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.[1] Some people are at a higher risk for the formation of blood clots than others. Prevention measures or interventions are usually begun after surgery as people are at higher risk due to immobility.

Thrombosis prevention
a blood clot blocking a blood vessel
Other names	Thrombosis prophylaxis
ICD-10-PCS	I80-I82
ICD-9-CM	437.6, 453, 671.5, 671.9

People undergoing surgery with cancer are at an increased risk of blood clots. Blood thinners are used to prevent clots, these blood thinners have different effectiveness and safety profiles. Research [2] 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. Less bruising following surgery occurred with some while others may have reduced the risk of getting a blood clot but the reliability of evidence varied from low to moderate.

Data from five studies with 422 participants [3] suggested the effect of low molecular weight heparin (LMWH) on death compared with unfractionated heparin was uncertain.

There are medication-based interventions and non-medication-based interventions.[4] The risk of developing blood clots can be modified by life style modifications, the discontinuation of oral contraceptives, and weight loss. In those at high risk both interventions are often used.[1] The treatments to prevent the formation of blood clots is balanced against the risk of bleeding.[5]

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.[6] Venous stasis can occur during the long periods of not moving. Thrombosis prevention is also recommended during air travel.[7] 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.[1] Clarence Crafoord is credited with the first use of thrombosis prophylaxis in the 1930s.

Pathophysicology 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 the use of medications that interrupt the complex clotting cascade and changing the proteins that are needed for clotting. Antiplatelet drugs also have an effect in preventing the formation of clots.

If a blood clot has already formed in a blood vessel, treatment will differ significantly from clot prevention. Hemolytic medications are used. These are medications that will help dissolve the clot. Physical interventions then become contraindicated due to the risk of the clot migrating to distant locations like the heart, brain, and lungs. Once a clot has formed, a person will be prescribed bed rest and remain relatively immobile until it the clot is undetectable.

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[8][9]

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 suffering 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.[10] 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.[11] 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.[12]

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[13]

As the population of the US ages, the development of blood clots is becoming more common.[14]

General risks and indications for blood clot prevention

Some risk factors for developing blood clots are considered higher that others. One scoring system analyzes the probability for clot formation by assigning a point value system to significant risk factors.[15] The benefit of treating those who are at low risk of developing blood clots may not outweigh the higher risks of significant bleeding.[16]

Risk factors for developing blood clots that are assessed prior to treatments

Risk factor Notes References Previous episodes of thrombosis also a risk factor for embolism formation[17] [18][19] Family History of Deep Vein Thrombosis [20][14] Gender, and race not firmly established increased prevalence in women during childbearing years [14] Smoking modifiable, difficult [19][21] Diabetes [18] Arteriosclerosis [18] Renal disease ”hypercoagulable state”[18] [18] Vasoconstriction [22] Myocardial infarction and other types of heart disease Heart attack, Unstable angina Dysrhythmias Heart failure [23][20][22][18] Slow or turbulent blood flow modifiable with exercise [22][23][24] Stroke heparins contraindicated[24] [18][24] Sedentary life style modifiable with exercise [22][19][14] Plaster cast transient [18] Dehydration modifiable also related to athletic activities and sports [22][20] Acute respiratory failure [18] Dysrhythmias [22][23] Shock [22] Obesity modifiable [15][25][1][22][18][23][19] Pregnancy and the post-partum period “hypercoagulable state”[18] [15][1][22][20][14] Varicose veins [18] Surgery length of the surgical procedure type of operation hip or knee surgery[14] related to subsequent state of hypercoagulability [13] [15][1][25][19][20][21] Lung disease [20] Trauma related to immobility [15][1][18][23][14] Estrogen-based oral contraceptive discontinuation reduces risk related to progestogen and ethinylestradiol[26] [15][1][22][20][26][14][21] Hormone replacement therapy discontinuation reduces risk [15] Ovarian hyper-stimulation therapy to treat infertility [15] Compression of a vein or artery by abnormality, tumor, hematoma [15] Pacing wires [1] Local vein damage, incompetent valves [1][22] Central venous catheters [1][23] Dialysis catheters [1][23] Repetitive motion injury [1] Immobility associated with air travel, long travel times and post-surgical – modifiable risk [1][18][23][19][14][21][13] Spinal cord injury [1] Age [1][15][22][18] Cancers [1][20][14] Sepsis [1] Polycythemia heparins contraindicated[24] [1] genetic deficiencies or autoimmune disorders, Protein C and/or S deficiency congenital; associated with warfarin necrosis, heparins contraindicated[24] [1][27][21] Antiphospholipid antibody syndrome altered coagulation; heparins contraindicated[24] [1] Factor V Leiden defect altered coagulation [1] Prothrombin G20210A defect altered coagulation; heparins contraindicated[24] [1] Hyperhomocysteinimia altered coagulation; heparins contraindicated[24] [1] Elevated factors II, VIII, IX, XI altered coagulation; heparins contraindicated[24] [1][14] Antithrobin III deficiency altered coagulation; heparins contraindicated[24] [1][14] Falls and hip fracture related to immobility [1][19] Selective estrogen-receptor modulators [15] Erythropoiesis-stimulating agents [15] Acute medical illness [15][14] Inflammatory bowel disease [15] Nephrotic syndrome [15] Myeloproliferative disorders [15] Paroxysmal nocturnal hemoglobinnuria [15] Thrombophilias heparins contraindicated[24] [15][14] Post-menopausal hormone replacement therapy discontinuation reduces risk [15] Right heart failure [22] Venous inflammation/phlebitis when a thrombus forms, it is thrombophlebitis [22] Sickle cell disease Artificial heart valves [24]

