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Coagulation and Anticoagulants

Must KnowApplied Basic SciencesthinKbox SBA

Haemostasis

Haemostasis involves:

  1. vasoconstriction
  2. platelet adhesion and aggregation
  3. activation of the coagulation system
  4. fibrin formation
  5. clot stabilisation and later fibrinolysis

The classic intrinsic/extrinsic pathway model is useful for laboratory interpretation, although in vivo coagulation is better understood as a cell-based process.

Normal haemostasis requires coordinated interaction between:

  • vessel wall
  • platelets
  • coagulation factors
  • natural anticoagulant systems
  • fibrinolysis

Primary haemostasis forms a platelet plug. Secondary haemostasis stabilises it with fibrin.

The traditional intrinsic/extrinsic pathway diagram is useful for laboratory interpretation, but in vivo coagulation is better understood as a cell-based process initiated by tissue factor and amplified on activated cellular surfaces.

Laboratory tests

Prothrombin time

PT mainly reflects the tissue-factor/extrinsic and common pathways.

Common clinical uses:

  • monitoring vitamin K antagonist effect using INR
  • assessing selected acquired or inherited factor abnormalities

Activated partial thromboplastin time

APTT mainly reflects intrinsic and common pathway factors.

It may be prolonged in:

  • haemophilia
  • unfractionated heparin effect
  • some factor deficiencies or inhibitors

Platelet disorders

Platelet number and platelet function are not adequately described by PT or APTT alone.

PT/INR predominantly reflects the extrinsic/common pathway and is used to monitor warfarin.

aPTT reflects the intrinsic/common pathway and is used in some settings to monitor unfractionated heparin.

A normal PT and aPTT do not exclude every clinically important bleeding disorder, particularly platelet dysfunction or von Willebrand disease.

Important factor deficiencies

  • haemophilia A: factor VIII deficiency
  • haemophilia B: factor IX deficiency

Both classically prolong APTT with a normal PT when the defect is isolated.

Anticoagulant mechanisms

Heparins

Enhance antithrombin activity. Unfractionated heparin has strong activity against thrombin and factor Xa; low-molecular-weight heparins have proportionally greater anti-Xa effect.

Warfarin

Reduces synthesis of vitamin K-dependent factors II, VII, IX and X and also affects proteins C and S.

Direct oral anticoagulants

  • direct factor Xa inhibitors include rivaroxaban and apixaban
  • dabigatran directly inhibits thrombin

Antiplatelet drugs

Aspirin irreversibly inhibits platelet cyclo-oxygenase and reduces thromboxane production.

Clopidogrel inhibits the platelet P2Y12 ADP receptor.

Virchow triad

Venous thrombosis is promoted by:

  • venous stasis
  • endothelial injury
  • hypercoagulability

Orthopaedic trauma and surgery may contribute to all three.

Perioperative assessment

Before surgery consider:

  • indication for anticoagulation
  • thrombotic risk if treatment is interrupted
  • bleeding risk of the procedure
  • renal function
  • drug half-life
  • whether neuraxial anaesthesia is planned
  • availability of reversal strategies

Specific perioperative stop/restart intervals should follow current local or national guidance rather than a fixed memorised rule.

Platelets

Vascular injury exposes subendothelial structures. Platelets adhere, activate and aggregate. Von Willebrand factor is important in platelet adhesion, particularly under high shear.

Antiplatelet drugs interfere with platelet activation or aggregation and therefore affect primary haemostasis rather than the coagulation factor cascade.

Coagulation and fibrin

Thrombin converts fibrinogen to fibrin and also amplifies coagulation through several feedback mechanisms. Factor XIII stabilises the fibrin clot through cross-linking.

Vitamin K is required for normal synthesis of several coagulation proteins. Warfarin interferes with vitamin K recycling and therefore reduces functional levels of vitamin K-dependent factors.

Common anticoagulants

Low-molecular-weight heparin acts mainly through antithrombin with strong inhibition of factor Xa and some thrombin effect.

Unfractionated heparin has a shorter half-life and can be reversed with protamine, making it useful when rapid titration is needed.

Direct oral anticoagulants target either factor Xa or thrombin depending on the drug. Their perioperative interruption depends on:

  • renal function
  • bleeding risk of the procedure
  • drug half-life
  • urgency
  • thrombosis risk

Venous thromboembolism

Orthopaedic patients can have high VTE risk because of:

  • trauma
  • lower-limb surgery
  • immobility
  • inflammatory response
  • malignancy
  • previous VTE
  • patient comorbidity

Prevention combines early mobilisation, mechanical methods and pharmacological prophylaxis according to individual risk and local guidance.

Tranexamic acid

Tranexamic acid is an antifibrinolytic lysine analogue. It inhibits binding of plasminogen/plasmin to fibrin and reduces fibrin breakdown. It does not “make new clot” in the same way as a procoagulant drug; it stabilises clot by reducing fibrinolysis.

Perioperative reasoning

For an anticoagulated patient, determine:

  • indication for anticoagulation
  • thrombotic risk if interrupted
  • drug and last dose
  • renal function
  • urgency and bleeding risk of surgery
  • availability of reversal
  • plan for restarting therapy

FRCS synthesis

The exam-level skill is balancing bleeding risk against thrombosis risk. Avoid rigid rules without context; show that timing and reversal depend on the drug, renal clearance, operation and indication.

Written/reviewed by Kishore Puthezhath

Professor of Orthopaedics and Consultant Paediatric Orthopaedic Surgeon

FRCS (Tr & Orth) revision resource

Reviewed: September 2026