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Thrombophilia is a condition of elevated blood clotting disorder in the deep veins. Thrombophilia profile blood test helps in identifying acquired and inherited conditions by testing Protein C, Antithrombin, and Factor V Leiden mutation. Medicines like Warfarin, Heparin, and Thrombophob help in Thrombophilia treatment.
Thrombophilia is a condition of the predisposition of increasing blood clots in the body. It typically remains a severe medical condition of abnormal clotting of flowing blood to distinct parts of the body of the patient. The risk of excessive blood coagulation elevates in the presence of thrombosis (blood clots in veins). Almost 50 percent of people, who suffer from thrombosis are identified to possess Thrombophilia. For instance, patients who have Deep Vein Thrombosis (DVT) condition in their legs possess to have symptoms of thrombophilia. Usually, only a few cases are detectable with blood clotting abnormality, though, most of them only develop thrombophilia with additional risk factors. Thrombophilia blood clotting condition does not include any specific treatment rather than consuming blood thinners for a lifetime along with the implementation of certain lifestyle measures. However, recurring clotting is an indication of early detection of thrombophilia and might require long term preventive blood thinners or anticoagulation medicines. (1)People who are undetectable with thrombophilia have 12 percent chances by the age of 60 to develop its symptoms. About 60 percent of the people deficient of antithrombin, once in a lifetime usually experience thrombosis. Also, about 50 percent of patients suffering from a severe protein C deficiency and almost about one-third of the total population with protein S deficiency face increased chances of blood clotting condition Thrombophilia. These patients possess a substantial risk of thrombosis when have activated protein C resistance in their body due to factor V Leiden, which is genetically passed to the patient. These people at least once face an event of a thrombotic condition until the age of 60. A patient possessing factor V Leiden prevails to be at a lower risk of thrombosis. However, it dwells prominent chances of additional factors like immobilization. Most of the people with prothrombin mutation never generate thrombosis. (1)
In this article we will look at the following points:
- What is Thrombophilia?
- What are the signs and symptoms of Thrombophilia?
- What are Thrombophilia and Venous Thromboembolism?
- What are the causes of Thrombophilia?
- What is the significance of diagnosis in Thrombophilia?
- Who to test for Thrombophilia?
- Why screening of Thrombophilia is done?
- What is the treatment of Thrombophilia?
- How does Thrombophilia affect Pregnancy?
The two major types of thrombophilia include a group of acquired and inherited disorders. It increases the tendency of clotting in the blood. A human body maintains a sophisticated balance of blood coagulation (clotting) system for healthy circulation of the blood. Our blood contains platelets (clotting blood cells) and multiple proteins of coagulation which helps the blood to function properly. These essential platelets encourage the body in preventing excessive clotting and bleeding.
It is very crucial for our body to produce blood clot (thrombus) in the injured area. The blood starts to overflow when these injuries are caused to the sensitive blood vessels. Injuries from severe trauma, accidental cuts, fractured bone, and surgery are cured on time by the spontaneous formation of the blood clotting. Bleeding becomes unstoppable during these minor to severe injuries if clot formation does not appear. Clotting of blood prevents the severe overflow of the blood and to heal the injury naturally. In case, a patient is suffering from blood clotting disorder like thrombophilia, then the balanced coagulation system involves a tendency of the thrombosis. Excessive clotting in the blood vessels in different parts of the body is known as hypercoagulability or hypercoagulable state of blood vessels in patients. (2) (3)
People with thrombophilia do not possess any specific symptoms, neither any health problems are evident in the current health status. The symptoms start indicating when blood clotting begins due to thrombophilia. One who is already diagnosed with thrombophilia is usually at an elevated risk of developing Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE). DVT is a medical condition, which causes the formation of blood clots in the deep blood vessels. Patients suffering from thrombophilia are usually detected with DVT in their legs. The symptoms include swelling, redness, pain, or warmth in the affected area. Pulmonary embolism is another relentless condition often tested with thrombophilia. A pulmonary embolism develops because of blood clotting being lodged in the arteries of the lung. In rare cases, thrombophilia produces air bubbles moving towards the lungs. These air bubbles are the main reason for causing shortness of breathing. Lungs are mainly affected by the condition of thrombophilia when pulmonary embolism is taken into consideration. (4)
Both the conditions of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) are associated with thrombophilia. Both DVT and PE are collectively referred to as Venous Thromboembolism (VTE). Below we have mentioned the warning signs of DVT and PE in association with thrombophilia.
