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From the Mayo Clinic, Rochester, Minnesota.
Grant Support: In part by grants from the National Institutes of Health (HL-60279, HL-66216, AR-30582), U.S. Public Health Service, and by the Mayo Foundation.
Potential Financial Conflicts of Interest: None disclosed.
Requests for Single Reprints: John A. Heit, MD, Hematology Research, Stabile 660, Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Current Author Addresses: Drs. Heit, Bailey, and Melton and Ms. Petterson: Mayo Clinic, 200 First Street SW, Rochester, MN 55905.
Dr. Kobbervig: Meriter Hospital, 202 South Park Street, Atrium 3, Madison, WI 53715.
Dr. James: Maternal–Fetal Medicine, Duke University Medical Center 3967, Durham, NC 27710.
Author Contributions: Conception and design: J.A. Heit, C.E. Kobbervig, T.M. Petterson, K.R. Bailey, L.J. Melton III.
Analysis and interpretation of the data: J.A. Heit, C.E. Kobbervig, A.H. James, T.M. Petterson, K.R. Bailey, L.J. Melton III.
Drafting of the article: J.A. Heit, C.E. Kobbervig, A.H. James, T.M. Petterson, K.R. Bailey, L.J. Melton III.
Critical revision of the article for important intellectual content: C.E. Kobbervig, A.H. James, K.R. Bailey, L.J. Melton III.
Final approval of the article: J.A. Heit, C.E. Kobbervig, A.H. James, L.J. Melton III.
Statistical expertise: T.M. Petterson, K.R. Bailey.
Obtaining of funding: J.A. Heit.
Administrative, technical, or logistic support: J.A. Heit, T.M. Petterson.
Collection and assembly of data: J.A. Heit, T.M. Petterson.
Altogether, 50 080 births occurred among Olmsted County women who were 15 years of age or older during the 30-year study period, 1966 to 1995. Within this time frame, both the population of Olmsted County and the number of pregnancies increased. However, the pregnancy rate (births per female population) decreased in the early 1970s but remained stable thereafter (Figure 1). A shift toward older maternal age also occurred during the study period. Among women of childbearing age, the rate of live births ranged from a low of 590.6 per 100 000 for women 35 years of age or older to a high of 14280.3 per 100 000 for those 25 to 29 years of age.
Actual age-specific and year-specific rates are shown as data points, and modeled age-specific and year-specific rates derived from the Poisson regression analyses are shown as lines.
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I have 3 pacients pregnants that had prescribe the profilaxis of DVT with sodic Enoxaparin 40mg since the last trimester until puerperium (loquia rubra). The first have Antiphosfolipid Sindrome diagnosticated, the second had an DVT in the past without screen of ethiology, and the third had DVT in the past with Leiden factor presenÃ§e. None of the three pacients had DVT in the post partum.
It is my hypothesis that low DHEA may result in thrombosis (http://www.anthropogeny.com/Thrombosis%20May%20Be%20Caused%20by%20Low%20DHEA.htm). A number of conditions that may be caused by low DHEA also exhibit increased thrombosis.
Maternal DHEA declines postpartum. I suggest the increased incidence of thrombosis postpartum is due to reduced DHEA.
I found this study (1) very interesting since this is a 30 years study. Here in this study John A. Heit at el concluded that "incidence of venous thromboembolism during pregnancy remained relatively constant whereas the postpartum incidence of pulmonary embolism decreased more than 2-fold". The author John A. Heit at el could showed the study more meaningful if they were able to stratified all the patients in different group by age, presence of any medicoligal condition (like antiphospholipid syndrome), leiden factor deficiency, previous history of DVT. How many patients were treated by drugs as prophylaxis for DVT also did not showed up in this study.
Over the 30-year study period, the incidence of venous thromboembolism during pregnancy remained relatively constant, so this needs to be identified.
In reference to DVT another study (2) which was done to determine the frequency of deep venous thrombosis (DVT) in medical intensive care unit (MICU) patients in Boston, MA. The author D. R. Hirsch, E. P. Ingenito at el concluded that "An unexpectedly high rate of DVT was detected by ultrasound in these MICU patients despite prophylaxis in 61%. Traditionally recognized DVT risk factors failed to identify patients who developed DVT. This proves that even with prophylaxis incidence of DVT rates did not fall.
1. John A. Heit, Catie E. Kobbervig, Andra H. James, Tanya M. Petterson, Kent R. Bailey, and L. Joseph Melton, III Trends in the Incidence of Venous Thromboembolism during Pregnancy or Postpartum: A 30-Year Population-Based Study Ann Intern Med 2005; 143: 697-706.
2. D. R. Hirsch; E. P. Ingenito; S. Z. Goldhaber Prevalence of deep venous thrombosis among patients in medical intensive care JAMA, Jul 1995; 274: 335 - 337.
