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:

Parameter	Patient Value	Normal Adult Range
Prothrombin Time	12 seconds	12 – 16
Acivated Partial Thromboplastin Time	38.3 seconds*	25.0 – 37.0
Fibrinogen	3.8 G/L	2.2 – 4.3
D-Dimer	> 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

Discussion

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

References

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.

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