Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 8  |  Issue : 2  |  Page : 125-128

Management of deep-vein thrombosis in pregnancy


1 Department of Obstetrics and Gynaecology, AIIMS, Bibinagar, Telangana, India
2 Department of Vascular and Endovascular Surgery, Apollo Hospital, Hyderabad, Telangana, India

Date of Submission19-May-2020
Date of Decision01-Jul-2020
Date of Acceptance06-Aug-2020
Date of Web Publication13-Apr-2021

Correspondence Address:
Nabnita Patnaik
Department of Obstetrics and Gynaecology, AIIMS, Bibinagar, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijves.ijves_63_20

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  Abstract 


Introduction: Pregnancy and puerperium are well-established risk factors for deep-vein thrombosis (DVT) and pulmonary embolism (PE), which are collectively referred to as venous thromboembolism (VTE). Objectives: Treatment of VTE in pregnant patients is unique in several ways. A subset of pregnant patients requires anticoagulation during pregnancy and/or in the postpartum period, including women at high risk of DVT and some women with fetal loss. Materials and Methods: It was a retrospective study of all DVT patients with pregnancy, referred to the vascular surgery department of a tertiary care hospital from December 2015 to November 2019. Results: A total of 56 DVT patients with pregnancy were admitted in the vascular surgery department during the above period. Sixteen of them had a past history of DVT in previous pregnancy. Thirty-two patients presented in the first trimester, 14 in the second trimester, and 10 in the third trimester of pregnancy. Eight of them had associated PE and managed with intensive care unit care. All patients were managed with long-term anticoagulant with low-molecular-weight heparin. Conclusion: Use of anticoagulants during pregnancy is challenging due to the potential teratogenic effects and dosing complexities of the various agents and the management of anticoagulation during the time of labor. The need for thromboprophylaxis should be assessed antepartum, postpartum, and at any time the patient transitions from the outpatient to the inpatient setting. When it is determined that thromboprophylaxis is warranted, an appropriate strategy should be selected and prescribed.

Keywords: Deep-vein thrombosis, low-molecular-weight heparin, pulmonary embolism, pregnancy, symptoms


How to cite this article:
Patnaik N, Pradhan NR. Management of deep-vein thrombosis in pregnancy. Indian J Vasc Endovasc Surg 2021;8:125-8

How to cite this URL:
Patnaik N, Pradhan NR. Management of deep-vein thrombosis in pregnancy. Indian J Vasc Endovasc Surg [serial online] 2021 [cited 2021 May 7];8:125-8. Available from: https://www.indjvascsurg.org/text.asp?2021/8/2/125/313560




  Introduction Top


Sequelae of deep-vein thrombosis (DVT) and pulmonary embolism (PE) include complications such as pulmonary hypertension, postthrombotic syndrome, and venous insufficiency. Pregnancy increases the risk of venous thromboembolism (VTE) 4–5 folds, compared to that in the nonpregnant state.[1],[2] The two manifestations of VTE are DVT and PE. Although most reports suggest that VTE can occur at any trimester in pregnancy, studies suggest that VTE is more common during the first half of pregnancy. VTE may occur at any time during gestation. Studies report conflicting data as to the timing in pregnancy. One study of 165 episodes of VTE in pregnancy documented a higher incidence in the first trimester; most evidence suggests that VTE is more common in the postpartum period.[1] In a 30-year population-based study, Heit et al. documented that the risk of VTE and PE was 5-fold and 15-fold, respectively, in the postpartum period compared to during pregnancy. DVT is approximately three times more common that PE in pregnancy.[2]

In pregnancy, DVT is much more likely to occur in the left leg compared with the right leg. One study examined sixty cases of DVT in pregnancy: 58 occurred in the left leg, two were bilateral, and none occurred in the right leg.[3],[4],[5],[6],[7],[8] The predilection for left lower extremity DVT is postulated to be the consequence of May–Thurner syndrome, in which the left iliac vein is compressed by the right iliac artery. A large Indian study on DVT and PE reported similar data, but a specific large study on DVT in pregnancy is not available.