To the Editors:
In "Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study", (1) the authors state that there are few data regarding the relative risks of venous thromboembolism (VTE) during pregnancy. Based on 105 patients with deep venous thrombosis (DVT) or pulmonary embolism (PE) during pregnancy or postpartum, the authors estimated that the incidence of DVT during pregnancy remained essentially unchanged over the 30-year period of study and the incidence of postpartum DVT declined. The authors speculate that early mobilization and shorter hospitalization after delivery may have contributed to this result. This apparently advantageous observation, based on a limited database, may cause physicians to become complacent. A much larger database, the National Hospital Discharge Survey (NHDS), showed pregnancy related DVT in 24,000 women throughout the United States from 1979 through 1999 (2). Pregnancy-associated DVT clearly increased over the last 2 decades, whereas nonpregnancy-associated DVT among hospitalized women declined. Importantly, older age, being black and delivery by cesarian section were associated with higher rates of pregnancy-associated DVT (2).
The NHDS during this period of study (1979-1999) was based on data abstracted annually from 181,000 to 307,000 sampled patient abstracts from 400 to 480 non-federal short-stay, non-institutional hospitals in 50 states and the District of Columbia (2, 3). This represented approximately 8% of all such hospitals and 1% of all discharges (3). Strengths of the NHDS include the huge number of patients, the widely varying regions in which patients were hospitalized, the extended period of time over which data were collected, and the broad spectrum of patients evaluated. Weaknesses include an inability to determine the basis of the diagnosis of DVT and PE, if antithrombotic prophylaxis or treatment was administered, or if patients were hospitalized more than once in a given year.
Based on the data we reported (2), there is good reason for continued vigilance concerning pregnancy-associated DVT.
1. Heit JA, Kobbervig CE, James AH, Patterson TM. Bailey KR, Melton LJ III. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: a 30-year population-based study. Ann Intern Med 2005;143:697-706.
2. Stein PD, Hull RD, Kayali F, Olson RE, Alshab AK, Meyers FA, Ghali WA, Silbergleit A, Gibson P. Venous thromboembolism in pregnancy: 21 year trends. Am J Med 2004;117:121-125.
3. Stein PD, Hull RD, Ghali WA, Patel, KC, Olson RE, Meyers FA, Kalra NK. Tracking the uptake of evidence: Two decades of hospital practice trends for diagnosing deep venous thrombosis and pulmonary embolism. Arch Intern Med 2003;163:1213-1219.
To the Editor: The population based study for Incidence of Venous Thromboembolism during pregnancy and postpartum identify age and postpartum period as key issues. (1) Incidence of Caesarean Section in USA has been 21 percent in last few decades of last century. (2) This study does not identify women undergoing caesarean sections as a separate high risk group. The operative vaginal delivery, Emergency Caesarean section in labor, high body mass index, previous venous thromboembolism and family history were described as major risk factors. (3) In one small study thromboembolism incidence was very low in women with no additional risk factors when Caesarean sections rate was 20 percent in the selected population. (4). Even though there is no consensus on prophylaxis after caesarean section. This population study could have given more guidance to further research and clinical trials for women with increasing age undergoing caesarean section. There is phase III clinical trial underway to assess the effectiveness and safety of low molecular weight heparin in women who are at moderate to high risk of venous thromboembolism after a caesarean section. (5)
Reference: 1.Heit JA, Kobbervig CE, James AH, Petterson TM, Baily KR, Melton JL. Trends in the incidence of Venous Thromboembolism during pregnancy or postpartum: A 30 year population based study. Ann Intern Med. 2005; 143:697-706 2.National Center for Health Statistics, Curtin SC. Rates of cesarean birth and vaginal birth after previous cesarean, 1991-95. Mon Vital Stat Rep 1997; 45:Suppl 3-Suppl 3. 3.Greer IA. Prevention of venous Thromboembolism in pregnancy. Best Pract Res Clin Haematol. 2003; 16(2): 261-78 4.Jacobsen AF, Drolsum A, Klow NE, Dahl GF, Qvigstad E, Sandset PM. Deep vein thrombosis after elective caesarean section. Thrombo Res. 2004; 113(5): 283-288 5.The STOP CLOT pilot study: at Clinicaltrials.Gov accessed on 12/13/2005
We congratulate Heit and colleagues1 on their study on the incidence of venous thromboembolism during pregnancy and the puerperium. However, we take issue with their statement that the venous thromboembolic incidence was 3.6% and 1.5% in the first and second weeks postpartum respectively, comparable to the 2% to 5% incidence of symptomatic venous thromboembolism after elective hip replacement in patients not receiving prophylaxis. This seems unlikely when only 105 maternal cases of venous thromboembolism were diagnosed during pregnancy or postpartum in 50,000 births.
This discrepancy relates to the manner the authors have used to calculate the incidence. For some purposes it makes sense to compare incident rates per person year at risk, as the authors have done. In this instance, in consideration of the possible benefit of thromboembolic prophylaxis, it is more relevant to know the chance of an individual having an event postpartum. It is misleading of the authors to compare the two types of measure. The incidence rate per 100,000 person years in week 1 postpartum is 3573 per 100,000. However this is not 3.6% of pregnant women who have an event in the first week postpartum. Because by this point they have only been at risk for 1/52th of the year, only 68 per 100 000 or 0.68 per 1000 will have had an event in that week.