- Pain, inflammation, and tenderness in your leg (usually in calf)
- Increased pain in the affected area of the patient
- Warm skin in the clotting area
- Redness of skin at the back of the leg and below the knee
- Severe pain in the chest or upper spine
- Shortness of breathing
- Dry coughing, but one may cough blood out or secrete mucus including blood
- Light-headedness or dizziness
As it is known, that thrombophilia involves inherited or acquired disorders, which are directly associated with an increased propensity to Venous Thromboembolism (VTE) in patients. Thrombophilia acts as one of the essential determinants of VTE. A maximum number of patients, who are suffering from VTE, possess one or more defects of thrombophilia. Causes of thrombogenic factors in VTE are deficiencies of natural coagulation inhibitors like antithrombin deficiency, protein C deficiency, and protein S deficiency. A high risk of thrombosis is also identified in the case of antiphospholipid syndrome and in the homozygous forms of factor V Leiden and specific prothrombin. (5)
Patients with VTE need personal attention from the doctors, as they are suffering from a chronic condition which requires proper medical care and management. The patients require a thorough medical examination, timely monitoring tests, and treatment for a prolonged time. In rare cases, the treatment extends for a lifetime. A positive result of thrombophilia affects the therapy or treatment of VTE. If endogenous anticoagulant deficiencies, homozygous forms of factor V Leiden, and specific prothrombin (antiphospholipid syndrome) are found in the patient, then it influences the treatment of VTE prominently. Treatment should be separated not only as per the type of thrombophilia but as per the patient’s present condition and additional risk factors associated with the patient. (6)
Thrombophilia is caused because of two major reasons inherited deficiency or abnormalities and acquired abnormality. The most common known cause for years for the occurrence of thrombophilia includes inherited abnormalities. These deficiencies are present due to the natural inhibitor protein of the coagulation system. These inhibitors progressively work to control the formation rate of blood clots in the body. The deficiency of the fibrinolytic system in the body is the major of thrombophilia. This protein helps in breaking down the blood clots after their formation. Fibrinolytic system deficiencies are rare and do not require a medical test to confirm the same. (7)
Below we are mentioning a few numbers of deficiencies and abnormalities, which causes thrombophilia:
- Protein C
- Free Protein S
- Protein C
- APC Resistance Assay
- Factor V Leiden mutation
- Prothrombin gene mutation (G-20210-A)
- Lupus anticoagulant (LA)
The details of these components are given below:
- Free Protein S: Protein S is a cofactor of anticoagulant activity depending upon the amount of Vitamin K in the body. The anticoagulant activity here refers to the movement of Activated Protein C (APC). The activity involves two forms of protein S in plasma. The two forms are free protein S (40%) and protein S linked with C4b-binding protein (60%). Only the free form of protein S is present in the functional cofactor activity. The deficiency of protein S is caused mainly because of reasons either hereditary or acquired after the birth of the baby. Protein S deficiency is highly associated with an elevated risk of developing venous Thromboembolism (VTE), particularly in young people. As the free protein S form is only involved as a cofactor, therefore it counts to be a measure to check thrombophilia.
- Protein C: Deficiency of protein C has been associated with a high risk of thrombotic disorder. It plays an important part in the anticoagulant regulatory mechanism. It gradually converts thrombin to an Activated Protein C (APC).
- Antithrombin (AT):It is a natural and most important inhibitor of blood coagulation. For successful and effective heparin (Anticoagulant) therapy inclusion of Antithrombin is very important. It also comprises of protease enzyme, which performs a function of cutting and splitting of enzymes. The deficiency of AT promotes a higher risk of thrombotic disorders.
- APC Resistance Assay: Protein C is the main element, which activates factor V and Viii in the human body. It possesses a naturally occurring inhibitor of blood coagulation. In an APC resistance condition, plasma inpatient does not produce sufficient anticoagulant response towards Activated Protein C (APC). This medical condition is caused due to VQ506 gene mutation. This produces an essential factor of V Leiden, a factor V molecule. These factors are resistant to the formation of cleavage by activated protein C.
- Prothrombin gene mutation (G-20210-A):A mutation (alteration) in factor ll gene (G-20210-A) is present in the untranslated portion of the gene. The factor ii gene is present from the start of the gene. This mutation factor is also an important part of the regulatory system for the gene. Individuals who possess this mutation factor possess higher levels of factor ll than normal. The elevated risk of thrombosis is also another function of Prothrombin gene mutation.
