D-dimer in Pregnancy: Ready for Prime Time?

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確定PE評估中的策略是否在策略準備好。

The evaluation of dyspneic pregnant patients at risk of pulmonary embolism (PE) presents a significant challenge to most emergency physicians.

背景


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孕婦通常很年輕,否則健康,但錯過的PE的後果可能是災難性的,並且對由此產生的過度的醫療輻射產生的評估和過度成像的風險是我們想要避免/減少的東西。這些介紹的額外複雜性特征是,懷孕的預期生理變化可能導致其第二和第三個三個月的婦女在基線上經曆腿部腫脹,心動過速和呼吸困難的感覺;靜脈血栓栓塞(VTE)的常見跡象/症狀。

The estimated incidence of PE in pregnancy is 1.72 cases per 1000 deliveries, with a death rate of 1:100,000 deliveries. [1]

以前的發現


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D-dimer use as a strategy to reduce the need for advanced imaging in the evaluation of VTE is a well-established practice in the non-pregnant population, and most studies that evaluate the use of D-dimer diagnostic strategies have excluded pregnant patients in the past.

Historically, D-dimer use in pregnant patients has not been recommended. There is good evidence that baseline D-dimer levels in pregnant women will progressively increase as their pregnancy progresses. This reduces the likelihood of a negative result below the established threshold of 500 ng/ml.

In 2011, the American Thoracic Society clinical practice guideline recommended against the use of D-dimer in the evaluation of VTE in pregnancy. [2] This recommendation was based on the admittedly weak evidence of one retrospective study of 37 pregnant patients with suspected PE who had V/Q scan and D-dimer testing. Sensitivity of D-dimer for PE in this study was 73%. Additional indirect evidence used in the recommendation was three prospective studies evaluating a total of 389 patients for DVT. D-dimer was 100% sensitive for DVT, however there was a very low rate of DVT in this population.

D-dimer Adjustments


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Jeff Kline, MD, proposed a strategy of trimester specific pregnancy adjusted D-dimer cutoffs in a 2013 interview on Rob Orman’s ERCast podcast [4] Kline is an emergency physician, and an expert in venous thromboembolism.

該擬議的策略是對孕婦進行D-Dimer測試,預先預測概率小於40%(井得分小於或等於4),以及105 bpm的調整後心率截止的陰性Perc規則。推薦調整的D-DIMER閾值為750/1000/1250 ng / ml,分別為第一,第二和三個三三聚氰酯。該策略具有生理合理性(以與老年人的年齡調整D-Dimer截止值相同的方式,但是,這一策略尚未探討。

Another study to deliberately evaluate the utility and accuracy of D-dimer testing as a diagnostic strategy in the evaluation of VTE in pregnancy was the DiPEP study (Diagnosis of PE in Pregnancy) published in 2018. [5] This was a prospective observational cohort study of 310 pregnant or postpartum patients in the UK who were suspected of having a VTE.

The authors measured multiple biomarkers, including D-dimer, that was compared between patients with confirmed VTE and those where VTE was excluded. A group of women with known DVT were added to the study population to increase the prevalence of VTE in the study, and to improve the estimates of biomarker sensitivity. This study did not identify a threshold for any biomarker (including D-dimer) that would optimize sensitivity in the upper 90% range while maintaining reasonable specificity.

One specific weakness of the study is that a large proportion of patients were already on anticoagulation at the time of D-dimer measurement. This can impact the accuracy of this test. An additional weakness of the study was that there was no incorporation of pretest probability included in the diagnostic pathway employed. For more on the statistics, strengths, and weaknesses of this study check out therebelem.comblog post by Rick Pescatore DO. [5,6]

在2018年末,Righini和他的同事試圖inc .orporate pretest probability into a testing strategy using a D-dimer threshold of 500 ng/ml, compression ultrasonography, and CT pulmonary angiography. [7] This was a multicenter, multinational prospective diagnostic outcome study of 395 pregnant women who were clinically suspected of PE with signs of acute onset of new or worsening shortness of breath or chest pain without another obvious cause.

基於其修訂的日內瓦評分(見下表),患者被歸類為低,中間或高風險。具有低或中間預測試概率的那些具有D-二聚體篩選,如果它們的D-二聚體<500ng / mL,則沒有進一步的成像。風險高風險或D-二聚體> 500 ng / ml患者進行雙側壓縮超聲檢查。如果超聲波呈陽性,則對它們進行憑經驗進行治療。如果超聲波為陰性,則進行CT肺血管造影。所有患者均遵循三個月,主要結果是在婦女的後續期間沒有基於否定結果的初步處理的婦女的後續期間發生的VTE事件。

Table One: Revised Geneva Score

Variable Points
風險因素
Age > 65 1
Previous DVT or PE 3.
Surgery (under GA, or lower ext. fracture within 1 month) 2
Active malignant condition (or cured <1 year) 2
Symptoms
單側下肢疼痛 3.
咯血 2
Clinical Signs
Heart rate 75-94 beats/min 3.
Heart rate >95 beats/min 5.
Pain on lower limb deep venous palpation and unilateral edema 4.
臨床概率
低的 0-3總計
Intermediate 總計4-10.
High > / = 11總數