From Table 1, in women over 35 (the highest risk group) the risk postpartum of a venous thromboembolism is ~900/100,000 person years. As the postpartum period defined by the authors is 3 months, the risk to a woman who has delivered is ~225 per 100,000 (13/52 of the rate per 100,000 person years). This is ~2 per 1000, a tenth of the 2-5% rate for having a symptomatic thrombosis after elective hip surgery.
References 1. Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ III. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: A 30-year population-based study. Ann Intern Med 2005;143:697- 706.
Dr. MacCullum and co-workers argue that we incorrectly reported our venous thromboembolism incidence rates for the first and second postpartum weeks as "3.6%" and "1.5%", respectively, because of incorrect denominator calculations. The denominator calculations were based on the total number of live births in Olmsted County (n=50,080) and "period at risk" definitions of 9 and 3 months for pregnancy and the postpartum period, respectively. A one-week period of risk is 1/52 of a year (0.019), such that the woman-years at risk during the first postpartum week were 0.019 times the number of live births (0.019*50,080=951 woman-years). Thirty- four women had documented incident venous thromboembolism during this week, providing an incidence of 34/951=0.036, or 3.6 per 100 woman-years (i.e., 3.6%). The second postpartum week incidence rate was calculated similarly. However, while the incidence rates are correct as reported, we incorrectly compared these rates to the proportion of patients developing venous thromboembolism after total hip replacement. Using data reported from the California Patient Discharge Data Set, among 56,720 patients undergoing elective total hip replacement between January 1, 1992 and September 30, 1996, 1358 developed symptomatic venous thromboembolism within 3 months (0.25 years) after surgery.1 Thus, the person-years at risk were 56,720*0.25=14,180 person-years, and the venous thromboembolism incidence was 1358/14,180=0.096, or 9.6 per 100 person-years, which is similar to our first and second postpartum week incidence rates.
Drs. Rajput and Rana suggest that Caesarean section is a risk factor for venous thromboembolism. Our present study was not designed to address this question. However, in a previous population-based case-control study specifically addressing risk factors for pregnancy-associated venous thromboembolism, we could not identify Caesarean section as a risk factor for postpartum venous thromboembolism (univariate odds ratio=1.17; 95%CI: 0.39, 3.47).2
Dr. Stein and co-workers cite their study reporting an analysis of administrative data from the National Hospital Discharge Survey (NHDS) and indicating that pregnancy-associated deep vein thrombosis rates increased between 1979 and 1999.3 Pregnancy-associated pulmonary embolism was too infrequent to analyze for trends. In contrast, we found a decrease in the overall incidence of pregnancy-associated venous thromboembolism, mostly due to a decrease in postpartum pulmonary embolism; the incidence of pregnancy-associated deep vein thrombosis declined slightly and nonsignificantly. These differences may be explained by different study designs. The timeframe of our study was longer (1966-1995). Moreover, we only included women with a first lifetime event, while the NHDS database does not separate incident from recurrent events. Finally, almost 70% of women coded by the International Classification of Diseases, 9th Edition, Clinical Modification (ICD-9-CM) as having pregnancy-associated deep vein thrombosis may be miscoded.4 Nevertheless, we certainly agree with the need for continued vigilance regarding pregnancy-associated venous thromboembolism.
John A. Heit, MD Kent R. Bailey, PhD L. Joseph Melton III, MD,MPH
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1. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003;90:446-55. 2. Danilenko-Dixon DR, Heit JA, Watkins T, Silverstein MD, Yawn B, Petterson TM, Lohse CM, O'Fallon WM, Melton LJ III. Risk factors for deep vein thrombosis and pulmonary embolism during pregnancy or the postpartum period: a population-based case-control study. Am J Obstet Gynecol 2001;184:104-110. 3. Stein PD, Hull RD, Kayali F, Olson RE, Alshab AK, Meyers FA, Ghali WA, Silbergleit A, Gibson P. Venous thromboembolism in pregnancy: 21-year trends. Amer J Med 2004;117:121-5. 4. White RH, Brickner LA, Scannell KA. ICD-9-CM codes poorly identified venous thromboembolism during pregnancy. J Clin Epidemiol 2004;57:985-8.
Evaluating the Risk for Pregnancy-Associated Venous Thromboembolism: A 30-Year Study
The summary below is from the full report titled “Trends in the Incidence of Venous Thromboembolism during Pregnancy or Postpartum: A 30-Year Population-Based Study.” It is in the 15 November 2005 issue of Annals of Internal Medicine (volume 143, pages 697-706). The authors are J.A. Heit, C.E. Kobbervig, A.H. James, T.M. Petterson, K.R. Bailey, and L.J. Melton III.
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