Hypercoagulability

What are the best tests to exclude thrombophilia as a cause of my patient's DVT?

The patient is on coumadin. What tests can I still order?

The Protein S level came back low (40%). How should I interpret this result?

The Protein C level was only 25% today. The patient is on coumadin, but he only started the medication yesterday. Does he have Protein C deficiency?

My patient has a history of DVT and the lab said that her FVIII level was elevated. Is this significant?

The patient may have been on heparin when the blood was drawn. How can I tell?

How can I get rid of the heparin?

I treated the patient's plasma twith heparinase twice, but the thrombin time is still long. What can I do now?

What are the best tests to exclude thrombophilia as a cause of my patient's DVT?
To some extent, this depends on the patients age. Younger patients (<60 years) with a venous thrombosis are more likely to have one of the more serious thrombophilic risk factors such as deficiency of Antithrombin, Protein C or Protein S. Older patients (>60 years) are less likely to have one of these defects. Either group could have one of the more common genetic mutations (FV Leiden and/or Prothrombin 20210) and acquired risk factors such as hyperhomocystemia or antiphospholipid antibodies / Lupus Anticoagulant.

For further information on the individual tests, please refer to the Available Tests or Panel Tests pages.

The patient is on coumadin. What tests can I still order?
Protein C and Protein S are Vitamin K-dependent and their levels fall during coumadin therapy. It is therefore not advisable to make a diagnosis of congenital Protein C or S deficiency during coumadin treatment. Protein C levels may fall quickly after coumadin has been started, and as Protein C has a much shorter half life than Protein S, their levels may be quite disparate in the first few days of treatment.

Anithrombin activity, genetic tests for FV Leiden and Prothrombin 20210 mutations and homocysteine are not affected by coumadin. Tests for Lupus Anticoagulant are not directly affected, but it should be noted that patients on therapeutic coumadin will have moderate prolongations of the APTT. These may not correct completely to normal because the so-called PIVKA (Proteins Induced by Vitamin K Absence or Antagonism) do not function normally and may exert a slight inhibitory effect.

The Protein S level came back low (40%). How should I interpret this result?
A low Protein S level should first be repeated on a fresh plasma sample. Also a Factor VIII level should be performed as an elevated level points to the presence of an acute phase reaction. As Protein S is normally partly bound to C4-Binding Protein, which is an acute phase reactant, this may be associated with less free Protein S activity. Levels will return to normal when the inflammatory response resolves. Low levels are usually found in pregnant women for the same reason.

If there is no evidence for an acute phase reaction and the Protein S level remains low, the possibility of congenital deficient should be considered. Measurement of Protein S antigen levels (free and total) will assist in classifying a congenital Protein S deficiency.

The Protein C level was only 25% today. The patient is on coumadin, but he only started the medication yesterday. Does he have Protein C deficiency?
Probably not. Protein C has a very short half life (~3 hours) and levels will fall quickly when coumadin is initiated - especially if a loading dose is used. We recommend checking the Factor VII level. If this is also low, the findings are almost certainly due to coumadin or hepatic insufficiency. If the FVII level is near-normal, then the low Protein C is more likely to be due to a pre-existing deficiency.

My patient has a history of DVT and the lab said that her FVIII level was elevated. Is this significant?
It could be. FVIII is now considered to be an independent risk factor for venous thrombosis. Of course, it is also an acute phase reactant and may be elevated post-thrombosis as part of an inflammatory response. It is best to wait at least three months after the thromboembolic event, and repeat the FVIII activity.

The patient may have been on heparin when the blood was drawn. How can I tell?
The best way is to run a thrombin time. This test can detect as little as 0.1 units/ml of thrombin, and is typically non-coagulable with therapeutic levels of heparin.

How can I get rid of the heparin?
The patient's plasma can be treated with the enzyme Heparinase. This is available commercially as Hepzyme(R).

I treated the patient's plasma with heparinase twice, but the thrombin time is still long. What can I do now?
It is possible that the patient has a very high plasma heparin level, and the heparinase is unable to remove it all. Alternatively, the patient may have been given a direct thrombin inhibitor (DTI) such as lepirudin, argatroban or bivalirudin. Heparinase does not remove these agents.