Prevention Of Venous Thromboembolism In Clinical Settings: A Proposed Research

Venous Thromboembolism (VTE)

Question:

Does the administration of subcutaneous injections of Low Molecular Weight Heparins (LMWHs) prevent Venous Thrombo-embolism (VTE) in hospitalised patients?

The role of a paramedic practitioner in a clinical setting is a valuable one that entails adequate knowledge and practical skills. Continual professional development is essential for this group of professionals to address the evolving trends of healthcare services. The primary strategy to enhance skills and knowledge is to carry out primary research that addresses any clinical concern. Through such research one can gain insights into a clinical topic that has drawn the attention of practitioners and researchers with the aim of improving patient outcomes (Bledsoe et al., 2016). The present paper is on a proposed research on the topic of prevention of Venous thromboembolism in clinical settings. Venous thromboembolism (VTE) has been indicated as a major and adverse complication arising in clinical settings among adult patients that this group of professionals is to address (Agnelli et al. 2013). Low molecular Weight Heparin (LMWH) are anticoagulant molecules that are used in clinical practice to address different patient complications (Szummer et al., 2015). The relation between LMWH and VTE has been the topic of interest at present. The study is proposed in this regard that is based on principles of research study methods. The significance of the study, research question, study design and methodology are discussed in details in the following sections.

Venous thromboembolism (VTE) is the disease including both pulmonary embolism (PE) and Deep vein thrombosis (DVT) that is lethal and affects hospitalised as well as nonhospitalised patients. The disease is more common in hospitalised patients and recurs frequently. It leads to long-term complications such as post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension (Heit et al., 2016). As opined by Grosse et al., (2016) VTE is most common cardiovascular disease after stroke and acute coronary syndrome. Schulman et al., (2017) explained the pathophysiology behind VTE. Venous thrombi are made up of red blood cells, leucocytes and platelets that are found to be present in bound condition by fibrin. Such thrombi are formed in the locations within the body where damage has been suffered to the vessels. Thrombi might be remaining in the peripheral veins or might be embolisingto the pulmonary arteries. In peripheral area it undergoes recanalisation after endogenous fibrinolysis. Risk factors for VTE include surgery-related factors, trauma and patient-related factors. Some of the noteworthy patient-related factors include thrombophilia, obesity, respiratory failure and cardiac failure. Some of the other factors that increase the risk of VTE include fracture of the femur, blood transfusion, injury to the spinal cord and shock suffered due to admission to hospital.

Low Molecular Weight Heparin (LMWH)

Low molecular weight heparin (LMWH) is a category of anticoagulant medications are being used widely for preventing blood clots. Heparin is a polysaccharide occurring naturally that is capable of inhibiting coagulation, the process leading to thrombosis. Since administration of heparin can be done subcutaneously, it permits treatment of patient conditions related to diverse conditions (Laubli et al., 2016). One example of LMWH is Enoxaparin that acts as an anticoagulant and research is going on to understand the applicability of this molecule against various diseases. The molecule acts by binding to the antithrombin for forming a complex molecule. This molecule then acts by irreversibly inactivating clotting factor Xa. Enoxaparin can be metabolised into unfractionated species with lesser weights by depolymerisation in the body (Rodger et all., 2016). 

A rich pool of research has highlighted the effectiveness of low molecular weight heparins (LMWH) in addressing medical complications. There has been a growing amount of interest to point out and understand the conditions that can be prevented with the suitable administration of LMWH. One such area has been Venous thromboembolism the draws attention at present. Clinicians have considered intravenous unfractionated heparin (UFH) as the standard treatment for VTE. Though the effectiveness of this treatment has been established across studies, the effectiveness of such heparin as a preventive medication for VTE has not been given much prominence. With the emergence of LMWH, its efficacy and safety has been time and again compared to that of UFH.

Whether Low Molecular Weight Heparins (LMWHs) when administered as subcutaneous injections prevents Venous Thrombo-embolism (VTE) in hospitalised patients is the concerned research problem in the present case. The proposed study is therefore based on this context and puts forward a PICO question to gain insights into this research topic. The PICO research question that would be addressed in the proposed study is as follows:

“Does the administration of subcutaneous injections of Low Molecular Weight Heparins (LMWHs) prevent Venous Thrombo-embolism (VTE) in hospitalised patients?”

