Question 13.2

A 44-year-old male presents with dyspnoea and is diagnosed as having multiple pulmonary emboli on a computerised tomography pulmonary angiogram (CTPA). He is commenced on 1000 units of heparin per hour IVI after a 5000 unit intravenous bolus. During the night his heparin infusion has steadily increased to 1500 units per hour.
These blood results are from the following morning:


Patient Value

Normal Adult Range

Prothrombin Time

12 seconds

12 – 16

Acivated Partial Thromboplastin Time

38.3 seconds*

25.0 – 37.0


3.8 G/L

2.2 – 4.3


> 20.0 mg/ml*

< 0.5

a) Give two reasons for the relatively low APTT despite heparin therapy.
b) List four causes for an increased predisposition to venous thromboembolic disease.

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College Answer


  • ATIII deficiency
  • Increased heparin clearance
  • Increased heparin binding proteins
  • Technical problems such as drug preparation error, disconnected IV line, pump problem, extravasated IV cannula


  • Protein C def Protein S def
  • AT III def
  • Malignancy
  • Factor V Leiden Lupus anticoagulant
  • Immobility
  • Smoking
  • Cardiac failure
  • Local venous obstruction
  • Surgery
  • Trauma
  • Obesity



Some discussion of the management of heparin resistance goes on in the end of my brief pharmacological entry on unfractionated heparin.

Reasons one might be resistant to heparin:

  • Increased heparin-binding protein levels (all of them are acute phase reactants)
  • Low antithrombin-III levels (i.e. nothing for heparin to bind)
  • Increased heparin clearance (eg. due to splenomegaly in liver disease)
  • Factitious heparin resistance (eg. the heparin is not even connected to the line)

Predisposing factors for PE:

  • Major general surgery
  • Major orthopedic surgery
  • Spinal cord injury
  • Hip, pelvis and long bone fractures
  • Multiple trauma
  • Malignancy
  • Myocardial infarction
  • CCF
  • Prior PE
  • Obesity
  • Age (>40)
  • Immobility
  • Varicose veins
  • Pregnancy
  • Oral contraceptives
  • Smoking
  • Antiphospholipid syndrome
  • Protein C and S deficiency
  • Antithrombin deficiency
  • Factor V Leiden mutation


Anderson, J. A. M., and E. L. Saenko. "Editorial I Heparin resistance." British journal of anaesthesia 88.4 (2002): 467-469.

Young, E., et al. "Heparin binding to plasma proteins, an important mechanism for heparin resistance." Thrombosis and haemostasis 67.6 (1992): 639-643.

Hirsh, J., et al. "Heparin kinetics in venous thrombosis and pulmonary embolism." Circulation 53.4 (1976): 691-695.

Anderson, Frederick A., and Frederick A. Spencer. "Risk factors for venous thromboembolism." Circulation 107.23 suppl 1 (2003): I-9.