Help with understanding clotting disorder

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I came across, while googling, a thread where someone asked about INR and Thrombin time, or protime. There were so great answers so I figured, why the heck not, I will just throw out my children's disorder and see if anyone has some helpful or thoughtful input.

All three of my children have a rare clotting disorder called hypodysfibrinogenemia. All three have elevated protime. They all range around 16 seconds and their INR is around 1.6 (for the twins) and my daughter's runs about 1.4. Their fibrinogen level is all

Now my daughter's cousin, a 16 year old boy, on her father's side was diagnosed a couple weeks ago after a football injury that would not heal. After that I decided to have my identical twins tested and they both have low levels of fibrinogen, increased protime and decreased INR. I do know my daughter also has increased reptilase time. None of my children have spontaneous bleeding, none had umbilical bleeding and of course, my daughter is too young to have her period so I have no clue what that holds.

I guess one of my questions is, if you were to see labwork with increased clotting time but decreased INR, what would be your first thoughts? What are the risks associated with this and why would someone have increased clotting time but low INR? Isn't that sort of oddly inconsistent? Wouldn't you expect to see someone with high INR who doesn't clot? Or is the low INR the body's way of staying homeostatic based on the high clotting time?

**** I want to clarify, that based on the labwork for all 3 kids-and my daughter had 3 or 4 rounds of it-the thrombin time differs in each one-my understanding is that is because different controls are used. But without question my kids all exhibit thrombin time that is elevated by about 6 seconds from the norm.

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I think I just found an answer as to how she diagnosed my daughter as dysfibrinogenemic as well as hypo...

"Patients with a decreased fibrinogen activity, but normal fibrinogen antigen, produce fibrinogen that does not function normally in the clotting mechanism, i.e. dysfibrinogenemia"

That is from another website. I just looked at my daughter's original lab work and she does have normal levels of fibrinogen antigen. Hmmm.

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INR is only valid for patients on coumadin, it is a standardizing ratio- normal Protime for adults is 10-13 seconds, hth!

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Specializes in Cardiac Telemetry, ED.
INR is only valid for patients on coumadin, it is a standardizing ratio- normal Protime for adults is 10-13 seconds, hth!

It's not that simple. INR is specific for Vitamin K dependent clotting factors, which are produced by the liver. Also, since the liver produces bile, which is involved with the ability to absorb Vitamin K from the diet, INR can be helpful in evaluating patients with liver disease.

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Ok so I am focusing too much on INR? It was tested on all three kids, well more specifically the prothrombin time was tested, and that included INR. At any rate, the prothrombin time is elevated. For my daughter both prothrombin and thrombin times are elevated.

Like I said, I guess my major question is here, at what point do I worry about thrombosis as a result of the dysfibrinogen or is that mostly seen when fibrinogen numbers are normal but all the other numbers are not?

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Specializes in Cardiac Telemetry, ED.

Per TOS we can't give medical advice. I was just responding to celclt's post about INR. Sorry.

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INR is only valid for patients on coumadin, it is a standardizing ratio- normal Protime for adults is 10-13 seconds, hth!

I wont give you advice on your family as it is not permitted here. What I will tell you about is the INR (international standardization ratio ). It is a calculated number using the Protime result, the mean normal prothobin time (MNPT)( it is spacific to each lab) and the ISI (international sensitivity index). It is not itself a test it just helps people on coumadin who go to different labs for testing, to staderdize the results. There are many different analizers and thromboplastin (reagent or chemical used for testing) used for testing the protime. The ISI is derived by the manufactur of the reagent and spacific to the analizer that the lab is useing to run the PT. So although the PT result will be different at two seperate labratorys, lets say that the PT result is 18 sec. at one lab and the other lab gets a result of 21 sec. each result depends on each labs analizer and the brand or even Lot number of reagent that is running the test ( even if running the same specimen ) the calculation is then made useing the ISI making the INR the same at both labs. The coumadin can then be regulated more percicely because all the labratorys are now, no matter where the patint went for testing, reporting the same standerdized value the INR.