The details of the PICO elements are as follows-

Population: Hospitalized adult patients

Intervention: Use of low molecular weight heparin, Enoxaparin

Comparison: No treatment

Outcome: Reduced incidence of VTE

Though there has a considerable research to understand the link between administration of heparins and patient complications in a healthcare setting, there is a lack of suitable studies that establish the relationship between heparins and VTE. After an analysis of the present research articles, it can be stated that there has been no specific study that has studied whether heparin of low molecular weight can prevent VTE. Since VTE is a serious concern in the medical domain, the possibility of LMWH to act as a preventive agent for the same is to be exploited optimally. The proposed research has been thought of against this background that would predominantly carry forward research in this direction. The aim of the proposed study is to carry out an evaluation of administration of LMWH in adult hospitalised patients for preventing Venous Thrombo-embolism. On the basis of the research and further studies in this line, reforms can be brought about in the clinical guidelines for prevention of VTE in clinical settings. The study would, therefore, act as significant one that would change the course of preventive care provided by nurses to patients admitted to hospitals for preventing adverse outcomes. If found effective, LMWH can be considered as a real therapeutic advance made in the long-term prevention of VTE.

Proposed Research Study

Panneerselvam (2014) highlighted that methodology of any research is a crucial dimension that determines the effectiveness of the study. The methodology acts as the systematic plan for carrying out research which can be either quantitative or qualitative. The proposed study would be a prospective, nonblinded, active, randomised, controlled trial in any clinical setting where around 1000 surgical procedures are carried out in a year. As opined by Miles, P and Fisher (2016) a randomised controlled trial is the form of scientific experiment that has the aim of reducing bias while testing a new form of treatment. In such a study, participants are allocated to the treatment group or the placebo group as a control in a random manner. The purpose is that randomisation eliminates chances of selection bias and permits the researchers to understand the impact of the treatment as compared to no treatment with constant variables. The method is highly reliable and acts as the most rigorous scientific evidence in the hierarchy of evidence (Panneerselvam, 2014). A nonblinded study is the one in which the researchers are aware of the treatment that is to be given to the participants. In addition, the participants are also aware of the treatment that is given to them (Hulbæk et al., 2016). Prospective studies are those which observes for outcomes during the study, relating them to any factor that is considered for the study (Parkin et al., 2017).

Participants

Patient data would be collected for physical examination, medical history, blood sampling and duplex examination. Patients above the age of 18 and below the age of 80 years would be considered for the study. The patients would further required to be undergoing surgery.  The risk assessment model for the study to require the assignment of each patient to a total risk factor score. This coud be then categorised into low, moderate, high and highest scores. Subjects would be found to be having low, high and higher risk for VTE would be excluded from the study. Patients will be excluded from the study if they are found to be bleeding. Other exclusion criteria would include significant liver disease, need for anticoagulation therapy, pregnancy and breastfeeding, use of fibrinolytic therapy and use of HIV protease inhibitors. Statistical calculation would be done for deciding upon the sample size with an equal number of male and female participants. The study participants would be divided into two groups. In the first group, participants would be given Enoxaparin, a commonly used LMWH, subcutaneously once daily for ten days. The participants would be considered for postoperative thromboprophylaxis consisting of compression stockings and early mobilisation. For the second group, no Enoxaparin would be administered; this group would act as the control group. Each participant would be randomised to the single treatment with the help of randomly permuted blocks.

Methodology

Preoperative evaluation

Gender, age and medical comorbidities of the patient, such as renal insufficiency, diabetes, congestive heart disease, active malignancy, the chronic pulmonary disease would be entered into a particular database. Presence of risk factors for VTE, such as recent surgery, tobacco use, trauma, postpartum site and hormonal therapy would also be recorded appropriately. The patients would be considered for diagnosing superficial venous insufficiency preoperatively as per the duplex ultrasound (DUS). A basic protocol would be used that aids in DUS-directed vein mapping. This would consider a bilateral lower limb duplex venous compression ultrasonography scan that uses 3-7.5 MHz transducers. It is to bee noted that the veous ultrasound examination would use imaging equipment that is of high definition and would consider imaging the venous segments without and with compression. The bilateral iliac, profunda femoris, inferior cava, femoral, common femoral, and popliteal veins would be checked in the supine position. Further, the bilateral calf veins, encompassing peroneal, posterior tibial, soleal and gastrocnemial would be studied in the sitting position.

