Deep Vein Thrombosis - Essay Example

Paul Mc Cauley Number: 459444 Module Heapp 1002 Word Count: 2,795 Module Biological Basis for Health Module Leader: Denise Dixon Case Study: Deep Vein Thrombosis 1 Introduction This case study will discuss Deep Vein Thrombosis (DVT) and will underpin key research on how DVT affects the individual and how it impacts overall health. The study will explore current literature on the topic as well as treatments that have been shown to work. Approximately 1 in 1,000 patients in the UK each year develop a DVT and about 25,000 people die of blood clots that develop when an individual is in the hospital (Ford and Kenny, 2010). The behavioural changes associated with DVT are those that instruct the patient to stop any activity that will restrict the “free flow of blood within the lower extremities” (Skinner and Moran, 2008). It is interesting that there are so many different ways that a DVT can develop. According to Marsh and Hall (2002) ‘a total of 21 airlines, including British Airways and Virgin, are named in the unprecedented High Court action. The airlines are facing 33 test cases on deep vein thromboses. 2.0 Definition of DVT DVT is defined as a blood clot that appears in the thigh or lower leg (National Health Lung and Blood Institute, 2009). According to Qutub (2007), venous thrombi majorly develop within a deep vein at a site of vascular trauma and in areas of sluggish blood flow (e.g venous sinuses of the calf and within a valve cusp). An accumulation of fibrin and platelets causes rapid growth in the direction of the blood flow, potentially reducing venous return (Qutub, 2007). Endogenous fibrinolysis causes partial or complete resolution of the thrombus. The residual thrombus will reorganize and the vein may recanalize incompletely, resulting in the narrowing of the lumen and valvular incompetency, and an extensive collateral network may develop. DVT is very prevalent with an annual occurance of 80 cases in every 100,000 (Patel, 2011). A blood clot in a deep vein can break off and travel through the bloodstream. The loose clot is called an embolus. When the embolus travels to the lungs blocking the blood flow, the condition is called Pulmonary Embolism (PE) (National Health Lung and Blood Institute, 2009). PE can become so severe, damaging other organs and eventually cause death. 2.1 Pathophysiology of DVT The haemostatic system is made up of two systems: platelets and the coagulation proteins. In the absence of vessel injury or inflammation, platelets do not adhere to the endothelium because unstimulated endothelium has no receptors for unstimulated platelets, and also because the endothelium produces nitric oxide and prostacyclin that maintain the platelets in the unactivated state, which impairs their adhesion (Conde and Lopez, 2004; Baird and Walsh, 2002). When the endothelial layer is lost, platelets are exposed to subendothelial ligands for which they have specific receptors (Conde and Lopez, 2004). The coagulation system has both the extrinsic and the intrinsic pathways. The intrinsic pathway involves circulating plasma factors. Both pathways are united at the factor X that is activated to form the Xa factor (Conde and Lopez, 2004; Lourens, 2007). This promotes the conversion of prothrombin to thrombin (factor II). This is the major step in the formation of a clot because active thrombin is required to transform fibrinogen into a fibrin clot (Patel, 2011). Three naturally occuring anticoagulant mechanisms exist to prevent an inadvertent clotting process. They are: heparin-antithrombin III (ATIII), protein C and thrombomodulin protein S, and the tissue factor inhibition pathways (Patel, 2011; Isermann, et al. 2001). When trauma occurs or surgery is performed, circulating ATIII decreases thus increasing likelihood for coagulation (Patel, 2011). This is according to studies that indicate that ATIII levels are reduced after surgery (Gray, et al. 1981; Schipper, et al. 1981). The first contact between the flowing platelets and the subendothelium is mediated by the platelet glycoprotein (GP) Ib-IX-V complex binding Von Willebrand factor (VWF) in the subendothelium. By this interaction, platelets roll and decelerate allowing other platelet receptors with slower rates to bind subendothelial proteins. As the platelets adhere to the wall of the injured vessel, transmembrane signalling caused by ligated receptors such as GPIb-IX-V and the collagen receptor GPVI, activate the platelets, causing conformational activation of the integrins, primarily the IIb and 2 b1. Calcium currents produced during platelet activation induce -granule release, with the secretion of several procoagulant molecules like factor (F) V, VWF, and fibrinogen. Activated platelets undergo the flip-flop reaction where phosphatidylserine is exposed on the outer membrane leaflet (Zwaal, et al. 1989; Conde and Lopez, 2004), and phosphatidylserine then provides the surface for the assembly of coagulant enzyme complexes, which produce thrombin and enable deposition of fibrin (Conde andLopez, 2004). 