Probability and risk estimation for developing blood clots

Major risk (=1 point)	Minor risk (=2 points)
Cancer	Family history of deep vein thrombosis
Immobility	Hospitalization within the past 6 months
Calf swelling	superficial vein dilation
Recent major surgery	redness of area
Edema or swelling of only leg	Recent trauma to leg
Tenderness in the calf and/or thigh

Scoring of the risks associated with 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 utilizes the Well's test. It has been inconsistently modified by a number of publishers with the results listed below:[28]

Well's and modified Well's risk scoring

Well's and modified Well's scoring

Finding	points	references
D-dimer abonormal one month after stopping anticoagulants	2	[28]
Age > or = to 50	1	[28]
male	1	[28]
use of hormone at DVT onset	1	[28]

Adapted for the emergency department

modified Well's scoring

Finding	points	references
Malignancy	1	[29]
Age > or = to 50	1	[29]
cast on lower leg/Paralysis/paresis/	1	[29]
Recent surgery or immobility	1	[29]
tenderness over deep vein	1	[29]
entire leg swollen	1	[29]
difference of 3 cm between legs	1	[29]
pitting edema of affected leg	1	[29]
Collateral superficial veins	1	[29]
another diagnosis more probable than DVT	-2	[29]

Scoring:

• less than 2 points – low risk (3%)
• 2–6 points moderate risk (17%)
• > 6 points high risk (75%)[29]

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 having been 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 of time, 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.[7]

^{a lower leg vein with good flow – statis of blood would occur if this vein was compressed and blood flow decreased or was stopped}

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 thrombosis embolism 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.[30]

Compression devices

The use of fitted intermittent pneumatic compression devices before, during and after procedures is another way to It consists of an air pump and inflatable auxiliary compartments that sequentially inflates and deflated to provide an external 'pump' that returns venous blood toward the heart.[31] The use of intermittent pneumatic compression is common.[31][19][5] 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.[32]

The application of antiembolism stockings (TED stockings) can be used to prevent thrombosis. The correct use and properly fitted graded compression stockings can reduce the rate of thrombosis by 50%.[15][19]^: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.[33] Differences between the use of thigh-high compression stockings and shorter types to prevent blood clots exist, but remain inconsistent.[5]

Assessment

There has been some success in preventing blood clots by an early risk assessment upon admission to the hospital, which is 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.[34] Some of the hospitals developed a mandatory assessment quantifying the risk for developing blood clots and a plan of care developed from the assessment. The person's risk for developing blood clots is entered into their record, ‘following’ them through their treatment regime. If the hospital stay exceeded three days, the person was reassessed for risk. Clinicians were then able to apply protocols for prevention based upon best clinical practices.[35][36]

Interventions to treat immobility

The poplitial vein can be one site of venous stasis in the lower leg. Obstruction of this vein during travel contributes to statis.

