Question 3.3

A 75-year-old patient weighing 78kg was admitted with an acute pulmonary embolism. A heparin infusion was commenced with a dose of 1550 U/hr. Forty-eight hours later the following results were obtained:

Parameter

Patient Value

Adult Normal Range

Prothrombin time

16 sec

12.0-16.5

INR (International Normalized Ratio)

1.1

0.9-1.3

APTT (activated partial thromboplastin time)

40 sec*

27.0-38.5

Platelet count

339 x 109/L

150-350

Fibrinogen

4.0 g/L

2.0-4.0


3.3.1    Explain the above results and list the most likely cause.    (1 mark)
3.3.2    List two potential treatment strategies.    (1 mark)
 

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College Answer

Syllabus topic/section:

2.1.21 Applied Pharmacology in Intensive Care.

Aim:
To identify, assess and manage common coagulation abnormalities of critically ill patients.

Discussion:
Candidates should be commended for the depth of knowledge displayed here. Causes of thrombocytopenia were correctly noted and prioritised, Investigations including BMAT, SRA, PF4 ELISA test and were correctly identified.
Coagulation tests, Heparin resistance and the corresponding treatment strategies were explained well.
 

Discussion

Heparin resistance again? This has come up in  Question 13.2 from the first paper of 2012,  Question 8.1 from the first paper of 2011 and Question 6.2 from the second paper of 2008. In short, the patient's APTT has failed to inrease with heparin for some reason. Possible explanations include:

There are several 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)
  • High Factor VIII levels
  • Factitious heparin resistance (eg. the heparin is not even connected to the line)

Potential treatment strategies include:

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.

Beresford, C. H. "Antithrombin III deficiency." Blood reviews 2.4 (1988): 239-250.

The PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group Dalteparin versus Unfractionated Heparin in Critically Ill Patients N Engl J Med 2011; 364:1305-1314April 7, 2011

Koster, Andreas, et al. "Management of heparin resistance during cardiopulmonary bypass: the effect of five different anticoagulation strategies on hemostatic activation." Journal of cardiothoracic and vascular anesthesia 17.2 (2003): 171-175.

Isil, Canan Tulay, et al. "Management of heparin resistance in an emergency cardiac surgical patient." Indian journal of anaesthesia 56.4 (2012): 430.