Venous thromboembolism (VTE) includes two important clinical manifestations of pulmonary thromboembolism (PTE) and deep venous thrombosis (DVT), and almost all PTE originates from DVT in the limbs, most of which are clinically asymptomatic and often present as fatal PTE. Therefore, the identification and targeting of populations at risk for VTE and the implementation of effective prevention strategies are the only effective ways to reduce the morbidity and mortality associated with VTE.
Awareness of the severity of VTE and the need for VTE prevention
In the United States, there are at least 20,000,000 new cases of VTE each year, and nearly 1 in 10 of these patients die, which is known as the “hidden killer”. The incidence of recurrent VTE and chronic post-thrombotic syndrome (PTS) is significantly higher in patients who survive VTE, and most hospitalized patients have at least one or more risk factors for VTE, the interaction of which further increases the likelihood of VTE. 40% to 60% of orthopedic patients and 10% to 60% of medical patients have VTE. Nearly 1/4 to 1/3 of these thromboses occur in the proximal deep veins, which are more likely to be clinically symptomatic and to lead to PTE. Some studies on the occurrence of VTE are available in China. A retrospective analysis of 103 DVT cases at Peking Union Medical College Hospital found that the incidence of PTE in these cases was 44.7%, with risk factors accounting for 88.3%; a study of 488 stroke patients in neurological surgery at Beijing Chaoyang Hospital between December 2001 and December 2002 found that the incidence of DVT was 21.7%.
VTE is a common and serious complication in many disease populations, so it is particularly important to take effective measures to prevent the occurrence of VTE in high-risk populations. In determining the need for VTE prevention, clinicians must take into account the thrombogenic risk of a risk factor itself, the interaction of multiple risk factors, and the risk of VTE recurrence versus anticoagulation therapy in the context of the patient’s specific situation, and determine the risk group to be prevented, the strategy and means of prevention, and the duration of prevention.
Identification of Clinical Risk Factors and Determination of Thrombogenic Risk
The occurrence of VTE has remained stable or even increased in recent years. The reasons for this may be related to the increase in the number of people at risk, increased exposure to risk factors, inadequate identification of high-risk groups, and untimely prevention or inappropriate measures. A variety of conditions can increase the risk of VTE, but the degree of embolic risk is not the same.
I. Environmental and population-related risk factors
In recent years, some risk factors related to people’s social life have attracted attention, such as the occurrence of “economy class syndrome” (econcomic class syndrome) and “computer thrombosis” (e-Thrombosis) and The incidence of VTE correlates with increasing age, with an annual incidence of less than 5/100,000 in children under 15 years of age, and up to (450-600)/100,000 in people >80 years of age (about 0.15%). The increased incidence of VTE in elderly patients may be related to decreased physical activity, decreased muscle tone, increased disease, and decreased vascular endothelial function. The incidence of VTE during pregnancy and puerperium is (71-85)/100,000, the incidence of PTE is approximately 15/100,000, and the incidence of fatal PTE is 1/100,000. The relationship between gender, seasonal changes, obesity, diet and smoking and the occurrence of VTE needs to be confirmed by further studies.
II. Surgical or trauma-related risk factors
The relationship between surgery and VTE has been studied. In addition to the condition of patients before surgery, the damage to tissues and blood vessel walls caused by surgery itself, the activation of coagulation system, the slow blood flow caused by anesthesia and extracorporeal circulation, and the increase of blood viscosity caused by blood transfusion are all risk factors for surgery-induced VTE. Major abdominal or thoracic surgery with anesthesia lasting ≥30 min is an independent risk factor for VTE. Hip and knee replacement, urological surgery, neurosurgery and obstetrical and gynecological surgery can increase the risk of VTE by 6 to 22 times, and severe trauma can increase the risk of VTE by 13 times. The incidence of thrombosis in fracture, spinal cord injury and head injury is as high as 30% to 60%, the incidence of fatal PTE is 0.4% to 2.0%, and patients with severe head injury and coma, spinal cord injury, pelvic and long bone demolition have 21 to 54 times more chance of PTE than patients with other trauma. VTE is one of the main causes of disability or death in critically ill patients in ICU wards, and ICU Most patients have 1 or more risk factors for VTE. Thirty percent of DVTs in ICU units are not treated with anticoagulation, of which 15% develop PTE, and 5% are lethal.
