A clotting tendency due to certain metabolic conditions is usually associated with some derangement of normal bodily functions. The typical scenario is a patient with cancer who develops a DVT after surgery. Numerous acquired conditions predispose one to be in a hypercoagulable state. These include the following:
- Myeloproliferative syndromes: These are conditions where the bone marrow is unable to produce blood cells effectively.
- Antiphospholipid antibodies: These are antibodies that are normally not formed against certain types of lipids in the body. These antibodies include a) anticardiolipin antibodies, b) lupus anticoagulant and c) antibodies directed against specific molecules including a molecule known as beta-2-glycoprotein 1.
- Hyperhomocysteinemia: a condition where there is an abnormal amount of the amino acid homocysteine in the blood.
- Heparin-induced thrombocytopenia: Heparin is normally a blood thinner, but it can rarely lead to clotting inside arteries and veins.
- Pregnancy and exogenous estrogen use(including use of oral contraceptive pills-birth control pills).
- Recent trauma or surgery.
- Hormone replacement therapy.
- Prolonged bed rest or immobility.
- Heart attack, stroke and other illnesses that lead to decreased activity.
These conditions tend to be passed from family member to family member, or can rarely occur as a genetic point mutation is an individual without a family history of clotting disorders. The list of conditions that can cause a genetic or inherited hypercoagulable condition include:
- Factor V Leiden (the most common).
- Prothrombin gene mutation.
- Elevated levels of fibrinogen.
- Deficiencies of natural proteins that prevent clotting (called anticoagulant proteins – such as antithrombin, protein C and protein S).
- “Sticky” platelets.
- The abnormal fibrinolytic system, including hypoplasminogenia, dyspasminogenia, and elevation in levels of PAI-1.
- Elevated levels of factor VIII (still being investigated as an inherited condition).
HOW IS A HYPERCOAGULABLE CONDITION DIAGNOSED?
If there is a suspicion of a clotting disorder, then a careful history and physical examination will reveal a lot of information that can direct subsequent work-up and treatment. Certain conditions such as cancer do increase a person’s risk for developing blood clots but do not necessarily indicate a genetic hypercoagulable state. Some of the important factors that are involved in the evaluation include:
1. A family history of abnormal blood clotting abnormality.
2. Abnormal blood clotting at age less than 50 years.
3. A history of frequent miscarriages.
4. Blood clots that occur without a clear reason such as recent surgery.
5. Recurrent blood clots.
6. Blood clotting in unusual parts of the circulation, such as in the intestinal veins or arteries, brain vessels, or liver vessels.
LABORATORY TESTING FOR BLOOD CLOTTING PROBLEMS
Testing for a hypercoagulable condition is quite extensive. It is best performed when one is not taking blood-thinning agents such as Coumadin since these types of medications will affect the results. Typical lab tests include the following:
- Protime with International Normal Ratio(PT with INR): This test is used to monitor your condition if you are taking Coumadin.
- Activated partial thromboplastin time (aPTT): This test measures the time it takes blood to clot. It is often used to adjust the dose of heparin.
- Fibrinogen level 3. Thrombin time (tt): This test also measures the time it takes the blood to clot.
- Anticardiolipin antibodies (ACA), and Lupus anticoagulants (LA), part of the antiphospholipid antibody syndrome. These tests are important in patients with women of childbearing age repeated miscarriage.
- Factor V Leiden (activated protein C resistance). This is the most common genetic defect causing clotting disorders in Caucasians but is not as prevalent in African-American or Asian populations.
- Prothrombin gene mutation (G20210A).
- Antithrombin activity.
- Protein C activity.
- Protein S activity.
- Fasting plasma homocysteine.
- Heparin antibodies.
These blood tests may also help identify family members who may be at risk for a hypercoagulable condition.
WHAT ARE THE TREATMENT OPTIONS FOR A CLOTTING PROBLEM?
The main management technique for hypercoagulable conditions is with medication that thins the blood, so-called “anticoagulants”. The typical medication that is often used for this purpose is Coumadin (a generic name is a warfarin). Yes, Coumadin has been used as a rat poison. It works by blocking the production of certain pro-clotting proteins in the liver that depend on Vitamin K. If there is an under the production of these pro-clotting proteins, then blood tends to clot less. The dose of Coumadin is adjusted using the PT with the INR test to achieve an INR level between 2-3.5, depending on the condition for which one is being treated.
Things to look out for when taking Coumadin are if you have excessive nose bleeds, blood in bowel movements or urine, dizziness, or frequent headaches. These symptoms can indicate a problem with blood thinning. Also, certain medications will affect the response of the body to Coumadin. Specifically, commonly prescribed antibiotics such as Levaquin and Cipro can make the effect of Coumadin stronger, and thin out the blood more despite staying on the same dose of Coumadin. Therefore, do not take any other medications without first consulting your doctor and pharmacist to make sure there is no interaction with Coumadin. Taking Coumadin is contraindicated if one is pregnant or planning to become pregnant.
Other types of anticoagulation include heparin, low molecular weight heparin (Lovenox) and fondaparinux (Arixtra). Coumadin is given orally. Heparin can be given either subcutaneously (SQ) or intravenously (IV). Low molecular weight heparin is injected SQ, either once or twice a day and can be taken at home. Fondaparinux (Arixtra) is also injected SQ. The typical duration of anticoagulation depends on the underlying issue that caused the blood clot. If there is a DVT without any underlying tendency to clot, then 3-6 months of treatment is usually sufficient. In cases where there is a defined hypercoagulable condition, then lifelong anticoagulation may be indicated.