Protein S deficiency

What causes protein S deficiency?

Protein S deficiency is usually hereditary, but may be acquired. The hereditary form of protein S deficiency is caused by a mutation in a gene called PROS1. This condition is inherited in an autosomal dominant manner, which means that an individual who inherits only one mutated copy of PROS1 has an increased chance of developing symptoms of this disease. Individuals who inherit one mutated copy of the PROS1 gene are said to be heterozygotes while those that inherit two mutated copies of the PROS1 gene are called homozygotes. Blood clots (thrombosis) may occur in both heterozygotes and homozygotes; however, homozygotes may develop a severe form of thrombosis called purpura fulminans. Purpura fulminans involves severe clotting throughout much of the body and is a life- threatening condition.

Rarely, protein S deficiency is acquired, meaning it develops as a result of another condition such as liver disease or vitamin K deficiency.

Last updated on 05-01-20

Are there any reports of individuals diagnosed with cryoglobulinemia and protein S deficiency?

We identified two cases reported in the medical literature that you might find helpful. Case reports document clinical findings associated with individual cases. It is important to keep in mind that although there are often symptoms or clinical findings that are documented in these case reports, they are based on the specific individuals that are studied and may differ from one affected person to another. Click on each link to read a summary of the article.

1. Hernández JL, Zarrabeitia R, Fernández-Llaca H, Hortal L, González-Macías J. Multifactorial thrombotic-type microangiopathy with skin ulcers and hepatitis C infection. Eur J Intern Med. 2000 Jun;11(3):165-167.

2. Ho BL, Huang P, Khor GT, Lin RT. Simultaneous thrombosis of cerebral artery and venous sinus. Acta Neurol Taiwan. 2008 Jun;17(2):112-6.

Last updated on 05-01-20

How common is protein S deficiency?

Protein S deficiency is estimated to occur in 1 out of every 20,000 individuals.

Last updated on 05-01-20

Can protein S deficiency be hereditary if my parents did not have it?

Protein S deficiency can be hereditary if an affected individual's parents do not have symptoms of this disease. Some individuals with this condition never develop symptoms; in fact, approximately 20-40% of individuals with protein S deficiency never develop a clot. This means it is possible for a parent of an affected individual to have protein S deficiency without showing signs of the condition. Though a parent with protein S deficiency may not have symptoms, they still have a chance of passing the conditon to offspring.

Last updated on 05-01-20

Has any correlation been found between cryoglobulinemia and protein S deficiency?

We identified one study that investigated the contribution of blood clotting disorders (including protein S deficiency) to the symptoms of mixed cryoglobulinemia. In this study, researchers found that having high levels of homocysteine in the blood (hyperhomocysteinemia) was a risk factor for severe purpura and for the presence of skin ulcers. None of the other causes of blood clotting (thrombophilia) that were studied influenced the clinical presentation of mixed cryoglobulinemia.

Last updated on 05-01-20

What is protein S deficiency?

Protein S deficiency is a disorder that causes abnormal blood clotting. When someone bleeds, the blood begins a complicated series of rapid chemical reactions involving proteins called blood coagulation factors to stop the bleeding. Other proteins in the blood, such as protein S, usually regulate these chemical reactions to prevent excessive clotting. When protein S is missing (deficient), clotting may not be regulated normally and affected individuals have an increased risk of forming a blood clot called a thrombosis. People at risk to have protein S deficiency are those with an individual or family history of multiple blood clots in the veins. Treatment may include taking medication known as blood thinners to decrease the chance of developing a blood clot.

Last updated on 05-01-20

Can a person with protein S deficiency participate in contact sports?

In general, individuals with protein S deficiency are able to participate in sports. However, there have been case reports in the medical literature that indicate a connection between exercise and the onset of thrombosis. We strongly suggest you discuss with your doctor your options for participating in contact sports and what efforts can be taken to help prevent the onset of thrombosis. For an athlete, these efforts might include avoiding dehydration, and taking breaks when traveling long distances. The advocacy organization, ClotConnect, provides additional information and resources on athletes and blood clots at the following link.

Last updated on 05-01-20

What complications may be associated with protein S deficiency?

The following complications may arise due to protein S deficiency:

The most common manifestation is venous thrombosis of the lower extremities (i.e. the legs), and this accounts for approximately 90% of all events associated with protein S deficiency. The other 10% of manifestations include those listed above. The warning signs for a venous thrombosis are generally pain, tenderness, redness, or swelling in extremity or affected areas. Approximately 60-80% of individuals with the inherited form of protein S deficiency will go on to have a venous thrombosis at some point in their life, with the majority occurring before ages 40-45. The remaining 20-40% are considered asymptomatic, meaning that they never go on to develop these clots. For individuals whose lives are shortened by protein S deficiency, the cause of death is a pulmonary embolism, or the passage of a blood clot to the lungs. Symptoms of a pulmonary embolus include difficulty breathing, abnormal coughing, chest pain, fainting or heart palpitations.

