Question 30.1

Created on Mon, 05/18/2015 - 18:54
Last updated on Tue, 09/05/2017 - 17:07
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A 62 year old lady has very significant bleeding following an uncomplicated total hip replacement. Her coagulation profile post blood transfusion is as follows:

Test

Value

Normal Range

PT

13.5 sec

(12.0 – 15.0)

INR

1.0

(0.8 – 1.1)

APTT*

45 sec

(25.0 – 37.0)

APTT (After mixing with normal plasma)

29 sec

(25.0-37.0)

Platelet count

225 X109/L

(150 – 450)

(a)        List two (2) likely causes of her deranged coagulation profile.

(b)        List two (2) additional  pieces  of information  from her history  which  might  be of importance.

(c)        Name  two  (2)  further  tests  you  will  undertake  to  elucidate  the  cause  of  her coagulopathy and bleeding tendency.

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College Answer

(a)        List two (2) likely causes of her deranged coagulation profile.

•    Factor 8 deficiency
•    Factor 9 deficiency
•    Dilutional coagulopathy
•    vWD

(b)        List two (2) additional  pieces  of information  from her history  which  might  be of importance.

•    Patient – past history of bleeding
•    Family history of bleeding
•    History of anti-platelet drugs

(c)        Name  two  (2)  further  tests  you  will  undertake  to  elucidate  the  cause  of  her coagulopathy and bleeding tendency.

•     Factor assay.
•     A Von Willebrands Disease screen.

Discussion

Abnormal coagulation studies and the physiological relatioships of coags tests to the clotting cascade are discussed in greater detail elsewhere. The breakdown of various abnormalities is presented as a table below.

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

  • Heparin therapy
  • 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)
  • Antiphospholipid antibodies

Intrinsic and extrinsic pathway failure

  • DIC
  • Massive transfusion
  • Massive warfarin overdose
  • Primary fibrinolysis
  • Post thrombolysis
  • Snake bite

In the patient presented by the question, the APTT is deranged, whereas the PT is normal.

Because at least one of them is normal, the final common pathway must be intact, otherwise there would be a derangement of both PT and APTT.

Thus, this is some sort of intrinsic pathway failure. Quoting from the table above:

  • Heparin therapy
  • 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)
  • Antiphospholipid antibodies

One assumes that heparin has been ruled out as a cause. Decreased levels of Factors 8, 9, 11 and 12 can be responsible; antiphospholipid syndrome is ruled out by the negative mixing study (which demonstrates that there is no anticoagulant factor, and the coagulopathy is completely reversed by the addition of replacment factors).

Additionally, Factor 8 production may be normal, but there may be a deficiency of von Willebrand factor which normaly complexes with Factor 8 and keeps it from being rapidly degraded by the plasma. In this way vWF deficiency manifests as a raised APTT.

The college offer a model answer with Factor 8 and Factor 9 deficiency in it. They also mention von Willebrands disease and dilutional coagulopathy (which should ideally result in the deterioration of both intrinsic and extrinsic pathway activity).

As for the pieces of history which might be "of importance" - yes, a family history and a personal hisory of bleeding diathesis might be useful, as it would cause you to launch a series of tests for rare and unusual hereditary conditions.

For some reason, the college would also like to know about the recent use of antiplatelet drugs. Sure, this has real-world relevance, because with antiplatelet drugs on board the patient will bleed more vigorously. Buut I have no idea how to relate this to the coagulation parameters. Thus far I have not been able to find any evidence of antiplatelet agents causing a factor deficiency.

The specific tests one would launch in such a situation would be the assay of all intrinsic pathway clotting factors, which would be 12, 11, 9, and 8. Additionally, one would send off a vWF assay.

References

Kamal, Arif H., Ayalew Tefferi, and Rajiv K. Pruthi. "How to interpret and pursue an abnormal prothrombin time, activated partial thromboplastin time, and bleeding time in adults." Mayo Clinic Proceedings. Vol. 82. No. 7. Elsevier, 2007.

Wagenman, Benjamin L., et al. "The laboratory approach to inherited and acquired coagulation factor deficiencies." Clinics in laboratory medicine 29.2 (2009): 229-252.