Venous thrombosis
Venous thrombosis | |
---|---|
A deep vein thrombosis in the right leg. There is striking redness and swelling. | |
Specialty | Hematology, pulmonology, cardiology |
Frequency | 1-2 per 1,000 per year[1] |
Venous thrombosis is the blockage of a vein caused by a thrombus (blood clot). A common form of venous thrombosis is deep vein thrombosis (DVT), when a blood clot forms in the deep veins. If a thrombus breaks off (embolizes) and flows to the lungs to lodge there, it becomes a pulmonary embolism (PE), a blood clot in the lungs. The conditions of DVT only, DVT with PE, and PE only, are all captured by the term venous thromboembolism (VTE).[2]
The initial treatment for VTE is typically either
There are other less common forms of venous thrombosis, some of which can also lead to pulmonary embolism. Venous
Classification
Common forms
When a blood clot breaks loose and travels in the blood, this is called a thromboembolism. The abbreviation DVT/PE refers to a VTE where a deep vein thrombosis (DVT) has moved to the lungs (PE or pulmonary embolism).[4]
Since the veins return blood to the heart, if a piece of a blood clot formed in a vein breaks off it can be transported to the right side of the heart, and from there into the lungs. A piece of thrombus that is transported in this way is an embolus: the process of forming a thrombus that becomes embolic is called a thromboembolism. An embolism that lodges in the lungs is a pulmonary embolism (PE). A pulmonary embolism is a very serious condition that can be fatal depending on the dimensions of the embolus.[citation needed]
Rare forms
While venous thrombosis of the legs is the most common form, venous thrombosis may occur in other veins. These may have particular specific risk factors:[5]
- Cerebral venous sinus thrombosis, cavernous sinus thrombosis and jugular vein thrombosis: thrombosis of the veins of the brain and head
- Central retinal vein occlusion and branch retinal vein occlusion: despite the name these conditions have much more in common with arterial thrombosis and are not treated with anticoagulants
- Paget–Schroetter disease: thrombosis of the veins of the arms (axillary and subclavian veins)
- hepatic vein)
- Thrombosis of the hepatic portal system, also known as splanchnic venous thrombosis:
- Thrombosis of the mesenteric ischemia(insufficient blood flow to the intestine)
- Portal vein thrombosis
- Thrombosis of the splenic vein
- Thrombosis of the
- Renal vein thrombosis (thrombosis of the veins of the kidneys)
- Ovarian vein thrombosis[3]
Parodoxical embolism
Systemic embolism of venous origin can occur in patients with an atrial or ventricular septal defect, or an arteriovenous connection in the lung, through which an embolus may pass into the arterial system. Such an event is termed a paradoxical embolism. When this affects the blood vessels of the brain it can cause stroke.[6]
Causes
Venous thrombi are caused mainly by a combination of
Risk factors
Acquired
- Older age[8]
- Major surgery, orthopedic surgery,[9] neurosurgery[10]
- Cancers, most particularly pancreatic, but not cancers of the lip, oral cavity, and pharynx[11]
- Immobilization, as in orthopedic casts,[9] the sitting position, and travel, particularly by air[7]
- Pregnancy and the postpartum period[7][12]
- Antiphospholipid syndrome[9] (such as lupus anticoagulant)[7][8]
- Trauma[7] and minor leg injury[13]
- Previous VTE[14]
- Oral contraceptives[9]
- Hormonal replacement therapy,[9] esp. oral
- Central venous catheters[9][15]
- Nephrotic syndrome[18]
- Obesity[9]
- Infection[18]
- HIV[18]
- Myeloproliferative neoplasms including essential thrombocytosis and polycythemia vera[9]
- Chemotherapy[8][19]
- Heart failure[20]
Inherited
- Antithrombin deficiency[7]
- Protein C deficiency[7]