III. Risk factors associated with medical disease
Although VTE is often viewed as a complication following surgery and trauma, in fact, 50% to 70% of symptomatic thromboembolic events and 70% to 80% of fatal PTEs occur in non-surgical conditions, especially in the medical population, and the risk of VTE in patients hospitalized in the acute phase of medical disease is more than 8 times higher than in the general population. The incidence of VTE is approximately 15% in patients with congestive heart failure and 20% in patients hospitalized with acute myocardial infarction; acute exacerbations of chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome (ARDS), and interstitial lung disease can also significantly increase the risk of VTE; the incidence of venous thrombosis in patients with nephrotic syndrome is as high as 48%; Crohn’s disease The risk of DVT and PTE is 4.7 and 2.9, respectively, while in patients with ulcerative colitis it is 2.8% and 3.6%, respectively; the incidence of elevated antiphospholipid antibodies in the total population is about 2.0% to 4.0%, while in the VTE population it is about 8.5% to 14.0%; the annual incidence of VTE in the oncology population is 10% to 30%, and the risk of malignant tumors themselves is about 4.1. In addition, diabetes mellitus, hypertension, systemic lupus erythematosus (SLE), myeloproliferative diseases, etc. are also associated with the occurrence of VTE; people with a history of VTE have a higher risk of recurrence, especially in the presence of other risk factors (such as major surgery, braking or serious diseases).
IV. Factors associated with medical interventions
Various hematologic drugs such as anticoagulation, antifibrinolytic, antiplatelet, and antineoplastic drugs can cause pharmacogenic thrombosis, and cell growth factors and immunosuppressive agents such as cyclosporine also have a certain risk of thrombogenicity. The annual incidence of DVT in women taking oral contraceptives is (2-3)/10,000 compared to 0.8/10,000 in women of the same age not using oral contraceptives. Hormone replacement therapy can increase the risk of thrombosis by 2 to 4 times, with the most pronounced thrombogenic effect especially in the first to second year of use. In addition to pharmacologic thrombosis, venipuncture placement, use of intravenous catheters, and various interventional procedures significantly increase the risk of thrombosis.
Non-pharmacologic prevention strategies
Health education should be strengthened in the general population, including encouraging weight loss, appropriate activity, avoiding bad habits (such as quitting alcohol and smoking); and actively controlling underlying diseases such as maintaining stable blood pressure levels. For long-distance travelers who travel by airplane for more than 6 h and those who need to be sedentary for a long time due to their work, most scholars advocate frequent movement of the lower extremities and drinking more water, but the need for prevention with anticoagulants has not been determined.
Mechanical methods of prevention include graduated compression stockings (GCS), intermitrent pneumatic compression (IPC) and venons foot pumps (VFPs), etc. GCS stimulates the calf muscles by IPC is a plastic cuff device that is placed around the calf and is compressed with air pumps that rhythmically inflate and atrophy, emptying the deep gastrocnemius veins and increasing blood flow to the femoral veins. The calf compression pump also increases systemic fibrinolytic activity and may provide an adjunctive prophylactic effect, and IPC has a unique role in patients for whom anticoagulation alone is contraindicated or ineffective. Mechanical VFPs are simple mechanical pumps that produce a higher venous blood flow rate between the femoral and N veins by compression of the plantar venous plexus. There is no evidence to suggest that mechanical prophylaxis alone can reduce the morbidity and mortality of PTE, but it is still actively recommended for patients at high risk of bleeding and as an adjunct to anticoagulation.
Pharmacologic prophylaxis strategies
Pharmacological prophylaxis includes low-dose unfractionnted heparin (LDUH), adjusted-dose subcutaneous heparin, low molacular weight heparins (LMWH), and oral heparin. LMWH), the oral anticoagulant warfarin, the new anticoagulant synthetic pentose (Fondaparinux), and antiplatelet agents.
