Medical Screening Procedures for Venous Thromboembolism During Pregnancy - Dissertation Example

? An analysis of medical screening procedures for Venous Thromboembolism and related disorders during pregnancy INTRODUCTION Venous thromboembolism is the leading cause of maternal mortality in the United States. (VTE), includes deep vein thrombosis (DVT) and pulmonary embolism, and these conditions collectively represent a significant source of morbidity and mortality. It can be easily diagnosed with noninvasive promcedures when clinical factors justify the possibility. Most patients presenting with signs and symptoms of VTE symptoms have well-known risk factors, such as a familial history of VTE, illness, malignancy, or immobilization, and of course, pregnancy. Certain patient subsets display VTE pathologies of idiopathic causes, with no apparent identifiable risk factors. Therapeutic anticoagulation is the cornerstone of management in all patients with VTE, in many cases, standard anticoagulants such as heparin are included as therapeutic options in normal practice. (Schulman et al 2009) Adjunctive treatments, such as thrombolysis and the use of vena cava filters, are prescribed in certain cases. Pregnancy is among several risk factors for deep venous thrombosis, in addition to minor injuries and surgery. (Van Stralen et al. 2008) But those with a familial history of thrombophilia-related blood conditions are at an increased risk. (American College of Obstetricians 2000) Most physicians do not recommend general screening for the patient population at large, and several studies attest to the need for a regimen of targeted testing for VTE conditions only when a battery of predisposing factors is extant. ( Robertson et al. 2006) (Osinbowale et al. 2010) Of particular instance in this case is the degree to which proper screening is conducted for pregnant women, both upon admittance to Maternity, and postpartum. SCREENING Diagnostic testing for inherited or acquired thrombophilic conditions is advisable in the presence of personal or family history indicating heightened risk factors. The Factor V Leiden and prothrombin G20210A mutations are the most common genetic thrombophilic disorders, and antiphospholipid antibody syndrome is the most clinically significant acquired defect. Venous thromboembolism often results from the interplay between a series of risk factors. 50% of pregnant women with also exhibit thrombophilia. (Nelson-Piercey 2004) (Zotz et al. 2003) Understanding these VTE risks increases the probability of timely prevention and diagnosis. Virchow’s triad refers to 3 abnormalities that promote thrombogenesis: hypercoagulability, stasis, and endothelial dysfunction or injury. (Van Stralen et al. 2008) (Osinbowale et al. 2010) Several predisposing factors alter ? 1 components of Virchow’s triad. In a systematic analysis of 1231 consecutive patients treated for VTE, 96% exhibited > 1 recognized risk factor. Venous thromboembolism risk factors as may be hereditary or acquired. (Osinbowale et al. 2010) (Dresang et al. 2008) Osinbowale et al. 2010 Provides a ranking of predisposing risks from to lowest to highest in terms of probability: 1.) Obesity LOW 2.) Elderly 3.) Varicose veins (Varicosity) 4.) Laparoscopy 5.) Stasis (Immobility, due to long-term bed rest) 6.) CV catheterization 7.) Any other medical condition requiring hospitalization 8.) Previous VTE states 9.) Paralytic stroke 10.) Hormone Replacement Therapy 11.) Oral contraceptives, and pregnancy itself 12.) Arthroscopic knee surgery 13.) Malignancy and chemotherapy 14.) Spinal Cord injury 15.) Multiple traumas 16.) Major general surgery 17.) Major orthopedic surgery 18.) Long bone fractures, or fractures of hips and pelvis. HIGH Clinical examinations may prove unreliable, therefore decisions in terms of treatment and/or screening tests must be based upon signs, symptoms, and preexisting risk factors. In this manner, patients are grouped into low, moderate, or high clinical probability of risk. (Sandler et al. 1984) Clinical symptoms of VTE disorders may be subtle and difficult to distinguish from gestational edema, though