Signs and symptoms

The signs and symptoms of VTE are nonspecific and common in pregnancy. Diagnosis of VTE by physical[3] examination is frequently inaccurate, even though one study found that 80% of pregnant women with DVT experience pain and swelling of the lower extremity. The classic symptoms are as follows: dyspnea – 82%, abrupt onset of chest pain – 49%, and cough – 20%. The most common presenting signs of PE are as follows: tachypnea, crackles, and tachycardia. Patients with massive PE may present with the following: syncope, hypotension, pulseless cardiac electrical activity, and death.

Pathophysiology

Pregnancy is a state of hypercoagulability due to alterations of coagulation proteins. Factors I, II, VII, VIII, IX, and X increase in pregnancy. Pregnancy increases resistance to the antithrombotic factors such as protein C and protein S.[9] Thrombophilias can exacerbate these changes in coagulation proteins, further increasing the patient's risk for VTE. Hence, pregnancy is a state characterized by Virchow's triad (1: hypercoagulability, 2: venous stasis and turbulence, and 3: endothelial injury and dysfunction). Venous stasis also increases as dilation of lower extremity veins occurs followed by venous compression by the gravid uterus and enlarging iliac arteries. Situations of decreased mobility may exacerbate these factors. Endothelial injury may transpire at the time of delivery.[10] These factors work together to increase the risk of VTE in pregnant and postpartum patients.

Diagnosis

Laboratory studies

Limited data suggest that D-dimer may have lower sensitivity in the setting of suspected PE. D-dimer testing is often used in the diagnosis of DVT in nonpregnant patients due to its high negative predictive value. Pregnancy decreases the specificity of D-dimer testing, however D-dimer retains a good negative predictive value in the setting of suspected DVT.

Imaging studies

The current initial test of choice in the evaluation of VTE is compression ultrasonography (CUS) of the lower extremity veins. Imaging for DVT and/or PE is the best means of screening and evaluation for these conditions. CUS has been shown to be with >95% sensitivity and specificity for proximal lower extremity DVT. In pregnancy, CUS should be performed in the patient in the left lateral decubitus position and with Doppler analysis of flow variation during respiration to maximize the study's ability to diagnose pelvic DVT.[4],[6] CUS is less accurate in the diagnosis of pelvic DVT.[5] If the suspicion of pelvic DVT is high, further evaluation with serial CUS or magnetic resonance imaging (MRI) is recommended.[7],[8],[9] MRI has been shown to have 97% sensitivity and 95% specificity for pelvic DVT in nonpregnant patients.[4],[10] Ventilation/perfusion (V/Q) scanning: in a pregnant patient with no known pulmonary disease and a normal chest radiograph, V/Q scanning is the recommended study to evaluate for PE. If the patient has an abnormal chest radiograph, known pulmonary disease, or a nondiagnostic V/Q scan, then spiral computed tomography-pulmonary angiography is recommended.[11]


  Materials and Methods Top


It was a retrospective study of all DVT patients with pregnancy, referred to the vascular surgery department of a tertiary care hospital from December 2015 to November 2019. DVT/PE presentation in the first/second/third trimester of pregnancy was noted and managed with intensive care unit (ICU) care. All the patients were managed with long-term anticoagulant with low-molecular-weight heparin (LMWH). Long-term follow-up was done to evaluate postthrombotic syndrome, and the group with protein C/S deficiency and antithrombin 3 deficiency was treated with long-term anticoagulation with novel oral anticoagulants (NOACSs).


