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Thromboembolic Disease in Pregnancy: Peeling back the layers Rachel Johnson MS4 OHSU.

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Presentation on theme: "Thromboembolic Disease in Pregnancy: Peeling back the layers Rachel Johnson MS4 OHSU."— Presentation transcript:

1 Thromboembolic Disease in Pregnancy: Peeling back the layers Rachel Johnson MS4 OHSU

2 Observation & Question: Over a 9 year period, Dr. Gosselin has observed that none of the “eval for PE” CTs have been positive in pregnant or postpartum patients. Is there any evidence in the literature to support this observation?

3 Basic Definitions Venous thromboembolism (VTE) Venous thromboembolism (VTE) any thromboembolic event in the venous system any thromboembolic event in the venous system Deep Venous Thrombosis (DVT) Deep Venous Thrombosis (DVT) occlusion of the deep venous system of the legs sufficient to produce symptoms of pain or swelling radiologically confirmed occlusion of the deep venous system of the legs sufficient to produce symptoms of pain or swelling Pulmonary embolism (PE) Pulmonary embolism (PE) occlusion of pulmonary arteries, sufficient to cause symptoms of breathlessness, chest pain, or both radiologically confirmed occlusion of pulmonary arteries, sufficient to cause symptoms of breathlessness, chest pain, or both Fitzmaurice et al,

4 Thromboembolic Disease in Pregnancy and the Postpartum Period – Can we trust the information we are given? Diagnosis Virchow’s Triad Incidence An example of misused mortality data An example of a recent population based study What proof do we have of venostasis? Do we have proof of hypercoagulability? Endothelial damage – didn’t get to this one The tests and their risks An example of misused population studies to estimate incidence Is there too much suspicion?

5 Maternal Mortality After reading about 50 articles and several textbooks, the first sentence usually goes like the following: Thromboembolic disease is a leading cause of maternal mortality. A few of them are quoting information from the following MMWR, but most of them are just. A few of them are quoting information from the following MMWR, but most of them are just quoting each other. Laros

6 MMWR Causes of 4200 Pregnancy-Related Deaths in the United States, Cause Percent Embolism 19.6 Hemorrhage 17.2 Hypertensive disorders 15.7 Infection 12.6 Cardiomyopathy 8.3 Cerebrovascular accident 5.0 Anesthesia 1.6 Other a 19.2 Unknown 0.7 a The majority of the other medical conditions were cardiovascular, pulmonary, and neurological problems. Note: This says embolism, not pulmonary embolism Chang et al

7 Williams Obstetrics It was great to see the authors go to some original information, but… It was great to see the authors go to some original information, but… the authors concluded from this table without other data that, still remains a prominent cause of maternal death in the U.S.” the authors concluded from this table without other data that, “[thrombotic] pulmonary embolism still remains a prominent cause of maternal death in the U.S.” Perhaps a minor point, but ? Perhaps a minor point, but since when did the term embolism refer to pulmonary embolism alone? It may be likely that most emboli are pulmonary, but emboli is a broad term It may be likely that most emboli are pulmonary, but emboli is a broad term Also, considering that Gosselin says he has seen more amniotic emboli than thrombotic ones, then maybe it is important to differentiate between types of emboli Also, considering that Gosselin says he has seen more amniotic emboli than thrombotic ones, then maybe it is important to differentiate between types of emboli Cunningham et al

8 Thromboembolic Disease in Pregnancy and the Postpartum Period – Can we trust the information we are given? Diagnosis Virchow’s Triad Incidence An example of misused mortality data An example of a recent population based study What proof do we have of venostasis? Do we have proof of hypercoagulability? Endothelial damage – didn’t get to this one The tests and their risks An example of misused population studies to estimate incidence Is there too much suspicion?

9 Incidence based on population based studies “…the incidence of pulmonary embolism has decreased over time, [while] the incidence of DVT remains unchanged…” “We found a distinct upward trend for pregnancy- associated DVT…” “…this downard trend [in the overall incidence of fatal pulmonary thromboembolism] has been reversed…” Heit et al, Stein et al, Greer Conclusion: There is little agreement about what is happening Let’s look at the first of these studies (the one Gosselin has been quoting all month)

10 Trends in the Incidence of VTE during Preg or Postpartum: A 30-yr Pop-based Study Journal: Annals of Internal Medicine Journal: Annals of Internal Medicine Authors: from the Mayo Clinic Authors: from the Mayo Clinic Design: Cohort study out of Rochester Epidemiology Project in Minnesota Design: Cohort study out of Rochester Epidemiology Project in Minnesota Patients: Women with DVT or PE 1 st diagnosed , including those in pregnancy or postpartum period. Patients: Women with DVT or PE 1 st diagnosed , including those in pregnancy or postpartum period. Sounds very reputable, doesn’t it? Seems like a great idea to use 30 years of data from such a big project! Heit et al

