Hereditary Coagulopathies – an Article Review

Updated 3/2017 -- all links (except to my own posts) removed as many no longer active. 

For any of us surgeons this is a topic with which we should be familiar.  The article (full reference below) in the May issue of the Journal of Plastic and Reconstructive Surgery is a nice review of the topic.  The article begins with the reminder of why this topic is important:

There are over 200,000 hospital admissions for pulmonary embolism annually in the United States, with an estimated mortality of 50,000 to 100,000.  Most thromboembolic complications related to surgery and immobilization occur within 30 days of surgery.  Underlying hypercoagulable states, or thrombophilias, are a common risk factor for venous thromboembolism.….

It has been recently reported that a hypercoagulable state is present in more than half of the patients who present with an “unprovoked venous thromboembolism.”  There is also a significant incidence in patients with presumably provoked venous thromboembolism, and it is a reasonable approach to perform a thrombosis workup on all patients who suffer venous thromboembolisms.

The article then goes on to review the types of thrombophilias, dividing them into two main subsets based on the mechanisms involved:  (1) abnormal function of naturally occurring coagulation factors and (2) deficiencies of naturally occurring coagulation factors.  The first subset is approximately five times more common among the Caucasian population than the second subset.

Subset I: Abnormal Function of Coagulation Factors

Activated Protein C Resistance and Factor V Leiden:

Factor V Leiden was first described in 1994 and is responsible for at least 90 percent of the activated protein C–resistant conditions. It is the most prevalent thrombophilic defect, occurring in 5 to 15 percent of the general population………

The relative risk for venous thromboembolism among heterozygotes is 3 to 10, but this risk significantly increases when an acquired hypercoagulability factor is added, such as oral contraceptives, which increases the relative risk to 30 to 40.   Homozygotes develop more significant thrombophilia, with a relative risk of 79 increasing to 100 with oral contraceptives.

Prothrombin Mutation G20210a

….is the second most prevalent form of inherited thrombophilia, found in 1 to 5 percent of the population and up to 9 percent of patients presenting with their first episode of venous thromboembolism.  …. The relative risk for venous thromboembolism is 2 to 5 in carriers and increases to 16 when combined with oral contraceptive use.

Elevated Levels of Coagulation Factors

Increased levels of factor VIII, factor IX, and factor XI and fibrinogen may also increase the risk of venous thromboembolism.  This is most strongly supported for factor VIII, with a 10 percent increase raising relative venous thromboembolism risk by 10 percent.

Similarly, elevated factor IX and factor XI may increase the risk of venous thromboembolism by 2.5-fold and 2-fold, respectively.

Finally, elevated fibrinogen levels (>500 mg/dl) are associated with a 4-fold increased risk of venous thromboembolism.

Subset II: Deficiency of Coagulation Factors 

Antithrombin III Deficiency

Antithrombin III deficiency is an autosomal dominant trait found in 0.02 percent of the general population and in 0.5 to 7.5 percent of patients who present with their first venous thromboembolism.

Protein C Deficiency

is a rare thrombophilia, with a general population prevalence of 0.2 percent found in approximately 2.5 to 6 percent of patients presenting with their first venous thromboembolism.

Protein S Deficiency

is another rare thrombophilia with a prevalence of 0.026 to 0.13 percent and is found in 1 to 2 percent of patients presenting with their first venous thromboembolism episode.

Recommended Screening

Surgeons should inquire about a patient's personal and family history of any venous thromboembolism events and anticoagulation treatment.   The article includes some suggested questions to help get the history.  Here are a few of them:

• Have you or anyone in your family every had a blood clot?
• Have you or anyone in your family ever been diagnosed with a blood clotting disorder?
• Has anyone in your family had a disease called “purpura fulminans”? 
• Have you ever been diagnosed with lupus or any other autoimmune disease?
• For female patients:  Have you ever had a miscarriage?

Patients suspected to be at risk should be evaluated further. The plastic surgeon can initiate the workup by ordering the following lab work:  CBC, PT, PTT, Activated protein C resistance (factor V Leiden testing if abnormal), Prothrombin G20210A genotype (factor II mutation), Antithrombin III activity, Protein C activity, Protein S activity, and Antiphospholipid antibody testing (lupus anticoagulant, anticardiolipin, anti-Beta2-glycoprotein I).

Patients with a known diagnosis of a coagulopathy can be referred to a hematologist for specific recommendations on management so that the needed surgery can be safely done.

REFERENCE

Hereditary Coagulopathies: Practical Diagnosis and Management for the Plastic Surgeon; Friedman, Tali; O'Brien Coon, Devin; Michaels V, Joseph; Bontempo, Franklin; Young, V. Leroy; Clavijo, Julio A.; Rubin, J. Peter; Plastic & Reconstructive Surgery 125(5):1544-1552, May 2010; doi: 10.1097/PRS.0b013e3181d51344