  Results Top


A total of 56 DVT patients with pregnancy were admitted in the vascular surgery department during the above period. Sixteen of them had a past history of DVT in previous pregnancy. Thirty-two presented in the first trimester, 14 in the second trimester, and 10 in the third trimester of pregnancy. Eight of them had associated PE and managed with ICU care. All patients were managed with long-term anticoagulants with LMWH. Long-term follow-up showed that 14 patients developed postthrombotic syndrome and needed long-term anticoagulation with NOACS. Use of Class 2 stockings regularly helped the patients to get symptomatic relief of leg edema. After cessation of anticoagulants, all patients were evaluated for prothrombotic workup. Eighteen patients had protein C/S deficiency and six patients had antithrombin 3 deficiency, who were advised with long-term anticoagulation and thromboprophylaxis during subsequent pregnancies.

Management

Once the diagnosis of VTE is made, therapeutic anticoagulation should be initiated in the absence of contraindications. The common classes of anticoagulation drugs are as follows: indirect thrombin inhibitors which include unfractionated heparin (UFH) and LMWH [Figure 1] and [Figure 2] as well as synthetic heparin pentasaccharide and orally administered Factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban) and direct thrombin inhibitors which include argatroban, lepirudin, bivalirudin, and dabigatran. In addition, Vitamin K antagonist, warfarin, is included in this class.
Figure 1: Heparin (unfractionated) and low-molecular-weight heparin are the preferred drugs for managing venous thromboembolism in pregnancy[12]

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Figure 2: Treatment protocol: low-molecular-weight heparin, therapeutic dose of enoxaparin 1 mg/kg body weight sc 12 hourly, prophylactic dose once daily

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Consequence of venous thromboembolism

Mild postthrombotic syndrome occurs in 20%–40% of patients after VTE, and severe postthrombotic syndrome occurs in 5% of patients after VTE.[12],[13],[14],[15],[16] Sequelae of DVT and PE include complications such as pulmonary hypertension, postthrombotic syndrome, and venous insufficiency. Postthrombotic syndrome is not well defined; however, most definitions consist of a constellation of symptoms (pain, cramps, heaviness, pruritus, and paresthesia) and signs (edema, skin induration, hyperpigmentation, venous ectasia, redness, pain during calf compression, and in more severe forms, venous stasis ulcer) in the extremity affected by DVT [Figure 3].
Figure 3: Algorithm for diagnosis and treatment of deep-vein thrombosis in pregnancy[12]

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  Discussion Top


Use of anticoagulants in breastfeeding mothers

Heparin and LMWHs are not secreted in breastmilk, and two reports have shown that maternal administration of warfarin does not induce an anticoagulant effect in the breastfed infant. Thus, women using these agents can safely breastfeed.

Fetal complications of anticoagulants during pregnancy

Warfarin crosses the placenta and can cause fetal bleeding and teratogenicity, with the latter occurring mainly during the first trimester.[13]

Neither UFH nor LMWH crosses the placenta; therefore, these agents do not cause fetal bleeding or teratogenicity, although bleeding at the uteroplacental junction and fetal wastage are possible.

Maternal complications of anticoagulants during pregnancy

The rate of major bleeding in patients treated with UFH therapy is 2%.[14] Approximately 3% of patients receiving UFH develop immune thrombocytopenia (the so-called heparin-induced thrombocytopenia [HIT]), which predisposes them to venous and arterial thrombosis.

Heparin-induced osteoporosis causes vertebral fracture in 2%–3% of patients, and a significant reduction in bone density is seen in about 30% of patients receiving long-term UFH. LMWH causes less osteoporosis and HIT than UFH.[12],[15],[16]


  Conclusion Top


The following steps can be taken to reduce the risk of developing DVT during pregnancy:

  • Regular pregnancy-safe exercises
  • Walking for at least 1 h daily is recommended
  • Cessation of smoking.