pain, warmth, and erythema can be expected. (Osinbowale et al. 2010) Venous compression (Doppler) ultrasonography is the diagnostic test of choice. Pulmonary embolism typically presents postpartum with dyspnea and tachypnea. Multidetector-row (spiral) computed tomography is the test of choice for pulmonary embolism. Warfarin is contraindicated during pregnancy, but is safe to use postpartum and is compatible with breastfeeding. Low-molecular-weight heparin has largely replaced unfractionated heparin for prophylaxis and treatment in pregnancy. (Sandler et al. 1984) (Esther et al. 2010) While pregnant, the risk for venous thromboembolism disorders increases by five-fold. (Horne, 2008) Pregnant women have a five- fold increased risk of venous thromboembolism (VTE) compared with the general population due to hypercoagulability, stasis, and aforementioned injury risks, in this case endothelial. (Van Stralen et al. 2008) (Sukal et al. 2008) Pulmonary embolism, included in the broader category of VTE disorders, is the principle cause of maternal mortality, resulting in 20% of all pregnancy related deaths.      A variety of VTE screening methods have been implemented due to ongoing collaborative medical research to devise optimum VTE prophylaxis.  The IHI Perioperative Safety Committee developed a standardized VTE screening tool utilized for the surgical and obstetric patient populations. In addition to the inadvisability of screening the general patient population, some studies indicate that standardized VTE pharmacological prophylaxis in obstetrics is not presently warranted by the evidence. (Horne 2008) Typically, the standard practice employs intermittent use of compression devices on all C-sections, and acutely ill obstetric patients.   Extensive risk-assessment research programs are in the interest of any hospital with a Maternity ward. Attributes of such programs often include the three-part risk level analysis; (low to moderate or high, with mechanical and pharmacologic treatments recommended for high risk.  Bleeding risk assessments are ideally included along with contraindications to those pharmacological/mechanical prophylaxis measures.  Additional guidelines recommended use of regional anesthesia, intermittent compression devices until discharge, continuation of pharmacologic prophylaxis for the high risk patient following discharge, and consultation recommendations when appropriate for other hospital departments as needed. ( hematology, pharmacy etc.)  Physical therapy became involved with the utilization of a bed rest antepartum exercise program. (Horne, 2008) Analyses indicate that for the first 6 weeks postpartum, risk factors in women for thromboembolism increased from 21.5 - to 84 fold from the baseline general population in nonpostpartum women, and women who were not pregnant. After delivery, the incidence of venous thromboembolism declined quickly. Though there is uncertainty as to the point at which effective risk factors return to equality with the baseline population. (Jackson, et al 2011) Other studies echo this doubt, treatment is possible, and risks can be identified, but there are still ambiguities concerning a quantification of risk reduction following thromboprophylaxis, but risk reduction does occur following the conclusion of general surgery by up to 75%. (Mismetti et al. 2001) The following example is indicative of the risk factors anticipated by physicians prior to a screening or diagnosis of a VTE condition. Zalts et al. (2008) gave the following patient report: "A previously healthy 34-year-old woman, gravida 7, para 5, presented on postpartum day 14 with severe low back pain, chest pain, dyspnea, and substantial swelling of both legs after an uneventful cesarean section, performed with combined spinal–epidural anesthesia. During that period she was bedridden. Examination of the pelvis and legs with Doppler ultrasonography revealed bilateral deep venous thrombosis extending to the iliac veins. A computed tomographic (CT) scan of the abdomen and pelvis showed the thrombus extending through the inferior vena cava and both ovarian veins. A CT scan