What's in your lab?

So you have this coagulation laboratory that provides testing for a community, what is in your laboratory? Surely there are instruments, samples, reagents, consumables and last but not least technologists. How do you use all of these to provide optimum health care for your patients?

Coagulation testing give clinicians insight into how patients may respond during surgery, how their anticoagulation is performing or if they have some type of coagulapathy. A large problem in coagulation testing is pre-analytical variables, over 64% of errors are caused by this! In your lab, you need to have standard guidelines to minimize errors:

1. Accepting samples that have a 90% fill rate, keeping that 9 to 1 ratio of blood to anticoagulant.
2. Making sure that you have platelet poor plasma, platelets are phospholipids and they will falsely shorten samples especially if they are freeze/thawed and used for lupus testing.
3. Making sure that you don't add APTT's onto samples that have been sitting on the cells longer than four hours. The PF4 will be released and neutralize any heparin in the sample.
   

So we have some basic pre-analytical criteria in place. Next thing is to make sure that you have good standard operating procedures. Everyone should be on the same page, there is a lot to be said in just observing how techs perform. Also before procedures are put into place, they should be edited by the people who are going to use them, what may be obvious to them, may not be to the person who is writing the procedure. Also, make sure that when a procedure is updated, you have a form that demonstrates that all personnel are aware of the changes. This must be dated and signed.

Next, review the test menu. Instrumentation has greatly improved, and most have the capability to run not only clot based testing, but chromogenic and immunological testing. What should laboratories be running? The PT and APTT are very important. These screening tests give the clinicians a tremendous amount of information, from the presence of a factor deficiency, to an inhibitor, or to monitor anticoagulation. Understanding how your reagents perform is very important. Is your reagent lupus insensitive? That means it has a high concentration of phospholipids and will mask the presence of an antibody. Therefore, the presence of a lupus inhibitor will not prolong your APTT. Also, is your reagent heparin sensitive, will just a small amount of heparin greatly prolong your APTT? This will be important in determining your therapeutic range. In regard to your PT reagent, do you want a high or low ISI. CAP recommends that you use a reagent with an ISI <1.5. This is all important in diagnosing and treating patients. And that is just your basic screening tests. Most labs also perform fibrinogen testing; this test will mostly be decreased that is consumed in DIC. Fibrinogen deficiencies are rare; however, fibrinogen is an acute phase reactant, meaning it is elevated in times of inflammation and stress. Also, pregnant women will have an elevated level. This is very important to know, because you should expect fibrinogens from labor and delivery to be increased, a normal level might just be an indication that women is going into DIC. Some people have a hereditary persistence of elevated fibrinogen. It can be confirmed by running a CRP, the most sensitive marker of inflammation. If this is normal, the elevated fibrinogen is not due to an inflammatory condition. Elevated levels of fibrinogen are considered independent risk factors for myocardial infarcts, more so than cholesterol.

A thrombin time should be among your screening tests. This test is the best test for residual heparin, and can detect up to 0.1U/ml! It can be helpful in determining if a sample is contaminated with heparin and be very cost effective. If a sample contains heparin, additional workups should not be performed, Factor assays will look like inhibitors, and many other assays will be affected. Also, when samples are drawn for Anti-Xa assays or Heparin levels, you sometimes will see a result of 0 U/ml, and worry if your analyzer is working correctly, you can run a thrombin time to see if any heparin is present. The sample may have been drawn at the wrong time, reflecting an undetectable level.

Another important test to have on board is the d dimer. Most instruments can provide this test 24/7. The validity of the test lies in the negative predictive value, the ability to rule out the presence of a clot. A positive d dimer means many things. Be careful when using the latex agglutination test for d dimer, it is really more specific in determining DIC then the presence of a clot. Get them on the analyzer and out the door! As far as FDP's, they are polyclonal antibodies and very non-specific, the only advantage is to distinguish between fibrinolysis and fibrinogenlysis- you can do a fibrinogen test for that, it really isn't cost effective to keep both on board.

What about more specialized testing? Many laboratories feel it is too expensive, but in reality it may be more expensive to send it out, or not perform it and a patient have a delay in diagnosis. A mixing study can help to determine an inhibitor or a factor deficiency. Pooled normal plasma must be used in the mix, not a control or a lyophilized plasma. It is important that the matrix is the same and that all of the levels of the factors are in the normal range. Make sure that you have these values; it will be something an inspector wants to see.

Heparin levels are important. Low Molecular Weight Heparin (LMWH) can not be monitored by an APTT. It's dose is determined by body weight, but should be monitored in pediatric patients, pregnant women, and severe trauma patients. This is an important test to have available.

Hypercoaguable testing is expensive and can be performed in stages. If the laboratory wants to offer one test, it should be the clot based test for Activated Protein C Resistance. This is the most common hypercoaguable disorder, and affects up to 3% of the general population. It is easy and can be put on any analyzer.

Providing these tests can give the clinician the tools required to make informed decisions and provide optimum patient care. So maybe it is time to not only see what is in your lab, but what can be in your lab!