2.2 Risk Factors Risk factors or clinical conditions that increase the probability of DVT may be said to increase the baseline propensity for thrombosis, or precipite the thrombotic event acutely. These factors do so by inducing a state of hypercoagulability, venous stasis or direct injury to the vein walls (Conde & Lopez, 2004). While hypercoagulability may result from both congenital and acquired risk factors, most circumstances in which stasis contribute to DVT risk result from acquired conditions such as surgery or paralysis (Chee, Culligan and Watson, 2001). DVT has been described in patients with congenital venous malformation (Saito, et al. 1995; Zamboni et al, 1997). In addition, congenital absence of the Inferior vena cava has been proved to predispose to DVT. Deep venous anomaly is an unusual example of a congenital condition that predisposes to DVT by affecting blood flow (Chee, Culligan and Watson, 2001). Factors that contribute to hypercoagulability may be genetic or acquired. Examples of genetic factors are: increased coagulants caused by prothrombin mutation G20210A, decreased anticoagulants resulting from antithrombin deficiency, protein C and S deficiency and Factor V Leiden. The acquired factors include Hyperhomocysteinemia, malignancy, nephrotic syndrome, antiphospholipid syndrome and increased levels of clotting factors (Conde and Lopez, 2004). In a study conducted by Cogo et al. (1994) to investigate acquired risk factors for DVT in symptomatic outpatients, it was found that 50% of the DVT cases were considered to be secondary to a major risk factor (immobilization, trauma and/or recent surgery). Among the additional factors, only increased age (over 60 years), male gender, malignant neoplasm, heart failure, systemic lupus erythematosus and arteriopathy were independently associated with the risk of acute DVT. Examples of low-grade, chronic vessel injury that increase the baseline propensity for thrombosis may include: endothelial injury secondary to chemotherapy, hyperhomocysteinemia, vasculitis, antiphospholipid syndrome, intravascular catheters, trauma and surgery (Conde and Lopez, 2004). Blood stasis most commonly functions as an acute insult precipitating thrombosis rather than increasing the baseline propensity of thrombosis. Some of the factors involved include: obesity, pregnancy (gradual immobility/stasis), sedentarism, hospitalisation, limb paralysis (eg stroke, plaster casts), right heart failure, height (taller than 1.9 M or shorter than 1.6 M), long-haul flights and vein compression (e.g enlarged lymph node) (Conde and Lopez, 2004; World Health Organization, 2007; Samama, 2000). Thomas and Van Kampen (2011) found that the percentage of patients with plaster cast immmobilization who were affected by DVT ranged from 4.5 to 18%, with lower risk when there was no fracture. Stasis can lead to haemoglobin desaturation, causing a hypoxic insult to the endothelium. Venous oxygen levels drop to almost undetectable levels when blood flow is halted. Since the endothelium is oxygenated and perfused directly by the blood in the vessel lumen, hypoxia can result to cell activation and even cell death depending on its degree and duration (Michiels, et al. 2009; Conde and Lopez, 2004). Ischaemia rapidly activates endothelial cells to express P-selectin and is a hallmark of ischemia/reperfusion injury. Endothelial P-selectin expression in ischaemia is essential for leukocyte infiltration of the vessel wall and target tissues, in this case the binding of TF-bearing microvesicles (Conde and Lopez, 2004). The intake of steroid hormone contraceptives is also a strong and independent risk factor. This has been found in women taking oral contraceptives who are carriers of the G20210A mutation in the prothrombin gene (Lapecorella et al, 2007). 2.3 Signs and Symptoms of DVT Only 40-50% of the people have obvious signs and symptoms of DVT and they vary depending on the severity of the condition. The signs and symptoms are: 1. Legs swelling or swelling along a vein in the leg. 2. The leg has pain and tenderness. 