Thromboembolism prophylaxis

Thrombophylaxis would consist of thigh-length compression stockings together with early mobilisation. In addition, a daily injection of LMWH, Enoxaparin would be given at the dose of 2500/3500 IU/day. Compression bandages would be used as the form of mechanical prophylaxis at 25mmHg. This would be done for the initial one week after which stockings would be used at 12-15mmHg. The participants would be required to wear thee compression devices in a continuous manner for three months after they have undergone the surgery. The heparin administration would start six hours after closure of the wound.

Postoperative followup

The proposed study would entail follow-up visits at one month, three month and six months. For each case of followup visit, an interview is to be carried out for understanding the outcomes of the given intervention. This would include cases of VTE. These interviews would be face-to-face and as per the convenience of the patients. All details are to be recorded appropriately. The primary end point for the study. Episodes of VTE would be confirmed when he following conditions would be present; signs and symptoms of VTE together with diagnosis through proper diagnosis procedure encompassing compression ultrasonography. Laboratory examination would include international normalised ratio (INR), partial thromboplastin time (PTT), haemoglobin, D-dimer, platelet count, creatinine level and hemotocrit. Platelet control is to be performed after one week for excluding thrombocytopenia type II induced by heparin.

Patient Data Collection Criteria

End points

The primary end point of the study would be the absence of VTE as proven sonographically. Primary safety end points and secondary efficacy would be superficial venous thrombosis, major bleeding, hematoma formation and other bleedings. Some other efficacy outcomes would be a determination of D-dimer at one, three and six months follow up. The primary safety outcome would be incidences of major bleeding starting after the first administration of heparin and at six months follow up. The definition for major bleeding would be that which are fatal and into any critical organ such as cranial, retroperitoneal, intraspinal and intraocular. Bleeding requiring reoperation and those which would be clinically overt and at the extrasurgical site would also be determined as major bleeding. The secondary safety outcomes would include non-major and on treatment bleeding, wound complications related to haemorrhage, postoperative bleeding, adverse events and mortality (Chai-Adisaksopha et al., 2017).

Statistical analysis

The basis for the calculation of sample size would be assumed event rate of 15% in the moderate risk group and a risk reduction of 10% with LMWH. Differences between research outcomes and patient characteristics would be calculated with the help of the Mann-Whitney U-test. In addition, two-sided Fisher’s exact test would be done. A value of P< 0.05 would be statistically significant. An interim analysis would be done at three months. The Mann-Whitney U test is a commonly used nonparametric test that determines whether a randomly selected value from one sample would be lesser than or greater than a randomly selected value from another sample. It does not need the basic assumptions of normal distributions though the efficiency is as that of the t-test. The utility of the test lies when two samples that are independent from each other are to be selected from a population with same distribution (Beins & McCarthy, 2017). Two sided Fisher’s exact test is a test of statistical significance that is used in case of categorical data (Connelly, 2016).

The protocol for the study is to be approved by the institutional review board at the hospital and in accordance with the local regulations. Ethical considerations remain when human participants are considered for a study. In this view it would be necessary to obtain informed consent from patients who would take part in the study. Informed consent refers to the process of agreeing to take part in any research procedure after understanding the benefits and risks of the such participation. The process entails explaining the participants the purpose and objective of the research and outlining the potential risks and complications. Informed consent is primitive on the basis of legal and moral premises of the patient’s autonomy. The patients would not be influenced in any manner to take part in the study (Panneerselvam, 2014). The primary outcome measure of the trial would be postoperative VTE over a followup period of six months. The secondary outcome measure would include superficial venous thrombosis, postoperative bleeding complications.

Sample Size Calculation

Conclusion

Research is significant for paramedic professionals that enables them to focus on clinical issues related to their practice. Development of more in-depth understanding of clinical strategies enhances clinical decision making. Critical thinking is also augmented in this process. The proposed research would be suitable to highlight whether VTE can be prevented by LMWH such as enoxaparin in adult patients who are hospitalised. The study would be valuable in bridging the gaps in existing studies in this context. The research would further add valuable information to the already existing pool of literature of wide application of LMWH. Based on the results of the study, clinical guidelines can be modified so as to incorporate the novice finding. Further trials can also be conducted taking insights from the proposed research that can further bring into light novice concepts. The overall objective would be to allow better delivery of care to patients who are hospitalised in different settings and present the risk of suffering VTE. Timely implementation of the proposed research with the help of adequate funding would be highly warranted. It is to be hoped that the research would be praiseworthy in the field of paramedicine.

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