • Prevention and treatment of venous thrombosis
      • Anticoagulants 
        • Heparin: mixture of polysaccharides, initially extracted from the liver. Binds to antithrombin, which increases inhibitory activity of antithrombin.
        • LMW heparin: potentiation of thrombin inhibition.
      • Direct thrombin inhibitors
        • Oral anticoagulants (characteristics, contraindications, and complications)
          • contraindications: severe uncontrolled hypertension, non-thromboembolic strokes, peptic ulceration, severe liver and renal disease, pre-existing haemostatic defects, non-compliance, pregnancy

    ]]>     2021-10-03 14:42:04 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787400108     Deep venous thrombosis dleather2000 https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787401868
  • When and where? immobility, pregnancy, risk factors (diagram below)


    • Clinical features: figure below

    • Investigations: D-dimer level, confirmed with CT or V:Q scan. Wells criteria can be used to determine risk of pulmonary embolism.
      • Venography in the lower leg

    • Treatment: anticoagulants
    ]]>     2021-10-03 14:43:01 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787401868     mankshbasel https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787644658 2021-10-03 17:05:55 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1787644658 Platelet adhesion, aggregation, release jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788766796 2021-10-04 07:09:30 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788766796 Diagnostics jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788797135 also: look back to lectures!]]> 2021-10-04 07:25:35 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788797135 Arterial v Venous thrombosis jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788816917 2021-10-04 07:35:33 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788816917 Virchow's triad jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788827884 2021-10-04 07:40:59 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788827884 jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788830019 2021-10-04 07:42:04 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788830019 Clinical Features of DVT jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788847466 2021-10-04 07:51:05 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788847466 jasminedragomir https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788857703 Look at terminology mentioned in problem (e.g. prothrombin time).

    Look at the lecture (very important) and study drugs mentioned there.]]>     2021-10-04 07:56:42 UTC https://padlet.com/dleather2000/20hvge3wjnkzt5n7/wish/1788857703