- Factor V Leiden mutation:The recognition of Factor V Leiden mutation is carried out by employing PCR technology. This process is used to distinguish the genotype in the already present abnormality. PCR examination is carried out on each of the samples that have a diminished APCR or have a family history of the presence of factor V Leiden in their body.
- Lupus Anticoagulant (LA): Lupus Anticoagulant (LA) is a distinctive acquired abnormality, which is associated with an elevated risk of venous thrombosis. Basically, LA refers to the important autoantibodies produced by our immune system. These antibodies mistakenly attack vigorously on our healthy cells present in the body. They specifically aim at phospholipids including their associated proteins. These antibodies also act to interfere with the blood clotting and increase the risk of blood clotting. LA results in prolonged coagulation tests depending upon phospholipid. Other medical tests which are recommended to check LA are Activated Partial Thromboplastin Time (APTT) or Dilute Russell's Viper Venom Time (dRVVT). In this medical test, no specific coagulation factor is inactivated for accurate medical test results. Lupus Anticoagulant (LA) test is basically associated with a spectrum of autoimmune disorders, infections and to find the exact medical treatment for the respective medical condition.
A requirement to test LA is suggested because of the following important factors:
- Unexplained prolongation of APTT
- Recurrent immature fetal loss believed to be due to placental infarct
- Unexplained thrombotic tendency
Patients with inherited thrombophilia are identified easily by coagulation experts knowing their few symptoms. The experts evaluate the patient's own or family history of Venous Thromboembolism (VTE). Thrombophilia usually does not require a separate thrombophilia profile blood test if there is any existence of VTE in any of the direct or indirect family members.(8) Thrombophilia should not be tested when a patient is consuming the medicines of anticoagulation. Preferably, one should wait for at least two weeks, after discontinuing the medicine for accurate medical results. An expectant woman or a patient taking combined oral contraceptives or hormone replacement therapy should avoid going for the medical tests for thrombophilia.
Below we have mentioned certain condition in which patient should go for thrombophilia profile blood test:
- In patients, who have unprovoked Venous Thromboembolism (VTE), before the advancing age of 40 years.
- Recurrent unprovoked thromboembolism
- Thrombosis in rare locations of the body like visceral vein thrombosis, cerebral veins, and upper extremities vein thrombosis.
- Presence of Venous Thromboembolism (VTE) in a first-degree family relative clearly indicates there are high chances of occurrence of this medical condition in the concerned individual himself.
- Women with a history of past fetal loss or three unprompted early miscarriages should go for thrombophilia profile test (it is essential to eliminate cardiolipin antibodies and lupus anticoagulant in these cases).
- Incomprehensible skin necrosis, particularly if one is consuming vitamin K antagonists (e.g. Warfarin)
- Babies and newborn with Purport Fulminant (a certain type of skin lesion)
- The patient should also get a checkup of thrombophilia profile blood test for the below-mentioned deficiencies:
- Protein C
- Protein S
- APCR and Factor V Leiden
- Protein gene mutation
- Lupus Anticoagulant (LA)
A screening of coagulation includes different assays of Protein C, Free Protein S, Antithrombin III, Activated Protein C Resistance, and Lupus Anticoagulant screening. Amongst all the acquired conditions connected with venous (and arterial) thromboembolism, an influential role is played by the antiphospholipid antibody syndrome. It also helps in moderate hyperhomocysteinemia screening. The antiphospholipid antibody syndrome is determined by repetitive positive tests for Lupus Anticoagulant (LA), solid-phase anti-phospholipid antibodies, thrombocytopenia, and fetal loss. Hyperhomocysteinemia is typically caused by an inherent deficiency of the enzymes associated with its metabolism. However, it has also been attributed to poor dietary consumption of vitamins, which serve as cofactors of folic acid and B12. Therefore, it becomes easy and effective to treat acquired thrombophilia with the help of dietary supplementation. (9)(10)
Thrombophilia treatment is available, but complete elimination is not possible in case of the inherited or genetic type of thrombophilia. Thrombophilia treatment depends on many factors like age, overall health, family history or lifestyle. One can perform the below-mentioned measures to lower the effects of thrombophilia:
- One should make efforts to get rid of the habit of smoking and opt for a healthy lifestyle
- Lose weight and maintain a healthy weight
- Exercise regularly
- Go for a healthy diet
- Try to avoid long periods of inactivity or sedentary lifestyle
Treatment of thrombophilia consists of Warfarin and heparin medicines. Warfarin being an oral drug involves some days to show its effects. Heparin is another helpful injectable medicine to treat the blood clotting fast. Heparin is usually taken along with Warfarin to show immediate results. A regular blood test becomes essential to know that one is consuming an appropriate amount of Warfarin. A blood test includes a Prothrombin Time Test (PT) and International Normalized Ratio (INR). Sufficient dose is very essential during thrombophilia treatment higher dosage leads to excessive bleeding.