- Protein S deficiency (type I)[18]
- Factor V Leiden[7]
- Prothrombin G20210A[7]
- Dysfibrinogenemia[9]
- Non O-blood type[21]
Mixed
- Low free protein S[18]
- Activated protein C resistance[18]
- High factor VIII levels[22]
- Hyperhomocysteinemia[7]
- High fibrinogen levels[7]
- High factor IX levels[7]
- High factor XI levels[7]
The overall absolute risk of venous thrombosis per 100,000 woman years in current use of
Regarding family history, age has substantial
Type | Route | Medications | Odds ratio (95% CI ) |
---|---|---|---|
Menopausal hormone therapy |
Oral | Estradiol alone ≤1 mg/day >1 mg/day |
1.27 (1.16–1.39)* 1.22 (1.09–1.37)* 1.35 (1.18–1.55)* |
Conjugated estrogens alone ≤0.625 mg/day >0.625 mg/day |
1.49 (1.39–1.60)* 1.40 (1.28–1.53)* 1.71 (1.51–1.93)* | ||
Estradiol/medroxyprogesterone acetate | 1.44 (1.09–1.89)* | ||
Estradiol/dydrogesterone ≤1 mg/day E2 >1 mg/day E2 |
1.18 (0.98–1.42) 1.12 (0.90–1.40) 1.34 (0.94–1.90) | ||
Estradiol/norethisterone ≤1 mg/day E2 >1 mg/day E2 |
1.68 (1.57–1.80)* 1.38 (1.23–1.56)* 1.84 (1.69–2.00)* | ||
Estradiol/norgestrel or estradiol/drospirenone |
1.42 (1.00–2.03) | ||
Conjugated estrogens/medroxyprogesterone acetate | 2.10 (1.92–2.31)* | ||
Conjugated estrogens/norgestrel ≤0.625 mg/day CEEs >0.625 mg/day CEEs |
1.73 (1.57–1.91)* 1.53 (1.36–1.72)* 2.38 (1.99–2.85)* | ||
Tibolone alone | 1.02 (0.90–1.15) | ||
Raloxifene alone | 1.49 (1.24–1.79)* | ||
Transdermal |
Estradiol alone ≤50 μg/day >50 μg/day |
0.96 (0.88–1.04) 0.94 (0.85–1.03) 1.05 (0.88–1.24) | |
Estradiol/progestogen | 0.88 (0.73–1.01) | ||
Vaginal |
Estradiol alone | 0.84 (0.73–0.97) | |
Conjugated estrogens alone | 1.04 (0.76–1.43) | ||
Combined birth control |
Oral | Ethinylestradiol/norethisterone | 2.56 (2.15–3.06)* |
Ethinylestradiol/levonorgestrel | 2.38 (2.18–2.59)* | ||
Ethinylestradiol/norgestimate |
2.53 (2.17–2.96)* | ||
Ethinylestradiol/desogestrel | 4.28 (3.66–5.01)* | ||
Ethinylestradiol/gestodene | 3.64 (3.00–4.43)* | ||
Ethinylestradiol/drospirenone | 4.12 (3.43–4.96)* | ||
Ethinylestradiol/cyproterone acetate | 4.27 (3.57–5.11)* | ||
Notes: (1) Bioidentical progesterone was not included, but is known to be associated with no additional risk relative to estrogen alone. Footnotes: * = Statistically significant (p < 0.01). Sources: See template.
|
Absolute incidence of first VTE per 10,000 person–years during pregnancy and the postpartum period | ||||||||
---|---|---|---|---|---|---|---|---|
Swedish data A | Swedish data B | English data | Danish data | |||||
Time period | N | Rate (95% CI) | N | Rate (95% CI) | N | Rate (95% CI) | N | Rate (95% CI) |
Outside pregnancy | 1105 | 4.2 (4.0–4.4) | 1015 | 3.8 (?) | 1480 | 3.2 (3.0–3.3) | 2895 | 3.6 (3.4–3.7) |
Antepartum | 995 | 20.5 (19.2–21.8) | 690 | 14.2 (13.2–15.3) | 156 | 9.9 (8.5–11.6) | 491 | 10.7 (9.7–11.6) |
Trimester 1 | 207 | 13.6 (11.8–15.5) | 172 | 11.3 (9.7–13.1) | 23 | 4.6 (3.1–7.0) | 61 | 4.1 (3.2–5.2) |
Trimester 2 | 275 | 17.4 (15.4–19.6) | 178 | 11.2 (9.7–13.0) | 30 | 5.8 (4.1–8.3) | 75 | 5.7 (4.6–7.2) |
Trimester 3 | 513 | 29.2 (26.8–31.9) | 340 | 19.4 (17.4–21.6) | 103 | 18.2 (15.0–22.1) | 355 | 19.7 (17.7–21.9) |
Around delivery | 115 | 154.6 (128.8–185.6) | 79 | 106.1 (85.1–132.3) | 34 | 142.8 (102.0–199.8) | –
| |
Postpartum | 649 | 42.3 (39.2–45.7) | 509 | 33.1 (30.4–36.1) | 135 | 27.4 (23.1–32.4) | 218 | 17.5 (15.3–20.0) |
Early postpartum | 584 | 75.4 (69.6–81.8) | 460 | 59.3 (54.1–65.0) | 177 | 46.8 (39.1–56.1) | 199 | 30.4 (26.4–35.0) |
Late postpartum | 65 | 8.5 (7.0–10.9) | 49 | 6.4 (4.9–8.5) | 18 | 7.3 (4.6–11.6) | 319 | 3.2 (1.9–5.0) |
Incidence rate ratios (IRRs) of first VTE during pregnancy and the postpartum period | ||||||||
Swedish data A | Swedish data B | English data | Danish data | |||||
Time period | IRR* (95% CI) | IRR* (95% CI) | IRR (95% CI)† | IRR (95% CI)† | ||||
