Interpretation of coagulation screen

• Tissue factor is added to blood in the laboratory to activate the extrinsic pathway. Clotting time (PT) is measured in seconds (normal usually = 12-13). However, the PT may vary depending on the reagent used, so the laboratory can use the PT to calculate the INR to standardise results (normal = 0.8-1.2).
• WEPT – Warfarin Extrinsic Prothrombin Time
• Only factor VII is involved in the extrinsic pathway, before the common pathway. Isolated factor VII deficiencies are rare, so PT/INR is only really affected by globally reduced clotting factor synthesis or increased
  • Warfarin/vitamin K deficiency
  • Liver disease
  • Disseminated intravascular coagulation

• A contact activator is added to blood in the laboratory to activate the intrinsic pathway. Clotting time (APTT) is measured in seconds (normal usually = 30-50). The APTT can be divided by the mean normal value to calculate the APTT ratio if required.
• The APTT involves similar clotting factors to the extrinsic pathway PLUS others (VIII, IX, XI) so is affected by:
  • Warfarin/vitamin K deficiency
  • Liver disease
  • Disseminated intravascular coagulation
  • PLUS anything which affects factor VIII (haemophilia A/von Willebrand disease), factor IX (haemophilia B), or factor XI (haemophilia C)

NB: factor XII is also involved in the intrinsic pathway but isolated deficiencies are rare.

NB: antiphospholipid syndrome is a common cause of a misleadingly prolonged APTT, due to antibody-mediated inactivation of the phospholipid added in the laboratory to activate the intrinsic pathway.

• Involves making an incision in the patient’s skin and timing how long it takes to stop bleeding
• Measures platelet plug formation so only affected by conditions involving platelet quantity/function
• Rarely used in practice

• Fibrinogen is a clotting factor involved in the final stage of coagulation
• The fibrinogen level reflects the blood’s clotting ability (low = increased bleeding risk; high = may increase clotting)
• Low levels are due to: increased consumption (e.g. disseminated intravascular coagulation) or decreased production (e.g. liver disease, malnutrition)
• Fibrinogen is an acute phase protein and high levels may be due to: inflammation, malignancy, trauma, or infection

• Vitamin K is a fat-soluble vitamin so may be deficient if there is fat malabsorption (e.g. in biliary obstruction – check LFTs) or a simple dietary deficiency
• Deficiency leads to reduced synthesis of vitamin K dependent clotting factors (2, 7, 9, 10) and so affects both intrinsic and extrinsic pathways
• If due to dietary deficiency, treat with oral vitamin K (phytomenadione) 5-10mg OD for 3 days; if due to fat malabsorption, give IV vitamin K or oral menadiol (a water-soluble vitamin K derivative)

• The liver synthesises most clotting factors so liver disease can result in a global deficiency, affecting both intrinsic and extrinsic pathways
• Platelets may also be reduced due to hypersplenism
• Liver-related coagulopathy is difficult to manage and is mainly supportive (e.g. FFP, cryoprecipitate, platelet transfusions as required). Vitamin K may be given if deficiency is suspected.

• In severe systemic illness, dying cells release procoagulants, resulting in fibrin generation, which can occlude small vessels
• This process consumes platelets and clotting factors, resulting in bleeding elsewhere
• Blood tests reveal thrombocytopenia; increased PT/INR and APTT; low fibrinogen; and raised D-dimer and fibrin degradation products
• Treat the cause and give supportive therapies (e.g. blood, platelets, FFP, cryoprecipitate)

• Reduces synthesis of vitamin K dependent clotting factors (II, VII, IX, X) and so affects both intrinsic and extrinsic pathways
• Its effect is monitored using INR, which is a measure of the extrinsic pathway
• It can be reversed using prothrombin complex concentrate and vitamin K

Heparin is an anticoagulant that increases antithrombin activity by enhancing its binding to factor Xa and thrombin. Types of heparin that are commonly used include:

• Subcutaneous LMWH (e.g. enoxaparin): most commonly used for prophylactic and therapeutic anticoagulation. LMWH consists of only short chain heparins, so most of its activity is mediated by inhibition of factor Xa. Its effects are therefore more predictable than those of standard (unfractionated) heparin. Monitoring is not routinely required, but its effect can be measured by anti-factor Xa assay.
• IV or subcutaneous unfractionated (standard) heparin: consists of heparin chains with a variety of molecular lengths. Its effect on the coagulation cascade is therefore more wide-ranging and less predictable
  • Subcutaneous therapy may be used for prophylactic anticoagulation in patients with reduced renal function, since unfractionated heparin is predominately cleared by the liver, whereas LMWH is not.
  • IV heparin has a short half life and stops working after 4 hours. It can therefore be used for therapeutic anticoagulation peri-operatively, or if there is significant risk of bleeding. It must be monitored regularly, using the APTT ratio, and dose-adjusted according to hospital guidelines.

Both types of heparin can be reversed with protamine sulphate if required.

• Haemophilia A = factor VIII deficiency
• Haemophilia B = factor IX deficiency
• Haemophilia C = factor XI deficiency

Clinical features depend on levels of affected factor but characteristically include haemarthroses and muscle haematomas.

• Antiphospholipid antibodies react against proteins that bind to plasma membrane phospholipids, resulting in arterial and venous thrombosis
• Antiphospholipid syndrome misleadingly causes a prolonged APTT because the antibodies inactivate the phospholipid added to activate the intrinsic pathway during the laboratory measurement of APTT
• Antiphospholipid antibody testing:
• • Lupus anticoagulant assay
  • Anticardiolipin antibodies
  • Anti-β2 glycoprotein I antibodies

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