With inherited thrombophilia, one can still prevent increased blood flow because of the intake of blood thinners. This can be checked with the aid of periodic blood testing. One may also use Thrombophob gel to receive a cure for such conditions. Thrombophob Gel (Heparin Sodium IP) is suggested to help manage a variety of ailments associated with thrombophilia such as circulation conditions, phlebitis, thrombophlebitis, varicose, bed sores, hemorrhoids, sprains, strains, contusions, grass burns, hematomas, and scars. Thrombophob uses are included in the advanced procedure of heparin therapy, which helps in penetrating the tissues to relieve symptoms with antiphlogistic and anti-exudative effects, which decrease inflammation and pain, increase metabolism, and aid faster healing.
The connection between thrombophilia with Recurrent Pregnancy Loss (RPL) has proved to be an indisputable fact. Thrombophilia produces a hypercoagulable state (excessive blood clotting). It produces arterial or venous thrombosis at the place of implantation of an embryo or in the placental blood vessels. Anticoagulants are an efficient treatment for RPL in pregnant women with acquired thrombophilia because of antiphospholipid syndrome. The positive results of RPL treatment with anticoagulants in women are supportive along with Inherited Thrombophilia (IT). Although the confined side-effects of anticoagulants are limited and mostly reversible, doctors today do not suggest using anticoagulants in women with RPL, IT, or those with unexplained pregnancy losses.
Recurrent Pregnancy Loss (RPL): Thrombophilia is a general cause of RPL and mostly seen in 40–50% of cases. Pregnancy is considered to be a hypercoagulable state. However, if gestation is affected by thrombophilia, the hypercoagulable state will become critical. It may also impair the bloodstream through the maternal veins, causing Deep Vein Thrombosis (DVT). Blood clots in the placental blood vessels because of thrombophilia leads to fetal growth restraint and even fetal loss. Therefore, anticoagulants have become a popular treatment of recurrent pregnancy loss. (11)
Thrombophilia turns out to be a major problem if ignored and not considered in the initial phase itself. Timely treatment will help the patient in soothing the pain and discomfort. It will also help them recover soon. Thrombophilia with inherited condition requires long term treatment whereas acquired thrombophilia can be cured with a healthy diet. Different thrombophilia profile blood test helps in evaluating the exact cause and dosage of the medicine for the appropriate treatment of the condition. Thrombophilia causes certain chronic as well as lifelong problems such as RPL, PE, swelling of legs and breathing problems. A regular test of thrombophilia can save the patient from any further blood clotting which can severe the patient's condition. A doctor may suggest blood thinner avoid such condition in the future. Maintaining a healthy lifestyle also prevents the body from being dehydrated. Consuming sufficient water keeps the toxins away from the blood and maintains a healthy flow of the blood in the patient.
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SOURCES AND REFERENCES:
- ^ Thrombophilia | Wikipedia En.wikipedia.org, 25 June 2019
- ^ What is Thrombophilia | Vascular Cures Vascularcures.org, 25 June 2019
- ^ The Genetics of Thrombophilia | Stop the Clot Stoptheclot.org, 25 June 2019
- ^ Thrombophilia Means That Blood Has an Increased Tendency to Form Clots | NHS Nhs.uk, 25 June 2019
- ^ Idiopathic Venous Thromboembolism and Thrombophilia | NCBI Ncbi.nlm.nih.gov, 25 June 2019
- ^ Inherited Thrombophilia and Venous Thromboembolism | NCBI Ncbi.nlm.nih.gov, 25 June 2019
- ^ When Should Thrombophilia Screening Be Done | Leeds Pathology Pathology.leedsth.nhs.uk, 25 June 2019
- ^ Thrombophilia Testing and Venous Thrombosis | ACC Acc.org, 25 June 2019
- ^ Thrombophilia Screening | HSE Hse.ie, 25 June 2019
- ^ Laboratory Investigation of Thrombophilia | Clinical Chemistry Clinchem.aaccjnls.org, 25 June 2019
- ^ Laboratory Investigation of Thrombophilia | Clinical Chemistry Clinchem.aaccjnls.org, 25 June 2019
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