What is Hypercoagulability?
Hypercoagulability, or thrombophilia, is a condition where the blood has an increased tendency to form clots. Normally, when you bleed, your body forms a clot to stop the bleeding in a process called coagulation. However, this process can be overactive, leading to the formation of clots even when there’s no wound or blood loss, which is what we refer to as hypercoagulability.
Various components of your blood work together to form a blood clot, or a thrombus. There are two types of thrombosis: arterial thrombosis, which can lead to a heart attack or a stroke, and venous thromboses, responsible for conditions like deep vein thrombosis (DVT) and pulmonary embolism (PE). While the occurrence and treatment of these conditions vary, they do share some common risk factors.
The term thromboembolism describes a situation where a clot formed in one part of the body travels to another area, causing blockage in the blood vessels. There are many conditions and diseases, often referred to as hypercoagulable states or thrombophilic diseases, that can cause your blood to clot too much.
Scientists have discovered several of these conditions over the years. As early as 1906, Wasserman and others identified a condition called antiphospholipid syndrome. In 1965, Egeberg found another condition called antithrombin III deficiency. In the 1980s, deficiencies of protein C and protein S were discovered. And in 1993, Dahlbäck highlighted a condition called activated protein C resistance, often caused by a specific genetic mutation known as factor V Leiden.
What Causes Hypercoagulability?
Hypercoagulability disorders, or conditions where the blood clots too much, can either be inherited (passed down through families) or acquired (developed over time). However, actual blood clot formation usually happens because of a mix of genetic and environmental factors, according to the multiple hit theory. This theory explains why patients with the same inherited mutation might experience different symptoms.
We can now identify genetic factors in approximately 30% of patients with blood clots in their veins, primarily from mutations known as factor V Leiden and prothrombin G2021A. These two conditions slightly increase the risk of forming blood clots. Other inherited disorders that cause excessive clotting, such as antithrombin III deficiency, or protein C and protein S deficiency, are rare (seen in around 1% of people) but increase the risk of clot formation significantly.
Several acquired factors also affect how your blood clots. They include surgery, pregnancy, hormone replacement therapy, the use of contraceptives, cancer, inflammation, infections, and a condition triggered by heparin medication known as heparin-induced thrombocytopenia.
Risk Factors and Frequency for Hypercoagulability
After heart attacks, venous thromboembolism – a condition where blood clots block your veins – is the second most common cardiovascular disorder, even more common than strokes. The number of cases varies with age and is between 1 and 5 in 1,000 people every year. It’s rarer in children, with about 1 case in 100,000 children each year, but it becomes more common in adults and the elderly.
As per a report by Thomas, disorders that result in blood clotting, such as APS, APC resistance, and elevated factor VIII, occur in 25 to 28% of patients. Other disorders, including protein C deficiency, protein S deficiency, high homocysteine levels and prothrombin mutation, are found in 5 to 10% of patients. Strokes due to these clotting disorders account for up to 4% of all strokes.
Signs and Symptoms of Hypercoagulability
To tell the difference between a provoked and unprovoked blood clot (thromboembolism), doctors will take a detailed history. This will include information about the patient’s personal and family medical history, any risk factors they may have, and what symptoms they are experiencing. A standard physical examination will also be performed.
Interestingly, up to 70% of people who experience a VTE, or venous thromboembolism (a blood clot in the vein), have a provoking factor or cause. Additionally, about one in three patients has a family history of blood clotting disorders.
There is a specific term called ‘early age thrombosis’, which refers to blood clotting events that occur in people who are younger than 40 or 50 years old. Furthermore, blood clots can occur in uncommon sites in the body, such as the brain, neck veins (as seen in Lemierre syndrome), abdominal organs, portal vein (as seen in Budd-Chiari syndrome), and even the veins of the upper extremities.
Based on the information gathered from the patient’s history and the physical exam, doctors can use a tool called the Wells score to decide how to further diagnose a first-time venous thromboembolism.
Testing for Hypercoagulability
To identify issues with your blood clotting more than it should, a condition known as hypercoagulability syndromes, doctors must take into account a mix of screening tests, confirmation tests, and risk factors. Thrombophilia is a condition where your blood clots more than normal, and to test for this, doctors may have to review your functioning levels for antithrombin III, protein c and s deficiency, check for specific gene mutations like factor V Leiden and prothrombin G2021A, and test for antiphospholipid antibodies and homocysteine level. Other standard blood tests could include coagulation panel, d-dimer, and complete blood count (CBC), to provide a deeper insight into your blood clotting abilities.
Moll and his team have suggested a rounded strategy called the “4P” approach: Patient selection, Pretest counseling, Proper laboratory test interpretation, and Provision of education and advice. This methodology helps decide if anticoagulation treatment is needed and how long it would take, based on the patient’s risk assessment. Remember, not everyone needs testing for a higher tendency to form blood clots. It’s generally not recommended to test during an acute intrusion of a clot (it’s better done in a 3-month follow-up), and when a person is already on anticoagulation therapy they don’t require testing.
In situations where a clot appears out of the blue, not provoked by an existing condition, guidelines on whether to begin anticoagulation therapy can vary. Testing to identify an excessive clotting disorder could also help justify stopping anticoagulation therapy. However, testing isn’t recommended to prevent blood clots in relatives of patients with asymptomatic VTE, a condition where a blood clot forms in the vein.
Regardless, primary prevention using anticoagulants during times of risk is something that doctors may consider. Different medical associations offer different guidance on when to use these kinds of tests. Some recommend thrombophilia testing for patients under 40 years of age, patients with a strong family history of the disorder, recurrent or unexplained clots and several other abnormal conditions related to clotting.