Outside pregnancy | Reference (i.e., 1.00)
| |||||||
Antepartum | 5.08 (4.66–5.54) | 3.80 (3.44–4.19) | 3.10 (2.63–3.66) | 2.95 (2.68–3.25) | ||||
Trimester 1 | 3.42 (2.95–3.98) | 3.04 (2.58–3.56) | 1.46 (0.96–2.20) | 1.12 (0.86–1.45) | ||||
Trimester 2 | 4.31 (3.78–4.93) | 3.01 (2.56–3.53) | 1.82 (1.27–2.62) | 1.58 (1.24–1.99) | ||||
Trimester 3 | 7.14 (6.43–7.94) | 5.12 (4.53–5.80) | 5.69 (4.66–6.95) | 5.48 (4.89–6.12) | ||||
Around delivery | 37.5 (30.9–44.45) | 27.97 (22.24–35.17) | 44.5 (31.68–62.54) | –
| ||||
Postpartum | 10.21 (9.27–11.25) | 8.72 (7.83–9.70) | 8.54 (7.16–10.19) | 4.85 (4.21–5.57) | ||||
Early postpartum | 19.27 (16.53–20.21) | 15.62 (14.00–17.45) | 14.61 (12.10–17.67) | 8.44 (7.27–9.75) | ||||
Late postpartum | 2.06 (1.60–2.64) | 1.69 (1.26–2.25) | 2.29 (1.44–3.65) | 0.89 (0.53–1.39) | ||||
Notes: Swedish data A = Using any code for VTE regardless of confirmation. Swedish data B = Using only algorithm-confirmed VTE. Early postpartum = First 6 weeks after delivery. Late postpartum = More than 6 weeks after delivery. * = Adjusted for age and calendar year. † = Unadjusted ratio calculated based on the data provided. Source: [25] |
Pathophysiology
In contrast to the understanding for how arterial thromboses occur, as with heart attacks, venous thrombosis formation is not well understood.[26] With arterial thrombosis, blood vessel wall damage is required for thrombosis formation, as it initiates coagulation,[26] but the majority of venous thrombi form without any injured epithelium.[7]
Red blood cells and fibrin are the main components of venous thrombi,[7] and the thrombi appear to attach to the blood vessel wall endothelium, normally a non-thrombogenic surface, with fibrin.[26] Platelets in venous thrombi attach to downstream fibrin, while in arterial thrombi, they compose the core.[26] As a whole, platelets constitute less of venous thrombi when compared to arterial ones.[7] The process is thought to be initiated by tissue factor-affected thrombin production, which leads to fibrin deposition.[8]
The valves of veins are a recognized site of VT initiation. Due to the blood flow pattern, the base of the valve sinus is particularly deprived of oxygen (
HIF-1 and EGR-1 pathways lead to monocyte association with endothelial proteins, such as
Diagnosis
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Prevention
Numerous medications have been shown to reduce the risk of a person having a VTE, however careful decision making is required in order to decide if a person's risk of having a VTE outweighs the risks associated with most
Surgery
Evidence supports the use of heparin in people following surgery who have a high risk of thrombosis to reduce the risk of DVTs; however, the effect on PEs or overall mortality is not known.[29] In hospitalized non-surgical patients, mortality does not appear to change.[30][31][32] It does not appear, however, to decrease the rate of symptomatic DVTs.[30] Using both heparin and compression stockings appears better than either one alone in reducing the rate of DVT.[33]
Non-surgical medical conditions
In hospitalized people who have had a stroke and not had surgery, mechanical measures (compression stockings) resulted in skin damage and no clinical improvement.[30] Data on the effectiveness of compression stockings among hospitalized non-surgical patients without stroke is scarce.[30]
The American College of Physicians (ACP) gave three strong recommendations with moderate quality evidence on VTE prevention in non-surgical patients:
- that hospitalized patients be assessed for their risk of thromboembolism and bleeding before prophylaxis (prevention);
- that heparin or a related drug is used if potential benefits are thought to outweigh potential harms;