of the chest showed pulmonary embolism in the right lung. The patient was treated with low-molecular-weight heparin together with oral warfarin, and her symptoms were alleviated. She was found to be heterozygous for a mutation in the gene encoding for 5,10-methylenetetrahydrofolate reductase (MTHFR). Since no other cause for her symptoms was detected, the mutation may have been the source of her susceptibility to hyper-coagulation. She was doing well at a follow-up visit 3 months after admission but did not return to the clinic again. " The 34 year old described above is not alone in her symptoms. Shifts towards clotting factors during pregnancy create predispositions towards fibrinogen and hyper-coagulation. (Lindqvist et al 2008) These changes are physiologically vital in minimizing the substantial risk of blood loss during delivery, the danger of thromboembolism is increased. Predisposing factors are immobilization, maternal age, Caucasian descent, operative delivery, heart disease, obesity, malignancy, and familial thrombosis and thrombophilia. STATISTICAL ANALYSIS A comprehensive analysis over 16 years by Lindqvist et al 2008 found a number of VTEs over the allotted time totaled 37, resulting in an incidence of puerperal VTE of 7.1 out of 10,000. Standard risk factors previously discussed are accounted for in the study. All VTEs were verified by objective methods: ultrasound (n = 14), intravenous phlebography (n = 25), CT (n = 8), and ventilation/perfusion scintography (n = 2), or pulmonalis angiography (n = 2). Some women were examined using multiple methods. Fifty-one percent (19 of the 37) of postnatal VTEs and 73% (8 of11) of cases presenting with pulmonary embolisms had two or more anamnestic high risk factors. Of the three women with pulmonary embolisms and a low risk score (0 or 1), one had a protein C deficiency, one a protein S deficiency, and one an anti-thrombin deficiency defect. Lower incidence of postpartum VTE was found over the final six years (2000–2005) 9 out of 21,702 or 4.1/10,000. This was a marked decrease over the ten previous years (1990–1999) (28/30,265 or 9.3/10,000), OR = 0.45, 95% CI 0.2–0.95 when compared with the first period. (Lindqvist et al. 2008) A case-control study of healthy women concluded that the occurrence of VTE in women of child-bearing age taking oral estrogen contraceptives is between 1 and 3 per 10 000 per year. Pregnancy increases this risk five times over the general population. Pulmonary embolism (A VTE associated-illness) is a leading cause of maternal death after childbirth, with 1 clinically recognized PE per 1000 births and 1 fatal PE per 100 000 births. (Osinbowale et al. 2010) An additional 30-year study of VTE pathologies also determined an absolute risk of venous thromboembolism of 199.7 per 100,000 – which would translate to 19.8 per 10,000. The annual occurrence was 5 times higher still among postpartum women than currently pregnant women (511.2 vs. 95.8 per 100?000). (Heit et al. 2005) The Heit study included a 98% white population, and data concerning relative incidence for other ethnicities is less certain. The Lindqvist 2008 study also lists Caucasian ethnicity as being a predisposing factor, so it can be surmised that screening protocols are develop with this assumption. Black and Hispanic women in this instance should be less likely to be considered for VTE testing, resulting in a blind-spot in terms of raw statistics. But previous studies can at least give us a clue that thromboembolisms are less of a threat in these other populations. It was previously mentioned that Jackson et al. 2011 also found sharply elevated risks of VTE phenomenon after delivery. And among pregnant women, the period of maximum risk for venous thromboembolism and pulmonary embolism in particular occurs during the postpartum period. For six weeks, the risk is greatest. Any prophylaxis against these events should be specifically targeted to postpartum women. Although the incidence of pulmonary embolism (Within the VTE category) has decreased over time, the occurrence of deep venous thrombosis does not appear to improve, creating both a