48.6%的患者的預測試概率低,中間體為50.6%,高0.8%。低/中間預測試概率患者的11.7%,D-Dimer測試是陰性的。陰性D二聚體檢測的比例隨著孕昔期的增加而降低:25.3%的孕期,11.1%孕孕孕中期和4.2%三三個月。整體PE率為7.1%。(正壓縮超聲,CTPA或V / Q掃描)。CT肺血管造影在84%的患者中進行。

在具有負D-二聚體測試的低/中間概率的患者中,在三個月後續期間沒有確診的VTE病例。有關該研究的統計,優勢和劣勢的更多信息,請參閱rebelem.com瑞克佩斯特雷的博客,做。[7,8]

發現

大多數主要體育決策規則研究故意排除懷孕患者。多年的研究小組沒有故意排除懷孕的患者,但隻注冊了一個非常低的數字。他們延長了他們的學習期,以刻意注冊更多懷孕患者,以評估懷孕適應年份算法。[9]這是一項令人前瞻性的研究,篩查了涉嫌PE的510名孕婦。篩選了原始年份算法的三個標準:DVT,咯血和PE的臨床跡象是最可能的診斷。患者0/3標準和小於1000ng / ml的D-二聚體無需進一步成像。1或更多標準和D-二聚體的患者較小,還排出500ng / ml。DVT臨床症狀的患者進行了雙側下肢壓縮超聲檢查。如果是陽性,則預測它們具有PE並置於抗凝血上,而不會確認CT肺血管造影。如果是陰性,並且D-二聚體小於500ng / ml,則它們被排出而無需進一步成像。

在三個月後續期間,主要結果是VTE的發生率。

體育是在4%的患者診斷的。六十一年全氯乙烯ent of patients in this study had a CT pulmonary angiogram performed. CT pulmonary angiogram was avoided in 65% of first trimester patients, 46% of second trimester patients, and 32% of third trimester patients. The three-month incidence of symptomatic VTE was 0.21%. One patient was diagnosed with a proximal DVT and there were no diagnoses of PE in the group that had negative D-dimer testing at the pre-specified thresholds of 500/1000 ng/ml depending on the number of YEARS criteria present.

Conclusion

The new data from 2018 and 2019 (Righini pretest probability study, and pregnancy adapted YEARS algorithm) provide clinicians challenged with safely ruling out PE and avoiding the harms of medical radiation with an option of using D-dimer in their diagnostic evaluation.

In the first trimester there is utility of a D-dimer testing strategy that can reduce the number of CT scans performed, reducing the risk of fetal teratogenicity. As D-dimer sensitivities for VTE drop in the second and third trimester D-dimer use becomes more of a challenge, however there is still demonstrated reduction in CT use in this gestational age group (YEARS reduced CT use by 46% in second, and 32% in third trimester patients). Reduction in maternal breast radiation exposure in the second and third trimester is an important goal, as is decreased resource utilization, and decreased cost of care.

Anytime you consider the incorporation of an evidence-based practice improvement that is a significant departure/progression from your usual practice it is reasonable to attempt to incorporate these changes on a departmental or even institutional level.

Bring the evidence to your department chair and your thrombosis team. Convincing the ‘needle experts’ that you have a better way of sifting through the ‘haystack of dyspnea’ in your emergency department, and then making an institutionally supported change may be better than blindsiding them with new evidence.

References:

[1] James AH. ET AL. Venous thromboembolism during pregnancy and the postpartum period: incidence, risk factors, and mortality. Am J Obstet Gynecol 2006;194:1311-5PMID: 16647915

[2] Leung An等。官方胸部學會/胸部放射學協會臨床實踐指南:妊娠疑似肺栓塞的評價。AM J111111111111115; 184(10):1200-8PMID:22086989.

[3] Rob Orman, ‘Pulmonary embolism in pregnancy with Jeff Kline’. ERCAST podcast, April 24, 2013. Available at:http://ercast.libsyn.com/pulmonary-embolism-in-pregnancy-with-jeff-kline

[4] Kline J. et al. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem. 2005 May;51(5):825-9.PMID:15764641

[5] Hunt, Beverly J., et al. The DiPEP (Diagnosis of PE in Pregnancy) biomarker study; An observational cohort study augmented with additional cases to determine the diagnostic utility of biomarkers for suspected venous thromboembolism during pregnancy and puerperium. Br J Haematol 2018 Mar;180(5):694-704PMID: 29359796

[6] Rick Pescatore. D-dimer and Pregnancy: The DiPEP Study, REBEL EM blog, March 19, 2018. Available at:https://rebelem.com/d-dimer-and-pregnancy-the-dipep-study/

[7] Righini, M., et al. Diagnosis of Pulmonary Embolism During Pregnancy. A Multicenter Prospective Management Outcome Study. Ann Intern Med. 2018 Dec 4;169(11):766-773PMID: 30357273

[8] Rick Pescatore. D-dimer in Pregnancy: Limiting Radiation with Pre-test Probability, REBEL EM blog, November 29, 2018, Available at:https://rebelem.com/d-dimer-in-pregnancy-limiting-radiation-with-pre-test-probability/

[9] van der Pol,L. M.等人。妊娠適應年診斷肺栓塞診斷算法。n engl J Med。2019年3月21日; 380(12):1139-1149PMID: 30893534

關於作者

Dr. Bryant is an Emergency Physician with Utah Emergency Physicians, Salt Lake City, UT.

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