Thrombophilia When to Suspect that Your Patient is Hypercoagulable

by Stephanie Dentoni, MD

Thrombophilia is a word that has not received much attention in the medical community. It is intimidating and often associated with a complicated and troublesome course. The heart of thrombophilia is the coagulation cascade which is the nemesis of every medical student. It is unfortunate that a “hypercoagulable state” is usually not identified until there has been a deviating complication such as Deep Venous Thrombosis (DVT), Pulmonary Embolism (PE), Arterial Occlusion, or even death.

Thrombophilia statistics in the the U.S.

In the United States, five to eight percent of the population has acquired or inherited a genetic defect that predisposes them to thrombophilia. A high clinical suspicion and an astute clinician can determine who is at risk. Risk managable by taking the appropriate measures.

In our daily practice, we will encounter patients that have a tendency to form a thrombosis. It is imperative that we identify these patients since our treatments for varicose vein disease carry a risk of venous thromboembolism (VTE). With a comprehensive history and physical examination as well as the information acquired by ultrasound evaluation, we can risk stratify these patients and provide optimal care.

Every patient that enters our office for treatment of their venous insufficiency should be thought of as potentially hy-
percoagulable. Instead of assuming the patient is “innocent of a thrombophilia until proven guilty,” they should be considered “guilty until proven innocent.” A thorough history is the initial step in identifying a potentially thrombophilic patient.

If you know what factors increase the risk of developing a thrombosis, the questioning process is simple. Information that should be elicited from every patient is a personal and family history of cancer, personal and family history of a deep venous thrombosis or pulmonary embolism, recurrent superficial thrombophlebitis, thrombosis in unusual sites, recurrent miscarriages, immobility and functional capacity of the patient, systemic illnesses, and current and recent medications.

VTE within other illnesses

Cancer remains common in our society. The prevalence of VTE in cancer patients is reported to be as high as 15%. Occasionally, DVT, PE or a recurrent superficial thrombophlebitis is the presenting sign of an occult malignancy. Particularly cancer of the gastrointestinal tract and ovary carry an increased risk of developing a VTE. However, any Cancer can be a strong risk factor and should not be overlooked.

Mucin-secreting adenocarcinomas confer the highest risk. Up to 50% of cancer patients have been found to have a venous thromboembolism at autopsy. Questioning about age-appropriate cancer screens is crucial for every patient. The relationship between VTE and cancer is underappreciated in the medical community.

Chronic medical illnesses are potential sources of a pro-thrombotic state. Systemic Lupus Erythematosus may have anticardiolipin antibodies or lupus anticoagulants which are strong risk factors for VTE. A high suspicion for possible lupus anticoagulant should be thought of in patients with a history of recurrent miscarriages. Gastrointestinal disorders such as crohn’s disease or ulcerative colitis have twice the risk of thrombosis over the general population.

In an acute flare, the risk increases another two-fold. Other disease states that impart a thrombophilic risk are paroxysmal nocturnal hemoglobinuria, nephrotic syndrome, liver disease, myeloproliferative syndromes, and hyperviscosity syndromes.

Medications & VTE

A current medication list should always be obtained. Many chemotherapeutic agents cause an acquired prothrombotic state as do some immune-modulating medications used to treat collagen vascular disorders such as methotrexate. It is also important to know recent changes in dosages especially when hormone replacement therapy or oral contraceptives are concerned.

The risk is increased when treatment is initiated or with a significant increase in the dose. Heparin, though an anticoagulant, can initiate a prothrombotic state. a thorough history of heparin products and the use of heparin flushes or heparin impregnated catheters are important.

Immune-mediated heparin induced thrombocytopenia (HIT), documented by the presence of an antibody to the immune complex between heparin and platelet factor 4, and may develop with initial fractionated or unfractionated heparin use or after repeated exposure. Up to 50% of patients with HIT will go on to develop a thrombosis, even with withdrawal of the heparin product. Treatment with a direct thrombin inhibitor is essential to prevent the formation of a VTE.

Special attention to female VTE patients

Female patients deserve to have a complete obstetrical history. Pregnancy and the post-partum state increase the risk of a thrombosis due to changes in protein c and protein S levels. Suspicion for Factor V Leiden heterozygosity and prothrombin gene mutation G20210 are common inherited genetic defects and a history of preeclampsia, low birth weight babies and recurrent miscarriages are signs that these abnormalities may be present. Documented unexplained fetal demise is always concerning for an underlying thrombophilia. Antiphospholipid antibody syndrome should also be considered in this situation.

A thorough physical examination compliments the history in a potentially thrombophilic patient. In addition to a
routine examination, pay particular attention to subtle abnormalities that may otherwise be missed. as the patient is examined, notice his/her general appearance and ambulatory status. The contour of the chest may imply a chronic lung disease or pulmonary hypertension. a patient with liver disease can have subtle ascites with or without hepatomegaly. cachexia is found in patients that are hypermetabolic and is a sign of an occult malignancy. Pyoderma gangranosum in inflammatory bowel disease mimics venous stasis ulcerations.

Abdominal or chest wall varicose veins are often collaterals that are formed from a chronic proximal venous obstruction. Presence of unilateral varicose veins or edema in the lower extremity may imply venous obstruction. Stigma of a recurrent superficial thrombophlebitis is easily identified. a comprehensive investigation for an occult malignancy is warranted in this situation. These clues indicate an underlying disease process that is important when assessing the patient’s thrombotic risk.

Even though evaluating a potentially hypercoagulable patient may seem daunting at first, a Phlebologist can easily recognize those at risk. With varicose vein treatment, we subject our patients to a risk of deep venous thrombosis, albeit small. It is our responsibility to identify those at increased risk of VTE and offer them counseling, alternatives treatment options, or appropriate prophylaxis.


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