3. Warmth in one area of the leg. 4. Skin discoloration (red or blue) 5. Discomfort when the leg is pulled forward. 6. PE—which can begin with “coughing up blood, shortness of breath, pain when deep breathing or rapid breathing with a fast heart rate.” (National Health and Lung Institute, 2009; Slowik, 2011). 3 The Management of Infection Inflammation is a response by the immune system to infection or irritation. It is stimulated by chemical factors released by injured cells to create a barrier against the spread of infection and to promote healing of damaged tissue after clearance of pathogens (Strvinova, Jakubovsky and Hulin, 1995). It is initiated by macrophages, dendritic cells, histiocytes, kupfer cells and mastiocytes. These cells have receptors on their surface called pettern recognition receptors (PRRs) that recognize moloceules contained in pathogens called pathogen associated molecular patterns (PAMPs). When infection, injury or burns occur, these cells are activated (the PRRs recognize PAMPs) and release inflammatory mediators responsible for inflammatory signs. The chemicals produced include histamine, bradykinin, serotonin, leukotrienes and prostaglandins. These sensitise pain receptors, cause vasodilation of blood vessels at the site and attract phagocytes (especially neutrophils). Neutrophils trigger other parts of the immune system by summoning leukocytes and lymphocytes. Cytokines produced by macrophages and other cells of the innate immune system participate in the inflammatory process. The cytokines include TNF, HMGB1, and IL-1 (Lotze and Tracey, 2005). In looking at how the body reacts to infection, it is clear to see that when DVT occurs, the immune system works towards healing the body. This is why the signs and symptoms of DVT are as mentioned. Most of them occur because of the nature of reactions that are going on inside the body. We shall discuss appropriate methods of regaining a balance in the body, also known as homeostasis, in dealing with DVT infections in a later section of this text. 4 Upper Extremity DVT As the use of central venous lines and pacemaker wires has increased, their role in the aetiology of upper extremity DVT has become prominent. In a study to determine the symptomatic upper extremity DVT and its association with symptomatic acute pulmonary embolism, Mustafa et al. (2003) found that 60% of their patients had central venous access lines while Baarlslag et al. (2002) reported 55%. In the study carried out by Mustafa et al (2003), it was found that 9% of the patients with upper extremity DVT had developed acute PE. Levin (2003) states that upper extremity DVT is uncommon but is growing in importance. There are three occassions in which upper extremity DVT can occur: in individuals who engage in strenuous exercise like weightlifting, it may be hereditary when others in the family have had some type of thrombosis, and in patients “with an underlying hypercoagulable state” (Levin, 2003, p. 637). The most common symptoms are discomfort, pain, paresthesias, weakness in the arm, swelling, oedema, discolouration and visible venous collaterals (Kucher, 2011). This type of DVT has been linked to cancer (Galanaud, et al. 2009). This is supported by the study carried out by Mustafa et al. (2003) because it was found that cancer was diagnosed in 46% of the patients with upper extremity DVT. 5. Treatments for DVT The aim of DVT treatment is threefold: to ease symptoms, prevent worsening of the clot and to prevent the clot from travelling to the lungs (WebMD, 2010). There are several forms of treatment that have been recommended and which have been seen to succeed in patients who have DVT. These are: anticoagulation, thrombolysis, thrombectomy and compression stockings. Anticoagulation alters certain chemicals in the blood to prevent clots from forming but does not dissolve the clot. It also prevents clots from getting bigger. Patients are introduced to a short course of heparin treatment (less than a week) as they start on a 3 to 6 months treatment of warfarin or related vitamin K inhibitors. It is preferred to administer low molecular weight heparin (LMWH) (Snow et al, 2007). Unfractionated heparin is administered to patients with contraindications to LMWH like renal failure or imminent need for an invasive procedure. For patients who have experienced recurrent DVT, anticoagulation is extended throughout their lives (Hutter and Prins, 2006). After thrombosis has been treated with anticoagulants, the affected area has a better chance of healing naturally by the body’s healing mechanism (Rivera-Bou, 2011; Newman, 2007). However, treatment with anticoagulants