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Ferritin and Prolonged PT/PTT?

From Natalie ShoreyStago, Inc. Regional Manager, Sydney, Australia:

This clinical case & related question came from the scientists at St George Hospital, one of our teaching hospitals here in Sydney. It prompted some discussion when I put it to other scientists, withour coming to any conclusion so I thought I’d pose the question to you.

A patient has multi organ failure with a grossly elevated ferritin of >99999 ug/mL and the following coagulation profile: prothrombin time (PT), 26.9 s; PT mix, 16.9 s; partial thromboplastin time (APTT125 s; APTT mix, 43.8 s ( partial correction), fibrinogen 1.9 g/L; thrombin time (TCT87.9 s; D-dimer <20 ng/ml, equivocal lupus, reduced extrinsic and intrinsic factors. Heparin has been excluded as a cause of the elevated APTT. Can the extremely high ferritin level be the cause or someway be attributed to the prolonged APTT?

Hello, Natalie, and thank you for your question, which I’ve distributed to several hematologists whose expertise is in hematology as well as coagulation. I received this response from Mary Ann McLane, PhD, University of Delaware: “Ferritin is stored in the liver, so were any liver studies done? It is also released significantly into the circulation in inflammation, almost making it a marker of that condition… if that helps.”

I believe Dr. McLane is on the right track; given there is no heparin, these results seem to partially support moderate to severe liver disease with loss of coagulation factor production. The low normal fibrinogen level seems to indicate advanced liver disease, as in early liver disease fibrinogen and factor VIII levels rise. It would be interesting to see the liver enzyme panel results.

A lit search reveals there is but one publication, Naithani R, Chandra J, Narayan S, Sharma S, Singh V. Thalassemia major– on the verge of bleeding or thrombosis? Hematology. 2006;11:57-61 that finds a weak positive correlation (r=.382) between ferritin and the PT but not with PTT. Let’s see what other colleagues have to say!

Comments (5)
Coagulation Factors
Oct 6, 2013 7:55pm

Heparin-like materials derived from liver dysfunction might
Heparin-like materials derived from liver dysfunction might cause prolonged clotting time, which also could explain the low D-dimer level: anticoagulant can reduce the secondary fibrinolysis, you can perform the protamine correct test on TCT to prove it.

Sep 24, 2013 12:15pm

If drugs can be ruled out as a cause of the prolonged clot-b
If drugs can be ruled out as a cause of the prolonged clot-based assays, then liver failure seems the most likely cause to me. It was noted that the patient has multiorgan failure, but what was it caused by? The most common outcome of multiorgan failure is death. Did this patient survive? I have seen major coagulation and hematologic derangements that defy explanation in patients just prior to death, so am curious as to the outcome of this patient.

Sep 16, 2013 12:29pm

I could not agree with the statement that DIC could be ruled
I could not agree with the statement that DIC could be ruled out only by normal D-dimer.

Very rare but D-dimer is negative in PE: Breen ME, et al. Pulmonary embolism despite negative ELISA D-dimer: a case report. J Emerg Med. 2009;37:290–2.

DIC: Constantinescu AA, et al. Disseminated intravascular coagulation and a negative D-dimer test. Neth J Med. 2007;65:398–400.

Several cases of false negative D-dimer are presented here: Yonsei. Incidence and possible reasons for discordant results between positive FDP and negative D-dimer latex assays in clinical specimens. Med J. 1999;40:107–11.

George Fritsma
Sep 14, 2013 2:11am

George forwarded this question to Prof. Bernadette Rodak, In
George forwarded this question to Prof. Bernadette Rodak, Indiana University, who in turn forwarded to Carla Clem in the IU lab. Carla responds, My first thoughts…since the TCT is prolonged, once need to think of what causes this:

* Decreased fibrinogen? no
* Heparin? no
* FSP? no
* LA? ??
* DIC> probably not, since D-dimer normal
* Thrombin inhibitor, like Pradaxa; don’t know

Since she/he had multi-organ failure, was the liver one of these organs? Since the liver makes all the factors, I would think of this first!

Also and without researching, I believe I remember that increased ferritin levels can be a measure of liver damage. Let me know what others say, okay? Carla

Sep 13, 2013 12:58pm

Clinical data and coagulation profile are very suggestive of
Clinical data and coagulation profile are very suggestive of ongoing DIC, in this situation I would rather recommend to re-check D-dimer level by different assay or check FDP. It is very unusual that patient with MOF has D-dimer level below the lower detection limit. Combination of MOF and highly elevated ferritin with low fibrinogen and abnormal coag. tests are not rare in hemophagocytic syndrome. D-dimer and FDP are also elevated in >90% cases of this disease. But D-dimer/FDP disrepancy sometimes is observed:

Sato N, Takahashi H, Shibata A. Fibrinogen/fibrin degradation products and D-dimer in clinical practice: interpretation of discrepant results. Am J Hematol. 1995 Mar;48(3):168-74.

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