For patients who are suspect for Antiphospholipid Syndrome (APS), a disease which makes your blood clot more easily and can cause miscarriages in women, unexplained Partial Thromboplastin Time (a blood test that measures how long it takes for your blood to clot), may lead to testing for APS using various methods. The Sapporo criteria combine a mix of clinical checks and lab tests to diagnose APS.
Because Deep Vein Thrombosis (DVT), where a clot forms in a deep vein, and Pulmonary Embolism (PE), a condition where a clot travels to the lungs, can be present in nearly 20% of patients with undetected cancer, unexplained clots in older adults should lead to investigations for possible cancer. Doctors use a series of routine and extended tests for this.
As high as 4% of strokes could be due to clotting disorders. The frequency of stroke in young adults is increasing progressively. For individuals with hypercoagulability syndromes, the risk of venous (vein) clots is more than that of an ischemic stroke (a condition where the blood supply to the brain is reduced). Certain forms of clotting disorders can result in arterial clots too, due to a rare manifestation where venous clots travel to the arteries. Therefore, young adults who suffer a stroke and have a right to left blood flow obstruction should be checked for venous clots, like DVT. Patients younger than 45 who experience a stroke should be tested for the antiphospholipid antibody syndrome, which can cause arterial strokes.
Treatment Options for Hypercoagulability
Coagulation factors, proteins in our blood that help it clot when we bleed, could be replaced as part of the treatment for certain conditions. This treatment is used when there’s a deficiency of a specific protein known as Antithrombin III (ATIII), which helps control blood clotting. The ATIII deficiency could be a condition you are born with, or it could arise due to other situations like sepsis, where the body’s response to an infection damages its own tissues.
Fresh frozen plasma, which is a blood product from donors, contains a balanced assortment of clot-inducing and clot-preventing factors.
The decision to use treatments designed to prevent blood clots should be made by assessing both the risks and benefits. Some of the factors to consider would be whether the individual is at a high or low risk of developing blood clots, which can be determined using different assessment tools and scores. In contrast, there are also different scores used to assess an individual’s risk of bleeding such as the HAS-BLED score, which was found to be the most effective in predicting the risk of bleeding in patients who have an irregular heartbeat.
The duration of treatment after a blood clot, termed as Venous Thromboembolism, can go through three phases – acute (immediately after the incident), intermediate (the first three months) and chronic (long term treatment beyond three months). Some factors that may contribute to a higher risk of recurrence include being male, older age and having unprovoked VTE. Specific tools can assess the risk of blood clot recurrence in cancer patients.
There are different medication options available to help prevent blood clots from happening again. These include Vitamin K antagonist, Aspirin, Rivaroxaban, Dabigatran, and Apixaban. Also, additional considerations, such as the type of medications used in specific patient groups, should be made. For example, heparin, an anticoagulant, has shown no risk of causing birth defects, therefore could be administered during pregnancy and after childbirth.
Aside from medications, preventive measures to avoid blood clots could include using compression stockings and staying mobile. Some medications, like Rosuvastatin, have also demonstrated effectiveness in helping to prevent blood clots.
What else can Hypercoagulability be?
When a patient has symptoms of thrombosis or blood clots, it’s essential to find out if there’s a specific cause (provoked thrombosis) or no apparent cause (unprovoked thrombosis). To find out, doctors usually take the patient’s history and perform a physical examination. Blood clots can happen due to a variety of reasons, so a wide-ranging check-up is important. Here are some of the common and less common conditions that could cause thrombosis:
- Limited movement or long-distance travel
- Heart conditions (irregular heartbeat, heart muscle disease, abnormalities in the heart’s valves, or artificial heart valves)
- A rare heart condition called non-bacterial thrombotic endocarditis (NBTE)
- Blood conditions such as disseminated intravascular coagulopathy (DIC) and heparin-induced thrombocytopenia (HIT)
Doctors may also use tools like the HIT score to better assess how likely it is that the patient’s symptoms are due to a specific cause, and to guide further diagnostic tests.
Blood clotting disorders, also known as thrombophilias, should be considered as a possible explanation for events where the blood vessels become blocked. Arterial thrombosis, which includes conditions like osteonecrosis, stroke, and heart attack, may all be related to thrombophilia.
In younger patients with heart attacks, existing cardiovascular risks play a bigger role than thrombophilias. Some studies, however, suggest considering thrombophilia when heart attacks occur without blood vessel blockage.
Thrombophilias could also be linked to strokes in young individuals via a blood clot in the veins coupled with a hole in the heart (patent foramen ovale).
Possible Complications When Diagnosed with Hypercoagulability
Deep vein thrombosis (DVT) can lead to two serious problems: pulmonary embolism, which is sudden and can be fatal, and a condition called postthrombotic syndrome (PTS) that can result in chronic skin ulcers on the legs. One study found that over 40% of patients who had these skin ulcers also had at least one blood clotting disorder. However, it’s still unclear how these disorders relate to the formation of small and large blood clots that can cause PTS and skin ulcers.
The main complications to keep in mind are the potential for the blood clot to come back and the risk of bleeding due to treatment. To avoid these complications, individual risk assessment and treatment planning is necessary. Additionally, small and large blood clots during pregnancy can not only be fatal to the mother, but can also lead to stunted fetal growth, miscarriage, high blood pressure during pregnancy, and premature separation of the placenta from the uterine wall.
Key Issues:
- Pulmonary embolism
- Postthrombotic Syndrome (PTS)
- Chronic venous ulcers (CVU)
- Risk of clot recurrence
- Bleeding as a side effect of treatment
- Complications during pregnancy
- Potential maternal death
Preventing Hypercoagulability
If a person has symptoms of hemophilia, like repeated blood clotting events, or if they have a strong family history of the disease, they might need to be tested for it. In such cases, they might want to consider seeing a hematologist, a doctor who specializes in blood disorders.
