# Thrombosis prevention

Thrombosis prevention or thromboprophylaxis is medical treatment to prevent the development of thrombosis (blood clots inside blood vessels) in those considered at risk for developing thrombosis. Some people are at a higher risk for the formation of blood clots than others, such as those with cancer undergoing a surgical procedure. Prevention measures or interventions are usually begun after surgery as the associated immobility will increase a person's risk.
Blood thinners are used to prevent clots, these blood thinners have different effectiveness and safety profiles. A 2018 systematic review found 20 studies that included 9771 people with cancer. The evidence did not identify any difference between the effects of different blood thinners on death, developing a clot, or bleeding. A 2021 review found that low molecular weight heparin (LMWH) was superior to unfractionated heparin in the initial treatment of venous thromboembolism for people with cancer.
There are medication-based interventions and non-medication-based interventions. The risk of developing blood clots can be lowered by lifestyle modifications, the discontinuation of oral contraceptives, and weight loss. In those at high risk, both interventions are often used. The treatments to prevent the formation of blood clots are balanced against the risk of bleeding.
One of the goals of blood clot prevention is to limit venous stasis as this is a significant risk factor for forming blood clots in the deep veins of the legs. Venous stasis can occur during the long periods of not moving. Thrombosis prevention is also recommended during air travel. Thrombosis prophylaxis is effective in preventing the formation of blood clots, their lodging in the veins, and their developing into thromboemboli that can travel through the circulatory system to cause blockage and subsequent tissue death in other organs. Clarence Crafoord is credited with the first use of thrombosis prophylaxis in the 1930s.

## Pathophysiology of blood clot prevention

The development of blood clots can be interrupted and prevented by the use of medication, changing risk factors, and other interventions. Some risk factors can be modified. These would be losing weight, increasing exercise, and the cessation of oral contraceptives. Moving during periods of travel is a modifiable behavior. Preventing blood clots includes medications that interrupt the complex clotting cascade and changing the proteins needed for clotting. Antiplatelet drugs also have an effect in preventing the formation of clots.

## Medical treatments

Thrombosis prophylaxis is not only used for the prevention of deep vein thrombosis but can be initiated for the prevention of the formation of blood clots in other organs and circumstances unrelated to deep vein thrombosis:
* cerebral complications
* abortion
* ectopic pregnancy
* molar pregnancy
* pregnancy
* childbirth and the puerperium
* coronary
* portal vein thrombosis
* intracranial, nonpyogenic
* intraspinal, nonpyogenic
* mesenteric
* pulmonary

## Epidemiology of developing blood clots

The risk of developing deep vein thrombosis, or pulmonary embolism is different than the total risk of the formation of blood clots. This is due to the observation that not all blood clots form in the lower legs. Most hospitalized medical patients have at least 1 risk factor for thrombosis that progresses to thromboembolism and this risk persists weeks after discharge. Those who remain undiagnosed and not treated prophylactically have a 26% chance of developing a fatal embolism. Another 26% develop another embolism. Between 5% and 10% of all in-hospital deaths are due to pulmonary embolism (as a consequence of thrombosis). Estimates of the incidence of pulmonary embolism in the US is 0.1% persons/year. Hospital admissions in the US for pulmonary embolism are 200,000 to 300,000 yearly. Thrombosis that develops into DVT will affect 900,000 people and kill up to 100,000 in the US. On average 28,726 hospitalized adults aged 18 and older with a VTE blood clot diagnosis die each year. Risk of thrombosis is related to hospitalization. In 2005 the UK the Parliamentary Health Select Committee determined the annual rate of death due to thrombosis was 25,000 with at least 50% being hospital-acquired.
The type of surgery performed prior to the formation of blood clots influences the risk. Without prophylactic interventions, the calculated incidence of clot formation in the lower leg veins after surgery is:
* 22% for neurosurgery
* 26% for abdominal surgery
* 45% for 60% in orthopedic surgery
* 14% for gynecologic surgery
As the population of the US ages, the development of blood clots is becoming more common.