- and that graduated compression stockings not be used.[28]
In adults who have had their lower leg casted, braced, or otherwise immobilized for more than a week, LMWH may decrease the risk and severity of deep vein thrombosis, but does not have any effect on the incidence of pulmonary embolism.[34]
Prior VTE
Following the completion of warfarin in those with prior VTE, the use of long-term aspirin has been shown to be beneficial.[35]
Cancer
People who have cancer have a higher risk of VTE and may respond differently to anticoagulant preventative treatments and prevention measures.
For people who are having surgery for cancer, it is recommended that they receive anticoagulation therapy (preferably LMWH) in order to prevent a VTE.[39] LMWH is recommended for at least 7–10 days following cancer surgery, and for one month following surgery for people who have a high risk of VTEs.[40][39]
Specifically for patients with various types of lymphoma, there is a risk assessment model, ThroLy, to help providers determine how likely a thromboembolic event is to occur.[41]
Treatment
American evidence-based clinical guidelines were published in 2016 for the treatment of VTE.[42] In the UK, guidelines by the National Institute for Health and Care Excellence (NICE) were published in 2012, updated in 2020.[43] These guidelines do not cover rare forms of thrombosis, for which an individualized approach is often needed.[5] Central and branch retinal vein occlusion does not benefit from anticoagulation in the way that other venous thromboses do.[5]
Anticoagulation
If diagnostic testing cannot be performed swiftly, many are commenced on empirical treatment.[43] Traditionally this was heparin, but several of the DOACs are licensed for treatment without initial heparin use.[42]
If heparin is used for initial treatment of VTE, fixed doses with
Once the diagnosis is confirmed, a decision needs to be made about the nature of the ongoing treatment and its duration. USA recommendations for those without cancer include
For those with cancer, LMWH is recommended,[42] although DOACs appear safe in the majority of situations.[43] For long-term treatment in people with cancer, LMWH is probably more effective at reducing VTEs when compared to vitamin K antagonists.[36] People with cancer have a higher risk of experiencing reoccurring VTE episodes ("recurrent VTE"), even while taking preventative anticoagulation medication. These people should be given therapeutic doses of LMWH medication, either by switching from another anticoagulant or by taking a higher dose of LMWH.[46]
In pregnancy, warfarin and DOACs are not considered suitable and LMWH is recommended.[42]
For those with a small pulmonary embolism and few risk factors, no anticoagulation is needed.[42] Anticoagulation is, however, recommended in those who do have risk factors.[42]
Thrombolysis
Inferior vena cava filters
Inferior vena cava filters (IVCFs) are not recommended in those who are on anticoagulants.[42] IVCFs may be used in clinical situations where a person has a high risk of experiencing a pulmonary embolism, but cannot be on anticoagulants due to a high risk of bleeding, or they have active bleeding.[46][47] Retrievable IVCFs are recommended if IVCFs must be used, and a plan should be created to remove the filter when it is no longer needed.[46]
Superficial venous thrombosis
While topical treatments for
Prognosis
After an episode of unprovoked VTE, the risk of further episodes after completing treatment remains elevated, although this risk diminishes over time. Over ten years, 41% of men and 29% of women can expect to experience a further episode. For each episode, the risk of death is 4%.[49]
See also
- Portal vein thrombosis
- Arterial thrombosis
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