You review a 40 year old male with chest pain and shortness of breath. He had been admitted with a deep vein thrombosis in his right leg. His coagulation profile is shown below.

INR

1

(0.9 TO 1.2)

APTT

61 seconds

(24 to 39 sec)

PT

11.5 seconds

(10.5 to 13.5 sec)

A. List 5 causes of the abnormality in the coagulation profile

B. List 5 tests that could differentiate the cause of this abnormality

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College Answer

A. List 5 causes of the abnormality in the coagulation profile

Heparin
Lupus inhibitor

Haemophilia A & B

Factor xii deficiency

Factor xi deficiency
Von Willebrands disease
Artefactual (incorrect amount of blood in the tube.)

B. List 5 tests that could differentiate the cause of this abnormality

Repeat test
Heparinase assay or antibodies
Mixing test
Thrombin time and reptilase time
Factor assay
Anti-cardiolipin antibody

Discussion

This is another "What is the cause of an isolated APTT elevation" question.

The abnormal coagulation studies page deals with this in greater detail.

The approach to a patient wth abnormal coags can be summarised in the form of a table:

Assessment of Prolonged Clotting Times
  Normal PT Raised PT
Normal APTT
  • von Willebrand's disease
  • Platelet dysfunction
  • Fibrinolysis disorder

Extrinsic pathway failure

  • Warfarin therapy
  • Vitamin K deficiency
  • Liver disease
Raised APTT

Intrinsic pathway failure

Factor deficiency or anticoagulant factor? This is answered by mixing studies.

  • Anticoagulant factor:
    • Normal TT and RT:
      • antiphospholipid antibodies
    • High TT, normal RT:
      • Heparin therapy (heparinase assay)
      • heparin-like anticoaguants (malignancy)
    • High TT, high RT:
      • Low fibrinogen
      • Abnormal fibrinogen
      • Paraproteinaemia
      • Excessive fibrin degradation products
      • Amyloidosis
  • Factor deficiency
    • von Willebrand's disease (de facto Factor 8 deficiency)
    • Factor 8 deficiency (Haemophilia A)
    • Factor 9 deficiency (Haemophilia B)
    • Factor 11 deficiency (Haemophilia C, 8% of Ashkenazi Jews)
    • Factor 12 deficiency (which is freakishly rare, and usually totally asymptomatic)

Intrinsic and extrinsic pathway failure

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

In brief, the raised APPT could be caused by either an anticoagulant factor, or by a deficiency of the factors involved in the intrinsic or final common pathway.

Thus, it could be any of the following:

  • Anticoagulant factor:
    • Antiphospholipid antibodies
    • Heparin therapy
    • Heparin-like anticoaguants (malignancy)
    • Low fibrinogen
    • Functionally abnormal fibrinogen
    • Paraproteinaemia
    • Excessive fibrin degradation products
  • Factor deficiency
    • von Willebrand's disease (de facto Factor 8 deficiency)
    • Factor 8 deficiency (Haemophilia A)
    • Factor 9 deficiency (Haemophilia B)
    • Factor 11 deficiency (Haemophilia C, 8% of Ashkenazi Jews)
    • Factor 12 deficiency (which is freakishly rare, and usually totally asymptomatic)

The tests one would wish to perform?

  • Mixing studies
  • Thrombin time
  • Reptilase time
  • Heparinase assay: detects the influence of heparin
  • Fibrinogen level
  • Individual factor assays

In their answer, the college also intelligently suggest that you repeat the APTT, as it could all be an artifact of sampling.

References

References

 

Hunt, Beverley J. "Bleeding and coagulopathies in critical care." New England Journal of Medicine 370.9 (2014): 847-859.