A 56 year old man was admitted to your ICU for monitoring of his deteriorating conscious state following an acute thrombotic stroke involving the carotid territory. Over the next 6 hours, the patient’s conscious state has improved significantly.  However, you are notified of an abnormal coagulation result from a sample taken at 6 hours after admission  to intensive care. There are no signs of bleeding.

PT

Baseline

13

6 hours

27

(12-16 sec)

APTT

34

120

(32-36 sec)

INR

1.1

2.1

TT

12

34

(12-14 sec)

Platelets

146

148

(150-300 X 109/L)

Fibrinogen

3.6

0.9

(2.5-4 G/L)

a)  Suggest a reason for the abnormal blood result.

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College Answer

a)  Suggest a reason for the abnormal blood result.

Patient has received thrombolysis. Release of brain thromoplastin causing a DIC is unlikely as patient is clinically getting better and platelets are normal.

Discussion

There are several good reasons for this "total coagulation failure" sort of picture, which are discussed in greater detail in the chapter on abnormal coags results. In brief, they are as follows:

  • DIC
  • Massive transfusion
  • Massive warfarin overdose
  • Primary fibrinolysis
  • Post thrombolysis
  • Snake bite
  • Direct thrombin inhibitor toxicity
  • Severe liver failure

However, with the detailed history given to us by the college, we can probably can rule out snakebite. The college really wanted to hear "post-thrombolysis coagulopathy". Following thrombolysis, all screening coagulation tests are prolonged. This is a state of "hyperplasminaemia".

Basically, the final common pathway doesn't work. A part of the reason for this is that fibrinogen is massively depleted. Secondly, the fibrin degradation byproducts increase in concentration to such a level that they inhibit the cleavage of fibrinogen, rendering the remaining fibrinogen useless. APTT and TT increase as a result. PT also measures the final common pathway, and it will also be increased.

The release of thromboplastin following brain injury leads to a widespread activation of the clotting cascade, which can lead to DIC following a massive brain injury. However, as the college has rightly pointed out, this is typically a process of consumptive coagulopathy, and in this patients the platelets are clearly not being consumed.

References

References

Schöffel, G., et al. "Blood coagulation changes during effective thrombolysis using urokinase and heparin." Thrombosis research 25.1 (1982): 11-21.

Fassbender, Klaus, et al. "Changes in coagulation and fibrinolysis markers in acute ischemic stroke treated with recombinant tissue plasminogen activator."Stroke 30.10 (1999): 2101-2104.

MARDER, VICTOR J. "The use of thrombolytic agents: choice of patient, drug administration, laboratory monitoring." Annals of internal medicine 90.5 (1979): 802-808.

Kovacs, Iren B., and Peter Görög. "Simultaneous measurement of all thrombosis parameters from native human blood: usefulness in monitoring efficacy and complications of thrombolytic therapy." Angiology 41.10 (1990): 829-835.

Garabedian, H. D., et al. "Laboratory monitoring of hemostasis during thrombolytic therapy with recombinant human tissue-type plasminogen activator." Thrombosis research 50.1 (1988): 121-133.

Bovill, Edwin G., Richard Becker, and Russell P. Tracy. "Monitoring thrombolytic therapy." Progress in cardiovascular diseases 34.4 (1992): 279-294.

Shafer, Kenneth E., et al. "Monitoring activity of fibrinolytic agents: A therapeutic challenge." The American journal of medicine 76.5 (1984): 879-886.

Illoh, Orieji C., and Kachi Illoh. "Thrombolytic-associated coagulopathy and management dilemmas: a review of two cases." Blood Coagulation & Fibrinolysis 19.6 (2008): 605-607.

Ludlam, C. A., et al. "Guidelines for the use of thrombolytic therapy." Blood coagulation & fibrinolysis 6.3 (1995): 273-284.

Prentice, C. R. M. "Basis of antifibrinolytic therapy." Journal of Clinical Pathology 3.1 (1980): 35-40.

Harhangi, B. S., et al. "Coagulation disorders after traumatic brain injury." Acta neurochirurgica 150.2 (2008): 165-175.