## General risks and indications for blood clot prevention

Some risk factors for developing blood clots are considered higher than others. One scoring system analyzes the probability of clot formation by assigning a point value system to significant risk factors. The benefit of treating those who are at low risk of developing blood clots may not outweigh the higher risks of significant bleeding.
Risk factors for developing blood clots that are assessed before treatments :
| Risk factor | Notes |
| Previous episodes of thrombosis | also a risk factor for embolism formation |
| Family History of Deep Vein Thrombosis | |
| Gender, and race | not firmly established increased prevalence in women during childbearing years |
| Smoking | modifiable, difficult |
| Diabetes | |
| Arteriosclerosis | |
| Renal disease | "hypercoagulable state" |
| Vasoconstriction | |
| Myocardial infarction and other types of heart disease | Heart attack, Unstable angina Dysrhythmias Heart failure |
| Slow or turbulent blood flow | modifiable with exercise |
| Stroke | heparins contraindicated |
| Sedentary lifestyle | modifiable with exercise |
| Plaster cast | transient |
| Dehydration | modifiable also related to athletic activities and sports |
| Acute respiratory failure | |
| Dysrhythmias | |
| Shock | |
| Obesity | modifiable |
| Pregnancy and the post-partum period | "hypercoagulable state" |
| Varicose veins | |
| Surgery | length of the surgical procedure type of operation hip or knee surgery related to subsequent state of hypercoagulability |
| Lung disease | |
| Trauma | related to immobility |
| Estrogen-based oral contraceptive | discontinuation reduces risk related to progestogen and ethinylestradiol |
| Hormone replacement therapy | discontinuation reduces risk |
| Ovarian hyper-stimulation therapy to treat infertility | |
| Compression of a vein or artery by abnormality, tumor, hematoma | |
| Pacing wires | |
| Local vein damage, incompetent valves | |
| Central venous catheters | |
| Dialysis catheters | |
| Repetitive motion injury | |
| Immobility | associated with air travel, long travel times, and post-surgical – modifiable risk |
| Spinal cord injury | |
| Age | |
| Cancers | |
| Sepsis | |
| Polycythemia | heparins contraindicated |
| Genetic deficiencies or autoimmune disorders, Protein C and/or S deficiency | congenital; associated with warfarin necrosis, heparins contraindicated |
| Antiphospholipid antibody syndrome | altered coagulation; heparins contraindicated |
| Factor V Leiden defect | altered coagulation |
| Prothrombin G20210A defect | altered coagulation; heparins contraindicated |
| Hyperhomocysteinimia | altered coagulation; heparins contraindicated |
| Elevated factors II, VIII, IX, XI | altered coagulation; heparins contraindicated |
| Antithrobin III deficiency | altered coagulation; heparins contraindicated |
| Falls and hip fracture | related to immobility |
| Selective estrogen-receptor modulators | |
| Erythropoiesis-stimulating agents | |
| Acute medical illness | |
| Inflammatory bowel disease | |
| Nephrotic syndrome | |
| Myeloproliferative disorders | |
| Paroxysmal nocturnal hemoglobinnuria | |
| Thrombophilias | heparins contraindicated |
| Post-menopausal hormone replacement therapy | discontinuation reduces risk |
| Right heart failure | |
| Venous inflammation/phlebitis | when a thrombus forms, it is thrombophlebitis |
| Sickle cell disease | |
| Artificial heart valves | |
       Probability and risk estimation for developing blood clots Major risk (=1 point)Minor risk (=2 points) CancerFamily history of deep vein thrombosis ImmobilityHospitalization within the past 6 months Calf swellingsuperficial vein dilation Recent major surgeryredness of area Edema or swelling of only legRecent trauma to leg Tenderness in the calf and/or thigh
Scoring of the risks associated with the formation of blood clots :
* Probability determination and scoring
* High probability scoring (12–7 points
* 3 major points OR 2 major points AND >2 minor points
* Low probability scoring (3–5 points)
* 0 major points AND > 2 minor points 1 major point AND >2 minor points 0 major points and >3 minor point 1 major point and more than one minor point
* Moderate probability scoring (varies)
* all other risk combinations

## Risk for subsequent blood clots

Developing blood clots is more probable after the first episode. Risk assessment and intervention for those with one or more episodes of deep vein thrombosis or blood clots in the veins utilize the Well's test. It has been inconsistently modified by several publishers with the results listed below:

### Well's and modified Well's risk scoring

Well's and modified Well's scoring :
| Finding | points |
| D-dimer abonormal one month after stopping anticoagulants | 2 |
| Age > or = to 50 | 1 |
| male | 1 |
| use of hormone at DVT onset | 1 |

### Adapted for the emergency department

modified Well's scoring :
| Finding | points |
| Malignancy | 1 |
| Age > or = to 50 | 1 |
| cast on lower leg/Paralysis/paresis/ | 1 |
| Recent surgery or immobility | 1 |
| tenderness over deep vein | 1 |
| entire leg swollen | 1 |
| difference of 3 cm between legs | 1 |
| pitting edema of the affected leg | 1 |
| Collateral superficial veins | 1 |
| another diagnosis more probable than DVT | −2 |
Scoring:
* less than 2 points – low risk (3%)
* 2–6 points moderate risk (17%)
* > 6 points high risk (75%)