11 Let’s look further Which patients were included for DVT? Tests: Venography, CT, MRI, impedance plethysmography, Doppler, Compression US, Radionuclide venography, Radiolabeled fibrinogen leg scan, Pathology Medical record: Physician diagnosis, signs and symptoms, anticoagulant therapy, surgical procedure Which Patients were included for PE? Tests: Pulmonary angiography, CT, MRI, perfusion lung scan showing high prob, V/Q lung scan showing high probability, Pathology Medical record: Physician diagnosis, signs and symptoms, anticoagulant therapy, surgical procedure ??? Remember the definitions for DVT and PE? There has to be radiologic evidence to make these diagnoses! Heit et al

12 The interesting thing about this study… Pulmonary Embolism PregnancyPostpartum “…the incidence of pulmonary embolism decreased dramatically during the last 10 years of the study...This observation is unlikely to have occurred by chance.” Heit et al

13 Theories as to why there were no PEs observed in the last decade The authors suggest earlier mobilization, associated with shorter hospitalizations However: OB patients are being treated more and more like surgical patients – get up and moving before leaving the hospital! Perhaps that original “mistake” of using signs and symptoms for inclusion criteria was made less in the last decade. We suspect the diagnostic methods in the last decade were based on more accurate tests and fewer diagnoses were based on signs and symptoms or old hospital records alone. Heit et al

14 Thromboembolic Disease in Pregnancy and the Postpartum Period – Can we trust the information we are given? Diagnosis Virchow’s Triad Incidence An example of misused mortality data An example of a recent population based study What proof do we have of venostasis? Do we have proof of hypercoagulability? Endothelial damage – didn’t get to this one The tests and their risks An example of misused population studies to estimate incidence Is there too much suspicion?

15 I just want to show another example of misuse of data Incidence of Thromboembolism in Pregnancy Deep Vein Thrombosis and Thromboembolism Incidence (per 1000 Pregnancies) Pulmonary Embolism StudyPregnanciesNo.TotalAntepartumPostpartumNoRateAP/PP% Cunningham35, :900050/50 Andersen63, :31000NS Gherman268, :700040/60 McColl72, :650050/50 Lindqvist479, :530050/50 Witlin88, :800050/50 Simpson395, :940065/35 Estimated averages 1,401, :700050/50 Guess what Williams Obstetrics did? They just took a bunch of different studies, did some addition and division and came up “incidences.” Please note: this is not a meta- analysis!! It is bad form to pass off this sort of practice as legitimate. Cunningham et al

16 Thromboembolic Disease in Pregnancy and the Postpartum Period – Can we trust the information we are given? Diagnosis Virchow’s Triad Incidence An example of misused mortality data An example of a recent population based study What proof do we have of venostasis? Do we have proof of hypercoagulability? Endothelial damage – didn’t get to this one The tests and their risks An example of misused population studies to estimate incidence Is there too much suspicion?

17 Virchow’s Triad Cotran et al

18 More questions: Why would it be evolutionarily advantageous to be in a hypercoagulable state during pregnancy or the postpartum period? Why would it be evolutionarily advantageous to be in a hypercoagulable state during pregnancy or the postpartum period? Wouldn’t it be an evolutionary disadvantageous if the mother died from a thromboembolic event before being able to care for a child or to reproduce again? Wouldn’t it be an evolutionary disadvantageous if the mother died from a thromboembolic event before being able to care for a child or to reproduce again?

19 Hypercoagulability Blood volume expands in pregnancy Blood volume expands in pregnancy There is a greater plasma:erythrocytes ratio in pregnancy There is a greater plasma:erythrocytes ratio in pregnancy Fibrinogen levels raise from mg/dL to mg/dL Fibrinogen levels raise from mg/dL to mg/dL Clotting factors are increased Clotting factors are increased in normal pregnancy 2/2 ↑ plasminogen-activator inhibitors The fibrinolytic activity is reduced in normal pregnancy 2/2 ↑ plasminogen-activator inhibitors I felt hopeless, until I read this… I felt hopeless, until I read this… Cunningham et al

20 Hypercoagulability “Studies of the fibrinolytic system in pregnancy have produced results…” “Studies of the fibrinolytic system in pregnancy have produced conflicting results…” There is literature that says that the “overall fibrinolytic activity by pregnancy,” even though there are numerous changes in the system!!! There is literature that says that the “overall fibrinolytic activity is not affected by pregnancy,” even though there are numerous changes in the system!!! Cunningham et al, Kruithof et al