  1. Step 1
    Obtain the patient's PT from records or elsewhere. Example: PT=15.2 s.
  2. Step 2
    Obtain the mean normal prothrombin time (MNPT). It's usually reported by a laboratory based on PT tests (with a particular thromboplastin) on blood plasma samples from 20 to 30 apparently healthy2.gif people. For example, Tripodi and co-authors (see References, below) reported an MNPT of 13.1 s for thromboplastin Neoplastin plus.
  3. Step 3
    Obtain the International Sensitivity Index (ISI) for the thromboplastin used. It's usually specified in the reagent certificate. An example of ISI for thromboplastin is 1.297.
  4. Step 4
    Calculate the International Normalized Ratio using the numbers above as an example.
    INR=(patient PT/MNPT)^ ISI = (15.2 s/13.1 s)^1.297=1.213.
    Note: Normal INR should be between 0.8 and 1.3 Low values of INR (less than 0.5 ) indicate a high risk of a clot, while high values (3 to 5) are associated with risk of bleeding.

So what I wanted to say all along is that using the INR for anything but regulating coumadin is not usefull. The INR is not a test it is just mathmatics at work. I hope this clears up any misunderstandings of the results. Jeff

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Specializes in Cardiac Telemetry, ED.
So what I wanted to say all along is that using the INR for anything but regulating coumadin is not usefull.

...not exactly.

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it's not that simple. inr is specific for vitamin k dependent clotting factors, which are produced by the liver. also, since the liver produces bile, which is involved with the ability to absorb vitamin k from the diet, inr can be helpful in evaluating patients with liver disease.

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i cant seem to edit my original post to add this:

you are right it can be helpful in evaluating a patient with liver disease, but not usefull for treatment. it would be like doing a patient assessment but only taking the temperature of the patient. jeff

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blood coagulation or clotting takes place in 3 essential phases. the first phase is the activation of a prothrombin activator complex. the second phase is the activation of prothrombin. the third stage is clot formation as a result of fibrinogen cleavage by activated thrombin.

the prothrombin activation complex is formed by two pathways each of which results in a different form of the prothrombin activator. the extrinsic mechanism of prothrombin activator formation begins with trauma to vascular walls or extravascular tissues. the damaged tissue releases tissue thromboplastin also known as tissue factor (tf). the formation of a clot by this mechanism usually takes as little as 15 seconds. this cascade is initiated by the activation of factor x by tf and factor vii. activated factor x combined with factor v, factor vii and tf constitutes the prothrombin activator. calcium (ca++) is required for each of these steps. the prothrombin activator in the extrinsic pathway is very similar to the activator in the intrinsic pathway.

antithrombin iii inhibits the activity of thrombin and also the step leading to the activation of factor x. antithrombin iii is a hundred to a thousand times more effective when bound by heparin. protein c is activated by thrombin and with the protein s cofactor provides a strong negative feedback in this phase of clot formation.

most of the clotting factors are formed in the liver. diseases of the liver or damage to the liver can depress the levels of these factors in the blood resulting in excessive bleeding. vitamin k deficiency can also result in a similar condition since vitamin k is essential for the formation of factor vii, ix, x and prothrombin. vitamin k is synthesized in the intestinal tract by bacteria.

so, what i meen to say is there is alot to the extrensic pathway that could be misinterpreted as liver problems if you just used the inr. i don't know why i keep sounding like a all knowing self absorbed ass in my post, i am not trying to do that. i am trying to be helpful, but when i read my post after posting i can't edit it out. jeff

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Specializes in Cardiac Telemetry, ED.
shim.gif

I cant seem to edit my original post to add this:

You are right it can be helpful in evaluating a patient with liver disease, but not usefull for treatment. It would be like doing a patient assessment but only taking the temperature of the patient. Jeff

True.

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When their blood is tested, request a cbc instead of only specific labs, so you can chart any patterns that may happen. Your daughter's levels may vary with her cycle (when she gets it -- assuming she gets AF).

I suggest that you contact the Hematology associations including Hemaphilia, since they can send you in the right direction. PDSA could also probably send you in the correct direction.

Hope this helps some.

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