A preventive dose of heparin/LMWH can be given to women at high risk of DVT during the entire period of pregnancy or at 6 to 8 weeks postpartum. DVT is not common in pregnancy but is a serious condition that can be lethal. Awareness of the symptoms and risk factors is important to prevent DVT. Early treatment is helpful in ensuring the safety of the baby.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Pomp ER, Lenselink AM, Rosendaal FR, Doggen CJ. Pregnancy, the postpartum period and prothrombotic defects: Risk of venous thrombosis in the MEGA study. J Thromb Haemost 2008;6:632-7.  Back to cited text no. 1
    
2.
Heit JA, Kobbervig CE, James AH, Petterson TM, Bailey KR, Melton LJ 3rd. Trends in the incidence of venous thromboembolism during pregnancy or postpartum: A 30-year population-based study. Ann Intern Med 2005;143:697-706.  Back to cited text no. 2
    
3.
Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: Clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER) Lancet 1999;353:1386-9.  Back to cited text no. 3
    
4.
Polak JF, Wilkinson DL. Ultrasonographic diagnosis of symptomatic deep venous thrombosis in pregnancy. Am J Obstet Gynecol 1991;165:625-9.  Back to cited text no. 4
    
5.
Pabinger I, Grafenhofer H, Kyrle PA, Quehenberger P, Mannhalter C, Lechner K, et al. Temporary increase in the risk for recurrence during pregnancy in women with a history of venous thromboembolism. Blood 2002;100:1060-2.  Back to cited text no. 5
    
6.
Macklon NS, Greer IA, Bowman AW. An ultrasound study of gestational and postural changes in the deep venous system of the leg in pregnancy. Br J Obstet Gynaecol 1997;104:191-7.  Back to cited text no. 6
    
7.
American College of Obstetricians and Gynecologists Practice Bulletin No 123: Thromboembolism in Pregnancy; 2011.  Back to cited text no. 7
    
8.
Nijkeuter M, Ginsberg JS, Huisman MV. Diagnosis of deep vein thrombosis and pulmonary embolism in pregnancy: A systematic review. J Thromb Haemost 2006;4:496-500.  Back to cited text no. 8
    
9.
Spritzer CE, Norconk JJ Jr, Sostman HD, Coleman RE. Detection of deep venous thrombosis by magnetic resonance imaging. Chest 1993;104:54-60.  Back to cited text no. 9
    
10.
Perrier A, Roy PM, Sanchez O, Le Gal G, Meyer G, Gourdier AL, et al. Multidetector-row computed tomography in suspected pulmonary embolism. N Engl J Med 2005;352:1760-8.  Back to cited text no. 10
    
11.
Leung AN, Bull TM, Jaeschke R, Lockwood CJ, Boiselle PM, Hurwitz LM, et al. ATS/STR Committee on Pulmonary Embolism in Pregnancy. Radiology. 2012;262:635-46.  Back to cited text no. 11
    
12.
Aguilar D, Barradas I, Guevara L, Luque L. Pharmacologic Management of Deep Vein Thrombosis in Pregnancy and Nursing Implications. Nursing FIU Published on 25 March, 2013. Available from: http://www.slideshare.net ' isabelbarradas ' dvt-in-pregnancy. [Last accessed on 2020 Apr 20].  Back to cited text no. 12
    
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Gherman RB, Goodwin TM, Leung B, Byrne JD, Hethumumi R, Montoro M. Incidence, clinical characteristics, and timing of objectively diagnosed venous thromboembolism during pregnancy. Obstet Gynecol 1999;94:730-4.  Back to cited text no. 13
    
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O'Connor DJ, Scher LA, Gargiulo NJ 3rd, Jang J, Suggs WD, Lipsitz EC. Incidence and characteristics of venous thromboembolic disease during pregnancy and the postnatal period: A contemporary series. Ann Vasc Surg 2011;25:9-14.  Back to cited text no. 14
    
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Ray JG, Chan WS. Deep vein thrombosis during pregnancy and the puerperium: A meta-analysis of the period of risk and the leg of presentation. Obstet Gynecol Surv 1999;54:265-71.  Back to cited text no. 15
    
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Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium–a register-based case-control study. Am J Obstet Gynecol 2008;198:233.e1-7.  Back to cited text no. 16
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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