21 Hypercoagulability Perhaps in normal pregnancy, homeostasis is maintained Perhaps in normal pregnancy, homeostasis is maintained The bleeding time in pregnant and nonpregnant women are not significantly different! The bleeding time in pregnant and nonpregnant women are not significantly different! There is likely a difference between in vitro and in vivo studies There is likely a difference between in vitro and in vivo studies Berge et al

22 Hypercoagulability “[Thrombophilias] are responsible for more than 50 percent of all thromboembolic events during pregnancy” “[Thrombophilias] are responsible for more than 50 percent of all thromboembolic events during pregnancy” one author thought that all VTEs during pregnancy might someday be associated with a thrombophilia one author thought that all VTEs during pregnancy might someday be associated with a thrombophilia Perhaps VTE is not inherent in pregnancy unless there is a predisposition Perhaps VTE is not inherent in pregnancy unless there is a predisposition Cunningham et al

23 The rest of the triad Endothelial Damage Endothelial Damage Venostasis/Venous distensibility – I’d guess this that this might be the most important part of the triad Venostasis/Venous distensibility – I’d guess this that this might be the most important part of the triad

24 Thromboembolic Disease in Pregnancy and the Postpartum Period – Can we trust the information we are given? Diagnosis Virchow’s Triad Incidence An example of misused mortality data An example of a recent population based study What proof do we have of venostasis? Do we have proof of hypercoagulability? Endothelial damage – didn’t get to this one The tests and their risks An example of misused population studies to estimate incidence Is there too much suspicion?

25 Clinical Suspicion So in rethinking Gosselin’s original observation of not seeing any positive CTs, I thought perhaps clinical suspicion is too high. So in rethinking Gosselin’s original observation of not seeing any positive CTs, I thought perhaps clinical suspicion is too high. Typical Signs of VTE are also common during pregnancy Typical Signs of VTE are also common during pregnancy Leg swelling and pain Leg swelling and pain Dyspnea Dyspnea Chest pain Chest pain

26 Clinical Suspicion ” “the prevalence of VTE in clinically suspected cases is significantly lower in pregnant women when compared to the nonpregnant population” True DVT Suspected DVT True PE Suspected PE Nonpregnant1414 Pregnant Moores et al

27 Clinical Suspicio Normal V/Q Non-dx V/Q High Prob V/Q Nonpregnant27-36%47-59%8-14% Pregnant73.5%24.8%1.8% “The high percentage of normal scans in the pregnant population probably reflects the youth and fewer comorbid lung conditions.” “The lower percentage of high prob scans in the pregnant population probably reflects the lower prevalence of PE in those presenting with clinical suspicion of PE.” Moores et al

28 Thromboembolic Disease in Pregnancy and the Postpartum Period – Can we trust the information we are given? Diagnosis Virchow’s Triad Incidence An example of misused mortality data An example of a recent population based study What proof do we have of venostasis? Do we have proof of hypercoagulability? Endothelial damage – didn’t get to this one The tests and their risks An example of misused population studies to estimate incidence Is there too much suspicion?

29 Diagnosis There is limited evidence for a best approach There is limited evidence for a best approach Have to rely on studies in the nonpregnant population Have to rely on studies in the nonpregnant population

30 Diagnosis of DVT Should probably begin with Compression Ultrasonagraphy Negative Low clinical suspicion No further workup or Serial CUS over 7 days High clinical suspicion Venography, Magnetic Resonance Venography, Impedance Plethysmography, or serial CUS Positive Consider anticoagulation therapy

31 Compression Ultrasonography E:\Radiology 3\uhrad_com Nuclear and SPECT Teaching Files3.htm

32 Venography

33 MR Venography Superficial vein thrombosis MR venography compared with venography Hauge et al

34 Impedance Plethysmography

35 Diagnosis of PE Take your pick: V/Q scan Helical CT Pulmonary Angiography Angiography Of course, you could always get a CXR first

36 V/Q scan uniform distribution of Xenon gas <0.01 mGy to fetus Perfusion (Tc-99m) scan with significant areas that are not perfused 0.9 mGy to fetus Huda

37 Helical CT 0.14 mGy to fetus A CT scan of the female thorax (20–80 sections, average of 30 sections) will give a dose of 100–250 CXRs to the lungs and mammograms to the breasts Patel et al, Huda, Milne