need and an opportunity for advancements in procedures that would identify pregnant women at increased risk. (Heit et al. 2005) PREVENTION Where substantial risk factors exist, studies indicate Vitamin E can be effective at preventing venous thrombosis. (Glynn et al. 2007) As mentioned above, common medications that have proven efficacious in treatment include anticoagulants such as fondaparinux, heparin, and dabigatran as well, has more recently shown potential. (Geertz et al. 2008) Warfarin, being a Vitamin K antagonist is also part of a standard treatment modality. (Schulman et al 2009) There is ambiguity concerning the ideal duration of anticoagulation, a maximum effective length of treatment is unknown. Typically, anti-coag treatment modalities are maintained long-term in patients with acquired or inherited thrombophilia, placing them at risk for VTE. Warfarin is the only oral anticoagulant approved by the US Food and Drug Administration. And it carries a substantial annual risk of bleeding complications, with continuous necessity for ongoing monitoring, and has extensive drug–drug interactions, which are causes for concern in patients requiring long-term anticoagulation. Alternative oral anticoagulants, including direct thrombin inhibitors and factor Xa inhibitors, such as Enoxaparin (Warwick et al. 1995) are targets of active research in alternative agents for oral anticoagulation, and have already seen approval for prophylaxis in the European Union and Canada. (Osinbowale et al. 2010) CONCLUSION A variety of long-term comprehensive studies have been conducted and documented on the pathology of venous thromboembolism, its relation to pregnancy, and how and under what circumstances most hospitals will screen for it. Likely symptoms and risk factors have also been described, both here and in the available literature. Both treatments and preventative measures are known. VTE conditions, including deep-vein thrombosis and pulmonary embolisms are five times more likely in pregnant women than in the general population, and it appears the risk itself elevates another five-fold over the pregnant state for 6 weeks postpartum. But actual incidences are comparatively rare, and in multiple studies covering decades a physician should not expect to encounter more than 20 cases per 10,000 patients. The process by which hospitals screen for the illness is informed by the frequency of its occurrence. Medical institutions will very rarely (normally never) screen for this condition without the aforementioned battery of predisposing factors. In general, surgeries and medical conditions requiring prolonged bed rest create a strong likelihood for the pathology to develop. This can include the consequences of hospitalization during pregnancy. While it would be up to each individual physician to proceed with the process of diagnosis as he or she sees fit; there is supporting consensus that patients with at least 2 medical risk factors should be screened, but the risks vary in accordance with the specific medical indicators. Patients experiencing hypercoagulability, endothelial injury or dysfunction, having experienced prolonged bed rest are under specifically high risk. Pregnant women can experience all of these conditions. Nonetheless, medical professionals must remain on guard, as serious adverse events involving these conditions can and do continue to occur even in the industrialized world. References American College of Obstetricians and Gynecologists. (2000) Thromboembolism in pregnancy. ACOG Practice Bulletin No. 19. Obstet Gynecol. 