does not significantly reduce the chances of PE (Hirsh and Hoak, 1996). In a Cochrane review by Kakkos et al (2008), combining anticoagulation with leg compression is more effective than anticoagulation alone. According to Ford and Kenny (2010), regular heparin injection is preferred to warfarin tablets for pregnant women since warfarin has the potential of causing birth defects to the unborn child. Buller et al. (2004) recommend the initial treatment of DVT to include a vitamin K antagonist together with LMWH or UFH at the first day of treatment. When the international normalised ratio is greater than 2.0 and stable, heparin may be discontinued. Thrombolysis, also called clot busting, is reserved for cases of serious embolism or when other medications seem not to work (Pedroza, 2011; Goliath, 2003; Health Search, n.d). An example of such drugs is the tissue plasminogen activator (TPA). They are administered intravenously but according to studies in the University of Cincinnati (2007), may have complications like serious bleeding (intra-cerebral haemorrhage). Currently, in addition to tissue plasminogen activator, two agents are approved by the US Food and Drug administration and they are streptokinase and urokinase. These agents convert plasminogen to plasmin, which in turn breaks down fibrin and promotes clot lysis. However, these agents also cause systemic plasminogen activation. By cleaving and inactivating fibrinogen and dotting factors II, V and VIII, they interfere with blood coagulation and produce a systemic hypercoagulable state. In addition, elevated serum fibrin and fibrinogen degradation products inhibit the conversion of fibrinogen to fibrin by negative feedback; and thus interfere with fibrin polymerization. Thrombolysis may also cause platelet dysfunction since they affect platelet surface receptors Gplb and GpIIb (Almoosa, 2002). Thrombectomy is the process of removing a thrombus using a mechanical device. A combination of thrombectomy and use of thrombolytics has shown better results. An example is in the study that was done by Kim et al (2006). Compression stockings are elastic, special support hoses and should be applied routinely starting within one month after diagnosis of proximal DVT. Prandoni et al (2004) recommend that it would be more effective to start within one week. According to Ford and Kenny (2010), this treatment reduces the risk of recurrent DVT and post-thrombotic syndrome. One should wear these daily for at least two years and if one develops post-thrombotic syndrome, they may be advised to use it for more than two years. They should be fitted professionally. These stockings have proved to be more effective than routine anti-embolism stockings (Kolbach, et al. 2003). Inferior vena cava (IVC) filters are usually inserted into the veins. According to Decousus et al (1998), these have been shown to reduce PE. They are intended for patients with absolute contraindication to anticoagulation treatment like cerebral haemorrhage, or who have had recurrent PE after anticoagulation. However, some research has shown that these filters are prone to thrombosis (Prepic Study, 2005; Poletti, et al. 1998; Kalva, et al. 2011). Studies on the safety of insertion and retrieval of these filters show a high percentage in safety of insertion and retrieval (Kalva, et al. 2011; Stein, et al. 2004). In a study by Jamjute et al. (2006), IVC filters can be used safely during labour by pregnant women. Finally, hospitalisation is recommended by the Cochrane Collaboration by Othieno, Abu Affan and Okpo (2007). For patients exhibiting more than two of the following risk factors, hospitalisation is recommended: bilateral DVT, renal insufficiency, low body mass, recent immobility, chronic heart failure and cancer (Kahn and Ginsberg, 2002). 6. Conclusion Not many people may know that they are at risk of DVT. It may occur after surgery, especially when there is trauma (Matharu and Porter, 2010) or when someone is using a venous catheter, or pace maker is used extensively (Meetoo 2010). More research is needed on upper extremity DVT since most resources are directed towards lower extremity DVT (Joffe, et al. 2004; Levin, 2003; Meetoo, 2010). Both types of DVT have different symptoms. The National Quality Measures Clearinghouse (2007) recommends that asymptomatic patients should undergo routine thromboprophylaxis. 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Appendix What the blood clot looks like in leg Reference: Mayo Clinic Duplex Ultrasound for detection of DVT Compression stockings Reference: Vascular Web Read More