Last updated on 05-01-20

What barrier contraceptive methods are available for people with protein S deficiency?

Barrier contraceptive method options, include contraceptive sponge, female condom, male condom, and diaphragm, cervical cap, and cervical shield. You can learn more about these methods at

When using barrier contraceptive methods it is generally recommended that people with ****protein S deficiency use a "double barrier" method, such as a diaphragm and condom.

Last updated on 05-01-20

What other birth control options are available to people with protein S deficiency?

Both short-acting and long-acting birth control options are available for people with protein S deficiency.

For a short-acting contraceptive, barrier methods (such as condoms and diaphragm) have the lowest risk for blood clots. However, progestin-only birth control is another option. This option is possibly associated with a small increased risk for venous thromboembolism (VTE).

Progestin-only methods can be taken as pills, IUD, or shots. Some doctors recommend pills over shots, believing pills a safer option. The American College of Obstetricians and Gynecologists offers more on progestin-only birth control.

Copper IUD is a long-acting birth control option that has the lowest risk for blood clots. A copper IUD is effective in preventing pregnancy for years after insertion. Fertility returns after removal of the IUD. Progestin-only methods are options for long-acting reversible birth control as well. The American College of Nurse-Midwives offers more on Intrauterine Devices (IUD).

We strongly recommend that you discuss the pros and cons of each birth control option with a healthcare provider.

Last updated on 05-01-20

Are there different types of protein S deficiency?

Protein S deficiency has been divided into 3 different types based on the measurement of protein S antigen (presence of the protein in the bloodstream), functional protein S activity (ability of protein S to appropriately perform its function), the free protein S (or unbound protein S) and total protein S (includes free protein S and protein S that is bound to another protein in the blood):

  • Type I deficiency: Characterized by a decrease in the total protein S antigen and free protein S antigen together (quantitative deficiency).
  • Type II deficiency: Characterized by normal total and free antigen levels but reduced protein S activity (functional deficiency).
  • Type III deficiency: Characterized by low free protein S levels, whereas the total plasma concentration of protein S is normal.

Types I and III are most common and result in the same types of symptoms. Type II is considered to be very rare.

Last updated on 05-01-20

What is the life-expectancy of individuls with protein S deficiency?

Although associated with an increased risk for forming blood clots, many people with protein S deficiency will never have complications. For those with symptoms, the outcome is usually good with treatment, but symptoms may return.

The greatest life-theatening risk to patients with protein S deficiency is a pulmonary embolism (PE), a deep vein thrombosis (DVT) that travels through the bloodstream and gets stuck in the lungs. People with hereditary protein S deficiency have about a 2- to 11 times increased risk for developing a DVT or PE in comparison with those without a deficiency. After an extensive search of the resources available to us, we were unable to find information on the average life-expectancy of individuals with protein S deficiency, although it greatly depends on the severity of symptoms.

In rare, severe cases of protein S deficiency, infants develop a life- threatening blood clotting disorder called purpura fulminans soon after birth. Individuals who survive the newborn period may experience recurrent episodes of purpura fulminans.

Last updated on 05-01-20

How might protein S deficiency be treated?

Treatment of protein S deficiency occurs either in patients who have had a venous thrombosis or in patients with asymptomatic carrier states without a thrombotic event, depending on the decisions made by the patient's health care provider. Following a venous thrombosis, patients are treated with anticoagulant drugs (blood thinners) including heparin followed by warfarin. In most patients, specialists recommend 6-9 months of initial treatment with warfarin. The question of whether to continue lifelong warfarin in patients with identified protein S deficiency after their first thrombotic event is controversial. If the first thrombotic event was life threatening or occurred in multiple or unusual sites (i.e. cerebral veins, mesenteric veins), most experts recommend lifelong therapy initially. If brought about especially abruptly by a strong event (i.e. trauma, surgery) and the thrombosis did not meet the criteria of life threatening or multiple or unusual sites, some experts argue that these patients may have a lower risk of recurrence and deserve a trial without warfarin after 9 months.

In patients who are asymptomatic carriers of protein S deficiency, the goal of therapy is prevention of the first thrombosis. In such patients, drugs that predispose to thrombosis, including oral contraceptives should be avoided. If these patients require surgery or an orthopedic injury occurs, prophylaxis with heparin may become necessary.

Last updated on 05-01-20

Name: National Blood Clot Alliance 8321 Old Courthouse Road Suite 255
Vienna, VA, 22182, United States
Phone: +1-703-935-8845 Toll Free: 1-877-466-2568 (877-4NO-CLOT) Email: Url:
Name: Clot Connect UNC Hemophilia and Thrombosis Center 6340 Quadrangle Drive, Suite 50
Chapel Hill, NC, 27517, United States
Email: Url:

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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