## General interventions

The Centers for Disease Control and Prevention have issued general guidelines describing the interventions that can be taken to reduce the risk of the formation of blood clots:
   The Centers for Disease Control and Prevention recommend the following:
   * Move around as soon as possible after being confined to bed, such as after surgery, illness, or injury.
   * If you're at risk for DVT, talk to your doctor about:
   ** Graduated compression stockings (sometimes called "medical compression stockings")
   ** Medication (anticoagulants) to prevent DVT.
   * When sitting for long periods, such as when traveling for more than four hours:
   ** Get up and walk around every 2 to 3 hours.
   ** Exercise your legs while you're sitting by:
   *** Raising and lowering your heels while keeping your toes on the floor
   *** Raising and lowering your toes while keeping your heels on the floor
   *** Tightening and releasing your leg muscles
   ** Wear loose-fitting clothes.
   * You can reduce your risk by maintaining a healthy weight, avoiding a sedentary lifestyle, and following your doctor's recommendations based on your individual risk factors.

### Interventions during travel

Seat-edge pressure from the seat on an airplane on the popliteal area may contribute to vessel wall damage as well as venous stasis. Coagulation activation may result from an interaction between cabin conditions (such as hypobaric hypoxia) and individual risk factors for the formation of blood clots. Studies of the pathophysiologic mechanisms for the increased risk of venous thromboembolism or VTE after long-distance travel have not produced consistent results, but venous stasis appears to play a major role; other factors specific to air travel may increase coagulation activation, particularly in passengers with individual risk factors for VTE.

### Interventions for those hospitalized
#### Compression devices

Mechanical compression devices are used to prevent thrombosis and are beneficial enough to be used by patients at low to moderate risk. The use of fitted intermittent pneumatic compression devices before, during, and after procedures is used in inpatient settings. It consists of an air pump and inflatable auxiliary compartments that sequentially inflate and deflate to provide an external 'pump' that returns venous blood toward the heart. The use of intermittent pneumatic compression is common. These devices are also placed on a surgical patient in the operating room (the intra-surgical period) and remain on the person while recovering from the surgery.
The application of antiembolism stockings can be used to prevent thrombosis. The correct use and properly fitted graded compression stockings can reduce the rate of thrombosis by 50%.$^{:745–46}$ Contraindications for the use of antiembolism stockings include the presence of advanced peripheral and obstructive arterial disease, septic phlebitis, heart failure, open wounds, dermatitis and peripheral neuropathy. Differences between the use of thigh-high compression stockings and shorter types to prevent blood clots exist, but remain inconsistent.

### Assessment

There has been some success in preventing blood clots through an early risk assessment upon hospital admission, a strategy recognized by the Centers for Disease Control and Prevention. Hospitals that have participated in this effort to reduce the incidence of thrombosis found that rates of DVT decreased in some instances. Some hospitals developed a mandatory assessment quantifying the risk of developing blood clots and a plan of care developed from the results. The person's risk for developing blood clots is entered into their record, 'following' them through their treatment regime. If the hospital stay exceeds three days, the person will be reassessed for risk. Clinicians can then apply protocols for prevention based on best clinical practices.

#### Interventions to treat immobility

Immobility is a significant risk factor in the development of thrombosis. Immediate post-surgical interventions, such as out of bed orders (OOB), are typically ordered by the physician to prevent thrombosis. These orders, typically delegated to a nurse, but may include the participation of a physical therapist and others trained to perform the intervention, are to perform range of motion (ROM) activities that include: muscle contractions of the lower legs for those who are very weak, moving the feet, wiggling the toes, bending the knees, raise and lower the legs. In addition, changes in positioning prevent immobility and shift areas of venous stasis. If the person is too weak to perform these preventative activities, hospital personnel will perform these movements independently. Exercise of the lower extremities is a post-operative method of prophylaxis. Nursing personnel will often perform a range of motion exercises and encourage frequent moving of the legs, feet, and ankles. Frequent positioning changes and adequate fluid intake. After a surgical procedure, ambulation as soon as possible is prophylactic in preventing the formation of blood clots.
Early ambulation also prevents venous stasis and physicians order OOB activities on the same day of surgery. This is accomplished in increments. The progression of increasing mobility proceeds by: raising the head of the bed, sitting up in bed, moving to the edge of the bed, dangling the legs off the bed, and then ambulating to a closed chair.
Patient education and compliance reduce the risk of developing blood clots. These exercises and the use of equipment and follow-up by clinicians reduce the risk of developing blood clots.
If a blood clot has already formed in the deep veins of the leg, early movement out of bed is usually prescribed, except in some severe cases of deep vein thrombosis or in people who have phlegmasia cerulea dolens. The treatment to prevent blood with physical intervention (e.g., sequential compression device) is contraindicated.