38 Pulmonary Angiography Reid et al

39 References Berge LN, Lyngmo V, Svensson B, Nordoy A. The Bleeding Time in Women. Acta Obstet Gynecol Scand 1993: 72; Berge LN, Lyngmo V, Svensson B, Nordoy A. The Bleeding Time in Women. Acta Obstet Gynecol Scand 1993: 72; Chang J, Elam-Evans LD, Berg CJ, Herndon J, Flowers L, Seed KA, Syverson CA. Pregnancy-Related Mortality Surveillance --- United States, 1991—1999. MMWR Surveillance Summaries February 21, (SS02);1-8 Chang J, Elam-Evans LD, Berg CJ, Herndon J, Flowers L, Seed KA, Syverson CA. Pregnancy-Related Mortality Surveillance --- United States, 1991—1999. MMWR Surveillance Summaries February 21, (SS02);1-8 Cotran, et al. Robbins Pathologic Basis of Disease 7th ed. W.B. Saunders Co., Philadelphia, 2004 Cunningham FG et al Eds. Section VIII – Medical and Surgical Complications 47. Thromboembolic D isorders Williams Obstetrics McGraw-Hill 22nd Ed. (2005) Cunningham FG et al Eds. Section VIII – Medical and Surgical Complications 47. Thromboembolic D isorders Williams Obstetrics McGraw-Hill 22nd Ed. (2005) Fedullo PF, Morris TA. Section L - Disorders of the Pulmonary Circulation. Murray & Nadel's Textbook of Respiratory Medicine. Saunders. 4th ed, Fedullo PF, Morris TA. Section L - Disorders of the Pulmonary Circulation. Murray & Nadel's Textbook of Respiratory Medicine. Saunders. 4th ed, Fitzmaurice DA, Hobbs R, McManus RJ. Thromboembolism. American Family Physician 2004; 69(1) Fitzmaurice DA, Hobbs R, McManus RJ. Thromboembolism. American Family Physician 2004; 69(1) Greer IA. Thrombosis in Pregnancy: maternal and fetal issues. The Lancet. 1999; 353: Greer IA. Thrombosis in Pregnancy: maternal and fetal issues. The Lancet. 1999; 353: Haage P. Krings T. Schmitz-Rode T. Nontraumatic vascular emergencies: imaging and intervention in acute venous occlusion. European Radiology. 12(11): , 2002 Nov. Heit, John A. MD; Kobbervig, Catie E. MD; James, Andra H. MD; Petterson, Tanya M. MS; Bailey, Kent R. PhD; Melton, L Joseph III MD Trends in the Incidence of Venous Thromboembolism during Pregnancy or Postpartum: A 30-Year Population-Based Study. Annals of Internal Medicine 2005; 143(10): Heit, John A. MD; Kobbervig, Catie E. MD; James, Andra H. MD; Petterson, Tanya M. MS; Bailey, Kent R. PhD; Melton, L Joseph III MD Trends in the Incidence of Venous Thromboembolism during Pregnancy or Postpartum: A 30-Year Population-Based Study. Annals of Internal Medicine 2005; 143(10): Huda W. When a pregnant patient has a suspected pulmonary embolism, what are the typical embryo doses from a chest CT and a ventilation/perfusion study?. Pediatric Radiology. 35(4):452-3, 2005 Apr. Kruithof EKO, Tran-Thang C, Gudinchet A, Hauert J, et al. Fibrinolysis in Pregnancy: A Study of Plasminogen Activator Inhibitors. Blood, Vol 69. No 2 (February), 1987: pp Laros RK. Chapter 47: Thromboembolic Disease. Maternal-fetal medicine : principles and practice. Eds, Creasy RK, Resnik R, Iams JD. Philadelphia, Pa. : Saunders, 2004: Laros RK. Chapter 47: Thromboembolic Disease. Maternal-fetal medicine : principles and practice. Eds, Creasy RK, Resnik R, Iams JD. Philadelphia, Pa. : Saunders, 2004: Milne ENC. Coment: Breast: The Forgotten Organ. Radiology 233(3) Dec Milne ENC. Coment: Breast: The Forgotten Organ. Radiology 233(3) Dec Moores L. Bilello KL. Murin S. Sex and gender issues and venous thromboembolism. Clinics in Chest Medicine. 25(2):281-97, 2004 Jun. Moores L. Bilello KL. Murin S. Sex and gender issues and venous thromboembolism. Clinics in Chest Medicine. 25(2):281-97, 2004 Jun. Patel S. Kazerooni EA. Helical CT for the evaluation of acute pulmonary embolism. AJR. American Journal of Roentgenology. 185(1):135-49, 2005 Jul. Reid JH. Multislice CT pulmonary angiography and CT venography. British Journal of Radiology. 77 Spec No 1:S39-45, Stein PD, Hull RD, Kayali F, Olson RE, Alshab AK, et al Venous Thromboembolism in Pregnancy: 21 year trends. The Amer J Med 2005; 117: Stein PD, Hull RD, Kayali F, Olson RE, Alshab AK, et al Venous Thromboembolism in Pregnancy: 21 year trends. The Amer J Med 2005; 117:

40 “The one generalization about venous thromboembolism that is free from controversy is that many aspects of this disorder remain controversial” Fedullo et al


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