2000;96(2):1–10. Esther, Kim S.H. Bartholomew, John R. (2010) Venous Thromboembolism. Cleveland Clinic, Center for Continuing Education. Publications: Disease Management Project. Copyright © 2000-2011 The Cleveland Clinic Foundation. All Rights Reserved.Center for Continuing Education Dresang, Lee T MD. Fontaine, Pat MD. Leeman, Larry MD. King, Valerie J MD. (2008) Venous Thromboembolism During Pregnancy. American Family Physician, a peer reviewed journal of the American Academy of Family Physicians. Copyright © 2008 by the American Academy of Family Physicians June 15, 2008 Geerts WH, Bergqvist D, Pineo GF, Heit JA, Samama CM, Lassen MR, Colwell CW; American College of Chest Physicians (2008). "Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)". Chest 133 (6): 381S-453S. doi:10.1378/chest.08-0656. PMID 18574271. http://hinari-gw.who.int/whalecomchestjournal.chestpubs.org/whalecom0/content/133/6_suppl/381S.long Glynn RJ, Ridker PM, Goldhaber SZ, Zee RY, Buring JE (2007). "Effects of random allocation to vitamin E supplementation on the occurrence of venous thromboembolism: report from the Women's Health Study". Circulation 116 (13): 1497–503. doi:10.1161/CIRCULATIONAHA.107.716407. PMID 17846285. Heit, John. Kobbervig, Catie..Petterson, James AH. Bailey, KR. Melton, LJ. (2005) Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med. 2005;143(10):697–706. Horne, Gina A. RNC (2008) , VTE Risk Assessment and Prophylaxis in Obstetrics Labor &Delivery/Antepartum, Baptist Memorial Hospital for Women, Memphis, TN Jackson, Emily MD, MPH; Curtis, Kathryn M. PhD. (2011) Gaffield, Mary E. PhD Risk of Venous Thromboembolism During the Postpartum Period: A Systematic Review. Obstetrics & Gynecology: March 2011 - Volume 117 - Issue 3 - pp 691-703 doi: 10.1097/AOG.0b013e31820ce2db Lindqvist, PG. Kublikas, M. Dahlback, B. (2002) Individual risk assessment of thrombosis in pregnancy. Acta Obstet Gynecol Scand. 2002a;81:412–16. [PubMed] Lindqvist, Pelle G.Torsson, Jelena. Almqvist,Asa. Bjorgell, Ola. 2008 Postpartum thromboembolism: Severe events might be preventable using a new risk score model. Department of Obstetrics and Gynecology;Radiology, Malmo University Hospital, Lund University, Malmo, Sweden;Department of Obstetrics and Gynecology, Karolinska Hospital, Huddinge, Sweden. Robertson L, Wu O, Langhorne P, et al., (2006) for the Thrombosis: Risk and Economic Assessment of Thrombophilia Screening (TREATS) Study. Thrombophilia in pregnancy: a systematic review. Br J Haematol. 2006;132(2):171–196. Mismetti P, Laporte S, Darmon JY, et al. (2001) Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg. 2001;88:913–30. [PubMed] Nelson-Piercy, C. (2004) Thromboprophylaxis during pregnancy, labour and after vaginal delivery. Royal College of Obstetricians and Gynaecologists, 2004. Guideline no. 37. http://www.rcog.org.uk/resources/Public/pdf/Thromboprophylaxis_no037.pdf. Accessed February 23, 2008 Osinbowale, Olusegun. MD; Ali, Lobna. MD; and Chi, Yung-Wei DO (2010) Venous Thromboembolism: A Clinical Review.OPEN ACCESS ARTICLE Postgraduate Medicine: Volume: 122 No.2 DOI: 10.3810/pgm.2010.03.2122 Salonen, Ros H. Lichtenstein, P. Bellocco, R. et al. (2001) Increased risks of circulatory diseases in late pregnancy and puerperium. Epidemiology. 2001;12:456–60. [PubMed] Sandler, DA. Martin, JF Duncan, JS. et al: (1984) Diagnosis of deep-vein thrombosis: Comparison of clinical evaluation, ultrasound, plethysmography, and venoscan with X-ray venogram. Lancet. 1984, 2: (8405): 716-719. Schulman S, Kearon C, Kakkar AK, et al (2009). "Dabigatran versus warfarin in the treatment of acute venous thromboembolism". N Engl J Med 361: Online first. doi:10.1056/NEJMoa0906598. PMID 19966341. http://content.nejm.org/cgi/content/abstract/NEJMoa0906598v1. Sukal S, Geronemus R. "Deep Venous Thrombosis Following Mohs Micrographic Surgery: A Case Report" Dermatol Surg. 34(3):414-417. 2008 Van Stralen, Karlijn J. MSc; Rosendaal, Frits R. MD, PhD; Doggen, Carine J. PhD(January 14, 2008). "Minor Injuries as a Risk Factor for Venous Thrombosis". Arch Intern Med 168 No. 1 (1): 21–26. Warwick, D; Bannister, GC; Glew, D; Mitchelmore, A; (1995) Thornton, M; Peters, TJ; Brookes, S (1995). "Perioperative low-molecular-weight heparin. Is it effective and safe". The Journal of bone and joint surgery. British volume 77 (5): 715–9. PMID 7559695. Zalts, Ronen M.D., Hayek, Tony M.D. (2008) Images in Clinical Medicine, Postpartum Venous Thromboembolism Images in Clinical Medicine N Engl J Med 2008; 359:2706 December 18, 2008 Zotz RB, Gerhardt A, Scharf RE. Prediction, prevention and treatment of venous thromboembolic disease in pregnancy. Semin Thromb Hemost. 2003;29(2):143–154. Read More