## Medication
### Anticoagulants and antiplatelets

Thromboprophylaxis, such as anticoagulants or perioperative heparin, is effective for hospitalized patients at risk for VTE. Additional risk factors such as obesity, disease, malignancies, long surgeries, and immobility may influence the prescribed dosage. Anticoagulant medications may prevent the formation of blood clots in people who are at high risk for their development. Treating blood clots that have already formed is managed by the use of anti-hemolytic ("clot busters"). Despite its effectiveness, the use of thromboprophylaxis remains under-utilized, though alerts (computer or human) in hospitals are associated with increased prescription and reductions in symptomatic VTE. The list below describes some of the more common medications used to prevent blood clots. Note that generally since blood clotting is inhibited, a side effect typically is increased bleeding, though it can be reversed by administering a medication that stops the bleeding or by discontinuation of the medication itself. Anti-coagulant administration is often given before the start of the operation. Medications that inhibit blood clot formation include:
Medications used to prevent blood clots :
| Name of medication | Therapeutic/pharmacologic class | Action | Route | Notes | Side effects |
| aspirin | | antiplatelet | | | risks for GI tract bleeding and hemorrhagic stroke |
| dipyridamole | platelet aggregation inhibitor | | oral or intravenous | | Abdominal or stomach cramps, diarrhea, dizziness or lightheadedness |
| clopidogrel | antiplatelet | | | | |
| ticlid | | | | | |
| enoxaparin | anticoagulant | activation of antiprothrombin, prevents fibrin formation | slow IV | platelet count is monitored | |
| dalteparin | anticoagulant | activation of antiprothrombin, prevents fibrin formation | IV | | |
| fondaparinux | anticoagulant | inhibits thrombin production | injection | aspirin not recommended with this medication | |
| dabigatran | | inhibits prothrombin | | | |
| bivalirudin | | inhibits prothrombin | | often given with aspirin | |
| argatroban | anticoagulant | inhibits prothrombin | IV | alternative to heparin in those developing heparin-induced thrombocytopenia | |
| desirudin | anticoagulant | inhibits prothombin | injection | used with hip replacement | |
| Eptifibatide | antiplatelet | | | | |
| tirofiban | antiplatelet | | | | |
| ticlopidine | antiplatelet | | | | |
| pentoxifylline | antiplatelet | | | | |
| cilostazol | antiplatelet | | | | |
| rivaroxaban | | inhibits factor Xa | | use with antiplatelets cautioned | GI bleeding |
| warfarin | anticoagulant | Thrombin inhibitor; | IV | | |
| lipirudin | anticoagulant | inhibits prothrombin | IV | treatment may extend to 10 days | |
| dextran | | | | | |

### Heparins

Adding heparin to the use of compression stockings may prevent thrombosis for those at higher risk.
             Heparin Prophylaxis nameactionstructurereferences Low-molecular weight heparin (example: Reviparin)
The discontinuation of contraceptives also prevents blood clots.

#### Herbal interactions

The therapeutic effects of warfarin may be decreased by valerian. Chamomile can affect the action of anticoagulants. Dong quai, garlic, ginger, Ginkgo biloba, bilberry, and feverfew can increase bleeding time. These same herbal supplements taken with warfarin increased prothrombin time.

#### Dietary interactions

By containing significant content of vitamin K, some foods act as antagonists to antiplatelet and anticoagulant medications; these include green leafy vegetables, like spinach, legumes, and broccoli.

#### Contraindications

Preventing blood clots with medication is not considered safe in the following circumstances:
* uncooperative patient
* recent childbirth
* gastrointestinal bleeding
* reproductive system bleeding
* genitourinary system bleeding
* hemorrhagic blood dyscrasias
* peptic ulcers
* alcohol use disorder
* infection
* eye surgery
* brain surgery
* spinal cord surgery
* recent intracranial hemorrhage$^{:877}$

## Research

An international registry and risk assessment calculator is being used to centralize data on post-surgical venous thrombosis and its prevention. Hospitals are implementing a multidisciplinary approach to prevent of blood clots. This includes adequate assessment of the risks, follow-up on missed doses of medication, and instituting a 'patient-centered' approach endorsed by the Joint Commission. Recommendations regarding the prevention of blood clots vary widely between clinicians and treatment facilities. Research continues to clarify these discrepancies. The metabolic state of hypercoagulability (the tendency to form blood clots) tests are being developed. These include the evaluation of the thrombin–antithrombin complexes (TAT), low levels of the anticoagulants ATIII and protein C, but these tests are not yet widely available.