Immobility is a significant risk factor in the development of thrombosis.[37][38][22][25] 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 prevents immobility and shifts 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 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.[38][22][25]

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 close chair.[19][25]

Patient education and compliance reduces the risk of developing blood clots. These exercises and use of equipment and follow up by clinicians reduces the risk of developing blood clots.[25]

Note that if a blood clot has already formed in the deep veins of the leg, bedrest is usually prescribed and the treatment to prevent bloods with physical intervention is contraindicated.

Medication

Anticoagulants and antiplatelets

Thromboprophylaxis, such as anticoagulants or pre-operative low-molecular weight heparin, is effective for hospitalized patients at risk for VTE.[39] Additional risk factors such as obesity, disease, malignancies, long surgeries, and immobility may influence the prescribed dosage. Anticoagulant medications 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.[39] The list below describes some of the more common medications used to prevent blood clots.[24] Note that generally that since blood clotting is inhibited, a side effect typically is 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. There are concerns with the potential of increased risk of bleeding and so many surgeons start giving anti-coagulants the first 6 hours after surgery.[25] Medications that inhibit blood clot formation include:

Medications used to prevent blood clots

Name of medication Therapeutic/pharmologic class Action Route Other uses Notes Side effects References aspirin antiplatelet risks for GI tract bleeding and hemorrhagic stroke[40][41] [32][42][43] dipyridamole platelet aggregation inhibitor oral or IV Abdominal or stomach cramps, diarrhea, dizziness or lightheadedness [44][45][46][41] clopidogrel antiplatelet [45][41] ticlid enoxaparin anticoagulant activation of antiprothrombin, prevents fibrin formation slow IV platelet count is monitored [45][41] dalteparin anticoagulant activation of antiprothrombin, prevents fibrin formation IV [41] fondaparinux anticoagulant inhibits thrombin production injection aspirin not recommended with this medication [41][24] dabigatran inhibits prothrombin [41] bivalirudin inhibits prothrombin often given with aspirin [41] argatroban anticoagulant inhibits prothrombin IV alternative to heparin in those developing heparin-induced thrombocytopenia [41][24] desirudin anticoagulant inhibits prothombin injection used with hip replacement [41][24] eptifiatide antiplatelet [41] tirofiban antiplatelet [41] ticlopidine antiplatelet [41] pentocifylline antiplatelet [41] diyridamole anitplatelet [41] cilostazol antiplatelet [41] rivaroxaban inhibits factor Xa use with antiplatelets cautioned GI bleeding [41] warfarin anticoagulant Thrombin inhibitor; IV [24] lipirudin anticoagulant inhits prothrombin IV treatment may extend to 10 days [24]

Heparins

Heparin Prophylaxis

name	action	structure	references
Low-molecular weight heparin (example: Reviparin)			[47][48][49][50][51]

The discontinuation of contraceptives also prevents blood clots.[15]

Herbal interactions

The therapeutic effects of warfarin may be decreased by valerian. Anticoagulants can be affected by chamomile. Dong quai, garlic, ginger, Ginkgo biloba, bilberry and feverfew can increase bleeding time. These same herbal supplements taken with warfarin increased prothrombin time.[24]

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.[24]

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
• alcoholism
• infection
• eye surgery
• brain surgery
• spinal cord surgery
• recent cerebrovascular hemorrhage[1]^:877

Adding heparin to the use of compression stockings may prevent thrombosis.[52]

Research

An international registry and risk assessment calculator is being used to centralize data on post-surgical venous thrombosis and its prevention.[53] Hospitals are implementing a multi-disciplinary 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.[34] Recommendations regarding the prevention of blood clots vary widely between clinicians and treatment facilities. Research continues to clarify these discrepancies.[5] 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.[13]

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