Studies have confirmed that enoxaparin 40 mg/d, dalteparin 5000 U/d or synthetic pentose 2.5 mg/d applied continuously for 10 d can effectively reduce the incidence of VTE in patients with acute medical lesions. subcutaneous injection of LDUH 5000 U at 2 h preoperatively and every 8 h or 12 h postoperatively can significantly reduce the incidence of postoperative VTE in high-risk patients. incidence in high-risk patients. The use of LDUH has no serious bleeding complications except for a slightly higher incidence of wound bleeding, but it should be used with caution in those patients at risk for abnormal bleeding and is contraindicated in patients undergoing brain, spinal cord and eye surgery. lMWH has a long half-life, 1 injection/d, and is as safe and effective as LDUH. Studies suggest that LMWH has a lower risk of bleeding than LDUH with the same antithrombotic effect. Warfarin may prevent VTE by prolonging prothrombin time (PT), but warfarin has bleeding side effects that need to be monitored, limiting its use in people at risk for bleeding. Low-dose warfarin can be used postoperatively, and when the risk of severe bleeding is reduced, a conventional dose is used to maintain an INR of 2.0 to 3.0. The effectiveness of synthetic pentose 215 mg once/d for DVT prophylaxis is gradually being established. The role of antiplatelet agents in VTE is not entirely clear, and most of the current literature suggests that aspirin is ineffective in preventing VTE, especially in high-risk patients, providing insufficient protection, and therefore is not recommended as a routine prophylactic agent for VTE.
Pharmacoeconomics and safety evaluation in the implementation of prevention strategies
VTE prophylaxis in patients at risk for VTE can reduce the incidence of symptomatic VTE and fatal PTE, which is of great value in improving patient prognosis and reducing health care expenditures. When considering DVT prophylaxis, the risk of VTE, the efficacy-safety of prophylaxis, and the cost-benefit ratio should be taken into account. Pharmacoeconomic data suggest that the increased cost of prophylaxis with low-molecular heparin is offset by a reduction in the incidence of VTE, recurrence, or adverse events. Results from a recent cost analysis model suggest a significant cost-benefit ratio for the use of 40 mg of enoxaparin orally daily for the prevention of thromboembolism in a population with acute medical disease.
The risk of thromboembolism and bleeding should be weighed in the context of pharmacologic prophylaxis for certain serious diseases (e.g., malignancy, sepsis). If the risk of bleeding is high, it is preferable to skip anticoagulant prophylaxis or opt for mechanical prophylaxis. Some patients may develop heparin-induced thrombocytopenia (HIT) during common heparin (UFH) prophylaxis, which may be associated with direct heparin-induced platelet aggregation and increased heparin-dependent IgG antibodies, and may clinically manifest as thrombosis of arteries and veins with a tendency to bleed, at which point the option of lepirudin or argatroban ( LMWH is not used as an alternative to UFH, as nearly 50% of patients may experience exacerbation when switching to LMWH. In these cases, each patient’s specific situation should be fully evaluated and a comprehensive analysis should be performed.
Although more empirical studies and data are needed, most scholars believe that VTE prevention should be routinely performed for most hospitalized patients, as an important healthcare problem with significant mortality, disability, and serious health care resource waste. Prevention strategies derived from evidence-based medicine are already providing benefits to an increasing number of patients. Much research is needed to investigate the epidemiology of VTE and to develop strategies for thrombosis prevention, including the following: incidence of VTE in hospitalized patients; relative importance of different risk factors in the development of VTE (including genetic and acquired risk factors); in-hospital mortality, disability, and hospital cost ratios associated with VTE; safety of anticoagulation prevention strategies; and evaluation of hepatic and renal insufficiency. evaluation; evaluation of the effects of hepatic and renal insufficiency on anti-factor Xa levels and bleeding complications; evaluation of the effects of new antithrombotic factors; evaluation of the therapeutic effects of antithrombotic drugs on infectious toxicity and organ insufficiency; evaluation of compliance with different preventive treatment strategies for VTE, etc. Based on this, we urgently need to carry out standardized primary and secondary prevention of VTE in China, deepen basic and clinical research, and develop PTE-DVT prevention strategies applicable to the national population on this basis.